Primary Exam Reports 2011 To 1999

AUSTRALIAN AND NEW ZEALAND COLLEGE OF ANAESTHETISTS
ABN 82 055 042 852

EXAMINATION REPORT

PRIMARY FELLOWSHIP EXAMINATION

AUGUST /SEPTEMBER 2011

Please note that this report is prepared to provide candidates and their teachers and
supervisors of training with information about the performance of candidates in the recent
examination, so that candidates and teachers may prepare appropriately for future
examinations. The individual reports are not intended to represent model answers nor
imply that all points mentioned are necessary in order to achieve a pass. All trainees are
urged to read the questions carefully and answer the question asked. All teachers and
supervisors of training are encouraged to discuss this report in detail with candidates they
are preparing for future examinations.

PHARMACOLOGY WRITTEN SECTION
________________________________________________________________________________

MULTIPLE CHOICE QUESTIONS:

76% of candidates achieved a pass in this section of the Pharmacology Examination.

SHORT ANSWER QUESTIONS:

1. Compare and contrast the clinically significant cardiovascular and central nervous
system effects of desflurane and sevoflurane.
66% of candidates passed this question.

Most correctly appreciated the changes in systemic vascular resistance (SVR),
myocardial contractility and consequent changes blood pressure due to sevoflurane
and desflurane. Also changes in cerebral blood flow, cerebral metabolic rate and
intracranial pressure were well understood. However a deeper level of understanding
was not universal, a common error being that falls in SVR equates to a fall in cardiac
output whereas this tends to be well maintained with these agents initially due to a
preserved baroreceptor reflex. Also a loss of cerebral autoregulation at higher MAC
values was not universally acknowledged. More than half recognised the effect of
myocardial preconditioning which was awarded marks due to a broad definition of the
term 'clinically significant'. Better answers correctly discussed differences without
getting too bogged down as of course there is a remarkable similarity between the two
agents. Only two candidates discussed the QT interval and none mentioned that
impaired diastolic function is also a cause of a reduction in stroke volume.

2. What is meant by the term "two compartment model" in pharmokinetics? Use
PROPOFOL as an example in explanation.

A systematic approach is needed to answer such a broad question. Areas which could
be addressed include:
What the model attempts to do, the structure of this kind of model and the mathematics
of the model.
Properties of propofol which suggest it might fit a multi, rather than a one
compartment model.
A description of the model, implications of the model, what such a model might be
used for and how this model differs from other pharmacokinetic models.
Assumptions implicit in using this model, and how this might affect its clinical
application. Sources of error in collecting data to test the model.

It was not necessary to cover all of these areas to obtain full marks.

Many candidates wasted time writing random pharmacokinetic data, details on the
structure and use of propofol, definitions of pharmacokinetics, or frameworks for
pharmacokinetic answers such as absorption, distribution, metabolism & excretion.

Commonly misunderstood concepts included:
Compartments being a theoretical construct only.
Models fit a curve to observed plasma concentrations plotted against time. No-one
described how such a curve might be fitted.
The y axis of the plasma concentration time curve is not half life.
The words saturated, equilibrium, steady state, and context sensitive half time.
It is difficult to explain the offset of propofol if the effect site is considered to be in the
peripheral compartment.
Calculating a loading dose of propfol using the Vdss would be fatal.
A two compartment model is conventionally drawn with two, rather than three or four
compartments.
Diagrams often depicted excretion as being bi-directional, or occurring through the
brain. Both practices are discouraged.

3. What is the mechanism of action of -adrenoreceptor antagonists? Outline the
therapeutic uses and side effects of these drugs.
78.3% of candidates passed this question.

Generally this was a very well answered question and most candidates covered all that
was asked of them. There was usually sufficient detail on the various cardiovascular
uses of the drug, and many candidates added other uses of beta blockers such as
treatment of glaucoma and migraine prophylaxis. With regard to the mode of action,
obviously they act by blockade of the beta receptor, but extra points were gained by
pointing out that this is a form of competitive antagonism and that this group of drugs
have very selective action on the beta receptors alone. There were some minor areas of
confusion. While beta adrenergic antagonists can be used to suppress the physical
stigmata of anxiety, such as dry mouth and tremor, they have no significant anxiolytic
properties per se the patient (or candidate!) is just as anxious on the inside. In fact
most of the CNS effects of these drugs are quite deleterious and include, insomnia and
sleep disturbance as well as vivid dreams. The effects on the peripheral circulation are
complex. Older, non selective agents cause peripheral vasoconstriction (not dilatation)
and can worsen or precipitate Raynauds disease, because the blockade of peripheral
beta 2 receptors allows the vasoconstricting alpha effects to predominate unchecked.
However, newer agents that are used in the management of cardiac failure, often
possess vasodilating properties, possibly mediated through nitric oxide release. Lastly
confusion also reigned with regard to the effects of these drugs on the uterus, with
candidates claiming that beta blocking drugs possessed both oxytocic and tocolytic
effects.

4. Describe the pathogenesis and management of paracetamol toxicity.

This question was phrased in 2 parts, Describe the pathogenesis and management of
paracetamol toxicity. Equal marks were allocated for each half of the question.

The pathogenesis of paracetamol toxicity requires a detailed discussion of the
metabolism of paracetamol and how it changes when toxic doses of paracetamol are
ingested. Mechanisms of toxicity primarily involving the liver and N-acetyl-p-
benzoquinone imine (NAPQI) were also important. Mention of typical doses of
paracetamol that could cause toxicity and subpopulations at increased risk of toxicity
with lower doses of paracetamol also attracted marks. Candidates who described
paracetamol metabolism in overdose using applied principles of pharmacokinetics
generally scored well.

Discussion of management of paracetamol toxicity needed to be balanced and mention
general measures such as resuscitation and early consideration for liver transplantation
as well as the specific therapies such as N-acetyl cysteine and methionine and the
specific principles relating to their use.

Candidates who were able to discuss these aspects of the question in sufficient detail
achieved a pass mark. Some answers were held back by too much discussion about
other aspects of paracetamol pharmacodynamics and unrelated pharmacokinetics.

5. Describe the mechanism of action of protamine when used to reverse effects of
heparin. Outline the side-effects of protamine.

Candidates were required to describe the mechanism of a basic cationic binding protein
combining with an acidic anionic compound to form a stable salt complex including
some indication of relative doses required and the time course of the drugs actions.
Higher marks were awarded for explanations of why excessive doses may cause
hypocoagulability and the inconsistent reversal of Xa activity.

Side effects which required outlining were not only that it causes allergy but the types
of allergy caused and the side effects that would be observed because of it. Similarly
hypotension either due to rapid infusion or IgE mediated effects, the problems of
thromboxane mediated pulmonary oedema and pulmonary vasoconstriction and the
phenomenon of heparin rebound attracted higher marks.

6. Discuss the relative advantages and disadvantages of using morphine and fentanyl
for post-operative Patient Controlled Analgesia (PCA).

This question was not well answered. A pass answer needed to demonstrate both a
clear understanding of the objectives of Patient Controlled Analgesia, knowledge of the
relative pharmacokinetics and pharmacodynamics of morphine and fentanyl, and
translation of that knowledge to the PCA technique to indicate the relative advantages
and disadvantages of the opioids. An opening statement outlining that the aims of post-
operative PCA using opioids aimed for effective analgesia with rapid onset and a
duration of action that could maintains analgesia, without causing sedation, was well
regarded, but infrequently given.

Discussion of pharmacological parameters of morphine and fentanyl, including
differences, needed to be in the context of their administration by PCA, highlighting
how the pharmacology determined their advantages and disadvantages. Indicating
differences in lipophilicity, redistribution profile, metabolism and elimination of the
opioids and their metabolites was important. These features then related to the
advantages and disadvantages including relative onset and offset times, speed of
redistribution, half-life, accumulation of the opioid or metabolites and safety, including
in specific settings, such as PCA in the elderly, hepatic or renal impairment. Some
candidates appreciated that advantages in some contexts could be disadvantages in
another. Answers suffered from lack of any statement relating to objectives of PCA,
inadequate consideration of pharmacokinetics, lack of translation of the relative opioid
pharmacology to the PCA method of administration, errors of fact, and inclusion of
imprecise comments. Statements relating to clinical experience were considered where
the pharmacological principles behind these statements were provided.

7. Briefly outline the acute management of malignant hyperthermia (during a relaxant
general anaesthetic). Describe the important aspects of dantrolene pharmacology
relevant to treating malignant hyperthermia.
62 % of candidates passed this question.

Equal weighting was given to each part of the question. Most of the candidates who did
not attempt the second part of the question did not achieve a pass mark. A brief
definition of malignant hyperthermia (MH) was expected. Lengthy discussion of the
different ryanodine receptors was not required.
The acute management of malignant hyperthermia was generally well described. An
outline of specific tasks and actions was required, such as hyperventilate with 100%
oxygen at flows of greater than 10 litres per minute. Statements like provide airway
support or obtain an ICU consult are too nonspecific. It was pleasing to see
descriptions of the anaesthetist in recruiting help, and as leader and coordinator of the
team response in theatre.
Most candidates understood the pharmaceutical aspects of dantrolene. With respect to
pharmacokinetics, candidates often resorted to guesswork.
Dantrolene is metabolised in the liver. The major pathway produces 5 hydroxy
dantrolene (which is active). A minor pathway produces an inactive metabolite. Both
metabolites are cleared renally. The half life of dantrolene is variably reported between
5-10 hours. Further dantrolene doses may be required in intensive care.
Dantrolene binds to the ryanodine receptor in skeletal muscle, inhibiting calcium
release from the sarcoplasmic reticulum. Side effects of dantrolene are rare. The alkaline
solution can cause thrombophlebitis, and skin necrosis can occur if the solution
extravasates. Hepatic dysfunction (including fatal hepatic failure), sedation and
gastrointestinal side effects have been described. Mild to moderate skeletal muscle
relaxation occurs. Dantrolene has no direct cardiac effects. The diluent volume required
to administer large doses of dantrolene may precipitate acute pulmonary oedema. Co-
administration of verapamil is associated with marked hyperkalaemia, which may
precipitate ventricular fibrillation. Dantrolene potentiates the skeletal muscle
relaxation of non-depolarising muscle relaxants.

8. Describe the terms train-of-four stimulation and double burst stimulation with
respect to the peripheral nerve stimulator. Describe their advantages and
disadvantages when used to evaluate non-depolarising neuromuscular blockade.

Train of Four is delivered by 4 identical supramaximal stimuli at about 20 50
milliamps, each of .1 sec duration, at 2Hz (2 per second); the sequence may be repeated
every 10 20 seconds if used continuously.
A synopsis of the twitch height and receptor blockade along with a description of the
ratios was well described. Interpretation of depth of blockade based on TOF
count/ratio was also well discussed
Confusion about millivolts and milliamps often cropped up.
Double Burst Stimulation described as 2 bursts of 3 tetanic stimulations (.2 msecs
duration each) 20 msecs apart at 50 Hz bursts separated by 750 msecs pause. The
repeatability takes into account the fatigue of the junctions following tetanic stimuli.
Discussion of advantaged vs. disadvantages including such topics such as ease of use,
accuracy to manual / visual assessment, need for extra objective measurement with eg
accelomyography, painful or not, able for awake patients, painful or not, use for depth
of block, use for assessing presence of residual blockade, use in reversibility of
blockade, need or value of a baseline measurement form a choice of headings to make a
comment on. Most candidates were able to mention a few to demonstrate the
physical/pharmacological/clinical rationale for the choice of technique used.
Detailed descriptions of where and how to place electrodes, comparison of depolarising
and non-depolarising blocks were not part of the question.

PHYSIOLOGY WRITTEN SECTION


66.9% of candidates achieved a pass in this section of the Physiology Examination.


9. Outline the physiological roles of prostaglandins in the body.

This question was answered very poorly, which was surprising as it a recycled question
that has been asked relatively recently
Many candidates scored poorly by answering it as a Pharmacology question The
insertion of prostaglandin pessaries and the use of intravenous prostaglandins for
neonatal Duct closure have no place in a Physiology answer
Other common errors were a very narrow answer particularly focusing on one
system (commonly renal)
Candidates who scored well wrote legibly, had a well-laid out/ presented answer and
used a system-based approach

10. Describe the effects of resonance and damping on an invasive arterial blood pressure
tracing.

Basic material required to pass:
Description of the measurement system was useful only if related to the following
discussion
Definition of resonance and damping
Explanation of their importance and their effect on the timely measurement of the
components of the blood pressure (systolic pressure, diastolic pressure, mean pressure)

Advanced material:
Quantification of the effects

Common errors/omissions/unnecessary inclusions:
Equations without definition of symbols
Input frequency is not 0 40Hz!
Natural resonant frequency is a property of the measuring system

Details of transduction were not required
directionless relationships; in a connected universe, everything influences everything
else. To be of use, a relationship should include a direction of the effect, and a
qualitative/quantitative indicator of the importance/magnitude

Organisational errors:
Planning in the margins or on the back of the cover is a waste of time (headings can be
used in the answer)
Long lists of definitions before any factual content is a poor use of time (definitions
should be embedded within the answer itself)

11. Describe the ionic basis of automaticity of cardiac pacemaker cells.

Most candidates provided a reasonable account of the relevant sodium, calcium and
potassium fluxes that occur in the sinoatrial node of the heart and could relate these to
the action potential.

Extra marks were awarded for discussion of factors that influence automaticity. Many
candidates discussed the effects of the autonomic nervous system and some were able
to provide details on the mechanism of these effects. However, no candidate discussed
the effects of age or fever on automaticity.

Several candidates described the anatomy of the conducting system of the heart, which
did not attract any marks for this question.

12. Outline the similarities and differences between myoglobin and adult haemoglobin,
explaining the physiological relevance of the differences.

Some candidates used a tabular format, others an essay format to answer this question.
Both were equally effective strategies.

A brief description of the structure and location of these proteins, their respective
dissociation curves and P50s with a simple overview of the function of each of these
proteins would round out a good answer.
An answer offering more detail about the environments these proteins function in was
awarded with further marks. Additional credit was given for answers that explored
the buffering and nephrotoxicity of these proteins.

The most common reason for not passing this question was simply because not enough
relevant content was included. Many candidates spent a lot of time describing in detail
the process of buffering and the process of oxygen binding. This detail was not asked
for and only received a few marks. The P50 given for myoglobin was frequently
incorrect and many answers indicated that myoglobin WAS NOT a haeme containing
protein. There was also a misconception in the minds of many that both haemoglobin
and myoglobin bound four oxygen molecules. No answer mentioned that myoglobin is
located in cardiac muscle in addition to skeletal muscle.

13. Outline the physiological role of cerebro spinal fluid, including a description of its
production and fate.

This question had 3 distinct sections that needed to be addressed in the answer. Main
points included the amount of CSF and where it is distributed, its role in protection of
brain, and its role in compensation for physiological changes in intracranial pressure,
acid base regulation, maintenance of stable ionic environment, role nutrition and waste
removal. Also, the chemistry of CSF and how it differs from plasma, how much is
produced and where; its circulation and where it is absorbed, and finally, describing
the relationship between ICP and the production and absorption of CSF.

Additional points were awarded for explaining CSFs protective role, its method of
production, and describing the relationship between the chemistry of CSF and its role.

Common mistakes included inclusion of pathology or pharmacology, detailed
descriptions of Monroe Kellie Doctrine without outlining the role of CSF, defining
terms before answering the question rather than as part of the answer, incorrect
anatomical understanding of production, circulation or absorption of CSF and equating
ICP measurement mm of CSF to mm of Hg.

14. Describe the changes in respiratory function tests that occur with long term increases
in small airways resistance.

This question required an answer that was focused on the respiratory function tests that
help assess the effects of chronic increased airway resistance.
Changes in the following tests needed to be discussed:
Forced expiratory volumes
Flow volume loops
Pressure volume loops
Appropriate diagrams and graphs were expected with a description of the changes that
happen when airway resistance is raised. Indicating which test provided a quantitative
assessment of raised airway resistance was important.

Candidates also gained marks for discussing simple peak flow meter testing, simple
spirometry changes, and closing volume changes. Arterial blood gas changes and
reduced oxygen uptake on exercise testing all gained additional marks.
Care needs to be taken when drawing and labelling graphs so that they are accurate.
Simply listing some respiratory changes but not relating the changes to a test was not
sufficient to score marks. Details on factors that determine resistance and flow was not
part of the answer and in depth descriptions on how to perform a test was not required.
Some candidates confused obstructive lung disease with restrictive lung disease.

15. Outline the physiological changes that may explain why an otherwise well patient
may have a reduced urinary output intraoperatively

On the whole, this question was generally well answered. Candidates who
demonstrated a clear understanding of renal physiology appropriately mentioned the
determinants of urinary output, renal blood flow, glomerular filtration rate and factors
affecting it, as well as the Starling's forces acting across the glomerular capillaries.
Marks were awarded to candidates who recognised that surgery is a stressful
"condition" which results in secretion of various stress hormones. Humoral factors, in
fact, play an important role in maintaining water and sodium homeostasis but some
candidates failed to even mention the hormones in this setting.

The commonest mistake was the assumption that a reduction in urinary output is
ONLY a reflection of a reduction in blood pressure. In reality, physiological processes
that serve to conserve water and sodium are already in place even prior to any
noticable drop in blood pressure. This is because osmoreceptors in the anterior
hypothalamus are very sensitive to the plasma osmolality and a change as little as 1%
due to a fasting state will cause increased antidiuretic hormone secretion. This results in
a concentrated urine with a low volume.

Extra marks were given to candidates who were able to explain in detail the actions of
ADH and other hormones such as the renin-angiotensin-aldosterone system. However,
an extensive list of plausible causes of hypotension does not translate to an outline of
physiological changes that result in reduced urinary output.

16. Describe the formation, fate and role of lactate in energy production.

A good answer followed the headings of the question thereby obtaining max marks.
Many candidates spent a lot of their answer on describing the citric acid cycle and
aerobic metabolism, which gained no marks. Lactate is produced daily by red blood
cells and during strenuous exercise where a patient is not hypoxic. It supplies a rapid
energy source when oxygen demand is not met by supply but is not sustainable over a
prolonged period. It can be reutilised by the cells it is formed in(when pyruvate is able
to enter the citric acid cycle the equilibrium shifts to allow lactate -> pyruvate) when
oxygen is resupplied or can diffuse out of cells into the plasma for transfer to the
1.liver, to under go gluconeogensis(from pryuvate), this glucose can a)enter into the
ATP inefficient cori cycle for further energy production during anaerobic conditions in
the muscle, b) be stored as glycogen and c)enter the citric acid cycle, and 2.heart as an
energy substrate. There was some confusion where the ATP is produced during
anaerobic metabolism, ie; during glycolysis not on the conversion of pyruvate to
lactate, and the enzyme for this is lactate dehydrogenase. Concepts such as the Law of
mass action and including recycling of the substrates for biochemical equations
(particularly NAD+) were appreciated.

PHARMACOLOGY ORAL SECTION
________________________________________________________________________________

OPENING PHARMACOLOGY QUESTIONS:

Pharmacodynamics
What is ED 95?

Drug variability
How can the liver affect pharmacokinetics?

Inhalational agents
Factors influencing the rate of rise of Fa/Fi (speed of induction of an inhalational
induction). Metabolism. Why recovery different from induction.

Local anesthetics
Factors that affect the onset of action.
What additives are found in L.A. solutions and why?
Calculate amount of drug in 2% solution. Toxic amount. Effects on RMP. Mechanism
of action. Differential block. Frequency dependent block.

Pain
Classification of drugs to treat neuropathic pain.
Side effects of TCA.
Opioid sparing drugs.
Why is pethidine unpopular?
Advantages, s/e tramadol.
Duration of action and side effects of NSAIs.

Opioids
Compare fentanyl to alfentanil.
Time to peak effect of opioids.
Structure of morphine, receptor interaction.
Oxycodone.

Neuromuscular blocking drugs
Effects on fast c.f. slow twitch muscles.
What is a nondepolarising block?
Fatal effects of suxamethonium.

Anticholinesterase agents
Does neostigmine cross the BBB?
Onset and duration of neostigmine.
Anticholinesterases other than neostigmine.

Anticholinergics
Side effects of atropine. Atropine c.f. glycopyrrolate.

Autonomic nervous system
Compare metaraminol, ephedrine and phenylephrine (effects at alpha and beta
receptor, heart rate changes).
Effects in labour.
Overdose of phenylephrine.
What is tachyphylaxis?
What are beta 2 effects?
Structure activity relations of catechols.
Vasopressin.

Antiarrhythmics
Classes. What is type 3. Amiodarone, why loading dose? Is it used in torsade? Why
not?

CPR guidelines
Outline the CPR guidelines.
Mono phasic c.f. biphasic defibrillation.
Why is adrenaline used?

Anti emetics
Classify antiemetic drugs. Side effects. Prolonged QT syndrome

Obstetric drugs
Tocolytic drugs.
Oxytocin side effects

Diuretics
Classification

Anticoagulants
Classification of antiplatelet drugs.
Why is a loading dose of clopidogrel required?
Low versus high dose aspirin.
Side effects heparin.

Endocrine
Insulin side effects

GIT
Drugs affecting gastric acidity

IV fluids
What is tonicity?
What is meant by isoosmolar?
What is a colloid?
Excretion HES, T c.f. gelofusine, HAS.
HES what is substitution grade?
HES side effects.
HAS does it require cross match? Why? Can it contain viruses?

Statistics
Types of data.
When is ANOVA used? What is one way ANOVA?
Chi square test?
What is meant by degrees of freedom?
When would Fisher exact test be used?
Paired and unpaired T- test.
Systematic review vs meta-analysis.
Measure of dispersion from central tendency. 95% C.I. when used?

Phases of a clinical trial.

PHYSIOLOGY ORAL SECTION
________________________________________________________________________________

OPENING PHYSIOLOGY QUESTIONS:

Measurement / Physics
What is a normal adult temperature?
What is a pulse oximeter?
Oximetry
Capnography
How is CO2 analysed
Temperature measurement methods
Draw a Capnograph trace

Respiratory
Comment on this Blood gas Analysis (Resp acidosis with increased A-a Do2)
When we exercise, oxygen consumption increases. How much can it increase?
Compare to cardiac output and explain how there can be a difference.
What is a normal Pulmonary Artery pressure? Why does it not increase with
exercise?
What do you understand about shunts in the lungs?
What do you understand by the term oxygen flux?
What are the causes of arterial hypoxaemia?
Control of Ventilation
Oxygen cascade
Carbon dioxide carriage
Aging and Respiratory Function
Lung compliance definition and factors affecting
Causes of hypoxeamia
Effects of Alveolar ventilation on PCO2
Dead space
oxygen stores breathing air and 100% oxygen
ventilation distribution in lateral position
capnography
Cardiac
Draw a Pressure-Volume Loop for adult LV. Superimpose changes caused by
clamping the abdominal aorta
What heart rate would you expect in a person with all the nerve supply to the heart
removed?
What are determinants of cardiac output?
What are the determinants of coronary blood flow?
Starlings law of the Heart
Distribution of Cardiac Output
Pressure Volume Loop of Left Ventricle
Cardiac contractility and frank-starling curve
Define afterload and what factors contribute to afterload
What changes occur in the CVS as we age
Afterload
What is Contractility
Draw lead 2 of a standard ECG trace.
determinants of venous return
Renal/Acid-base
What is a normal serum Na? What physiological mechanisms can be responsible for
development of hyponatraemia.
What is Clearance
renal excretion of an acid load
effects of changing afferent and efferent tone on renal blood flow and GFR
Nervous system
What would happen to my heart rate and blood pressure if I was woken up by an
earthquake?
Pain transmission
Sleep
Autonomic Nervous System
How can nerves be classified
Factors affecting cerebral blood flow
normal cerebral blood flow and measurement

Gastrointestinal
Gastric Emptying

Endocrinology / Prostaglandins
What hormones are secreted by the posterior pituitary?
Control of Blood Glucose

Haematology
When you have a sharp cut in your hand, what stops it from bleeding continuously?
Blood Cross Matching
Platelet function

Muscle
Microscopic appearance of skeletal muscle. Action potential for skeletal and smooth
muscle

Neonatal/Maternal
Describe the features of the foetus that allow for maximization of oxygen delivery to
the brain.
What are the various stimuli for the baby to make its first breath?
Take me through the foetal circulation.
What factors affect the movement of oxygen across the placenta

Immunology
Hypersensitivity Reactions
What different immune systems protect the body

Metabolism.
What are the effects of a 48-hour fast in an otherwise healthy adult?
How is calcium distributed in the body?
What is a normal blood sugar level?
Fasting
heat gain and loss in operating theatre and sauna

Associate Professor Ross MacPherson
CHAIR
Primary Examination Sub-Committee

ABN 82 055 042 852

EXAMINATION REPORT


FEBRUARY /APRIL 2011

Please note that this report is prepared to provide candidates and their teachers and supervisors
of training with information about the performance of candidates in the recent examination, so
that candidates and teachers may prepare appropriately for future examinations. The individual
reports are not intended to represent model answers nor imply that all points mentioned are
necessary in order to achieve a pass. All trainees are urged to read the questions carefully and
answer the question asked. All teachers and supervisors of training are encouraged to discuss this
report in detail with candidates they are preparing for future examinations.

General comments relating to ALL short answer questions.

Many examiners have written the same comments for their question and for the general
information of candidates the following suggestions are provided.

The main mistake that candidates continue to make is a failure to answer the question asked. Much
time is spent providing pages of information that is irrelevant to the question being asked and for
which no marks can be awarded.

Examiners are unable to award marks for illegible handwriting.

Answers can be validly presented as diagrams, lists or a mini essay. When the former two methods
are used, the labelling must be clear and the answer to the question made obvious. In order to
obtain marks from graphs, these must be accurately drawn, clearly labelled, and be able to
demonstrate understanding of the question asked. It may be necessary to include a sentence to
demonstrate understanding with respect to a graph.

Where essay form is used, correct spelling, especially relating to pharmacological or physiological
terms is important.

If candidates have contradictory statements in their answers, no marks will be awarded for correct
information that is later contradicted.

If candidates elect to draft an answer plan, and later cross out the plan, no marks will be awarded
for material that is included in the plan, but not in the answer proper. In practising for the short
answer question examination, candidates should consider whether using part of their time to write
a detailed plan before writing a ten minute answer is optimum use of the time available.

The syllabus lists basic sciences in anaesthesia and intensive care. Where appropriate, aspects of
clinical application of physiology and pharmacology that may appropriate in an answer can be
included. However, caution must be exercised not to overemphasise clinical information at the
expense of the underlying scientific principles.

________________________________________________________________________________




Q1 . Describe the factors which increase the risk of systemic toxicity with amide local anaesthetic
agents.

This question was passed by 34.6% of candidates.

This question requires an understanding that systemic toxicity is due to an excess in the plasma
concentration of local anaesthetic, which is dependent on the rate of absorption into the systemic
circulation, drug distribution and clearance. Successful candidates organised their answers into
drug factors including pharmacodynamic and pharmacokinetic factors and patient factors. Listing
factors such as pKa, lipid solubility and protein binding without a clear explanation of how these
contributed to toxicity did not gain high marks. Factors which affect systemic absorption were well
explained, however, drug distribution was poorly understood especially in the context of patient
factors such as age and cardiac status. Repeating a concept under different headings such as pKa,
degree of ionisation and ion trapping in the foetus or acidotic patient did not gain more marks.
Local anaesthetics bind to many proteins which affects systemic toxicity. Binding to plasma proteins
alters drug distribution, affinity for receptor proteins affects dwell time and binding to tissue
proteins affects release of drug into the systemic circulation.

Candidates were expected to know the relative toxicities between different amide anaesthetics.
Quantifying the differences gained extra marks. An understanding of why certain amide
anaesthetics are more toxic than others based on factors such as lipid solubility, chirality, intrinsic
vasoconstrictive properties and sodium channel affinity were expected. Defining the CNS/CVS ratio
without explaining why different amide anaesthetics have different values did not gain marks.

Q 2. Classify non-opioid drugs used for the treatment of neuropathic pain and indicate proposed
mechanisms of analgesic action and potential adverse effects.


This question was very clear in what was required. Discussion of neuropathic pain, opioids, and
non-drug treatments did not attract marks.

Many candidates omitted the mechanism of action, used vague statements such as, affects the
receptor, or described a non-analgesic mechanism of action. When discussing adverse effects avoid
statements such as, many side effects or many interactions, without providing additional detail.
Writing sedation as the only adverse effect of tricyclics did not attract marks. Many answers
contained a long detailed description of simple analgesics, and only a limited discussion of other
drugs used for the treatment of neuropathic pain.

Answers should have included the following main components: Antidepressants (tricyclics),
Anticonvulsants (Gabapentinoids), Membrane Stabilisers (lignocaine/mexiletine), NMDA
antagonists (Ketamine), and a brief discussion of simple analgesics. Additional marks were gained
for discussion of other drugs, or additional detail

Q 3. Outline the effects of liver failure on drug kinetics and dynamics.


Most candidates were able to point out that drug metabolism (predominantly phase 1 reactions) is
decreased with liver failure. However, few could indicate the change is only significant in drugs with
a low hepatic extraction ratio (e.g. benzodiazepines). A number of candidates spent a significant
amount of time describing the change in protein binding of drugs. Unfortunately, the direction and
magnitude of change in drug effect were vague in most answers.

Common omissions include that associated renal failure (hepatorenal syndrome) may decrease
renal clearance of drugs and their active metabolites, and that the production of plasma
cholinesterase is reduced with liver failure and this may affect metabolism of suxamethonium.
Important pharmacodynamic changes should include an increase in sensitivity of anesthetic agents
with hepatic encephalopathy, and down regulation of adrenoreceptors in liver failure.

Q 4. Describe the ideal properties of agents used for sedation using two examples.

This question was passed by 69.3 % of candidates.

Points expected for a pass:
Listing the ideal attributes of a sedation agent.
Most chose an intraveneous agent, with focus on pharmacokinetics, including rapid onset, short
equilibration effect site time, rapid offset, short context sensitive half time (CSHT), and organ
independent elimination.

Pharmacodynamic qualities should include high therapeutic ratio, minimal cardiovascular and
respiratory depression, amnestic and analgesic qualities

Most discussed the examples of midazolam and propofol, comparing them to the ideal qualities
and/or to each other. Other acceptable alternatives included dexmedetomidine, ketamine,
remifentanil and fentanyl.

Better answers demonstrated understanding of the pharmacokinetics, why organ independent
metabolism was better, how certain drugs had a short CSHT due to redistribution or high
metabolism. Some recognised that propofol had a lower therapeutic ratio as compared to
midazolam, as the dose required to produced sedation was close to that for producing general
anaesthesia.

These answers received more marks than just a bare list of ticks and crosses. Those that used only
one example or neglected to talk about pharmacokinetics were less likely to gain enough marks to
pass. Other mistakes were to regurgitate all known facts about the two agents, without reference
to what would make them ideal for use as a sedation agent.

Additional marks were given for mentioning drug interactions, increased sensitivity with age and
pain on injection with propofol.

Q 5. List the classes of drugs that may be used to manage hypertensive crisis and briefly outline
the mechanism of action.


The main points expected for a pass included a classification of drugs used in anaesthesia to
manage a hypertensive crisis, and include a brief description of those drugs mechanisms for this
particular action.

Most answers included only cardiovascular drugs such as sodium nitroprusside whose specific use is
in the management of a hypertensive crisis. However, most answers did not include drugs that
anaesthetists use every day to manage this problem, such as sevoflurane, fentanyl, propofol and
Local Anaesthetic agents. This was the main reason for the low pass rate.

Another common error was to overlook the mechanism of action for lowering blood pressure.
Reporting that beta receptor blockade lowers blood pressure, is too imprecise to score points in a
post-graduate specialty examination.

Q 6. Write a brief outline on the pharmacology of remifentanil.


A clear pass required:
Some sort of logical approach to the description of drug pharmacology incorporating:
Drug chemistry
Uses
Pharmaceutic information including presentation and recommended doses
A proposed mechanism of action
Pharmacokinetics
Pharmacodynamics

Key chemistry description needed to highlight: phenylpiperidine derivation from fentanyl, synthetic
preparation, unique ester linkage. There are multiple uses of this agent - simply stating as a
component of TIVA gained marks but did not gain maximum credit. Pharmaceutic information, in
addition to describing the powder filled ampoules or vials of remi, needed to identify the
powder as remifentanil hydrochloride and ideally note the presence of glycine (as this has
relevance to routes of administration).

To score well, both bolus and infusion dosing had to be given. Few candidates correctly stated any
mechanism of action, fewer correctly identified mu selectivity, and fewer still the mechanism of mu
agonism induced analgesia. The bulk of the available points were allocated to a description of the
agents pharmacokinetics reflecting its novel features. Whilst some recall of volume of distribution,
elimination half life, and context specific parameters was necessary, a clear pass required more
than a list of uninterpreted numbers.

Candidates needed to describe/explain: remifentanil has a fast onset and why this is so, that offset
is dependant on metabolism not redistribution, organ independent high capacity metabolism and
metabolic products. Pharmacodynamics was not well described - the requirement was for a logical
organ system approach outlining key effects in each system. Candidates who stated only that the
effects are those of morphine could not score well

Q 7. Describe the advantages and disadvantages of using nitrous oxide as part of a general
anaesthetic.

This question was passed by 73% of candidates.

Successful candidates structured their answers with a list of advantages and disadvantages from a
pharmaceutic, pharmacokinetic and pharmacodynamic perspective. The main advantages that
were expected were: rapid onset and offset, second gas effect, reduction in MAC, and analgesic
effect. The main disadvantages that were expected were: reduction in FiO
2
, diffusion hypoxia,
expansion of closed air spaces, PONV, increased CBF/ICP, and the long term effects of prolonged or
chronic exposure, e.g. megaloblastic anaemia, subacute combined degeneration of cord, and
possible teratogenicity.

Additional marks were awarded for clear explanations about why nitrous oxide is inappropriate as a
sole agent, and other concepts, e.g. second gas effect, and expansion of gas spaces. Common
mistakes were to discuss nitrous oxide in isolation rather than as part of a general anaesthetic.
There were misconceptions about the mechanism of analgesia, which is described in the prescribed
texts. There were inadequate explanations about how nitrous oxide is cheap, and very few
candidates discussed the set-up and maintenance costs associated with nitrous oxide.

Q 8 How may drugs potentiate the action of non-depolarizing muscle relaxants at the
neuromuscular junction?


The following answer would have gained a very high mark:

Drug interactions are relevant as there is a risk of failure to reverse neuromuscular blockade and
residual paralysis.
Drugs may interact either at the nerve terminal or the receptor to reduce the effect of acetylcholine
(ACh) in competitively overcoming the block.
Presynaptically there are at least three mechanisms that might reduce the release of acetylcholine
(ACh):
1. Reduced AMP/ATP synthesis frusemide
2. Blockade of presynaptic ACh receptors volatiles
3. Blockade of calcium channels calcium channel blockers, magnesium, aminoglycosides,
volatiles
Postsynaptically there are several mechanisms that interfere with ion flux through the nicotinic
receptor:
1. Direct blockade of the ACh receptor volatiles, aminoglycosides, quinidine, other
neuromuscular blockers
2. Desensitization block (binding to non-receptor sites) volatiles, barbiturates, local
anaesthetics

The most common error was irrelevance: detailed descriptions of the physiology of neuromuscular
transmission and a classification of non-depolarizing relaxants.
VIVA OPENING QUESTIONS

Parmacokinetics/Pharmacodynamics
How can genetics influence drug action?
How are drugs transformed in the liver?
Drug receptors
Tolerance and addiction
What is meant by pharmacogenetics?
What is the law of mass action?
What is a second messenger?
Dose-Response Curves
Therapeutic Index
Drug metabolism
Classify drug interactions
Low cardiac output and drug metabolism
What is potency?
Propofol concentration-time curves
Determination of Vd
Determination of dose of induction agent
What is bioavailoability?

Muscle Relaxants and reversal
Metabolism of suxamethonium
Pharmacology of rocuronium
Cardiovascular effects of NMBs
Prolongation of suxamethonium block
What is in the red syringe?
Drug-receptor kinetics of NMBs
Electrode placement for TOF
How do NMBs work?
What are anti-cholinesterase drugs
How does neostigmine work?
Adverse effects of neostigmine
Clinically useful anti-cholinesterase agents
Features of organo-phosphate poinoning
Effects of atropine
Management of atropine overdose

Autonomic Nervous System
Structure activity relationships of sympathomimetics
Pharmacology of nicotine
Noradrenaline
Ephedrine and mechanism of action
Lipid solubility of beta blockers
ACE inhibitors
Blockade of autonomic nervous system
Drugs fort myocardial ischaemia
Pulmonary hypertension
Metoproprol
What is an inotrope?
Tell me about nitric oxide
Treatment of anaphylaxis

Anti-arrhythmic agents
Management of ventricular fibrillation
What drugs are used to manage tachyarrhythmias?
Digoxin and toxicity
Amiodarone

Neuropharmacology
Management of Parkinsons Disease
Anti-epileptic agents
Drugs used to treat Post Operative Nausea and Vomiting
Classification of anti-emetics

Respiratory
Drugs used for asthma management
Manufacture of oxygen
What are the effects of histamine?

Diuretics
Classify diuretics
Mannitol
What are loop diuretics?

Coagulation
Low molecular weight heparin
Fibrinolysis
Heparin metabolism
Adverse effects of heparin
Classify anti-platelet drugs
Reasons for reduced effects of clopidogrel
Classify anti-coagulants

Obstetrics
Pharmacology of magnesium
Drugs affecting uterine tone
Placental transfer of drugs
PK/PD in pregnancy

Endocrine
Side effects of vasopressin
Oral hypoglycaemic agents

Gastrointestinal
How can gastric acidity be controlled?
Drugs affecting gastric pH

Volatile agents
Physico-chemical parameters of volatile agents
Structure Activity relationships of volatiles
MAC
Additives to volatile agents
Mechanism of action of general anaesthesia
Dose of volatile agents
Dose-response curves for volatile agents
Lipid solubility and potency
Wake up from GA
Wash in and wash out curves
Halothane toxicity
Partition coefficient

Pain
Activity of opioids
Fentanyl and alfentanil
IV analgesia for pain
Alfentanil
Intrathecal morphine
Oral paracetamol
Morphine toxicity
Naloxone
Opioid reversal

Pharmaceutical aspects
Contents of an ampoule of thiopentone and propofol
Why are substances added to pharmaceutical products?
Stages of drug development
What is a drug?
What additives are added to local anaesthetic solutions?

Statistics
What are categorical data?
What is the difference between meta analysis an systematic review?
Randomised controlled trials
Given a data set and asked to comment
Multi-centre trials
Bias in statistics
Box and whisker plot
Paired and unpaired t-tests

Miscellaneous
Colloids vs crystalloids
Digoxin toxicity
Organophosphate poisoning
Thiopentone and cardiovascular system
Drugs affecting GABA receptors
Dose-response curve for propofol
Mode of action of local anaesthetics
EMLA cream



82.8% of candidates achieved a pass in this section of the Physiology Examination.


Q 9. Describe the ways in which CO
2
is carried in the blood


In order to pass, candidates were expected to provide a detailed description of the three methods
by which CO
2
is carried in the blood, i.e. dissolved, as converted to bicarbonate, and combined
with proteins.

Extra marks were awarded to those candidates who explained the importance of red blood
cells/haemoglobin, reasons for differences between arterial and venous carriage, and clear concise
descriptions of Haldane effect.

Common errors included incorrect units in describing the carriage of CO
2,
and chemical equations
that did not balance with respect to chemical elements or electrical stability.

Q 10: Describe the factors that oppose left ventricular ejection.


As previously, this question was misinterpreted by many candidates and answered as for
determinants of left ventricular ejection fraction: descriptions of preload and contractility attracted
no marks. The main points expected included: recognition that afterload opposes left ventricular
ejection, definition of afterload, the contribution of SVR and factors determining SVR, and the
application of the law of LaPlace and the use of the Hagen-Poiseuille equation to describe factors
which contribute to afterload. Additional marks were awarded for the role of the aortic valve, aortic
compliance, IPPV, and for demonstrating understanding of the relative changes in pressure and
tension within the ventricle during systole.

Common mistakes included repetition, vague or non-directional statements, and incorrect
formulae.

11. Describe the functions of the loop of Henle, including the physiological mechanisms involved.


The question asked for both the functions of the loop of Henle, and physiological mechanisms
involved. Both these points needed to be addressed to pass this question.

Well structured answers included a brief relevant anatomical description of the loop of Henle, and a
description of the functions which included the physiological mechanisms.

Very few candidates mentioned functions apart from the development of a concentration gradient,
and many candidates were unable to describe the physiological process whereby that gradient is
developed. There was often confusion regarding the osmolality at various anatomical locations
within the loop. Many candidates did not mention or were unable to explain the role of the vasa
recta in the physiological mechanisms of concentration. Many answers were focussed on the
collecting duct rather than on the loop of Henle, and several answers listed general functions of the
kidney rather than those of the loop of Henle.

The examiner was aware of controversy relating to tubuloglomerular feedback in different
textbooks, and marks were awarded accordingly.

Many candidates obtained near-maximal marks for an accurate and well-labelled diagram
explaining the physiological mechanisms.

Q 12. Compare and contrast a single twitch and a tetanic contraction in a skeletal muscle fibre.


Better answers included a brief description of a skeletal muscle fibre and its contractile mechanism,
definitions of a single muscle fibre twitch and titanic contraction, an explanation of the difference
between the membrane electrical refractory period and fibre relaxation time and the implications
of each, the reasons re-stimulation within fibre relaxation time results in additional contraction, the
role of calcium, the impact of relaxation times for different fibre types on the frequency required to
create a titanic contraction (with example values for each), and the differences between single
twitch and titanic contractions with respect to the reasons that relaxation occurs, force achieved,
and energy requirements.

Common mistakes included providing excessive detail about synaptic events or excitation-
contraction coupling and missing the important points above, describing summation and tetany as
electrical events rather than mechanical events, and writing about the use of a nerve stimulator.

Q 13. Describe the determinants of work of breathing in an adult human at rest.

This question was best answered with an accurate labelled and annotated pressure-volume graph.
Previous examination reports have detailed the main points expected and these have not changed.
There were many poor diagrams that highlighted candidates lack of understanding. A common
mistake was to describe the determinants of FRC, not those of work of breathing. Discussing how
work of breathing changes when not at rest or in disease garnered marks if it helped to explain the
underlying concept that was asked for in the question.

Q 14. Describe the physiological effects of general anaesthesia on temperature regulation


In order to pass this question, candidates were expected to discuss temperature regulation with
induction, maintenance, and recovery from general anaesthesia. An understanding of dose
dependent, agent dependent, and age and sex dependent factors were required.
Additional marks were awarded for describing the differences between elderly patients and
neonates, for a correct description of the role of non-shivering thermogenesis, and for a description
of the additional effects of neuraxial blocks in conjunction with general anaesthesia.

Many candidates were confused by the differences between the interthreshold range and the
thermoneutral zone. Very few candidates mentioned temperature regulation during the recovery
phase. Graphs were often incorrectly drawn, and the thermoneutral zone was frequently
incorrectly defined. Some candidates gave a detailed account of the normal physiology of
thermoregulation, rather than answering the question as relevant to anaesthesia.

The main reason for candidates failing this question was insufficient core knowledge.

Q 15. Describe the functions of the gastric secretions.

This question was passed by 69% of candidates. In general this question was well answered.

Good answers were often in tabular format with headings for secretion and function. Equally good
answers were short notes under secretion headings. Poor answers gave lengthy descriptive prose
that added no detail to the answer. Some candidates discussed other digestive secretions from the
mouth, pancreas and intestine. These carried no marks and wasted valuable time. Repetitive
statements also carried no extra marks.

Q 16. Explain the difference between viscosity and density. Outline the effects of changes in
viscosity and density on the flow of gases and liquids.

This question was passed by 72% of candidates. In general this question was well answered.

Points required for a pass were to demonstrate some understanding of the definitions of viscosity
and density, the differences between laminar and turbulent flow and their dependence on viscosity
and density respectively, and the factors that might influence the transition between laminar and
turbulent flow.

Additional marks were given for illustrative examples taken from physiology or anaesthetic
equipment, understanding of flow-resistance relationships, and deeper understanding of the
underlying physics (e.g. inertial vs. resistive forces).

A common fault was that many candidates erroneously thought that density was defined as mass
per unit area.

VIVA OPENING QUESTIONS

OPENING PHYSIOLOGY QUESTIONS:
What are the SI units?
What is the difference between heat and temperature?
What are the physical mechanisms by which the body loses heat?
How can you measure intracellular water?
What does a pulse oximeter measure?
What is humidity?
What is a transducer?
Draw a tracing from a capnometer.
What factors affect the flow of fluid through a tube?
What is osmolarity?
How would you measure pH?
What is a resistor?

Respiratory
What respiratory function tests are commonly measured?
What is diffusion capacity?
How does the body control ventilation?
What are the physiological effects of IPPV?
How much blood goes through the lungs per minute?
How does oxygen get from the lung to the cell?
What is normal PaO
2
?
What is normal PaCO
2
?
Can you interpret this arterial blood gas result??
What will happen to the PaO
2
if you hold your breath for 1 minute?
What is the effect of posture on lung perfusion?
What are the factors that affect airway resistance
What is pulmonary vascular resistance?
What is shunt?
What is surfactant?
What do you understand by the term closing capacity?
What do we mean by the term work of breathing?
Define the functional residual capacity of the lungs?

Cardiac
What is the function of the circulation?
How is the cardiac output distributed?
Draw the action potential for the SA node.
Draw a lead II ECG.
Describe the coronary circulation.
What is the Frank-Starling Mechanism?
Draw a left ventricular pressure versus time curve.
How would you define afterload?
What are the cardiovascular changes associated with ageing?
What is venous return?
What happens to cardiac output if you increase venous return?
Show me the waveforms you see when you pass a pulmonary artery catheter?
How does the cardiovascular system respond to haemorrhage?
Draw a central venous pressure trace.
Draw the flow of blood in the aortic root.

Renal/Acid-base
How is renal blood flow controlled?
What is the glomerular filtration rate?
What is clearance?
How does the body clear a water load?
How does the body handle potassium?
What is the renal response to a metabolic acidosis?
What is renal response to metabolic alkalosis?
What is a colloid?

Nervous system
What is normal cerebral blood flow?
How is cerebrospinal fluid formed?
Describe a myelinated nerve.
What types of nerves do you know?
What happens if you stub your toe?
What are the mechanisms of visceral pain?
What is sleep?

Gastrointestinal
What are the functions of the liver?
Describe gastric emptying?
What are the physiological effects of fasting for 48hrs?
Describe the blood supply of the liver.

Endocrinology / Prostaglandins
What is a hormone?
What are the functions of adrenal medulla?
What are the functions of the thyroid gland?
How do insulin and glucose interact?
What is the role of prostaglandins in the body?

Haematology
Describe the processing of donated whole blood.
What is the bodys response to a damaged blood vessel?
What are the effects of storage on red blood cells?

Muscle
Describe sequence of events in neuromuscular contraction.
What is a muscle spindle?
Where do we find smooth muscle in the body?

Neonatal/Maternal
What are the functions of the placenta?
What are the cardiovascular changes in the third trimester of pregnancy?
What are the respiratory changes in pregnancy?

Immunology
What is the difference between innate and acquired immunity?

Metabolism.
What is in total parenteral nutrition?
What are the physical mechanisms by which the body loses heat?

Associate Professor Ross MacPherson
Chairman, Primary Examamination Sub-Committee
ABN 82 055 042 852

EXAMINATION REPORT


JULY/SEPTEMBER 2010

supervisors of training with information about the performance of candidates in the
recent examination, so that candidates and teachers may prepare appropriately for future
examinations. The individual reports are not intended to represent model answers nor
imply that all points mentioned are necessary in order to achieve a pass. All trainees are
urged to read the questions carefully and answer the question asked. All teachers and
supervisors of training are encouraged to discuss this report in detail with candidates they





Question 1 : Compare and contrast the pharmacokinetics of orally and intravenously
administered morphine and oxycodone.


Main Points expected for a Pass:
Both Morphine & Oxycodone are full- agonist opioid analgesics used peri-
operatively
They both can be administered orally or intravenously
They are roughly equipotent when administered intravenously but their oral
bioavailability differs.
Morphine has a high hepatic extraction, so Oxycodone is more potent when given
orally
Major differences or similarities in basic pharmacokinetic (PK) parameters such as
volume of distribution, clearance, protein binding, metabolism & half-life
Additional Points which attracted higher marks:
Actual numbers & content for PK parameters such as morphines bioavailability
being 30% compared to oxycodone which is 50-87%
Demonstrate an understanding of the role of pKa in ionization & lipid solubility in
comparing the 2 drugs.

2
Be able to calculate the dose adjustments & relative conversion between the 2
drugs based on their bioavailabilities.
Be able to discuss accurately volume of distribution & plasma concentration
Discuss the different pathways of metabolism & clearance

Question 2 : Describe the composition of 4% albumin and Normal Saline. Compare and
contrast the pharmacology of each.


Candidates are reminded that where a question is asked in two parts, as with this
one, it is best to answer it clearly in two parts. Most candidates were able to describe
the composition of normal saline, although some added other molecules such as
potassium and calcium to the mixture, and of albumin. Albumin also contains a
reasonable about of sodium chloride, which was often neglected.

Most answers correctly demonstrated an understanding of the distribution of normal
saline between the intravascular and extra cellular compartments, and of the oncotic
effects of albumin. Although albumin is a product derived from human plasma, it is
treated heating to 60 degrees C for 10 hours, thus virtually eliminating the risk of
transmission of disease.

Extra marks were gained by giving details about the mechanism of hyperchloraemic
acidosis seen with infusion of large volumes of sodium chloride.

Question 3: Describe the mechanism of action, pharmacokinetics and major side
effects of intravenously administered amiodarone.


A structured approach was expected and marks were distributed to the three main
areas MOA, pharmacokinetics and adverse effects. Candidates were expected
highlight the various mechanisms of action such that amiodarone can fit within most
elements of the Vaughan Williams classification. A clear structure addressing the main
areas relating to pharmacokinetics was helpful.
It was expected candidates would appreciate the very long half life, high protein
binding, significant tissue binding and large volume of distribution. Specific
comments regarding the main toxicities were expected. In particular, the pulmonary
toxicity (both acute and chronic variations) is important. In addition a variety of other
issues should be mentioned, including thyroid changes and the well described skin and
ocular changes.
Cardiac toxicity with bradycardia, QT prolongation and this risk of Torsades that this
may pose was mentioned by many candidates and gained specific credit.

Additional credit was given for more detailed explanations, comments on enzyme
metabolism and examples of drug interactions. Comments on dosing and infusions
gained additional marks. Well organized answers such as those with an ordered list of
subheadings were rewarded.

3

Question 4 : Briefly outline the effects of sevoflurane on skeletal, smooth and cardiac
muscle tissues. Include how these effects are mediated and their clinical
significance.


On first glance the question looks intimidating, as the exact mechanisms of these
actions are complex. The mechanisms, however, were only part of the question. A
systematic approach addressing each key issue easily scored enough marks to pass.

Areas which could have been covered included:

Skeletal muscle: Direct effect, interaction with muscle relaxants, malignant
hyperpyrexia, effects on muscle blood flow.

Smooth muscle: Effects on vascular smooth muscle, including regional circulations,
the uterus and the bronchioles. More marks were awarded for understanding the
clinical significance of these effects.

Cardiac: The direct effect, the overall effect on the circulation, overall effects on
myocardial work, ischaemic preconditioning and arrythmogenesis.

Candidates often confused the direct effect of volatiles on skeletal muscle, the
interaction with muscle relaxants, and surgical immobility. Many thought that the
contraction of skeletal muscle was controlled by the sympathetic nervous system. The
effects of sevoflurane on the pulmonary vasculature and hypoxic pulmonary
vasoconstriction was poorly understood. The risks of sevoflurane were commonly
overstated, particularly in the areas of coronary steal, myocardial ischaemia, heart
rate, hypotension; as well as bleeding following Caesarean Section.

The structure, physicochemical properties and anaesthetic uses of sevoflurane were
not part of the question and so did not attract marks. The question was not an essay
on malignant hyperpyrexia, the cerebral effects of sevoflurane, or muscle relaxants.
We no longer use general anaesthesia for labour, nor is sevoflurane used for
treatment of premature labour. Rewriting the question at the top of the paper is
unnecessary.

Question 5 : Describe the pharmacodynamic effects and clinical uses of
anticholinesterase drugs.

65%% of candidates passed this question.

A brief definition of an anti-cholinesterase and its effect on acetylcholine
concentrations at cholinergic receptors was expected.

Subsequently the marks were divided evenly between pharmacodynamics and
clinical applications. Briefly an increase in acetylcholine levels at muscarinic
receptors results in bradycardia, hypotension, salivation, bronchospasm, increased
gut and urinary motility, miosis and central effects if the drug crosses the blood
brain barrier.

4

Only a few candidates mentioned that muscarinic effects occurred at lower
concentrations than nicotinic effects.

However the single largest error in answering this question was candidates discussed
structure activity relationships and pharmacokinetics of individual agents at length
and failed to mention any pharmacodynamics.

Clinical uses of these agents are legion and were very well discussed. No value would
be gained in repeating these here.

Some candidates spent an inappropriate amount of time discussing organo-
phosphates but by elaborating the adverse effects of these agents ('SLUDGE'
acronym) they gained marks en passant for the pharmcodynamic effects

Question 6 : Describe the principles of how a computer-controlled infusion device
targets and maintains a constant effect site concentration of propofol.


Principles relevant to this question included: -

Propofols pharmacokinetic parameters making it suitable for this technique are
rapid equilibration between the central compartment (i.e. the vessel rich group) and
the effect site. Especially after the initial bolus producing only a short lag time.

A 3 compartment model is described and it is as well to consider the added effect
site compartment albeit small. Volumes of distribution of all those compartments
have been mathematically derived plus the constants describing the kinetics of
transfer using relevant studies on healthy volunteers.

This diagram explains the concept : - (Miller Chapter
12)

That time to equilibrate with the central compartment
correlates with the Keo (high for propofol indicating a
short time to peak effect).

Clinical effects by the agent at the effect site compartment were equated with a
measurable effect on the volunteers eg by using a BIS or EEG. This is a closed loop
system but most cases are done on the basis of a set plasma concentration desired
for a given procedure. Candidates did describe the different models available
(Schneider, Marsh, and Bristol)

The driver computer software incorporates derived algorithms, with information
using entered patient parameters such as weight, age, sex, height of the patient.
The driver calculates and delivers a loading dose, followed by a pause, then a
maintenance dose and fluctuation in dosage delivery as the compartments become
saturated followed by transfer of the excess into the central compartment.
Ultimately the agent is made water soluble, metabolised and renally excreted. A

5
target effect site concentration around 3 4 mcgm/ml, is also programmed into the
machine.

The machine alters the infusion rate based on its own mathematical calculations
taking into consideration the redistribution amongst compartments and the central
compartment, and the metabolism, clearance, and elimination which is pre-
programmed into the computer algorithm. The anaesthetist may alter rates for
effect or need to alter due to change of plasma concentration requirement. The
graph explains the concept: -

(Miller Chapter 12)

Describing the terms of the context sensitive half time and/or the clinically relevant
context decrement time helped to indicate an understanding of the kinetics and
dynamics at the end of the infusion.

Question 7 : List the physical properties of oxygen. Discuss the potential adverse
effects associated with oxygen administration.


The question was similar to that asked in a previous exam, and clearly some
candidates used this to their advantage.

Generous margins were accepted for some of the numerical physical properties of
oxygen, but marks could not be awarded for significant disparities. Although not
specifically asked for on this occasion, marks were awarded for descriptions of how
oxygen is manufactured where this was adequately linked to the relevant physical
property.

The adverse effects portion of the question was generally well done, but insufficient
to compensate for the absence of an answer for the first half of the question.

Question 8 : Discuss the statistical methods which can be used for analysis of groups
of categorical data.

6

Categorical data involves primarily nominal data but can include ordinal data
(ranked groups). Many candidates failed to provide a clear definition.

Marks were awarded for providing brief examples. Descriptive statistics were often
omitted, but could involve table of counts or graphical techniques such as bar graphs
or pie charts.

Inferential analysis could be divided into techniques for nominal data and ordinal
data. Chi-squared analysis forms the backbone of analysis for nominal data. A
discussion about how the test statistic is calculated and the underlying assumptions
involved was expected.

Extra marks were also awarded for the appropriate discussion of Fishers Exact Test
and Yates correction. Ratio analysis was rarely discussed, but extra marks were
awarded for discussion about relative risk and odds ratio.

A frequent mistake was to discuss parametric analysis for categorical data (eg.
Student T test, ANOVA). Categorical data do not generally meet the assumptions
required for parametric analysis.

A discussion about non-parametric analysis in relation to some types of ordinal data
(eg. Wilcoxon Rank Sum test and pain scores) was awarded extra marks.

PHARMACOLOGY VIVA SECTION

PHARMACOLOGY TOPICS:

Volatile agents
1. Inhalational agents
2. Wash out curves for volatile agents
3. Problems with halothane
4. Sevofluorane chemistry
5. ADRs and Volatile Agents.
6. Nitrous oxide
7. Define MAC
8. Types of MAC

Neuromuscular Blocking drugs
9. ED95 in NMBs
10. Fate of suxamethonium
11. Choice of muscle relaxant
12. Classification of neuromuscular blocking drugs
13. Effects of suxamethonium
14. Compare vecuronium and rocuronium
15. Dose Effect curve for vecuronium

Analgesics
16. How are NSAIDs classified?
17. What is the definition of pain?

7
18. Paracetamol pharmacology
19. Epidural morphine
20. Speed of onset of opioids.

Statistics
21. Students t test
22. Normal distribution
23. Classification of data

Local anaesthetic agents
24. Drug for IV regional analgesia
25. Toxicity of Local Anaesthetics agents
26. Physico chemical properties of lignocaine
27. Describe some local anaesthetics

Miscellaneous
28. Stages of clinical trial design
29. What are the effects of glyceryl trinitrate
30. Classify diuretics
31. Pharmacology of anti-coagulants
32. Pharmacokinetics of phenylephrine
33. Classify catecholamines
34. What is the role of additives
35. Benzodiazepines chemistry
36. The dose- effect curve
37. Classification of inotropes
38. Placental transfer of drugs
39. Management of anaphylaxis
40. Drug tolerance
41. Management of Hypotension
42. What is an isomer
43. Treatment of Parkinson Disease.
44. Name some Anti hypertensve agents
45. Classify antiseptics
46. Contents of an ampoule of Pentothal
47. Anti platelet agents
48. Bronchoconstriction management
49. Pharmacology of aspirin
50. Adverse effects of atropine
51. Chirality in Anaesthesia
52. Drug selection in liver failure
53. Syntocinon pharmacology
54. Describe ketamine and its uses

8



64% of candidates achieved a pass in this section of the Physiology Examination.


Question 9 : Describe the factors that affect respiratory system compliance.


A definition of compliance followed by a statement of the types of compliance along
with normal values for these would have completed a good introduction. A
compliance graph with an explanation of the importance of surfactant and how it acts
to reduce compliance followed by simple statements as to compliance changes
related to:
a) lung factors: aging, posture, changes in pulmonary blood volume, airways
resistance, emphysema, lung fibrosis, and
b) chest wall factors: obesity, scarring, fractures
as well as compliance changes occurring during anaesthesia would have rounded out a
good answer.

Additional marks were awarded for more detail on static and dynamic compliance,
compliance at high and low lung volumes and changes in compliance seen from the
top to the bottom of the lung in the erect position.

The most common reason for not passing this question was because of a paucity of
information provided. Additionally, there were frequent errors as to the effect of
some of the above factors on compliance, in particular, the effect of age and the
effect of emphysema.

Complex and detailed discussions regarding the interactions between chest wall and
lung compliance were only minimally rewarded.

Question 10 : Discuss the factors that influence coronary blood flow.


Many candidates did not perform well in this question as a result of failing to develop
a structured answer.

In order to pass, candidates were required to provide normal values for coronary
blood flow, a basic anatomical outline of the coronary blood supply, note the high
oxygen extraction and its consequence, and demonstrate an understanding of Ohms
law. Having demonstrated Ohms law, the factors affecting pressure and resistance
(within both the left and right ventricles) could then be further explained.

Further marks were allocated for clinical applications and the consequences of

9
common pathophysiological disturbances, including hypo/hypertension, coronary
artery disease, and severe valvular disease.

Common errors included discussing oxygen flux rather than coronary blood flow, and
failing to apply Ohms law to the coronary circulation. Many applicants spent
significant time explaining all the factors of the Hagen-Poiseuille equation, which
gained minimal marks.

A well labelled graph of the right and left coronary blood flow with respect to the
cardiac cycle often scored more highly than attempts to explain the flows in prose.

The description of coronary blood flow differs between the different recommended
text books, especially with respect to values and labelling of graphs. All variations
were considered acceptable within the examiners marking scheme.

Question 11 : Explain the physical principles of ultrasound imaging.


Important points to include were a description and explanation of the principles from
initial signal formation to tissue effects to signal reception to image formation. This
should cover both standard imaging and Doppler ultrasound. Better answers explained
the Doppler effect and the implications of the Doppler equation

Question 12 : Describe the function of the muscles involved in ventilation.


The principal muscles of ventilation are the diaphagm and the intercostals (internal,
external). Other important muscles are the abdominals and the accessory muscles of
the neck which are recruited in times of need. A precise description of the
mechanical effects of these muscles was expected i.e. how these muscles increase or
decrease the intrathoracic volume. Desciption of the anatomy of the diaphragm and
the chest wall was also helpful. Mention of the pharyngeal and laryngeal muscles and
their role in ventilation was also expected.

Most candidates who failed did so because they did not name and describe the actions
of most of these muscles or did so but only in vague terms.

Extra marks were available for the following: effects of posture; special patient
groups, including pregnancy and neonates; co-ordination in the medullary respiratory
centre; non-ventilatory actions of these muscles (cough, vomiting and defaecation);
muscle subtypes; smooth muscle.

Question 13 : Describe the cardiovascular changes in the neonate that occur at birth.

The cardiovascular changes that occur in the neonate at birth was well answered with
most candidates providing an adequate account of the effects of the first few breaths
and cessation of umbilical blood flow on the pulmonary and intracardiac circulations,
along with the sequence and timing of these events.

10
Extra marks were awarded for more detailed descriptions of the foetal circulation at
term and neonatal haemodynamics at birth, and the factors that modify them (such
as the inhibition of ductus arteriosus closure by hypoxia and prostaglandins).

Question 14 : Discuss the effects on intracranial pressure when a person is placed in
a head down tilt.


A good answer would have included a definition of intracranial pressure and its
regulation, including an accurate (not abridged) summary of the Monroe-Kellie
doctrine, then would have gone on to describe the effects of head down tilt, ie the
increase in hydrostatic pressure on the three elements within the fixed cranial vault,
ie: blood volume( both arterial and venous components), cerebrospinal fluid and brain
tissue, and finally described the ability to compensate for the increase. Some
quantification of the degree of increase in hydrostatic pressure rise vs. degree of
head down tilt was useful.

Unfortunately a number of candidates confused cerebral perfusion pressure with
cerebral blood flow in their explanations, therefore reproducing erroneous equations.
Graphical representation of concepts were useful to demonstrate knowledge when
labelled correctly and included in the discussion. If axis were unlabelled they gained
no marks.

The effects of general anaesthetic agents on the three components that generate
intracranial pressure was not asked for in the question and gained no marks in a
physiology question.

Question 15 : Explain the role of haemoglobin as a buffer.

This question has been asked previously and this time the pass rate was 27%.

Marks were awarded for a buffer definition, a brief description of haemoglobin
structure, and listing the factors that create an effective buffer. Haemoglobin acts as
an effective buffer for CO
2
due to the solubility of CO
2
, presence of carbonic
anhydrase, and the capacity of haemoglobin.

Important points that needed to be covered included; the importance of the large
volume of haemoglobin, the role and amount of the imidazole side chains on the
histidine residues, the effect that their pKa (6.8) has on buffering ability, and a clear
description of the reactions within the red cell that involves CO
2
conversion to HCO
3
-

and H
+
and the fate of these two products. Discussion about why the deoxy form of
haemoglobin is a better buffer due to its change in pKa (7.9), and that this occurs
where buffering is needed most, which limits the pH drop for venous blood. Some
candidates correctly identified that the dissociation of carbamino compounds within
the red cell adds H
+
which then needs to be buffered.

Discussing the haemoglobin oxygen dissociation curve, carbon dioxide dissociation
curve, and other buffers in the body did not attract marks.

11
Question 16 : Outline the clinical laboratory assessment of liver function.

29% passed this question.

Basic points to include to achieve a pass included a description of the battery of
tests commonly referred to as liver function tests; a description of what they
tested and an appropriate interpretation of an change.

Extra marks were available for suggestions of more sensitive clinical tests of liver
function, (Prothrombin time or INR) and integrating the understanding of common
derangements of hepatic function.

Common mistakes included listing all the functions of the liver and discussing how
these might be assessed.

PHYSIOLOGY - VIVA SECTION

PHYSIOLOGY TOPICS:


1. SI units
2. What is an electrical resistor?
3. What is heat?
4. Measurement of intracellular water.
5. Pulse Oximetry.
6. Measurement of saturated vapour pressure
7. Measurement of oxygen.
8. BP measurement
9. Principles of arterial pressure measurement.
10. Measurement of temperature
11. What factors determine flow
12. Osmolarity / Colligative properties.
13. CO
2
measurement /capnograph
14. pH measurement

Renal/Acid-base

1. Control of renal blood flow
2. What is the glomerular filtration rate
3. Define clearance.
4. How does the body clear a water load?
5. Physiologic effects of renal dysfunction
6. What is extra-cellular pH range?
7. Describe renal handling of a metabolic acid.

12
8. What is renal response to metabolic alkalosis?

Endocrinology / Prostoglandins

1. What is a hormone
2. What are the functions of adrenal medulla?
3. Pituitary hormones.
4. Thyroid hormones
5. Interaction of Insulin & Glucose
6. Glucose handling
7. What is normal blood sugar
8. Prostaglandins in the body

Nerve

1. Nernst Equation
2. Describe a myelinated nerve
3. Types of nerves
4. Pain transmission.
5. What is sleep
6. What is the blood brain barrier?

Haematology

7. Describe the processing of donated whole blood.
8. Describe red cell antigens.
9. Response to damaged blood vessel
10. Effects of storage of red blood cells

Muscle

11. Describe sequence of events in neuro muscular contraction.
12. What is a muscle spindle

Cellular

13. Features of a cell
14. Cellular energy sources

Neonatal/Maternal

15. Oxygen delivery to foetus
16. Cardiovascular response to pregnancy.

13

17. Respiratory changes in pregnancy

Immunology

18. What is the difference between innate and acquired immunity?
19. Mechanisms to stop bacteria reaching alveoli
20. Hypersensitivity

Metabolism/Thermal homeostasis

21. Normal body temperature
22. What is in Total Parenteral Nutrition?
23. Metabolic consequences of sepsis

Gastro-intestinal

24. Describe swallowing (physiologic principles)
25. Describe gastric emptying

Respiratory

26. Respiratory function tests
27. What is diffusion capacity
28. What affects the diffusion capacity of the lung
29. Control of ventilation
30. Dead space
31. Aging + respiratory function
32. Pulmonary circulation
33. O
2
cascade
34. What is the alveolar gas equation
35. O
2
supplies in body
36. What is normal PO
2

37. What is normal PaCO
2

38. Carriage of CO
2

39. Interpretation of blood gases
40. Consequences of apnoea
41. Effect of posture on lung perfusion
42. Interpretation of capnography
43. Describe airway resistance
44. What is O2 extraction?
45. Why do we produce CO2
46. Compare Pulmonary & Systemic circulation
47. What is pulmonary vascular resistance?
48. What is shunt?
49. What is surfactant?

14
50. Lung mechanics
51. Hb O
2
dissociation curve?
52. Ascent to altitude
53. Describe work of breathing

Cardiac

1. What is the function of the circulation
2. Distribution of cardiac output
3. Draw the action potential for the SA node
4. Arterial P waveform changes with age?
5. Describe ECG
6. Frank Starling Mechanism describe
7. Cardiac cycle
8. Draw left atrial pressure cycle
9. Draw an LV Pressure vs. Time curve
10. What is automaticity
11. Define afterload
12. Cardiovascular changes associated with aging
13. What is anaemia
14. Effects of chronic anaemia
15. Describe venous return
16. Interdependence of venous return and cardiac output
17. Starling curves draw
18. Pulmonary artery catheter
19. Effects of haemorrhage
20. Control of peripheral blood flow
21. What is the microcirculation

Dr. C Noonan
Chairman, Primary Examination Sub Committee

ABN 82 055 042 852

EXAMINATION REPORT


MARCH/MAY 2010

Please note that this report is prepared to provide candidates and their teachers and supervisors of
training with information about the way in which the performance of candidates in the recent
examination was assessed by the examiners, so that candidates and teachers may prepare
appropriately for future examinations. The individual reports are not intended to represent model
answers nor imply that all points mentioned are necessary in order to achieve a pass. All trainees
are urged to read the questions carefully and answer the question asked. All teachers and
supervisors of training are encouraged to discuss this report in detail with candidates they are
preparing for future examinations.





QUESTION 1 Describe how the chemical structure of local anaesthetic drugs determines their
efficacy and safety.


This could be considered core material, although many candidates lost marks by spent a time on
non-relevant information such as describing local anaesthetic toxicity, mechanisms of action, and
routes of administration.

Other common errors included: making imprecise statements (for example, the structure
determines what the pKa and lipid solubility will be, without saying how), writing lengthy
introductions that dont make a point, repeating the same point multiple times, and stating that
prilocaine is an ester local anaesthetic.

The answer needed to be related to the structure of local anaesthetics and could be divided into
effects on efficacy and safety. This means looking at the lipophilic, intermediate, and hydrophilic
components. Increases in side chain length generally result in increased lipid solubility, potency,
and protein binding up to a point. This also increases toxicity, duration of action, and slows the
onset/offset. The differences between the ester and amide link in regards to metabolism, allergy,
and duration of action need to be covered. Other aspects needed to gain marks included the
effects of chirality and acid-base changes.

2
QUESTION 2 Describe the methods of determining depth of neuromuscular block and list the
advantages and limitations of each.


This question covers material asked in previous questions.

The main points expected for a pass include:

Neuromuscular blockade can be assessed by both clinical means and by using the nerve stimulator.
Some examples of clinical means (eg head lift for 5 seconds) was expected, however clinical
methods are unreliable.
The characteristics of the required impulses from the nerve stimulator afforded the candidates
points.
Marks were awarded for the different modes of stimulation, such as single twitch, train of four
count and ratio, double burst stimulation, tetany and post tetanic count. It was expected that
candidates would describe their requirements, their advantages and disadvantages and how best to
clinically utilise them for e.g. for reversal, in deep block.
Some candidates went into great detail about the neuromuscular junction, which afforded them no
marks.
The concept that the strength of the muscular twitches produced is related to receptor occupancy
by the neuromuscular blocker and at what levels of occupancy one could expect how many
twitches. A few candidates did not appreciate that with a train of four count of 4, there was still a
70% receptor occupancy by the drug. Some thought that with a post tetanic count of 10, it was
reasonable to reverse the patient with conventional reversal agents.
Bonus marks were awarded if there was demonstration of how the depolarising and non-
depolarising blocks differed in their responses to the nerve stimulator, the different sensitivities of
different muscle groups to the neuromuscular blocker and mention of acceleromyography or more
sophisticated methods. Use of diagrams implied understanding and where appropriate, garnered
marks. Some candidates were confused about the TOF ratio, saying it was the ratio of the height of
the first twitch compared to the fourth twitch

QUESTION 3 Discuss the adverse effects that may occur with the administration of
desflurane.


This question was poorly answered by the majority of candidates. Better answers discussed adverse
effects by system or divided their response in to those effects peculiar to desflurane and those
common to many volatile agents. Even better answers compared some adverse effects to other
volatile agents. No marks were awarded for details which were clearly unrelated to the answer
such as chemical structure and physical characteristics.

The following material needed to be covered for a clear pass.

Desflurane is a volatile agent used mainly for the maintenance of general anaesthesia. An adverse
effect is an unwanted side effect of a drug.
Desflurane reduces systemic vascular resistance and thus mean arterial pressure in a dose
dependant manner, however cardiac output is usually well-maintained by an increase in heart rate.
Sudden increases in the inspired concentration can cause a marked sympathetic response with
tachycardia, hypertension and activation of the renin-angiotensin system.
Cerebral blood flow increases above 1.0 MAC but the rise in ICP is quite small (about 7mmHg). At
higher doses there is uncoupling of oxygen supply and demand. It is not known to trigger seizure
activity.
There is a dose-dependent reduction in tidal volume and increase in respiratory rate (overall
decrease minute ventilation) and an impaired response to hypoxia and hypercarbia. Desflurane is

3
pungent and can cause coughing and breath-holding so it is infrequently used for inhalational
induction. It can increase airways resistance (especially in smokers).
It can cause a fulminant antibody-mediated hepatitis (like halothane) through neoantigen formation
from metabolites, but this is very rare probably due to the very low rate of metabolism.
It reduces uterine tone (potentially worsening postpartum haemorrhage).
It is a trigger for malignant hyperthermia.
It can interact with carbon dioxide absorbants to produce toxic levels of carbon monoxide
(especially with high temperatures and low flows over dessicated Baralyme ).

QUESTION 4 Describe the time course between an intravenous injection of a general
anaesthetic agent to loss of consciousness. Explain the delay using
pharmacokinetic principles.


The delay to loss of consciousness after intravenous injection of an induction agent is a very
specific event that requires detailed knowledge of pharmacokinetics. Descriptions of the time
course had to indicate that the delay involved the build up of an adequate or threshold
concentration at the effect site for loss of consciousness to occur.

There were many facts that attracted marks in this question with the better answers providing
fuller justifications. For example simple knowledge such as using a bolus or loading dose and
injecting the dose faster attracted marks but explaining that these practices led to a higher dose of
agent in the central compartment which then leads to a larger concentration gradient driving the
agent into the effect site (CNS) more quickly attracted higher marks.

Similar discussions about the importance of cardiac output and pathological situations where the
cardiac output may be altered, injecting into a larger vein closer to the heart instead of a
peripheral vein, about smaller volume of distribution leading to a larger concentration in the
central compartment (despite the paradox that a lower lipid solubility is often associated with a
smaller Vd) all attracted marks.
Many candidates showed an appreciation of the complexity of pharmacokinetics, describing how
redistribution and metabolism begin to occur simultaneous to delivery and may slow the build up of
central compartment concentration and delay onset of action to a small degree.

Diagrammatic representation of a 3 compartment pharmacokinetic model with correct descriptions
with highlighting and description of the importance of the Keo also attracted marks. Comparisons
of Keos between differing intravenous induction agents were also central to the question. Graphs
depicting the change in plasma and superimposed effect site concentrations with time attracted
marks, with the better graphs indicating the threshold level needed at the effect site for loss of
consciousness to occur.

A discussion of the potential for speed of effect to be influenced at the neuronal membrane and by
the specific molecular characteristics of the induction agent and how this related to Ficks Law and
to unionized drug was also considered relevant.

Candidates often ran into difficulties with their answer if they spent too much time discussing how
the effect of induction agents wore off or how they were cleared from the circulation, or spoke at
length about unrelated facts concerning specific agents.

4
QUESTION 5 Describe how Non Steroidal Anti-Inflammatory Drugs exert their clinical
effects. Outline the advantages and disadvantages in using COX-2 selective
agents.


Candidates were expected to describe how the inhibition of cyclo-oxygenase results in both positive
and negative clinical effects of NSAIDs. Many candidates did not link the reduction in
prostaglandins, leukotrienes, thromboxane and interleukin to specific NSAID actions such as anti-
pyrexia, analgesia and anti-inflammation. Physiological actions of prostaglandins and thromboxane
were described but did not gain marks unless related to the clinical effects of NSAIDs. Marks were
awarded for differentiating the isoforms of cyclo-oxygenase and the logic behind preferentially
inhibiting COX-2. A structured approach naming the clinical effects of NSAIDs and how they occur
through manipulation of eicosanoid production gained higher marks.

Confusion occurred regarding the effect of COX-2 selective agents on asthma. Generally the
precipitation of asthma is reduced. Omitting the allergic potential of COX-2 inhibitors and the fact
that Parecoxib is a pro-drug were common. Extra marks were awarded for describing the effects of
NSAIDs on bone formation, the ductus arteriosus, the pregnant uterus and bowel cancer.

QUESTION 6 List the main drug groups used in the treatment of diabetes mellitus. For each
group explain the mechanism of action and give examples.


Diabetes mellitus is a common condition faced daily by anaesthetists. A thorough understanding of
its management is a clinical necessity.

This is a two parts question requiring candidates to list the various groups of drug for the treatment
of diabetes mellitus, and to describe their mechanisms of action. It is important that sufficient
details, such as molecular and metabolic effects after drug administration, are included for the
latter part of the question.

While most candidates were able to describe the classical oral hypoglycemic agents (i.e.
sulphonylureas and biguanides) in detail, it was surprising that a substantial proportion of
candidates did not consider insulin as a drug for the treatment of diabetes mellitus. Most answers
were also vague regarding the different preparations of insulin that produce variation in the speed
of onset and duration of action. Candidates who included the newer agents, such as
thiazolidinediones, alpha glucosidase inhibitors and meglitinides, were rewarded with extra marks.

QUESTION 7 Briefly describe the pharmalogical role of the nicotinic cholinergic receptor.


The key points that needed to be included were:
The types of the nicotinic receptor, their location and function
Structure activity relations of the receptor which account for drug specificity (e.g.why
ganglion blockers do not cause muscle relaxation), pharmacodynamics (e.g. prejunctional
receptors causing fade) and side effects (e.g. hyperkalaemia with suxamethonium)
Drugs can act either directly or indirectly as either agonists or antagonists (correct examples
attracted marks)
Many candidates failed to write that there is a structural difference between the neuronal and
muscle nicotinic receptor, this is important in understanding the specificity of action of
neuromuscular blockers. There was a frequent misconception that anti-muscarinic drugs act
primarily at the nicotinic receptor. Some candidates wrote at length about the physiology of the
nicotinic receptor without mentioning drugs and were thus unable to achieve a pass mark.

5
QUESTION 8 Classify drugs used in the treatment of depression. Outline the interactions
between antidepressant drugs and drugs that are commonly used during the peri-
operative period.


The main points expected for a pass included a classification of antidepressants according to
mechanism of action, and therefore making some mention of the amine hypothesis of
antidepressant effect. Then an outline of antidepressant perioperative drug interactions was
expected: including pharmacokinetic and pharmacodynamic interactions. Many relevant
interactions attracted marks, however, the important MAO inhibitor interactions were especially
rewarded.

Although most candidates classified antidepressants according to mechanism of action, few
connected this pharmacodynamically to the therapeutic antidepressant effect. Pharmacokinetic
drug interactions were rarely included in answers and an explanation of what type of
sympathomimetic that could be utilized perioperatively in patients taking MAO inhibitors was often
omitted. Similarly, serotonin syndrome was frequently discussed as a SSRI interaction (where the
severity is usually minor), but rarely so as a MAO inhibitor interaction where it can be severe.

Detailed descriptions of the pathology of depression were not expected.



IV Induction agents
Why do you believe propofol is widely used as an anaesthetic agent?
What are the pharmacodynamics of propofol?
What is in an ampoule of thiopentone?
How do you determine an induction dose of propofol?
Compare the pharmacokinetics of an infusion and a bolus of a drug
Thiopentone as an induction agent
What IV agents act on the GABA receptor?
Induction of anaesthesia in a volume depleted patient.

Pharmacokinetics and pharmacodynamics
Gaseous induction with sevoflurane
Dose Response curves
What drugs are administered by infusion
Wash out curve for a volatile agent
Concentration-time curve for fentanyl
Definition of half life
Pharmacokinetic parameters for propofol
Drug nomograms
Transdermal medications
Anaesthesia and liver failure
Modifications of drug dosage
Draw a quantal dose-response curve
Endotracheal administration of drugs
Mechanisms of drug clearance.
Changes in drug response with age.
How can genetics influence metabolism?

6
Anti-emetics
What drugs can be used for Post-Operative nausea and vomiting?
Compare anti-emetics
Pharmacology of ondansetron

Local anaesthetics
Cocaine
What drugs are added to local anaesthetics?
What drugs are used in topical anaesthesia?
Kinetics of local anaesthetics in CSF
What is lignocaine?
Local anaesthetic toxicity

Inhalational agents
How do you select an inhalational agent?
Draw a wash in curve for isoflurane
Draw a wash out curve for an agent
Manufacture of nitrous oxide
What are the advantages of sevoflurane?
When to avoid nitrous oxide
Fa/Fi curves
How does the addition of nitrous oxide affect inhalational agent uptake?
Changes in uptake of volatile agents
Effects of sevoflurane on the CNS
Isoflurane and the CVS
How does cardiac output affect inhalational uptake?
Autonomic Nervous System and Adrenoreceptor Blocking drugs
Alpha 2 agonist drugs
What drugs increase blood pressure?
How do you classify beta blockers?
What is an inotrope?
Anti-arrhythmic effects of beta blockers
Effects of clonidine
Adverse effects of adrenaline
What drug act on the renin-angiotensin system?
What is a catecholamine?
What is a beta blocking drug?
Hydrallazine and clonidine
Digoxin
Ephedrine

Statistics
Data types and study limitations
Box plots
Scatter plots
Regression analysis
Hypothesis testing
Case controlled studies
Data interpretation
What is probability?
Clinical trial design
Meta analysis
Students t test
What is a 95% confidence interval?

Neuromuscular Blocking Drugs and reversal
Monitoring of neuromuscular blocking drugs
Classification of NMBs

7
Pharmacology of suxamethonium
ED95 of muscle relaxants
What receptors exist at the NMJ?
Dose-response curves to NMBs
Receptor regulation
Changes in response to NMBs
Organo phosphate poisoning
Atracurium and rocuronium
Cardiovascular effects of NMBs
Dose response curve with anticholinergics

Analgesic agents
Non-opioid analgesics
COX-2 inhibitors
Structure and function of opioids
NSAID toxicity
Paracetamol pharmacokinetics
Parecoxib
Post-operative analgesic options
Onset time of analgesics
Ketamine as an analgesic
Methadone
Pharmacokinetics of fentanyl
Compare alfentanil and remifentanil
Tramadol pharmacology
How does paracetamol work?
IV analgesic drugs
Blood levels following oral paracetamol
What determines a dose of morphine

Miscellaneous Topics
What drugs relax the uterus?
How does drug development occur?
Allergic reactions in anaesthesia
How do you treat atrial fibrillation?
Pharmacology of amioderone
Management of hypertension
Classification of anti-hypertensive agents
Management of poisoning
Management of myocardial ischaemia
Principles of antibiotic prophylaxis
What is the difference between an anti-septic and a disinfectant?
How can we change the pH of stomach contents?
What types of heparin do you know of?
What anti-platelet agents do you know of?
What drugs are used in cardiac arrest?
With diuretics, how does site of action influence efficacy?
Classification of diuretics
What colloid IV fluids do you know of?
Classes of IV fluids
Classify drug interactions
What are the stages in drug development
Principles of clinical trials
Nitric oxide
How do anti-coagulants work
Tolerance and tachyphylaxis

8





QUESTION 9 Explain the physiological factors that may lead to a decrease in mixed venous
blood oxygen saturation.


This question required candidates to explain a decrease in mixed venous oxygen saturation.
The key issue in this question is the fact that the value of mixed venous saturation is the result of a
balance between oxygen delivery to the cells (oxygen flux) and cellular consumption of oxygen.
The net value of mixed venous saturation can thus be explained by unpacking the elements of
delivery and consumption, and explaining how their variation results in a change in mixed venous
saturation. Not acknowledging this issue made it difficult for candidates to accumulate sufficient
marks to pass the question.

A significant number of candidates approached this by providing flux equations or variants of Ficks
Law. This readily identified the elements, and their contributions could be clearly explained.
These candidates tended to comfortably accumulate sufficient marks to pass. However, some
candidates spent significant time on detailed derivations of formulae, leaving less time to address
more important aspects or to accumulate bonus marks for more detailed information. Further,
detailed derivations not uncommonly introduced simple errors. Simply using a formula or equation
to identify the elements or principles involved was sufficient.

Many candidates did not identify this basic principle of supply and demand, and therefore struggled
to pass the question. Instead, a significant number of candidates focused on details such as the
oxygen dissociation curve in both arterial and venous blood, sometimes in great depth and with
detailed figures. Some candidates focused on little else. The time spent on this aspect left little
opportunity to address more fundamental issues.

It was notable that the terms oxygen tension, saturation and content were used carelessly in a
significant number of answers. These are fundamental issues at this level of physiology.

QUESTION 10 Describe how white blood cells defend the body against infection.


The question required a description of the different white blood cells in the body and a discussion
of their activation and interaction. Successful candidates gave a comprehensive list of white cell
types and described how each defended the body. Some understanding of the roles they played in
innate and acquired immunity was also necessary. Better candidates structured their answer based
on the time course of activation so they could most effectively describe the interplay between
white cells.
Common areas of confusion were:
roles played by each cell, particularly the natural killer cell
the types of infective agent each cell was active against
the difference between acquired and innate immunity.

9
Marks were not gained for discussing hypersensitivity reactions or non-white cell mediated defence
such as physical barriers.

QUESTION 11 Describe the changes that occur in the urine and the plasma with renal
dysfunction.


28% scored 8 marks or less.

Marks were awarded for the following points:
That renal dysfunction could refer to abnormal function at any part of the nephron (glomerulus,
tubules, interstitium); most commonly a reduction in GFR was involved.

Plasma chemistry changes would include increased creatinine, urea, potassium and hydrogen ions.
Creatinine rises only after substantial (eg 50%) loss of nephron function and the rise is in a
curvilinear fashion, and creatinine clearance can be used to calculate eGFR and GFR. Urea
concentrations are subject to too many variables to be useful in estimating degree of renal
dysfunction. Potassium levels may rise to fatal levels, particularly in oliguric patients. Metabolic
acidosis is often of a raised anion-gap type due to accumulation of titratable acids, but with renal
tubular acidosis may not have a raised AG. Typically there is hypocalcaemia and
hyperphosphataemia, increased PTH and decreased VitD3, in chronic disease. Chronically, EPO
levels fall leading to anaemia. There may be hypoalbuminaemia in nephrotic syndrome.
Accumulation of renally-excreted drugs or their metabolites may occur. Plasma sodium levels tend
to remain within the normal range, except in rare situations where large volumes of dilute urine
are produced, because the reduction in GFR reduces elimination of both salt and water. (The
increase in osmolality is mostly due to urea, a point not understood by most candidates who either
said osmolality was unchanged or reduced).

Urine changes that scored marks included oliguria (preferably with a definition), possibly polyuria
(but this is not the same as non-oliguric renal failure, i.e. absence of oliguria does NOT imply
abnormal polyuria!); inability to concentrate the urine and also inability to dilute the urine, so that
in advanced renal failure the urine osmolality is similar to plasma (isotonic urine); in ATN there
may be granular casts; RBC casts occur in glomerulonephritis as do upper tractRBC; proteinuria
indicates glomerular dysfunction. Appropriate use of terms such as Fractional excretion of Na
scored marks if there was an indication the candidate understood the term.

Common errors included: Failure to mention creatinine and /or urea or oliguria. Many answers
spent lots of time discussing polyuric conditions such as nephrogenic diabetes insipidus, (and little
or no time discussing any other situation) leaving the examiner to wonder if this was their idea of a
common physiological abnormality.

By far the commonest urinary change is a reduced volume. Many candidates listed oliguria as
occurring with so-called pre-renal failure and then becoming polyuric with established renal
failure.

Only 2 answers noted that ability to concentrate AND dilute urine was impaired in most situations.
Oliguria in renal failure does NOT mean the urine is concentrated, it simply reflects a much-
reduced volume of glomerular filtrate and that small volume may hyper, hypo, or isotonic to
plasma.

The majority also incorrectly suggested that impaired tubular function would lead to Na and H2O
loss and polyuria, whereas as GFR is progressively reduced then tubular function bears less and less
relevance to urine volume. Hypovolaemia secondary to polyuria was mentioned more commonly
than volume overload due to oliguria. As mentioned above, plasma osmolality rises, due to urea in
the main. This does not lead to activation of humoral responses to decrease the osmolality because
urea is freely soluble across cell membranes, i.e. an ineffective osmole.

10
Many candidates wasted valuable time describing normal tubular function, or determinants of GFR.
It was also not asked to describe causes of renal impairment, or to give a description of the renin-
angiotensin-aldosterone axis. Only a handful realised that Creatinine levels reflect GFR, but that
creatinine clearance and eGFR reflect changes better than blood levels alone.

A large number of answers dwelt on glucose handling in the PCT, many saying that glycosuria at
normal BGLs, and even hypoglycaemia, occur in renal dysfunction, because of alteration in Tmax
for glucose. The opposite is closer to the truth- reduced filtration of glucose often leads to there
being no glycosuria in the presence of significant hyperglycaemia.

Too many candidates used vague statements like alterations in electrolyte balance, build up of
metabolic wastes and impaired acid-base balance. Creatinine and creatine are not the same
thing; Urea does not cause gout; and insulin is not used to measure GFR. The kidney produces
ammonia to excrete acid, it is not the site of ammonia elimination, levels of which rise in hepatic
failure not renal failure.

QUESTION 12 Briefly explain the changes that occur in stored whole blood.


Main Points expected for a pass:
What is in stored whole blood
How it is stored
The biochemical changes
The cellular changes

Additional points could be gained for:
The mechanisms of the changes in stored blood
How the preservative solution prolongs blood storage

Common problems:
Illegible handwriting
Poor layout and structure
Many candidates were unsure about what the current preservative solution is and what the
different components were for
The main reason for failing this question was insufficient core knowledge

QUESTION 13 Describe the autonomic innervation of the heart and the effects of autonomic
stimulation on cardiac function.


Main points expected for a pass included: origins & pathways of efferent sympathetic &
parasympathetic supply to the heart, including site of ganglia, neurotransmitters & receptors; and,
effects of increased sympathetic & parasympathetic tone on heart rate, contractility, AV nodal
conduction & coronary vasculature. This information could be effectively presented in tabular
format.

Additional marks were allocated for mention of: the reciprocal interaction between sympathetic &
parasympathetic systems; prevailing tone at rest; and, effect of both systems on propensity to
dysrhythmias. Further marks were awarded for indicating the time frame for onset & offset of
autonomic effects; and, for explaining changes in automaticity and demonstrating this
diagrammatically via the pacemaker potential.

Mistakes commonly made included: spelling errors (particularly for inotropy, chronotropy,
lusitropy) & failing to demonstrate an understanding of the meaning of such terms; and, poor
legibility of key words. Credit was not given for vague, non-directional statements regarding
autonomic stimulation, nor for pharmacological effects of drugs on the autonomic system. Many

11
candidates included details of afferent limbs or baroreceptor reflexes of the autonomic system,
neither of which was required. Furthermore, excessive detail on intracellular messaging systems
was not rewarded commensurate with the time taken to write such information.

QUESTION 14 Describe the factors that affect static respiratory system compliance.


Basic information required included the following:

A definition of static compliance
Respiratory system compliance is determined by elastic forces in the lung and chest wall (rib
cage and diaphragm)
Lung elastic recoil comprises surface tension of alveoli (La Places Law) and the elastic
properties of lung tissue
The importance of surfactant
Lung size (child v adult) compliance increases with increased size but specific compliance
is unchanged
Lung volume compliance is maximum at FRC and reduced at high and low lung volumes
Examples of disease processes (and direction of effect) that influence compliance e.g.
emphysema, pulmonary fibrosis, pulmonary oedema, pulmonary blood volume (but not
blood flow), chest wall scarring, increased intra-abdominal pressure, obesity

Additional marks were given for:
Units and a normal value
The equation relating total with lung and chest wall compliance
Influence of posture
Effect of anaesthesia
Effect of gravity on regional lung compliance

Graphs were commonly drawn but rarely provided additional information to that which was
written. The effects of pregnancy hormones on chest wall compliance were often mentioned but
the (opposite and greater) effect of the gravid uterus was ignored.

Common mistakes included discussion of time constants, fast and slow alveoli, and airways
resistance. Description of the measurement of compliance did not attract marks.

QUESTION 15 Explain how cardiac output is measured using a thermodilution technique.


Interpretation:
This question asked for an explanation of a specific technique of measuring cardiac output. Not
directly relevant are:

1) A detailed discussion on cardiac output and the factors affecting it
2) Other techniques of cardiac output measurement
3) Explanation on how a thermistor functions
Content:
The main points in the answer should include:

1) A discussion of the basic principles involved.
Thermodilution is based on the law of conservation of matter where heat lost from the
blood = heat gained by injectate

12
2) A description on the specifics of the technique mentioning the requirement of a Swan-Ganz
catheter, nature of injectate and temperature measurement using a thermistor in the
pulmonary artery.
3) An appreciation on how cardiac output is calculated from this technique
4) A discussion of sources of errors which might affect the accuracy of the technique
Errors or common mistakes:

Some candidates erroneously conclude that cardiac output IS the area under the curve. Other
candidates confuse the PiCCO as a thermodilution technique.

Organisation:
Better answers include a short list of advantages and disadvantages of the technique.

Clarity:
Good answers mentioned that the thermodilution technique is a variation of the indicator dilution
technique which uses the temperature decrease as the indicator.
Additional marks were given for a discussion on the Stewart-Hamilton Equation used to calculate
flow/Q.

QUESTION 16 Describe the processes whereby substances may cross cell membranes, giving
examples.


The following were the main points expected in answering the question:
Clear descriptions of the following mechanisms of transport across cellular membranes;
- Exocytosis and endocytosis
- Diffusion, with an appropriate explanation. Better answers included relevant application of
Ficks Law of Diffusion
- Movement through ion channels and aquaporins, with ion channel subtypes identified
- Carrier mediated transport, with discussion of facilitated diffusion, primary and secondary
active transport.
It was expected that relevant examples of each transport mechanism were included.

Extra marks were awarded for a clear, well structured answer, with appropriate examples offered
for key processes.

Common errors included;
- Detailed discussions of diffusion mechanisms, with inadequate attention to other processes
- Incorrect or absent examples of key processes
- Describing facilitated diffusion as an example of active transport
- Confusing co-transport and counter-transport mechanisms.

13

PHYSIOLOGY TOPICS:

1) What is a normal PaO2 value?
2) What is a normal PaCO2 value?
3) What are the oxygen stores in the body?
4) What is the EEG?
5) Draw a lead II ECG.
6) What is TPN?
7) Draw a radial arterial pressure trace?
8) Describe the coronary circulation.
9) What are the functions of the liver?
10) What are the functions of the stomach?
11) What is the difference between heat and temperature?
12) What determines the arterial blood pressure?
13) What determines the flow of fluid through a tube?
14) Define the functional residual capacity of the lungs.
15) What is the Frank-Starling mechanism?
16) Describe the blood supply of the liver.
17) What does a pulse oximeter measure?
18) How could you measure gas flow?
19) What types of muscle fibres do you know?
20) Draw a CVP trace.
21) What is normal renal blood flow?
22) What are the causes of hypoxaemia?
23) Describe how CO2 moves from the mitochondria to the air.
24) What are the mechanisms of visceral pain?
25) What is sleep?
26) What is hypothermia?
27) What are the functions of the placenta?
28) Describe the muscle spindle.
29) Where do we find smooth muscle in the body?
30) What are the causes of hypercapnia?
31) Draw the flow of blood in the aortic root.
32) How does the cardiovascular system respond to haemorrhage?
33) Draw an action potential from a SA node cell.
34) What are the causes of hypoxemia?
35) How does the body handle potassium?

14
36) What are the physiological effects of fasting for 48hrs?
37) What are the SI units?
38) What are the physiological effects of an increase in airways pressure?
39) Describe the fetal circulation.
40) Describe the valsalva maneuver
41) What is a colloid?
42) How can you be hypercapneic in the presence of a supernormal minute ventilation?
43) What is the range of urine osmolality?
44) Where does the body produce lactate?
45) What is the definition of afterload?
46) What is the definition of cardiac contractility?
47) What do you understand by the term closing capacity?
48) Can you interpret this arterial blood gas result?
49) What is a transducer?
50) What are the functions of the thyroid gland?
51) How could you measure cerebral blood flow?
52) How much oxygen does the body use in a minute?
53) What is a hormone?
55) Describe the principles of the use of ultrasound in medical practice.
56) What are the physiological effects of aging on the cardiovascular system?
57) What are the physical mechanisms by which the body loses heat?
58) How does the body control ventilation?
59) Why dont you faint when you stand up?
60) What is a normal blood glucose level?
61) Describe the pulmonary circulation.
62) Draw a pressure volume loop for the left ventricle.
63) How does oxygen uptake increase with exercise?
64) Can you draw the action potential in a skeletal muscle?

Dr. C Noonan

ABN 82 055 042 852

EXAMINATION REPORT


JULY/SEPTEMBER 2009

Please note that this report is prepared to provide candidates and their teachers and supervisors of
training with information about the way in which the performance of candidates in the recent
appropriately for future examinations. The individual reports are not intended to represent model
answers nor imply that all points mentioned are necessary in order to achieve a pass. All trainees
are urged to read the questions carefully and answer the question asked. All teachers and
supervisors of training are encouraged to discuss this report in detail with candidates they are
preparing for future examinations.





QUESTION 1 Sevoflurane and fentanyl are a common anaesthetic drug combination. Discuss
pharmacological reasons why it is useful to use them together.


This question required candidates to detail the beneficial uses and effects of combining sevoflurane
and fentanyl. Most answers began with a brief description of each drug and its usual indications of
use. The synergistic drug interaction was the primary focus expected. This included discussions
about reductions in MAC, MAC-BAR, MAC-awake. Additional marks were awarded for specifying
percentage reductions or proportionally greater reductions in MAC-BAR versus MAC-awake.
Successful candidates were able to detail the beneficial consequences of this synergistic
interaction, which primarily revolved around reduced drug doses of each resulting in reduced
adverse effects. This included discussions about enhanced cardiovascular stability with airway
instrumentation or surgical stimulation, reductions in sevoflurane adverse effects (hypotension,
increased CBF/ICP, reduced uterine tone), and reductions in fentanyl side effects (prolonged
sedation or respiratory depression, opioid induced nausea and vomiting). Some candidates were
confused about the whether sevoflurane provided analgesia. Whilst sevoflurane in high enough
doses can ablate responses to surgery via its global CNS depressant effect, it does not have a
specific analgesic action. Bonus marks were awarded for discussion about the possibility of using
fentanyl as a sole anaesthetic and the benefit of adding a volatile to an opioid based anaesthetic.

2
QUESTION 2 What are the potential side effects of propofol and its formulations?


Expected was a brief description of the clinical uses and the most common formulation of propofol.
At this point candidates who performed well divided their answer to adverse effects due to
propofol and those secondary to the formulation. Common cardio-respiratory effects of propofol
were well described. That propofol resulted in sedation and anaesthesia was almost universally
recognised but few commented on the narrow therapeutic window between the two. Again, most
candidates identified excitatory movements with induction but fewer correctly described the
mechanism or explained the contradictory EEG effects and the use of propofol for status
epilepticus. Common side effects related to the formulation including pain, bacterial
contamination, use of preservatives were well discussed. Metabolic effects from prolonged infusion
including lipaemia, propofol infusion syndrome and the propensity to produce green coloured hair
and urine was discussed by the majority. Few however mentioned alternative solvents including
liposomes, medium chain triglycerides and cyclodextrins. That subclinical doses of propofol
produce euphoria and explain the abuse potential unique to this drug also received a mark.
Common mistakes were to discuss the pharmacokinetics of propofol, adverse effects related to the
formulation only and beneficial central nervous system effects.

QUESTION 3 Discuss classes of drugs that influence Post-Operative Nausea and Vomiting
(PONV) including mechanisms where known.


Approaches to answering this question include choosing and naming a class followed by an example
of the group, acting especially at which receptor, where known, followed by designating the
location of action eg agents acting at D2 receptor at the chemoreceptor trigger zone.

To add a comment specific to the agent named would then complete a discussion for each agent eg
droperidol and the Q-T interval lengthening.

Lateral thinking would include agent groups which often induce PONV eg opioids such as morphine
acting at mu receptors in the area postrema increases the likelihood of PONV in a dose related
manner. Quite rightly, mention of N20, volatiles, ketamine or ergometrine is relevant, as all are
agents to which some of our patients are exposed.

The well known groups of 5HT3 antagonists, D2 antagonists including the benzamides to which
metoclopropamide belong, formed the nucleus of agents discussed. The use of propofol, use of
benzodiazepines and antihistamines all earned marks. Even the new group NK1 Antagonists received
mention by quite a few candidates.

The responses which explained very clinical information or extensive dosage regimes or opted to
leave out naming classes of drugs deprived themselves of credit focussing on the question at hand.

QUESTION 4 Describe the effect of obesity on pharmacokinetics and the potential clinical
implications, providing relevant examples.


This was a question with which most candidates struggled, possibly because it required bringing
together information from a variety of areas.

Most candidates started off, appropriately, with a definition of obesity and then went on to point
out that it was often associated with a range of other co-morbidities such as diabetes and gastric
reflux. Then, possibly relying on clinical experience, candidates often remarked that in the obese
patient FRC can be reduced, thus affecting uptake of volatile anaesthetic agents and that
transdermal, intramuscular and subcutaneous drug absorption was also likely to be affected.

3
Many candidates also mentioned that some computer based programmes for TCI could give variable
results when actual (rather than lean) body weight was entered. However there were few instances
where specific examples were given (as asked for in the question). Pharmacokinetic handling of
some opioids are altered in the obese patient, and only a few candidates mentioned the possible
pharmacokinetic advantages of poorly lipid soluble volatile agents such as desflurane over other
volatile agents in the obese patient.

With regard to non-depolarising muscle relaxant drugs, although their polarity generally restricts
their distribution, volume of distribution may be increased in the obese, simply by virtue of
increased absolute total body water. There will be differences in the distribution, and hence
duration of action depending on whether dosage is calculated on the basis of ideal body weight or
total body water. From a clinical context, obese patients are comprising an increasing proportion of
our population, and candidates should be aware of how this condition influences drug disposition.

QUESTION 5 Describe the factors that may decrease the clinical response to nondepolarising
neuromuscular blocking agents.


Candidates were expected to briefly mention the important measurable clinical responses (eg.
onset, depth and duration of neuromuscular blockade), and briefly mention how these might be
measured. Candidates who classified factors into such groups as physiological, pathological, drug
factors and drug interactions, with multiple examples usually scored well. Extra marks were
awarded for noting that the clinical response depends on which muscle group is monitored, and
that the clinical response is less intense and briefer in patients anaesthetised without volatile or
sedated in critical care.
Some candidates mistakenly listed factors that contribute to prolongation of neuromuscular
blockade (such as atypical plasmacholinesterase, aminoglycosides). Marks were not awarded for
arguing that absence of these factors leads to a (relative) decrease in clinical response. Nonspecific
pharmacokinetic statements (clinical response is determined by differences in absorption, volume
of distribution, protein binding and clearance) without clinical examples and explanation were not
awarded high marks. There was general confusion about the effect of various muscle disorders on
neuromuscular blockade.

QUESTION 6 Discuss the pharmacodynamics of drugs that affect uterine tone.


Candidates interpreted this question in a variety of different ways. The marking scheme was
structured so that it was possible to do well with any reasonable interpretation. As the question
clearly relates to uterine pharmacology, however, some part of the answer had to pertain to the
actions of the drug on the uterus. It was not possible to pass, for example, by writing an essay
purely on the non uterine effects of volatile agents.

A suitable approach would have been to list the common drugs which affect uterine tone, noting
which increase and which decrease tone, and then to discuss the important drugs in more detail.
Points which could be elaborated on include, a) the mode of action, b) the effect on basal tone and
contractions, both force and frequency, c) how that effect varies with stage of pregnancy and dose
of the drug, d) other actions on the uterus and cervix, e) important side effectsparticularly those
on the uterus, or those which might limit the drugs use.

Common mistakes were to confuse smooth and skeletal muscle; beta agonists and beta blockers; ,
1
and
2
effects; and the effects of nitrous oxide, volatile agents and intravenous anaesthetic
agents. Many candidates were unsure as regards the relationship between systemic vascular
resistance, heart rate and blood pressure. Candidates often included unnecessary information on
dosage, pharmacokinetics and usage. Vague answers attracted no marks.

4
QUESTION 7 Outline the pharmacological management of ventricular fibrillation in an adult
with reference to: drugs, dose, mechanisms of action, and potential adverse
effects.


Overall, the responses to this important question were disappointing. There was wide ranging depth
and breadth of understanding of the pharmacological management of ventricular fibrillation (VF).

The syllabus clearly states that candidates should be able to describe the international
cardiopulmonary resuscitation guidelines, and also the pharmacology of adrenaline, vasopressin,
amiodarone and lignocaine with reference to cardiopulmonary resuscitation; these areas of study
should enable candidates to understand the pharmacological management specific to VF. A
complete answer required that candidates address the drugs used for VF, and dose, mechanisms of
action and adverse effects specific to VF, and understood the role of these in current international
and local VF management guidelines.

Description of the role and current use of adrenaline, amiodarone, vasopressin, lignocaine,
magnesium and bicarbonate were expected. Few mentioned the specific role and supporting
evidence for each agent in VF resuscitation algorithms.

Additional points which attracted higher marks included specific indications for each agent in VF,
alternate routes of administration with dosages, understanding of current controversies in
medication selection, and management of VF in specific clinical scenarios, for example, local
anaesthetic toxicity with VF. In general, there was poor understanding of the mechanisms of action
pertinent to resuscitation from VF, of drug dose and timing regimes in this clinical situation, and of
adverse effects of acute administration. There was great variability in dosage regimes.

Common mistakes included misinterpretation of the question as general resuscitation for cardiac
arrest with inclusion of drugs such as atropine, and excessive focus on details of defibrillation and
basic CPR technique with little information on pharmacological therapy.

QUESTION 8 Mean arterial blood pressure has been measured in two groups of patients one
hour after the administration of either a placebo or an antihypertensive drug.
Explain how these data could be analysed.


This question examined basic knowledge regarding the ways in which data from two groups of
subjects is evaluated and then compared using statistical testing. The question required that
candidates apply their knowledge

Points that attracted marks included:
a) Discussions regarding the determination of a hypothesis and its relation to the aim of the
research: to disprove the null hypothesis (of no difference between groups)which indicates
that the medication may influence blood pressure in a significant way.

b) Detailed characterization of the data into numerical, ratio, discrete or continuous
depending on how it was measured, its distribution and ways of analysing the data if its
distribution were not clear on first evaluation. Marks were also given if candidates
discussed other ways of organising data to allow evaluation by other types of statistical tests
e.g. categorical by conversion of blood pressure measurements into discreet categories

c) Attempts to identify study and data characteristics in the best way possible to select most
accurate test to evaluate hypothesis. Note that all such information was not given with the
blood pressure readings allowing candidates to discuss different contingencies and different

5
tests which may be used. Mentioning characteristics such as independent measurement,
normal distribution, similarity of variances, number of observations etc.
d) Finally the tests which could be used to evaluate the data as well as their specific
characteristics : Students T for parametric, Mann Whitney U and Wilcoxon signed ranks for
non-parametric.

e) A brief description of the way the test was evaluated and the conclusions drawn from the
result.

f) The creation of and use of confidence intervals to indicate clinical significance.

The most common mistakes involved misinterpretation of the question with detailed discussion of
conduct of randomized controlled trials, power analysis, and use of contingency tables to
determine specificity and sensitivity. Lack of application of knowledge to the specific example of
the blood pressure readings was also a common characteristic of many answers.



Pharmacokinetics and pharmacodynamics:

1. Placental transfer of drugs
2. Drug handling in liver failure
3. Pharmacokinetics of phenytoin
4. What drugs are administered by infusion?
5. Draw dose- response curve for morphine
6. Tell me about remifentanil
7. Pharmacokinetics of propofol
8. Factors affecting effect site concentration
9. Draw a dose response cure.

Inhalational Agents:

1. Physical properties of isoflurane
2. FA/FI curve
3. Compare sevofluorane and desflurane
4. Sevoflurane in patients with heart disease
5. How do you define MAC?
6. Metabolism of the volatile anaesthetic agents
7. How does the addition of nitrous oxide affect the uptake of sevoflurane?
8. What are the advantages and disadvantages in using nitrous oxide?
9. Wash in curve for isoflurane.
10. How are inhaled anaesthetics removed from the body?

Intravenous Anaesthetic Agents:

1. Metabolism of benzodiazepines
2. Classify I.V. induction agents
3. Draw a concentration-time curve following an I.V. injection of propofol.

6
Local Anaesthetics:

1. Local anaesthetic toxicity
2. What is ropivacaine?
3. Structure Activity Relationships of local anaesthetics

Pain:

1. NSAIDS and drug interactions
2. Adverse effects of NSAIDS
3. Structure & function of opioids
4. Opioid agonists & antagonists
5. Where does morphine come from?
6. What kind of drug is aspirin?
7. What are the advantages of paracetamol?
8. Where does morphine act?
9. Epidural morphine
10. Tramadol and its effects
11. What are some of the advantages of tramadol as an analgesic?

Neuro Muscular Blocking Drugs and associated topcis:

1. What things can increase the response to NMBs?
2. Side effects of suxamethonium
3. Adverse effects of atropine
4. Atropine versus glycopyrrolate
5. Classification of anticholinesterase
6. Mechanism of action of anticholinesterase agent
7. Reversal of NMB
8. Compare vecuronium and rocuronium
9. What sort of drug is neostigmine?
10. What is meant by the term depolarising blockade?
11. How do you classify anti-cholinesterase agents?
12. Side effects of suxamethonium.

Autonomic Nervous System:

1. Draw a muscular cholinergic receptor
2. Naturally occurring sympathomimetic drugs
3. Structure activity relationship of sympathomimetic amines

Neuropharmacology:

1. What is GABA?
2. How do anticonvulsants work?
3. Pharmacokinetic of serotonin

Therapeutic Gasses:

1. Oxygen Toxicity
2. Diffusion hypoxia
3. Oxygen as therapeutic gas

Coagulation:

1. What sort of heparin do you know of?
2. What are the main group of anti-platelet agents?
3. Heparin & Protamine

7
4. What is protamine?
5. What is heparin?

Miscellaneous:

1. Aspirin toxicity
2. Outline the drug treatment of anaphylaxis.
3. What are some members of the H2 antagonist group?
4. How do you classify corticosteroids ?
5. What is meant by the word addiction?
6. What is the appropriate dose of paracetamol?
7. What are the contents of a Hartmanns solution?
8. Describe the phases of clinical drug development.

Statistics

1. Normal distribution
2. Meta analysis
3. Clinical trial
4. Randomisation in clinical trials both signs and symptoms must be present or this can be
diagnose.
5. What is meant by the term power in statistics?
6. What is meant by the term sensitivity & specificity?

Opioids and analgesics:

1. What are the features of opioid overdose?
2. What are the options to manage opioid induced constipation?
3. What is the cause of differences in speed of onset between fentanyl & alfentanil?
4. Concentration time curve for alfentanil?
5. What the first role of ketamine in pain management?
6. What is the base of ketamine to use in pain management as approach to anaesthetic dosage?
7. What are the adverse reactions associated with ketamine?

8





QUESTION 9 Classify the causes of hypotension in the early post-operative period, giving
relevant examples.

The minimum requirement to pass this question was to discuss the causes of hypotension and to
provide at least one example relevant to the postoperative period. Most successful candidates
classified the causes of hypotension by physiological mechanism (reduction in systemic vascular
resistance or cardiac output). This provided a logical framework to discuss the relevant causes of
reduced preload, contractility, heart rate and systemic vascular resistance. Provided that these
areas were covered adequately, those candidates who provided a clinical classification of the
causes of postoperative hypotension were also successful.

Few candidates correctly defined hypotension as a 20% fall in the patients mean or systolic blood
pressure or commented on its significance. Detailed descriptions of differing clinical situations
producing hypotension by the same mechanism (eg. causes of hypovolaemia) did not attract extra
marks.

QUESTION 10 Compare and contrast the neonatal respiratory system with the adult.


The neonatal period is from 0-28 days and this question predominantly concerned term neonates.
This is not a question about the transition from intra- to extrauterine life nor is it a question about
the pathophysiology of prematurity.

This is a wide ranging question concerning many aspects of respiratory physiology:- physiologically
relevant anatomy; ventilation and gas exchange; lung volumes; mechanics of breathing; pulmonary
circulation; control of breathing; and haemoglobin. The low pass rate resulted from most
candidates not producing enough relevant detail in each of these areas.

Differences and similarities are both absolute (neonates are small) and relative (values indexed to
weight or FRC). Mention of clinical implications gained extra marks. Well organised answers were
frequently in a table form.

QUESTION 11 Describe the role of insulin in fat metabolism


The following were the main points expected for a pass:
description of insulin and its actions as an anabolic hormone, and consequences of activation of
insulin receptors,
the effects of insulin on liver: increased uptake glucose; production of glycerol and free fatty
acids; and decreased ketogenesis,
the effects of insulin on adipose tissue: glucose uptake; synthesis of fatty acids and glycerol
and
the activation of lipoprotein lipase and inhibition of hormone sensitive lipase.

9
Bonus marks were given for
a structured approach to insulins action in fat metabolism,
key enzymes involved in liver and adipose tissue,
lipoprotein transport in blood and breakdown and uptake by adipose tissue.

Common mistakes included:
only focusing on one of the following: fat uptake from gut, fat synthesis in liver or adipose
tissue, or the role of increased glucose uptake;
confusing anabolic and catabolic actions,
providing information about actions of other hormones,
providing information about diabetes and carbohydrate metabolism while neglecting to cover
fat metabolism.

QUESTION 12 Discuss the production and function of red blood cells


Candidates who did not address both parts of the question were unlikely to pass, as approximately
half the marks were awarded for each part of the question.

RBCS are derived from a common precursor in the bone marrow and liver in adults This precursor
is a pleuripotential cell ie can differentiate into all blood cell lines. It differentiates into various
cell lines, including the Colony-Forming-Unit Erythrocyte (CFU-E), which is stimulated by various
colony stimulating factors to differentiate into smaller and smaller cells. Haemoglobin
concentration increases as differentation continues. Marks were obtained for correctly detailing
actions and production of erythropoietin; the structure of haemoglobin, and other structural
factors unique to RBCs (eg lack of nucleus and mitochondria).

The function of the RBC is related to its content of haemoglobin. RBCs transport oxygen and
carbon dioxide, and have a major role in the buffering capacity of the extracellular fluid.
Candidates were expected to briefly outline how the cells carries out these functions.

Common errors included mention of:
"half life of RBCs as 120 days" - rather than average life span
"myeloid stem cells" rather than erythroid.
Giving numerical ranges for Hb levels - but listing it as the RBC count.
reticulocytes having a nucleus - they do not

QUESTION 13 Explain the physiological processes that cause oliguria in response to
hypovolaemic shock


This is the fourth time that this question has been asked.

The main points would be: a brief definition of oliguria and of hypovolaemic shock followed by an
appreciation that oliguria occurs secondary to two main effects, namely a decreased RBF and GFR
and an associated increased sodium and water retention. Subsequent explanation as to why the RBF
and GFR drop and the neuro-endocrine responses occasioning the sodium and water retention would
result in a good pass. The answer would include a brief discussion of the systemic influences on
RBF and GFR as well as a description of the role of the sympathetic system, the Renin-Angiotensin-
Aldosterone system and of ADH on salt and water homeostasis.

Additional marks were rewarded for a mention of renal autoregulation, differential afferent and
efferent arteriolar effects, effects of ACTH and ANF and the effects of age. Only two candidates
mentioned the possibility that this situation could progress to acute renal failure.

10
A frequent error was to state that afferent constriction was greater than efferent. Many answers
gave incorrect values for the range in which renal autoregulation is seen, believing it occurs down
to a MAP of 50 mmHg.

Better answers demonstrated a structured and methodical approach to answering the question with
minimal repetition. Some of these answers were in narrative form, others in a graphical format.
Correct information, appropriately structured was rewarded regardless of the format chosen to
answer the question.

The main reasons for candidates not passing this question were either poor organisation, repetition
of information or just not enough substance in their answer.

QUESTION 14 Outline the central nervous system effects on an awake person breathing air
containing carbon dioxide.


Good answers included several effects including stimulating central respiratory centres, increased
cerebral blood flow, increased intracranial pressure, and stimulation of the sympathetic system.
Other points were that inspired air has negligible amounts of CO2 and that high partial pressures
can produce CO2 narcosis.

QUESTION 15 Describe the complement system.


The examiners were aware that there were several different descriptions of complement pathways
in different textbooks, and marking schemes reflected these variations.

In order to achieve a pass, candidates required a broad knowledge of the actions of complement
and the pathways by which these actions are initiated.

Further marks were obtained for more detailed descriptions of the pathways, and clinical
implications of the actions of complement. Additional marks were given for clinical relevance of
abnormalities in the pathways.

Common omissions included a lack of knowledge or understanding of the actions of complement,
and the methods of activation.

Although additional marks were awarded for a detailed description of the complement cascade, it
was possible to achieve a high mark without this information as marks were weighted towards
demonstrating an understanding.

QUESTION 16 List the gastric cell types and their secretions and the functions of these
secretions.


In general this was quite well answered. Many candidates had well structured answers which
enabled easy marking.

Candidates who did poorly were less organised and many candidates confused the secretions and
the cells which decreased their overall score.

Some candidates did not answer all parts of the question and this was reflected in their mark.
Other poor strategies included writing detail which was not required and repeating the same
statements.

11

PHYSIOLOGY TOPICS:

Cardiovascular:

Changes in the cardiovascular system with exercise.
Coronary blood flow.
Oxygen flux in coronary circulation
Cardiovascular effects of aging on arteries.
Relationship of VR to CO
Measurement of contractility
Wiggers diagram
Frank-Starling mechanism
Control of regional circulations
LA volume vs. time
Afterload: definition and measurement
Contractility: definition and measurement

Respiratory:

Respiratory mechanics
Alveolar gas equation
Effect of altitude on alveolar oxygen content
Control of pulmonary blood flow
Mixed venous blood gases
Factors affecting pulmonary vascular resistance
Factors affecting airway resistance
Changes in upright lung
Dynamic airway compression
Changes in oxygen saturation with aging
Oxygen flux
V/Q changes in lung in upright posture
Oxygen stores in the body
Oxygen cascade
Dead space and effect on blood gases
Measurement of FRC
Closing volume
A-a gradient
Control of ventilation

Nutrition/Metabolism:

Efficiency of anaerobic vs. aerobic metabolism
Consequences of fasting
Glucose homeostasis
Principles of total parental nutrition
Basal metabolic rate

Thermoregulation:

Effect of general anaesthesia on temperature
Comparison of heat and temperature

12
Renal:

Renal handling of water
Renal handling of metabolic acid
Define GFR and how measured
Physiological effects of renal dysfunction
Principles of glomerular filtration

Measurement:

Measurement of intracellular water
What is a transducer?
Calibration of arterial line
Describe a capnogram trace
Principles of non-invasive blood pressure measurement
Describe the principles of pulse oximetry
Utility of pulse oximetry
Utility of ECG
Role of the balloon in a PAFC.
SI units, examples of derived units.
EEG Measurement
Principles of temperature measurement
Principles of CO2 measurement

CNS:

Principles of cerebral blood flow
Autonomic nervous system anatomy
Blood- brain barrier

Nerve:

Classification of peripheral nerves
Nerve action potential
Changes in autonomic nervous system with aging

Endocrine:

Hormones of the posterior pituitary
Physiological roles of prostatglandins
Classes of hormones and their actions.

Muscle:

Cellular anatomy of skeletal muscle
Skeletal muscle contraction

Liver:

Laboratory assessment of hepatic function

Immunology:

Defence against bacterial infection
Specific and non-specific immunological defence mechanisms
Classification of hypersensitivity reactions.

13
Pain:

Acute pain pathways

Obstetric:

Changes in cardiovascular physiology during pregnancy
Changes in respiratory physiology

Haematology:

Preparation of stored blood
Changes associated with stored blood
Role of platelets in clotting

Fluid & electrolytes:

Distribution of water in the body.
Interpretation of blood gases
Role of calcium in the body

Acid- Base:

Handling of metabolic acid load
Assessment of acidosis

Dr. C Noonan

AUSTPALIAN AN0 NEW ZEALAN0 CDLLECE DF ANAESTHETISTS
A8N 82 055 042 852

EXAhINATIDN PEPDPT

PPIhAPY FELLDWSHIP EXAhINATIDN

MARCH/APRlL 2009

Please note that thIs report Is prepared to provIde candIdates and theIr teachers and supervIsors of
traInIng wIth InformatIon about the way In whIch the performance of candIdates In the recent
examInatIon was assessed by the examIners, so that candIdates and teachers may prepare
approprIately for future examInatIons. The IndIvIdual reports are not Intended to represent model
answers nor Imply that all poInts mentIoned are necessary In order to achIeve a pass. All traInees
are urged to read the questIons carefully and answer the questIon asked. All teachers and
supervIsors of traInIng are encouraged to dIscuss thIs report In detaIl wIth candIdates they are
preparIng for future examInatIons.

PHAPhACDLDCY - WPITTEN SECTIDN

MULTlPLE CH0lCE QUESTl0NS:
65 of candIdates achIeved a pass In thIs sectIon of the Pharmacology ExamInatIon.

SH0RT ANSWER QUESTl0NS:

UESTIDN 1 ExpIaIn the concept of hInImaI AIveoIar ConcentratIon (hAC) and Its cIInIcaI
utIIIty.
LIST the patIent factors whIch:
a) Increase hAC
b) 0ecrease hAC
c) Are known to have no effect on hAC

82 of candIdates passed thIs questIon.
The questIon was answered well by the majorIty of candIdates. Those who dId poorly omItted any
descrIptIon of clInIcal utIlIty or faIled to lIst a few factors that affect (or do not affect) |AC. The
followIng would have achIeved a clear pass:
|InImum Alveolar ConcentratIon (|AC) Is the alveolar concentratIon of an Inhaled anaesthetIc that
prevents movement In 50 of patIents In response to a standardIzed stImulus (e.g. surgIcal
IncIsIon).
t Is a measure of relatIve potency and Is used as a standard for experImental studIes.
There are other kInds of |AC value such as |AC awake, when 50 of patIents open theIr eyes on
request. |AC values for dIfferent agents are approxImately addItIve.

2
(a) ncreases |AC:
hyperthermIa
drugs that Increase CNS catecholamInes (such acute amphetamIne IngestIon)
(b) 0ecreases |AC:
elderly
pregnancy
other anaesthetIc agents (e.g. opIoIds, benzodIazepInes)
acute ethanol IngestIon
(c) No change In |AC:
duratIon of anaesthesIa
gender
ChronIc alcoholIsm eIther Increases |AC or makes no dIfference, dependIng on the source
consulted, therefore eIther statement gaIned credIt. The effect of thyroId dysfunctIon Is sImIlarly
controversIal and was treated the same way.

UESTIDN 2 0escrIbe the factors whIch Increase the rIsk of systemIc toxIcIty wIth amIde
IocaI anaesthetIc agents.

J1 of candIdates passed thIs questIon.

QuestIons on local anaesthetIc toxIcIty are frequently asked In thIs examInatIon and thIs questIon
has been asked prevIously.

The answer should have been structured Into pharmacokInetIc and pharmacodynamIc factors In
order to make coverIng all aspects of the questIon easIer. Factors expected Included dose, sIte,
vasoconstrIctors, reduced proteIn bIndIng, hepatIc functIon, C7S:CNS ratIos, patIent factors
(acIdosIs, Ion trappIng, altered seIzure threshold, lowered C7S reserve), as well as age and
pregnancy.

Extra marks were awarded for addItIonal detaIl or addItIonal factors such as Isomers, local
anaesthetIc specIfIc features, actIve metabolItes, and physIcochemIcal features.

There was confusIon over changes related to pH and pKa. AcIdosIs Increases the IonIsed fractIon
and the rIsk of toxIcIty and Ion trappIng. |any candIdates spent a lot of tIme descrIbIng local
anaesthetIc toxIcIty wIthout relatIng It to C7S:CNS ratIos and neglected other aspects of the
questIon.

nformatIon pertaInIng to the general nature of ester and amIde local anaesthetIcs, theIr
structures, mechanIsm of actIon, the management of local anaesthetIc toxIcIty, and FIck's law of
dIffusIon that dId not relate dIrectly to the questIon and generally dIdn't attract marks.

3
UESTIDN 3 DutIIne the factors that determIne the rate of recovery from non-depoIarIsIng
neuromuscuIar bIock!


Fecovery from neuromuscular block Is dependent on the competItIve balance of ACh and
nondepolarIsIng blockIng agent (N08A) at the ACh receptor. After a sIngle bolus of N08A the offset
Is as a result of redIstrIbutIon. Dnly after repeat boluses or InfusIon does metabolIsm and excretIon
become sIgnIfIcant. ThIs Important poInt was mentIoned In only one paper. |ost mentIoned that
recovery was slower after large doses wIthout further explanatIon. There was much confusIon as to
whether an Increased volume of dIstrIbutIon resulted In an Increased or decreased duratIon. ThIs Is
dependent on whether the drug Is admInIstered as a sIngle bolus.

The pharmacologIcal propertIes of the drugs were generally well done as were the lIsts of
physIologIcal and drug InteractIons. CandIdates who were able to gIve correct examples scored
addItIonal marks. The use of antIcholInesterase agents and theIr effectIveness dependIng of the
depth of block was seldom mentIoned.

UESTIDN 4 Compare and contrast atropIne and gIycopyrroIate. 0Iscuss the cIInIcaI
ImpIIcatIons of these dIfferences.


The maIn poInts expected for a pass Included an outlIne of how these two antIcholInergIc drugs are
sImIlar and also how they dIffer. 0escrIptIons of theIr chemIcal, pharmaceutIc, pharmacokInetIc
and pharmacodynamIc propertIes In a table helped In answerIng the fIrst questIon. Dnce a
dIfference between these agents had been outlIned, It was expected that a dIscussIon would ensue
as to how that dIfference could Influence your clInIcal use of these two alternatIve drugs.

The fIrst questIon was well answered In general, but the commonest omIssIon was to not answer
the second questIon. When a dIfference between these agents was correctly IdentIfIed, there was
no dIscussIon as to how that may affect clInIcal decIsIonmakIng. AnswerIng only half of the
questIon prevents a candIdate from scorIng hIghly.

UESTIDN 5 DutIIne the effects of an opIoId Injected Into the spInaI IntrathecaI space.


QuestIons on Intrathecal opIoIds have been asked In prevIous examInatIons and candIdates seem to
struggle wIth the concepts Involved.

The maIn poInts expected for a pass Include:
The fate of the Intrathecal opIoId I.e. passage across the menInges to exert Its actIon on spInal cord
opIoId receptors, some cephalad spread In the CSF to supraspInal centres and mInImal systemIc
absorptIon to exert systemIc effects.

The maIn effect Is segmental analgesIa, wIth lIttle motor or sympathetIc effects.
Some apprecIatIon that the extent of dIstrIbutIon Is determIned by lIpId solubIlIty of the agent and
that most of the effect of the opIoId Is due to Its actIon on the spInal cord.
The major sIde effects of Intrathecal opIoIds I.e. prurItIs, respIratory depressIon, nausea and
vomItIng, urInary retentIon, IncludIng mechanIsm of actIon. Dther sIde effects of opIoIds are
neglIgIble.

|ore detaIl was expected on respIratory depressIon, gIven Its clInIcal Importance. Early respIratory
depressIon Is more lIkely amongst the lIpophIlIc opIoIds eg fentanyl. Late depressIon Is more lIkely
wIth hydrophIlIc agents such as morphIne as It Is bound less to the spInal cord and so Is carrIed In

4
the CSF to respIratory centres In the braIn. PoInts were awarded for mentIonIng whIch opIoIds are
commonly used Intrathecally, In what doses and theIr onset and duratIon of actIon.

8onus marks were allocated for:
Statements about the low dose of Intrathecal as compared to Intravenous or epIdural opIoIds,
showIng understandIng of the fate of Intrathecal opIoIds, synergIsm wIth local anaesthetIcs,
neurotoxIc addItIves whIch render certaIn opIoIds unsuItable for Intrathecal use, development of
tolerance, other less common sIde effects.

UESTIDN 6 0escrIbe the mechanIsm of actIon and pharmacokInetIcs of phenytoIn.


A structured approach was expected addressIng both the mechanIsm of actIon and
pharmacokInetIcs. CandIdates were expected to outlIne relevant mechanIsms of actIon (such as
sodIum channel blockade) and how they relate to Its use as an antIconvulsant agent. AddItIonal
credIt was gIven for dIscussIng other potentIal mechanIsms and other uses such as paIn
management and antIarrhythmIc propertIes. PhenytoIn Is a drug that has many uses In IntensIve
care medIcIne and anaesthesIa and an adequate knowledge of thIs drug, wIth Its low therapeutIc
Index Is Important for safe clInIcal use.

PhenytoIn Is IllustratIve of several key concepts In pharmacology and mentIon of these was
expected. FaIlure to address these key concepts or provIde suffIcIent detaIl was a common
omIssIon. CandIdates were expected to dIscuss that phenytoIn Is hIghly proteIn bound, changes
from fIrst to zero order kInetIcs wIth escalatIng doses and Is metabolIsed by the cytochrome p450
enzyme system. Some dIscussIon of the sIgnIfIcance of these poInts was expected and extra credIt
was awarded for more detaIled explanatIons, comments on enzyme InductIon and examples of drug
InteractIons that are well known and clInIcally relevant. CandIdates were expected to comment on
the mode of delIvery and compare oral and Intravenous dosIng. t was expected that the need for a
loadIng dose followed by maIntenance dosIng would be mentIoned and extra credIt was gIven for
hIghlIghtIng the potentIal hazards of rapId Intravenous admInIstratIon. AddItIonal credIt was gIven
for mentIonIng the Importance of a narrow therapeutIc Index and the need for clInIcal monItorIng.
Well organIzed answers such as those wIth an ordered lIst of subheadIngs were rewarded.

UESTIDN 7 DutIIne the subtypes of serotonIn (5-hydroxytryptamIne) receptors. 0Iscuss
pharmacoIogIcaI agents that act at these sItes.


|aIn PoInts expected for a Pass:
Ceneral descrIptIon of locatIon of receptors as found In Central nervous system (CNS),
PerIpheral nervous system (PNS), on vascular smooth muscle and platelets.
Statement that 5HT receptors are CproteIn coupled except for the 5HTJ subtype whIch Is
a lIgandgated Ion channel.
An attempt at numberIng the quantIty of subtypes, some texts dIffer between 45 or 7
subtypes.
Correctly descrIbIng some agonIsts at the IndIvIdual subtypes.
Correctly descrIbIng some antagonIsts at the IndIvIdual subtypes.
ncludIng commonly used drugs such as ondansetron and correctly IdentIfyIng the
pharmacologIcal actIon as an antagonIst at the 5 HTJ receptor, also Tramadol and Its
IndIrect method of actIon on the receptors as a 5HT uptake InhIbItor

5
AddItIonal PoInts whIch attracted hIgher marks:
dentIfyIng the numbers of subtypes wIthIn the receptor famIlIes, for example, 5HT1 type 0
receptors, 5HT2 A,8 and C subtypes
ndIvIdually addressIng the receptor subtypes, sumatrIptan and Its use In the treatment of
mIgraIne as well as the mechanIsm of actIon
0escrIptIons of |etoclopramIde as a 5HT4 agonIst and Its pharmacologIcal actIon E sIte of
5HT4 receptors
|entIon of 5HT2 receptors and antagonIsts, such as ketanserIn, methylsergIde, pIzotIfen or
cyproheptadIne.
Extra credIt for mentIonIng less well known agents, for example, knowIng LS0 Is an agonIst
at the 5HT receptor, as well as buspIrone or tegaserod.
Common |Istakes:
ncorrectly IdentIfyIng all 5HT receptors as CproteIn coupled or mIsIdentIfyIng whIch sub
type Is lIgandgated
ncorrectly statIng that drugs are agonIsts, when they are antagonIsts and vIceversa
FaIlIng to descrIbe the actIvIty of the drug at the receptor
ConfusIng the mode of actIon and the receptor actIvIty, for example, claImIng 5HT1
agonIsts lIke sumatrIptan cause cerebral vasodIlatatIon when they cause vasoconstrIctIon.

UESTIDN 8 What Is meant by the term "5X confIdence IntervaI"! ExpIaIn the practIcaI
appIIcatIons of confIdence IntervaIs and IndIcate why they may be preferred to
-vaIues.

20.5 of candIdates passed thIs questIon.

A sIgnIfIcant number of candIdates scored a low mark.

|ost candIdates presented a defInItIon of the 95 ConfIdence nterval (95 C) but faIled to
demonstrate an understandIng of the concept. |any candIdates presented unnecessary detaIls of
how to desIgn a clInIcal trIal or conducted multIple comparIsons wIth drug InterventIons wIthout
demonstratIng the utIlIty of 95 C. There was sIgnIfIcant confusIon between standard devIatIon
and standard error of the mean wIth many candIdates usIng them Interchangeably wIthout any
qualIfIcatIon.

Any 95 C gIves a 95 probabIlIty that the true populatIon parameter wIll be found wIthIn that
Interval. t Is a range of values that gIve a lIkelIhood that the populatIon parameter beIng studIed
wIll be found wIthIn them. Contrary to what many candIdates stated, It does not mean that 95 of
observatIons are contaIned wIthIn 1.96 standard devIatIon.

95 C Is derIved from the Standard Error and hence Is dependent on sample sIze.
To attaIn a pass In thIs questIon, candIdates needed to present a clear defInItIon of the 95 C as a
concept, present an understandIng of how It Is calculated wIth clear understandIng of the
determInants of 95 C and demonstrate a good understandIng of the relatIonshIp and the
dIfference between 95 C and P value and Its advantages over the p value.

CandIdates who demonstrated practIcal applIcatIons of C and/or other forms of C achIeved bonus
marks.

6

PHAPhACDLDCY - VIVA SECTIDN

PHARMAC0L0CY T0PlCS:

IV InductIon agents
Why do you belIeve propofol Is wIdely used as an anaesthetIc agent:
What are the pharmacodynamIcs of propofol:
What Is In an ampoule of thIopentone:
How do you determIne an InductIon dose of propofol:
Compare the pharmacokInetIcs of an InfusIon and a bolus of a drug
ThIopentone as an InductIon agent

PharmacokInetIcs
Changes In drug dIsposItIon wIth age
v and | admInIstratIon pharmacokInetIcs
0efInItIon of half lIfe
PharmacokInetIc parameters
0rug nomograms
Transdermal medIcatIons

PharmacodynamIcs
Fesponse to thIopentone
CenetIc dIseases and thIopentone
AnaesthesIa and lIver faIlure
|odIfIcatIons of drug dosage

AntI-emetIcs
What drugs can be used for PostDperatIve nausea and vomItIng:
Compare antIemetIcs
0examethasone

InhaIatIonaI agents
|etabolIsm of Inhaled agents
How do you select an InhalatIonal agent:
0raw a wash In curve for Isoflurane
0raw a wash out curve for an agent
|anufacture of nItrous oxIde
What are the advantages of sevoflurane:
When to avoId nItrous oxIde
Fa/FI curves
How does the addItIon of nItrous oxIde affect InhalatIonal agent uptake:
Changes In uptake of volatIle agents

AutonomIc Nervous System and Adrenoreceptor IockIng drugs
Alpha 2 agonIst drugs
What drugs Increase blood pressure:
How do you classIfy beta blockers:
What Is an Inotrope:
AntIarrhythmIc effects of beta blockers
Effects of clonIdIne
Adverse effects of adrenalIne

7
StatIstIcs
0ata types and study lImItatIons
8ox plots
Scatter plots
FegressIon analysIs

NeuromuscuIar IockIng 0rugs and reversaI
|onItorIng of neuromuscular blockIng drugs
ClassIfIcatIon of N|8's
Pharmacology of suxamethonIum
E095 of muscle relaxants
What receptors exIst at the N|J:
0oseresponse curves to N|8's
Feceptor regulatIon
|argIn of safety
Adverse effects of neostIgmIne

AnaIgesIc agents
NonopIoId analgesIcs
CDX2 InhIbItors
NSA0 toxIcIty
Paracetamol pharmacokInetIcs
ParecoxIb
PostoperatIve analgesIc optIons
Dnset tIme of analgesIcs
KetamIne as an analgesIc
|ethadone
PharmacokInetIcs of fentanyl

hIsceIIaneous TopIcs
What drugs relax the uterus:
How does drug development occur:
AllergIc reactIons In anaesthesIa
Tolerance vs addIctIon
How do you treat atrIal fIbrIllatIon:
Pharmacology of amIoderone
|anagement of hypertensIon
ClassIfIcatIon of antIhypertensIve agents
ToxIcIty of sodIum nItroprussIde
What drugs work on the rennInangIotensIn system:
What Is the ratIonale for the use of ACE InhIbItors:
|anagement of poIsonIng
|anagement of myocardIal IschaemIa
|anagement of asthma
PrIncIples of antIbIotIc prophylaxIs
What Is the dIfference between an antIseptIc and a dIsInfectant:
How can we change the pH of stomach contents:
What types of heparIn do you know of:
What antIplatelet agents do you know of:
What drugs are used In cardIac arrest:

8

PHYSIDLDCY - WPITTEN SECTIDN

70 of candIdates achIeved a pass In thIs sectIon of the PhysIology ExamInatIon.


UESTIDN 0Iscuss the physIoIogIcaI factors that determIne IntracranIaI pressure (ICP), and
descrIbe how changes In posture affect ICP.


n general the candIdates answered thIs questIon well, based on the |onroKellIe doctrIne. The
answer should have Included:

1) Some Introductory defInItIon of IntracranIal pressure, normal values, and the |onroKellIe
framework.

2) The effects and causes of changes In IntracranIal blood volume, tIssue volume, and CSF
productIon cIrculatIon and reabsorptIon.

J) A dIscussIon of how supIne, erect, and Trendelenburg posItIons mIght alter CSF and blood
dynamIcs.

AddItIonal marks were awarded for graphs of changes In CP wIth IntracranIal volume, and the
relatIonshIp between CSF absorptIon, productIon and CP.

|any candIdates spent a lot of tIme explaInIng cerebral blood flow and cardIovascular responses to
change In posture that were not dIrectly relevant to the questIon. t was also common for
candIdates to erroneously rearrange varIous equatIons (e.g. CP = |AP * CPP, or even CP =
C8F/C7FesIstance); and use these as bases for the answer, rather than dIscussIng real physIologIcal
cause and effect.

UESTIDN 10 0escrIbe the physIoIogIcaI effects of the gIucocortIcoIds.


A large number of candIdates answered thIs questIon as a pharmacology questIon, IncludIng
Irrelevant detaIl such as the IndIcatIons and dosages for dexamethasone/steroId supplementatIon
for surgery.

A sImIlarly large number gave a descrIptIon of CushIng's dIsease.

PoInts that were expected to be Included:

An openIng statement IncludIng a defInItIon, orIgIn of and a statement that glucocortIcoIds are
catabolIc In nature

CandIdates who organIsed theIr answer Into categorIes such as:
|etabolIsm ( and then broke thIs down to : Carbohydrate, Fat and ProteIn)
nflammatIon
Effect on Foetus

9
Dther systems ( HaematologIcal, C, |usculoskeletal etc)
demonstrated a global understandIng and scored well

CandIdates should note that neIther nsulIn nor Clucagon are ClucocortIcoIds and that Clucose
cannot be derIved from Fatty AcIds

Extra marks were gIven for descrIbIng the actIons of glucocortIcoIds on an Intranuclear receptor
and mFNA transcrIptIon and the antI Inflammatory effects

UESTIDN 11 DutIIne the determInants and reguIatIon of extraceIIuIar fIuId voIume.

5J of candIdates passed thIs questIon.

The maIn poInts expected In answerIng the questIon Include

- a defInItIon of ECF volume as volume of fluId outsIde cells, IncludIng plasma and InterstItIal
volumes
- recognItIon of the Importance of Na+ as the major extracellular catIon, and that the amount
of Na+ In the ECF Is the most Important determInant of ECF volume
- better answers hIghlIghted the Important mechanIsms controllIng Na+ balance as the major
factors regulatIng ECF volume
- aldosterone Is the most Important sIngle controller of Na+ balance; outlInIng functIonal
control, stImulI for release IncludIng the renInangIotensIn system, and effects were
expected
- a more comprehensIve answer Included outlInIng renal water balance vIa antIdIuretIc
hormone(A0H), and the effect of atrIal natrIuretIc peptIde (ANP) on Na+ balance
- extra marks were awarded for clarIfyIng the tensIon exIstIng between ECF regulatIon and
water regulatIon (ECF volume v osmolarIty)
- a common mIstake was to concentrate on StarlIng Forces and the CIbbs0onnan Effect
wIthout mentIon of Na+ or water balance

UESTIDN 12 DutIIne the factors contrIbutIng to the generatIon and maIntenance of the
restIng membrane potentIaI.


A defInItIon and normal range for the FestIng |embrane PotentIal was requIred.
The FestIng |embrane PotentIal depends on two maIn factors: the membrane permeabIlIty to the
varIous Ions and the IonIc concentratIons on the InsIde and outsIde of the cell.
|embrane permeabIlIty requIred an understandIng of the domInant role of potassIum and the mInor
role of sodIum. 8etter answers Illustrated the role of multIple Ions wIth the ColdmanFIeld
equatIon.

The potentIal dIfference developed by a permeable Ion depends on the chemIcal and electrIcal
gradIents across the cell membrane for that Ion at equIlIbrIum. ThIs can be demonstrated by the
Nernst equatIon. 8etter answers Included the Nernst potentIals for the varIous Ions and theIr
Intracellular and extracellular concentratIons.

|Inor factors contrIbutIng to the membrane potentIal: the electrogenIc effect of the
sodIum/potassIum pump and the Intracellular proteIn anIons (CIbbs 0onnan).
A common error was to treat these mInor factors as major determInants.
|aIntenance of the FestIng |embrane PotentIal Is due to keepIng a large concentratIon gradIent for
potassIum between InsIde and outsIde the cell membrane. A descrIptIon of the sodIum/potassIum
ATP pump was requIred.

10
No marks were awarded for a descrIptIon of actIon potentIals or for detaIled descrIptIons of Ion
channels.

UESTIDN 13 What Is the Frank-StarIIng mechanIsm and descrIbe Its reIatIonshIp to
excItatIon contractIon coupIIng


|aIn poInts expected for a pass Included: defInItIon and graphIcal representatIon (wIth alternatIve
axes) of Frank StarlIng law; a statement of the concept of thIs beIng an IntrInsIc abIlIty of the heart
to adapt to IncreasIng volumes of venous return; optImal length of sarcomere; and, demonstratIon
of slIdIng fIlament theory and effect of InItIal fIbre length on actInmyosIn crossbrIdgIng.
AddItIonal marks were allocated for mentIon of: there beIng a famIly of curves; Increased calcIum
sensItIvIty of stretched myofIlaments; questIonable effect of excessIve stretchIng In cardIac
muscle; and, effect of Increased afterload or decreased heart rate upon myocardIal stretch and
response.

|Istakes commonly made Included: mIsInterpretIng the questIon and gIvIng Irrelevant detaIl
regardIng actIon potentIal transmIssIon and calcIum release wIthIn the myofIbrIl; usIng the terms
contractIlIty and force of contractIon Interchangeably; and, poor legIbIlIty of key words. CredIt was
not gIven for vague, nondIrectIonal statements of effect of muscle length, nor for statement that
stretch causes Increased release of calcIum.

UESTIDN 14 0escrIbe the physIoIogIcaI processes that InfIuence the rate of gastrIc
emptyIng.


The questIon has been asked prevIously and there was evIdence In the answers that scored well of a
structured, planned and practIsed format. ThIs meant candIdates were able to cover the local,
neural and hormonal control of the rate of gastrIc emptyIng. Extra marks were gaIned for an
explanatIon of mechanIsm of actIon and the InterrelatIonshIp between the controls.

Common omIssIons Included the reason why the rate Is controlled, Ie. allowIng for adequate
dIgestIon tIme wIth gastrIc acId and enzymes before passIng chyme through the pylorIc sphIncter,
the Importance of the "pylorIc pump" and the negatIve feedback control of the duodenal sensors to
ensure the adequacy of the dIgestIve process.

Some candIdates confused whIch hormones Increased or decreased the rate of emptyIng, thIs
detracted from theIr answers.

No marks were gIven for pharmacologIcal manIpulatIon of the rate of gastrIc emptyIng.

UESTIDN 15 0escrIbe the formatIon, fate and roIe of Iactate In energy productIon.


Serum lactate Is used as an IndIcator of anaerobIc metabolIsm In anaesthetIc practIce. Hence
candIdates should have a good understandIng of Its role In energy productIon so that they can
Interpret thIs IndIcator In clInIcal sItuatIons.

Lactate Is formed form pyruvate allowIng the regeneratIon of NA0
+
from NA0H whIch Is necessary
for the Embden|eyerhof pathway to proceed In anaerobIc condItIons or In cells wIth no
mItochondrIa. Lactate dIffuses out of the cells and Is eIther used by the heart as an energy
substrate or metabolIsed In the lIver to glucose.

11
Further detaIls requIred to pass thIs questIon Included:
Some descrIptIon of the Embden|eyerhof pathway and the fates of pyruvate, however a
detaIled descrIptIon of each IntermedIary was not necessary.
An understandIng of the cause of the normal serum lactate of 0.52.0 mmol/L
0etaIls of the CorI Cycle

Few candIdates could descrIbe the role of lactate In energy productIon. |ost attempted to descrIbe
the glycolytIc pathway but often wIth sIgnIfIcant errors. The fate of lactate was agaIn only covered
correctly by a few candIdates. |any candIdates gave lengthy answers addressIng exercIse and
oxygen debt whIch was not a key part of the questIon.

UESTIDN 16 DutIIne the effects of acute exposure to aIr at an aItItude where barometrIc
pressure Is 347mmHg. What compensatory mechanIsms occur wIth graduaI
exposure to IncreasIng aItItude!


|aIn PoInts expected for a pass:

0efInItIon of acute exposure
Correct use of the alveolar gas equatIon to calculate PAD2
How the body senses reduced oxygen levels and what compensatory mechanIsms are trIggered (esp.
respIratory and cardIovascular)
Some mentIon of acute adverse effects
0efInItIon of "gradual exposure"
ExplanatIon of bIphasIc changes In alveolar mInute ventIlatIon
ncreased tIssue oxygen uptake and utIlIsatIon
ncreased Hb and mechanIsm
|echanIsms that act on movIng the HbD0C

AddItIonal poInts could be gaIned for:

0escrIptIon of other effects at altItude - temperature, humIdIty, U7 lIght, radIatIon.
Upper lImIts of human survIval
PhysIologIcal dIfferences between hIghaltItude and lowaltItude natIves
Long term adaptatIon
Changes at the cellular level

Common problems:

llegIble handwrItIng
Poor layout and structure

|any answers were wrItten lInearly whIch dId not allow coverage of the breadth of the topIc
There was sIgnIfIcant confusIon regardIng the overall dIrectIon of movement of the HbD0C and the
causes of bIphasIc changes In alveolar ventIlatIon

The maIn reason for faIlIng thIs questIon was a lack of basIc knowledge

12
PHYSIDLDCY - VIVA SECTIDN

PHYSl0L0CY T0PlCS:

UItrasound
8asIc mechanIsms and prIncIples
0emonstrate understandIng of prIncIples of ultrasound when presented wIth a sImple U/S pIcture
0oppler - prIncIples
| mode - prIncIples
heasurement of carbon dIoxIde
DutlIne methods
Pros and cons of each
nfrared - prIncIples and merIts
F use for other gases
nlIne vs sIdestream samplIng
Lung dIffusIon
0IffusIon pathway - alveolus to Hb
PrIncIples and factors affectIng
0IffusIng capacIty
PrIncIples - dIffusIon vs perfusIon lImItatIon
FunctIons of the Iung
LIst functIons
FespIratory functIons - anatomIcal and physIologIcal features whIch assIst
NonrespIratory functIons - outlIne
mmune functIons - basIc outlIne
Cas FIow
|ethods to measure gas flow
Types of devIces
Pros and cons
Pneumotachograph prIncIples and errors
CardIc output
LIst methods for measurement
Pros and cons
ThermodIlutIon - detaIls of technIque, prIncIples and errors
(ContInuous CD - outsIde currIculum)
PreIoad
0efInItIon
8asIc defInItIon at a cell level
7entrIcular preload
|easurement
C7P/LAP vs atrIal volume
Effect of reduced ventrIcular complIance
Swan Canz catheter - use In determInIng preload

13
HepatIc cIrcuIatIon
8lood supply
0etaIls of relatIve features of portal and hepatIc vessels
DutlIne hepatIc mIcrocIrculatIon
Contents of blood In hepatIc and portal veIns
7alues
FelatIonshIp to hepatIc functIon
0Iaphagm
FunctIons
|uscle types - type 1 vs type 2 fIbres
FelatIonshIp to functIons
Effect of stretch on functIon
ArterIaI bIood pressure measurement
TechnIques for measurement
N8P vs 8P
Pros and cons of each technIque
FequIrements for dIrect measurement
basIc mechanIcs
Sources of error
|eans to Increase accuracy of 8P
PrIncIples and defInItIon - resonance and dampIng
HaemogIobIn
FunctIons
Structure
8ohr effect - detaIls and sIgnIfIcance
Effects of
pH
2,J0PC
Dxygen content - sIgnIfIcance of dIssolved component
SI unIts
DutlIne the unIts
0efIne amps and volts
0escrIbe Inductance and Impedance
ApplIcatIon of prIncIples - to actIon potentIal
e.g. Amps vs flux
CastrIc acId
FunctIons of stomach
Contents of secretIons
Phases of secretIon
0etaIls of parIetal cell functIon
Carbohydrate
0Iet contents
|echanIsms of absorptIon and dIgestIon
SkeIetaI muscIe
ActIon potentIal - outlIne
0raw potentIal
Add muscle force
Effect of IncreasIngly frequent stImulus (IncludIng tetany)
0Ifferences wIth cardIac muscle

14
Heat Ioss
|echanIsms of loss
FelatIve contrIbutIons of dIfferent mechanIsms wIth dIfferences In ambIent temperature
Effect of humIdIty
Latent heat of vaporIsatIon
Effect of ImmersIon of water
0etaIls of heat capacIty and conductIvIty
Lung
TIdal volume - defInItIon
Lund volumes
7olume, pleural pressure and flow vs tIme wIth quIet respIratIon
CerebraI bIood fIow
7alues
Effects of posture
Effects of CD2, |AP
TechnIques for measurement
reath hoIdIng
Changes In alveolar tensIons wIth tIme
Fate of oxygen consumptIon/CD2 productIon
Changes wIth e.g. AnaesthesIa, neonates
PuImonary cIrcuIatIon
7alues of PAP and P7F
Factors affectIng P7F
Changes In West zones
Changes wIth DL7
Effects of HP7
HypoxIa
Causes
0Iagnose an A8C - hypoxIc hypoxIa
ExplaIn the alveolar gas equatIon
Factors affectIng p50
SIeep
0efInItIon vs AnaesthesIa
Normal EEC
EEC features of sleep and anaesthesIa
Work of breathIng
0efInItIon
Factors affectIng: through pressurevolume loop
Changes wIth changIng complIance and resIstance
FIcks Law
PhysIcal prIncIples of gas exchange
Pressure gradIents
FesIstance to dIffusIon determInants
CaIcIum
FunctIon In the body
0IstrIbutIon
FegulatIon - roles and actIons of hormones
Effect of hyperventIlatIon

15
PenaI functIon
ClInIcal measures
|easures of glomerular functIon - nulIn, Cr clearance
Tubular functIon - concentratIng abIlIty, osmolarIty
Shunt
ClassIfIcatIon and types
Normal vs pathophysIologIcal
Shunt equatIon explaIn
Temperature reguIatIon
Normal temperature
|echanIsms for maIntenance
nterthreshold range
Heat transfer, and effect of ambIent temperature
Effect of anaesthesIa
Neonate - dIfferences
ControI of ventIIatIon
Feceptors, pathways and effectors
Chemoreceptors - detaIled functIons
7entIlatIon vs CD2 and D2 curves
Effects of drugs, anaesthesIa
Left ventrIcuIar pressure
Curve vs tIme
Effects of faIlure, Inotropes
Neonatal changes
Acute bIood Ioss
Effect of sudden loss of 1500 ml
0etaIls of autotransfusIon, vasoconstrIctIon
Effects on C8F and cerebral functIon
ohr effect
0escrIbe
Dxygen carrIage - methods
Changes wIth foetal Hb, 2J 0PC, double 8ohr

0r. C Noonan
ChaIrman, PrImary ExamInatIon Sub CommIttee

A8N 82 055 042 852

EXAhINATIDN PEPDPT


JULY/SEPTEMER 2008




84 of candIdates achIeved a pass In thIs sectIon of the Pharmacology ExamInatIon.


UESTIDN 1 DutIIne the potentIaI benefIcIaI and adverse effects of IsofIurane on the
cardIovascuIar system (IncIude mechanIsms of effect) In patIents wIth
IschaemIc heart dIsease.


To answer the questIon It was necessary to descrIbe the effects of Isoflurane on the cardIovascular
system, explaIn how these mIght affect myocardIal oxygen balance, and gIve some explanatIon as
to how these effects mIght occur. As the questIon Is not specIfIc, all mechanIsms from cellular to
organ system InteractIons were accepted.

A pass would have Included the fall In S7F and blood pressure, the compensatory rIse In heart rate,
a note on dIrect effects on contractIlIty, and an explanatIon as to how these effects mIght alter the
myocardIal oxygen supply and demand. A brIef descrIptIon of the concepts of coronary steal and
IschaemIc precondItIonIng, and somethIng on theIr purported mechanIsms was also expected.

Extra marks were awarded for candIdates who could lIst purported mechanIsms for Isoflurane
causIng these effects, such as altered sympathetIc outflow, or calcIum channel antagonIsm, the
alteratIon skeletal muscle vascular tone resultIng In lowerIng of S7F, the effect of concommItant
medIcatIons, age, dIsease, hypoxIa and rapIdly IncreasIng concentratIons on the vascular effects,
explaIn IschaemIc precondItIonIng In more detaIl, and comment on the clInIcal relevance of

2
coronary steal. Few candIdates commented on the overall effect on oxygen balance, eIther at
normal or hIgh concentratIons.

|any candIdates Included unnecessary data, such as physIcal propertIes, modes of admInIstratIon,
effects on other organ systems, or effects whIch are neIther benefIcIal or adverse. Common errors
Included cIrcular reasonIng-a fall In 7F causes a fall In CD, and confusIng the effects of Isoflurane
and halothane.

UESTIDN 2 0escrIbe the pharmacokInetIc prIncIpIes of totaI Intravenous anaesthesIa usIng
propofoI.


The essence of the questIon Is for candIdates to relate knowledge of the pharmacokInetIcs of
propofol to what Is beIng observed when propofol Is beIng admInIstered for total Intravenous
anaesthesIa. So It Is Important to explaIn why the rates of InfusIon vary at dIfferIng tImes such as
at commencement, slIghtly after commencement and after a long perIod of InfusIon through
reference to how the body Is dealIng wIth propofol.

There are many facts, dIagrams and equatIons that attracted marks relatIng to propofol but the
better marks were reserved for candIdates who poInted out the sIgnIfIcance of thIs InformatIon to
what Is happenIng wIth the syrInge drIver. t should be poInted out that candIdates who chose to
explaIn pharmacokInetIc behavIour In relatIon to total Intravenous anaesthesIa(T7A) usIng only
prose were not penalIsed If theIr explanatIons were clear and IndIcated an approprIate depth of
knowledge.

The most poInts that attracted marks Included brIef defInItIon of the goal of T7A I.e. to reach and
maIntaIn a central compartment serum or effect sIte concentratIon of propofol at a level adequate
for anaesthesIa, descrIptIons, dIagrams and equatIons whIch dealt wIth the Importance of an InItIal
InfusIon provIdIng a loadIng dose gIven hIgh lIpId solubIlIty and central compartment volume of
dIstrIbutIon, then the need to allow for redIstrIbutIon and metabolIsm and then largely metabolIsm
alone to maIntaIn a steady serum or effect sIte concentratIon. Also descrIptIons of how propofol
behaves pharmakokInetIcally when T7A Is ceased receIved credIt, as well as detaIls of Its
clearance.

Propofol Is a hIghly Important drug crItIcal to the practIce of anaesthesIa so a relatIvely hIgh
standard was expected.

t Is advIsable that candIdates not waste valuable tIme drawIng molecules of propofol or wrItIng
long IntroductIons that don't deal dIrectly wIth the questIon that was asked.

UESTIDN 3 LIst the anaesthetIc reIated uses of cIonIdIne. What are the effects of
cIonIdIne on the cardIovascuIar and centraI nervous system and how are these
effects medIated!


A lIst of anaesthetIc reIated uses Includes premedIcatIon/anxIolysIs, IntraoperatIve haemodynamIc
stabIlIty, and augmentatIon/prolongatIon of regIonal neural blockade. |arks were also awarded for
use In postoperatIve analgesIa and postoperatIve shIverIng. Extra marks were also provIded In
dIscussIng Its use In preventIon of perIoperatIve myocardIal IschaemIa. WhIlst a dry mouth Is a
common sIde effect of clonIdIne, It Is not typIcally used as an antIsIalogue for anaesthetIc
purposes. |arks were awarded for dIscussIon about Its anaesthetIc sparIng uses, but no marks were
awarded for statIng It could be used as an anaesthetIc alone. A clear statement about clonIdIne's
mechanIsm of actIon as a partIaI agonIst at receptors wIth a relatIve selectIvIty of 2:1 of 200:1
was requIred. Expected C7S effects Included hypotensIon, bradycardIa and perIpheral vasodIlatIon.

3
These are medIated vIa central 2 receptors whIch InhIbIt the vasomotor centre In braInstem.
There are no dIrect effects on the heart, but there Is reductIon In cIrculatIng catecholamInes.

|arks were also awarded for dIscussIng InItIal perIpheral vasoconstrIctIon and transIent
hypertensIon vIa dIrect actIon on perIpheral 2 receptors, extra marks for dIscussIng the changes to
the baroreceptor reflex, and bonus marks for mentIonIng the role of ImIdazolIne receptors In
braInstem. The CNS effects of sedatIon and analgesIa are medIated vIa central 2 receptors vIa
InactIvatIon of locus ceruleus and actIvatIon of descendIng InhIbItory paIn pathways. Further marks
were awarded for dIscussIng the spInal mechanIsms of analgesIa vIa spInal 2 receptors In the
dorsal horn whIch depress wIde dynamIc range neurons Involved In perIpheral nocIceptIve Input.
nformatIon regardIng clonIdIne's pharmaceutIc and pharmacokInetIc profIle was not requIred.

UESTIDN 4 rIefIy outIIne the pharmacoIogy of ketamIne wIth reference to Its use as an
anaIgesIc agent In the post-operatIve perIod.


A complete answer requIred that candIdates consIder pharmaceutIc, pharmacokInetIc and
pharmacodynamIc aspects of ketamIne used as an analgesIc. The nature of ketamIne, Its
formulatIon, major routes of admInIstratIon when admInIstered for postoperatIve analgesIa, dose
ranges used for analgesIa, and key factors InfluencIng the uptake, dIstrIbutIon, metabolIsm and
clearance of ketamIne were expected In a complete answer. Key pharmacokInetIc poInts Included
the hIgh lIpId solubIlIty, large volume of dIstrIbutIon, hIgh hepatIc metabolIsm to an actIve
metabolIte, short elImInatIon halflIfe, and relatIvely rapId offset after prolonged InfusIon.
nformatIon regardIng the sIte and mechanIsms of the potent analgesIc actIon of ketamIne,
partIcularly the roles as a noncompetItIve N|0A receptor antagonIst, and both a preventIve and
opIoIdsparIng analgesIc, were expected. 0osedependent adverse effects that may lImIt the use as
a postoperatIve analgesIc, and the advantages, IncludIng lack of respIratory depressIon, were
Important. Whereas most candIdates IndIcated the racemIc nature of ketamIne, few IndIcated the
relatIve dIfferences of the Isomers, In partIcular the Increased analgesIc potency of the S(+)
Isomer.

AddItIonal poInts whIch attracted hIgher marks Included InformatIon regardIng alternate routes of
admInIstratIon, abuse potentIal, specIfIc actIons on nocIceptIve pathways and actIons on other
receptor systems. Common mIstakes Included mIsInterpretatIon of the questIon wIth dIscussIon of
ketamIne as an anaesthetIc agent, undue focus on the physIology of N|0A receptors and
nocIceptIve pathways, and confusIon between the actIons of norketamIne and norpethIdIne.
Few apprecIated that hepatIc metabolIsm of ketamIne Is hIgh and flowdependent. 0osages
expressed as mg/kg are preferable. |any candIdates appeared to descrIbe local practIce and
formulatIons wIthout beIng aware of core InformatIon well descrIbed In the key texts.

UESTIDN 5 DutIIne how the pharmacokInetIcs of morphIne, bupIvacaIne and
suxamethonIum dIffer In the neonate compared to the aduIt.
rIefIy descrIbe the cIInIcaI ImpIIcatIons of these dIfferences.


ThIs questIon asked candIdates for some applIed pharmacology, lookIng at the effect of age on
pharmacokInetIcs of three commonly used drugs.

The questIon was generally well answered, and a pass mark could be obtaIned by cItIng the crItIcal
features of each. WIth regard to morphIne, both clearance and glucuronIdatIon Is decreased In the
neonate, leadIng to a prolonged half lIfe. The more permeable blood braIn barrIer and relatIvely
Increased braIn blood flow In neonates contrIbutes to a greater sensItIvIty to the drug In the
neonate. WIth regard to bupIvacaIne there Is an enhanced propensIty for toxIcIty as a result of

4
decreased proteIn bIndIng, because of decreased alpha 1 glycoproteIn levels, and decreased
hepatIc clearance. |arks were also awarded for mentIon of the Influence of pH on toxIcIty In the
neonate. WIth regard to suxamethonIum, there are opposIte forces at work. An enhanced ECF
volume would lead to an Increased volume of dIstrIbutIon whIch would tend to reduce actIvIty, but
thIs could be countered for by a decrease In pseudocholInesterase levels In the neonate. The end
result clInIcally Is lIttle change In duratIon of actIon. Extra marks were awarded where candIdates
were able to gIve approxImate dosages, or dosage ranges approprIate for the dIfferent drugs.

UESTIDN 6 DutIIne the IdeaI propertIes of a coIIoId Intravenous fIuId. CIve exampIes of
coIIoIds and brIefIy descrIbe the features of each.


Few candIdates were able to descrIbe the Ideal propertIes of a colloId In adequate detaIl and
frequently made statements that ImplIed a lack of understandIng about the fundamental propertIes
of a colloId as opposed to a crystalloId. A sIgnIfIcant number of candIdates only managed to
mentIon two or three of the four maIn classes, namely polygelInes, starches, dextrans and albumIn.
0escrIptIons of theIr features were often vague and ImprecIse, wIth a poor understandIng of what
sort of molecules they are, where they dIstrIbute In the body, theIr duratIon of actIon, theIr
elImInatIon and rIsks or sIde effects of theIr use.

UESTIDN 7 LIst the agents used therapeutIcaIIy to reduce pIateIet functIon. DutIIne theIr
mechanIsms of actIon, adverse effects, mode of eIImInatIon and duratIon of
actIon.


Felevant agents for thIs questIon Include aspIrIn, prodrugs at A0P receptor, antagonIsts at the
8/A receptor and phosphodIesterase InhIbItors.

ThIs questIon had the optIon of beIng answered In the form of a 'table' format usIng dot poInts
outlInIng the components asked for about platelet functIon reductIon. |arks were enhanced by
IncludIng explanatIon of how the drug actIon Interferes e.g. blockIng the 8/A receptor Interrupts
the bIndIng of fIbrInogen hence the faIlure of adhesIon and aggregatIon of platelets.

The 'thrombus/platelet' dIagram In Katzung page 544 Illustrates In summary form the InformatIon
and It was Included In some candIdate answers.

There Is always a rIsk of elaboratIng on adverse effects probably more than the marks allocated at
the expense of tIme spent on other agents. |edIcatIons whose unwanted sIde effects Include
platelet InhIbItIon are not used therapeutIcally for that purpose thus not gaInIng marks. Comments
on dextran and thrombIn InhIbItors gaIned credIt.

UESTIDN 8 What Is meant by the term PandomIsed ControIIed TrIaI (PCT)! What are the
strengths and weaknesses of randomIzed controI trIaI desIgn!

79 of candIdates passed thIs questIon, wIth 9 receIvIng a very low mark.

A clear explanatIon of a FandomIsed Controlled TrIal was requIred e.g. "a trIal In whIch patIents
are allocated by a form of randomIsatIon between groups; and In whIch an InterventIon group Is
compared to a control group, that may be actIve or InactIve". Thereafter a dIscussIon of the
strengths and weaknesses of such trIals was requIred. Strengths were consIdered to be that FCT
represents a hIgh level of evIdence and can be Included In metaanalyses, mInImIsatIon of bIas,

5
reductIon of the effect of confounders by beIng evenly dIstrIbuted between groups, ease of
blIndIng, ease of applyIng InclusIon/exclusIon crIterIa and provIdIng a good basIs to apply statIstIcal
analysIs. Weaknesses were consIdered to be that they are more expensIve, may not reflect real lIfe
sItuatIons, raIse the possIble ethIcal concern of recruItIng patIents to what may be consIdered a
less effectIve technIque, dIffIculty of meetIng ethIcal requIrements In obtaInIng Informed consent
from patIents who may receIve a less benefIcIal treatment.

|any candIdates appeared to confuse randomIsatIon wIth blIndIng and wrote entIrely on the
advantages and dIsadvantages of blIndIng. WhIlst blIndIng Is often added to an FCT, a dIscussIon of
the advantages conferred wIth blIndIng was approprIate and attracted addItIonal marks; however
candIdates who wrote solely about blIndIng wIth no acknowledgement of what constItutes an FCT,
receIved low marks. LIkewIse the "controlled" part of an FCT applIes to the use of a control agaInst
whIch to compare the InterventIon group and does not mean that there Is a "hIgh degree of
control" of the study or that the researchers "tIghtly control all aspects of the trIal".



0raw a dose - response cure.
DutlIne the drug treatment of anaphylaxIs.
What Is meant by the term "tolerance":
What are some members of the H2 antagonIst group:
0raw a concentratIon tIme curve followIng an .7. InjectIon of propofol.
What are the potentIal routes of admInIstratIon of drugs:
What are some problems assocIated wIth gIvIng drugs by the transdermal route:
How can drugs be gIven to control postoperatIve paIn:
What drugs can be used by management of neuropathIc paIn:
How do you classIfy cortIcosteroIds :
What Is meant by the word "addIctIon":
What sort of drug Is neostIgmIne:
What Is the role of cytochrome P450 systems In drug metabolIsm:
What specIfIc pharmaceutIc problems exIst In the elderly populatIon:
What sort of drugs can be gIven by the Intrathecal route:
How do volatIle agents affect the pattern of ventIlatIon:
What are the uses of beta blockIng drugs:
How do you assess the extent of neuromuscular blockade:
What Is meant by the term "depolarIsIng blockade":
What Is the mechanIsm of actIon of local anaesthetIcs:
What are the sIgns of local anaesthetIc toxIcIty:
0escrIbe the uses of antIcholInesterase agents.
What Is acetylcholIne:
0escrIbe the phases of clInIcal drug development.
0escrIbe the pharmacokInetIcs of fentanyl.
What Is the approprIate dose of paracetamol:
What Is meant by the term "probabIlIty":
What Is meant by the term "power" In statIstIcs:
What Is meant by the term sensItIvIty E specIfIcIty:
How do you classIfy adverse effects of local anaesthetIcs:
What are the contents of an ampoule of thIopentone:
What Is the cause of dIfferences In speed of onset between fentanyl E alfentanIl:

6
What are the advantages and dIsadvantages In usIng nItrous oxIde:
What are the contents of a Hartmann's solutIon:
How does the addItIon of nItrous oxIde affect the uptake of sevoflurane:
What drugs can be used In the management of ventrIcular fIbrIllatIon:
What Is the 7aughnWIllIams classIfIcatIon of antIarrhythmIc drugs:
What types of statIstIcal data are there:
What type of Intravenous drugs can be useful to control paIn:
ConcentratIon tIme cure for alfentanIl:
What are some of the advantages of tramadol as an analgesIc:
What agents can be used to reduce blood pressure:
What do you understand by the term IntrInsIc sympathetomImetIc actIvIty:
What Intravenous InductIon agents do you know of:
The normal dIstrIbutIon curve.
What Is syntocInIn:
What Is ropIvacaIne:
SIde effects of suxamethonIum.
Wash In curve for Isoflurane.
How are Inhaled anaesthetIc removed from the body:
|etabolIsm of the volatIle anaesthetIc agents
How do you classIfy antIcholInesterase agents:
What Is ephedrIne:
How do you defIne |AC:
What Is protamIne:
What Is heparIn:
What drugs cause hIstamIne release:

7



8J of candIdates achIeved a pass In thIs sectIon of the PhysIology ExamInatIon.


UESTIDN What Is humIdIty and how can It be measured!


The mInImum requIrement for a pass mark was an adequate defInItIon of humIdIty and a brIef
descrIptIon of two methods of Its measurement. CandIdates were expected to be able to defIne
absolute and relatIve humIdIty, extra marks were awarded for an explanatIon of the Influence of
temperature on humIdIty and for the provIsIon of the humIdIty of fully saturated aIr at 20 and J7
degrees. A common error was the descrIptIon of absolute humIdIty as a pressure, rather than as
mass of water vapour /volume of aIr. Successful candIdates could In general descrIbe haIr
hygrometers, wet and dry bulb hygrometers and Fegnault's hygrometer. Extra marks were awarded
for a descrIptIon of the relatIve merIts of these technIques and for descrIptIons of other methods
for measurIng absolute humIdIty (such as electrIcal transducers / mass spectrometry). However, no
marks were awarded for descrIptIons of humIdIfIers, or for dIscussIon on the envIronmental or
clInIcal consequences of hIgh or low humIdIty.

UESTIDN 10 0escrIbe sepsIs and descrIbe the metaboIIc consequences of sepsIs.


A basIc defInItIon of sepsIs was expected. FecognItIon of the spectrum of severIty encompassed by
the term sepsIs gaIned addItIonal marks, as dId a brIef descrIptIon of the mechanIsms and
medIators of sepsIs.

CIven the wordIng of thIs questIon equal marks were gIven for the general (nonmetabolIc) and
metabolIc features of sepsIs. The general features were best organIsed by a systems approach
namely cardIovascular, respIratory, haematologIcal, endocrIne and CNS. Df these the
cardIovascular features requIred the most detaIl.

mportant InformatIon to be Included In the metabolIc part of the answer Included the general
catabolIc state, hypermetabolIsm, fever, tIssue hypoxIa, metabolIc acIdosIs, InsulIn resIstance and
the effect of sepsIs on the metabolIsm of carbohydrates, proteIns and lIpIds.

Clear wrItIng and sImple organIsatIon InvolvIng underlIned headIngs and common abbrevIatIons
allowed candIdates to cover thIs broad questIon well. Those who faIled thIs questIon sImply dId not
provIde enough content and detaIl. The most common mIstake was to wrIte at length about
metabolIc acIdosIs to the exclusIon of a wIder rangIng answer. 0etaIled metabolIc pathways were
not expected.

8
UESTIDN 11 WrIte brIef notes on the physIoIogIcaI changes assocIated wIth sIeep.


A defInItIon of sleep, an IndIcatIon of the components of sleep and theIr duratIon followed by a
brIef notatIon of the physIologIcal changes occurrIng In the neurologIcal, cardIovascular, respIratory
and metabolIc systems was rewarded wIth a good pass. AddItIonal detaIl, partIcularly In regard to
the neurologIcal changes, was rewarded wIth addItIonal marks.

Sleep Is a NECESSARY RE\ERSl8LE reductIon In the conscIous state from whIch one can be easIly
ARD0SE0 by sensory or other stImulI. The most common reason for not passIng thIs questIon was a
poor defInItIon (or no defInItIon at all) and sImply not notatIng an adequate number of physIologIcal
changes. The most common error was to correctly state that parasympathetIc tone predomInates
durIng sleep only to then state that gut motIlIty was reduced. QuIte a few answers lacked any
structure what so ever.

CredIt was not gIven for descrIptIons of physIologIcal compensatory mechanIsms, such as for
reduced venous return or determInants of CFF.

UESTIDN 12 0etaII the protectIve and reguIatory roIes of the IIver.


ThIs questIon requIred a descrIptIon of the lIver as the Interface between the gut and the body,
and as a result of thIs, Its role In protectIon from organIsms and toxIns and regulatIon of nutrIent
levels.

The protectIve role Is prImarIly related to the removal of bacterIa, endotoxIns, and proteIn
denaturatIon. ThIs Is prImarIly undertaken by the Kupffer Cells whIch are In the hepatIc sInusoIds.
The actIon of these macrophages Is an example of Innate ImmunIty. FollowIng theIr actIvatIon a
serIes of events follows IncludIng phagocytosIs, completment actIvatIon, and recruItment of other
cells.

The prImary regulatory role of the lIver Is as a glucostat I.e. respondIng to both hIgh and low blood
glucose levels beIng presented to It by the portal cIrculatIon. 0etaIl on how the lIver achIeves thIs
balance was needed. Some candIdates were confused about the actIon of InsulIn and glucacon In
these processes.

8onus marks were also awarded for the followIng as examples of protectIon: toxIn/drug
modIfIcatIon, productIon of acute phase proteIns, complement and urea, actIon as a blood
reservoIr, and of regulatIon productIon of albumen In regulatIng oncotIc pressure, bIle In regulatIng
fat and fat soluble vItamIn absorptIon, bIlIrubIn metabolIsm, hormone InactIvatIon and productIon
of both coagulatIon and antIcoagulatIon proteIns.

LIstIng all lIver functIons dId not address the questIon, whIch asked for detaIl on a lImIted area of
lIver functIon. Some candIdates focussed on mInor detaIls whIle mIssIng the bIg pIcture such as
faIlIng to mentIon blood glucose regulatIon or any protectIve roles.

9
UESTIDN 13 ExpIaIn the concept of tIme constants and reIate these to "fast"
and "sIow" aIveoII


The answer should Include:

An objectIve (mathematIcallybased) defInItIon of a tIme constant,
n relatIon to lung unIts, the tIme constant Is often defIned as the product of complIance
and resIstance.
Some factors that Influence tIme constants (physIologIcal and pathologIcal causes of
alteratIons In complIance and resIstance)
The effects of heterogeneIty In tIme constants (statIc vs. dynamIc complIance and
respIratory rate)

AddItIonal marks were awarded for ways of measurIng the effects of heterogeneIty of tIme
constants. The capnogram and the peak vs. plateau pressures. |any candIdates spent a lot of tIme
explaInIng varIous other formulas pertaInIng to complIance, surfactant, and alveolar collapse that
were not dIrectly relevant to the questIon. |any candIdates thought that Increased complIance
causes fast tIme constants.

UESTIDN 14 ExpIaIn In physIoIogIc terms the effect of severe aortIc stenosIs on myocardIaI
suppIy and demand.


ThIs was an applIed physIology questIon. The fIrst part of an answer was a descrIptIon of aortIc
stenosIs, wIth addItIonal marks for gIvIng measure(s) of severIty. The maIn part of the answer
concerned the Interrelated effects of a severely stenosed aortIc valve that may produce both
Increased myocardIal work (descrIbed usIng Laplace's law) and compromIsed coronary blood flow.
AddItIonal marks were awarded for answers that dIscussed the varyIng effects of left ventrIcular
hypertrophy on both supply and demand. |arks were also awarded for dIscussIng how Increased
heart rate may both Increase demand and reduce supply. Errors Included: confusIng the effects of
altered pressure wIth altered flow; faIlIng to IndIcate that severe aortIc stenosIs Is a chronIc
condItIon; and IncludIng, often at length, the effects of anaesthesIa or the symptoms and sIgns of
aortIc stenosIs.

UESTIDN 15 0escrIbe the changes that occur wIth ageIng that can affect oxygen deIIvery
to the tIssues durIng moderate exercIse.


Dxygen delIvery Is the product of cardIac output and arterIal oxygen content. Dxygen delIvery
durIng exercIse Is Increased by raIsIng cardIac output globally and locally, and IncreasIng oxygen
extractIon. LInkIng these changes to agIng Is the key to answerIng thIs questIon.
CardIac output and respIratory changes wIth agIng both needed dIscussIon to gaIn a pass mark.
Key poInts:
CardIac output contractIlIty, heart rate responsIveness, stroke volume,
ventrIcular complIance, and cardIac work wIth agIng. These factors reduce the
abIlIty to Increase cardIac output to match exercIsIng tIssue demand.
FespIratory - PaD
2
, work of breathIng wIth a In chest wall complIance, closIng
capacIty encroaches on FFC, and dIffusIon capacIty from alveolar membrane
thIckness and functIonal surface area. The 7/Q mIsmatch that results reduces the
abIlIty to oxygenate blood when extractIon Increases.

10
AddItIonal marks were awarded for mentIonIng blood flow wIth atherosclerosIs, pulmonary
resIstance and heart straIn, anaemIa D
2
content, moderate exercIse Is below anaerobIc threshold,
and valvular defects can affect cardIac output.

Common errors Included focusIng on eIther cardIac or respIratory changes; lIstIng agIng and
exercIse physIologIcal changes wIthout lInkIng the Important factors of the two together; descrIbIng
anaerobIc metabolIsm of tIssues; statIng that FFC reduces wIth IncreasIng age; not dIfferentIatIng
between the chest wall complIance and lung complIance that happens wIth agIng.

UESTIDN 16 DutIIne the mechanIsms by whIch the kIdney maIntaIns potassIum homeostasIs


t was pleasIng to see some well structured answers coverIng all the maIn poInts.
The maIn poInts expected to achIeve a pass Included:
Normal Intracellular and extracellular potassIum concentratIons and the need for "tIght"
control.
A balance between Intake and excretIon of potassIum.
The transIt of potassIum through the nephron In the kIdney, excretIon = fIltered
reabsorptIon + secretIon, wIth the major controlled varIable beIng secretIon, and the places
wIthIn the nephron that these events occurred.
The control of the varIable secretIon In the dIstal convoluted tubule and collectIng duct
dependent on potassIum concentratIon, tubular flow rate and aldosterone. SecretIon of
aldosterone from the adrenal gland beIng under a feedback loop wIth plasma concentratIon
of potassIum.

Extra credIt was gIven for mechanIsm of actIon of any of the steps above, In partIcular a clear
explanatIon of how aldosterone achIeves further secretIon was rewarded. The exchange of
potassIum for hydrogen Ions wIthIn the renal tubule was also rewarded If explaIned correctly.
No credIt was gIven for InformatIon of drug actIons on the renal tubule.


PHYSl0L0CY T0PlCS:

CVS
FegIonal blood flow
WIggers' dIagram
Lead ECC
FrankStarlIng mechanIsm
ContractIlIty: defInItIon E measurement
C7P waveform
Afterload: defInItIon E measurement
Dxygen flux
7enous return / atrIal pressure curve
AnemIa; causes, consequences
SInoatrIal node actIon potentIal
L7 pressurevolume loop
Changes In mean aterIal waveform wIth propagatIon
Cerebral blood flow determInants

11
heasurement
CalIbratIon of pressure transducer
ComparIson of InvasIve E nonInvasIve blood pressure measurement
PA catheter waveform changes wIth InsertIon
CD measurement
Wheatstone brIdge
FIck prIncIple
CD
2
measurement
ElectrIcal cIrcuIts
Pulse oxImetry

FIuId eIectroIytes
Contents of one lItre bag of Normal SalIne

huscIe
ExcItatIoncontractIon couplIng

PenaI
HandlIng of water
CFF: defInItIon, determInants
Clearance
F8F; response to hypovolemIa
|etabolIc acId; handlIng by kIdney

PaIn
Fesponse to skIn IncIsIon
Fesponse to thermal Injury

PespIratory
8lood gas InterpretatIon
Alveolar gas equatIon
Dxygen cascade
Effect of pneumothorax on gas exchange
Control of ventIlatIon
Surfactant
Dxygen stores In the body
0Ifferences between base and apex of the lung
FFC
ComplIance
0ead space
Shunt
Work of breathIng
ClosIng capacIty
AltItude physIology
DxygenhaemoglobIn dIssocIatIon curve
CD
2
carrIage
Pulmonary cIrculatIon
AIrway resIstance

HaematoIogy
Fed cell metabolIsm
ProcessIng of blood donatIons
Platelets; structure and functIon

12
hetaboIIsm
Clucose: aerobIc E anaerobIc metabolIsm
Fuel sources
Effect of an eIght hour fast

EndocrIne
ProstaglandIns
ThyroId hormones
PItuItary hormones
nsulIn

Pregnancy
FespIratory changes In pregnancy
CardIovascular changes In pregnancy

haterno-fetaI
Dxygen transfer across placenta

Nervous
SympathetIc nervous system
N|0A receptors
FestIng membrane potentIal
Nernst equatIon
ColdmanFIeld equatIon

AIIergylImmune system
ClassIfIcatIon of ImmunologIcal reactIons
0efences agaInst InfectIon

Castro-IntestInaI
Lower oesophageal sphIncter
CastrIc emptyIng

0r. C Noonan
ChaIrman, PrImary ExamInatIon Sub CommIttee

A8N 82 055 042 852

EXAhINATIDN PEPDPT


FERUARY/APRlL 2008



6J of candIdates achIeved a pass In thIs sectIon of the Pharmacology ExamInatIon.


UESTIDN 1 An 80 year oId woman Is undergoIng major emergency surgery. 0escrIbe
the maIntenance InhaIed concentratIon of sevofIurane you wouId choose
and the factors that mIght InfIuence thIs.


ThIs questIon seemed to cause a lot of dIffIculty for many candIdates who struggled to relate theIr
answer to the clInIcal sItuatIon. Common mIstakes were the dIscussIon of uptake factors or lIstIng
the pharmacology of sevoflurance wIthout puttIng It Into context. Pregnancy does affect |AC, but
not In 80 year olds.

n order to pass candIdates were expected to cover the need to provIde enough sevoflurane to
prevent awareness and movement whIle mInImIsIng Its undesIrable cardIovascular effects. The
patIent's age, preoperatIve condItIon, type of surgery, and use of other |AC reducIng agents or
drugs needed to be mentIoned. 7ery few candIdates consIdered that dIfferences between the
Inhaled and endtIdal concentratIon of sevoflurane.

2
AddItIonal marks were awarded for awareness monItorIng, other factors affectIng |AC, and more
detaIls about the cardIovascular sIde effects of sevoflurane. Wellstructured answers that were
clInIcally relevant scored better marks.

UESTIDN 2 LIst the cIasses of drugs that are usefuI In InducIng dIuresIs cIInIcaIIy.
DutIIne theIr mechanIsm of actIon.

ThIs questIon Integrated the Ceneral nstructIonal DbjectIve and aspects of all the FequIred
AbIlItIes laId out In the PrImary Syllabus sectIon on dIuretIcs.
For just over 70 of the marks avaIlable It was expected that candIdates would lIst the classes
osmotIc, carbonIc anhydrase InhIbItIon, loop, thIazIde, aldosterone antagonIsm, and potassIum
sparIng, then outlIne the mechanIsm of actIon. The remaInIng marks were approxImately evenly
splIt between other drug classes exhIbItIng sIgnIfIcant dIuretIc actIon and theIr mechanIsms, and
overall understandIng demonstrated of the Interplay of renal physIology, dIuretIc pharmacology,
and clInIcal effect.
HIghly detaIled explanatIons of mechanIsm of actIon were not requIred, but answers demonstratIng
an understandIng of both the channel/enzyme/receptor sIte and the local, and more dIstal, tubular
consequences of that actIon scored very well. |any candIdates descrIbed only the sIte of actIon
and stated thIs reduced sodIum reabsorptIon.
Cellular level mechanIsm of actIon was most commonly mIsunderstood for carbonIc anhydrase
InhIbItIon where, amongst other problems, the majorIty of candIdates faIled to mentIon the
decreased bIcarbonate removal from the fIltrate and resultIng metabolIc acIdosIs.
The questIon asked about dIuretIcs that were useful....clInIcally." 7ery few candIdates mentIoned,
or showed understandIng of, the relatIve potencIes, the common condItIons dIuretIcs are used to
treat, nor related dIuretIc actIon to the pathophysIology of those condItIons.

UESTIDN 3 0escrIbe the IdeaI pharmacokInetIc and pharmacodynamIc propertIes of
agents used for sedatIon. DutIIne the pharmacoIogy of mIdazoIam and
propofoI wIth reference to these IdeaI propertIes.


The maIn poInts expected for a pass Included a descrIptIon of the Ideal pharmacokInetIc and
pharmacodynamIc features of an agent specIfIcally suIted to the clInIcal sItuatIon of provIdIng
sedatIon. Therefore, pharmacokInetIc features that result In a rapId onset and offset of effect wIth
boluses or InfusIon Is Ideal. Also the effects of anxIolysIs, amnesIa and arousable sedatIon were
consIdered desIrable, wIth low propensIty to Inadvertently progress to general anaesthesIa.

A dIscussIon about other Ideal features such as analgesIa and stable cardIorespIratory effects of
the sedatIon agents were also expected.

An outlIne of how mIdazolam and propofol fItted thIs Ideal agent's features was also requIred.

Extra marks were awarded for an opInIon comparIng the suItabIlIty of mIdazolam and propofol
suItabIlIty for the provIsIon of sedatIon, based upon the profIles generated above.
3
A common error was to Include pharmaceutIc InformatIon that was not requIred, and factual
pharmacokInetIc InformatIon about each drug was gIven lIttle credIt when not applIed to how It
affected the agents profIle wIth reference to the Ideal agent.

UESTIDN 4 DutIIne the pharmacoIogIc management If bronchoconstrIctIon In acute
severe asthma. IncIude mechanIsms of actIon and potentIaI adverse
effects.


ThIs questIon was asked In an earlIer examInatIon and comments from the examIner's report
remaIn relevant.

The maIn poInts to be covered Included:
A lIst of the maIn drugs useful In thIs sItuatIon
An example In each group and Its route(s) of admInIstratIon
SuffIcIent detaIl on how the drug works
mportant sIde effects

t was expected that most of the answer would be on 82 agonIsts, IncludIng the use of less selectIve
agents eg adrenalIne, steroIds, antIcholInergIcs and methylxanthInes. AddItIonal marks were also
gIven for notes on magnesIum sulphate, ketamIne, volatIles, oxygen and helIox.

Some InformatIon on 2
nd
messengers was expected, here some candIdates were confused wIth the
InhIbItIon of cA|P and the dIrectIon of Intracellular calcIum fluxes. Some candIdates faIled to gaIn
marks by not mentIonIng a mechanIsm of actIon or sIde effects. There were some excellent answers
that used a table format, succInctly gIvIng detaIled and relevant InformatIon. Extra marks were
gIven for answers that showed some perspectIve eg mInImal sIde effects of IpratropIum If gIven by
metered aerosol.

Some candIdates used tIme to dIscuss the pathogenesIs of asthma, whIch attracted no marks.
nsuffIcIent detaIl and maIn poInts not covered were the maIn reasons for faIlIng thIs questIon.

UESTIDN 5 CIassIfy drugs that aIter actIvIty at serotonIn receptors wIth exampIes.
0escrIbe theIr mechanIsms of actIon and cIInIcaI IndIcatIons.


The maIn poInts that needed to be made to demonstrate an understandIng of thIs topIc were an
overvIew that receptor actIvIty can be altered by drugs that are agonIsts (e.g. metoclopramIde,
sumatrIptan), antagonIsts (e.g. ergotamIne, ondansetron) and drugs that Increase the amount of
serotonIn and In turn Increase actIvIty at the receptor by IncreasIng release (tramadol), InhIbItIng
reuptake (fluoxetIne) or InhIbItIng breakdown of serotonIn. All of the serotonIn receptors are C
proteIn lInked except 5HTJ whIch Is lIgand gated. |any answers gave extensIve detaIl of the
vomItIng pathways whIch was of lImIted relevance. There was confusIon over the classIfIcatIon of
serotonIn reuptake InhIbItors. They were often descrIbed as agonIsts (thIs ImplIes a dIrect receptor
actIon); others descrIbed the same drugs as antagonIsts because they reuptake. The term
"IndIrect agonIst" Is the best descrIptIon. |ost candIdates focused only on the serotonIn reuptake
InhIbItors (SF) and the 5HTJ antagonIsts. The mechanIsm of actIon was often descrIbed as a
tautology (I.e. SF's InhIbIt the reuptake of serotonIn and 5HTJ antagonIsts antagonIze the 5HTJ
4
receptor). These explanatIons faIled to attract addItIonal marks makIng a pass ImpossIble to
achIeve.

UESTIDN 6 A surgeon wIshes to use topIcaI anaesthetIc In the nose before surgery In a
30 year oId 70 kg man. He normaIIy uses topIcaI cocaIne 5X pIus
IIgnocaIne 2X wIth adrenaIIne 1:100,000 InjectIon. What voIumes of
cocaIne 5X and IIgnocaIne can be used safeIy! What are the potentIaI toxIc
effects of cocaIne and how do IIgnocaIne and adrenaIIne affect thIs!


8etter answers came from candIdates who had gone to more than just one or two of the
recommended textbooks to get InformatIon on cocaIne (some of them contaIn very sparse
InformatIon). ConsIderable latItude was gIven to the range of toxIc doses, especIally when
accompanIed by a correct calculatIon. 7ery few candIdates noted that 1:100,000 adrenalIne Is 10
mcg/ml and that 10 ml would be an apprecIable dose of adrenalIne.
An answer that contaIned the followIng would have attracted a good pass:
toxIc doses and thus volumes
a statement that toxIcItIes are addItIve so doses should be modIfIed
mechanIsm(s) and manIfestatIons of cocaIne toxIcIty
o reuptake InhIbItor of noradrenalIne (and dopamIne and serotonIn)
o sympathetIc nervous system actIvatIon (tachycardIa, hypertensIon,
arrhythmIas, coronary vascoconstrIctIon, myocardIal IschaemIa)
o CNS effects (eg. euphorIa, delIrIum, seIzures)
lIgnocaIne enhances CNS toxIcIty
adrenalIne Increases cardIovascular toxIcIty

Long dIscursIons on sodIum channel blockade, factors that governed uptake of local anaesthetIcs
and the blood levels of lIgnocaIne at whIch dIfferent CNS effects mIght appear dId not attract
marks.

UESTIDN 7 0escrIbe the terms traIn-of-four stImuIatIon and doubIe burst stImuIatIon
wIth respect to the perIpheraI nerve stImuIator. 0escrIbe theIr advantages
and dIsadvantages when used to evaIuate non-depoIarIsIng neuromuscuIar
bIockade.


CandIdates were expected to provIde a clear descrIptIon of how traInoffour (TDF) and double
burst stImulatIon (08S) Is produced usIng a perIpheral nerve stImulator to evaluate nondepolarIsIng
neuromuscular blockade (N0|8). A good understandIng of the relatIonshIp between twItch heIght,
TDF ratIo and level of N0|8 In the context of reversIbIlIty and block depth Is ImperatIve.
A descrIptIon of the advantages, lImItatIons and drawbacks of usIng both technIques was expected
to achIeve a pass mark.

WhIlst many candIdates were able to outlIne the prIncIples of TDF and 08S, most faIled to provIde
precIse or correct descrIptIon of Important technIcal aspects lIke frequency, tImIng and voltage.
The descrIptIon of advantages and lImItatIons were vague, patchy and fragmented and showed
general lack of understandIng of neuromuscular monItorIng and Its applIed pharmacology.

5
Cood candIdates were able to descrIbe TDF correlates wIth receptor occupancy and provIde
comparIson wIth sIngle twItch and post tetanIc count.

UESTIDN 8 0efIne the mechanIsms of actIon and adverse effects of metoproIoI,
gIyceryI trInItrate and dIItIazem when used to manage myocardIaI
IschaemIa.


t was expected candIdates would dIscuss the general concept of a balance of supply and demand
and go on to descrIbe the maIn determInates of oxygen demand beIng heart rate and contractIlIty.
AddItIonal marks were gIven for dIscussIng the role of ventrIcular dIlatIon. For agents that slow the
heart rate extra credIt was gIven for an explanatIon about the proportIon of the cardIac cycle spent
In dIastole at hIgh and low heart rates and the Impact thIs has on coronary blood flow and
myocardIal perfusIon. t was expected that the mechanIsm of actIon for each agent would be
outlIned. Some dIscussIon of both the general clInIcal effect and more detaIled mechanIsm of
actIon were expected. For example, metoprolol Is a selectIve beta 1 receptor antagonIst that
results In decreased cyclIc A|P as a second messenger. The resultant clInIcal effects are prImarIly a
reduced heart rate and reduced contractIlIty. Extra marks were awarded for reIteratIng why thIs Is
benefIcIal for patIents wIth myocardIal IschaemIa. t was expected that the potentIal adverse
effects for each agent would be mentIoned. Extra credIt was gIven for comments regardIng the
development of tolerance to glyceryl trInItrate. AddItIonal marks were gaIned for dIscussIng the
potentIal adverse Impact that InducIng tachycardIa or hypotensIon can have on myocardIal
IschaemIa. Further credIt was gIven for notIng that both the clInIcal effects and the potentIal for
adverse effects are synergIstIc wIth each of these and other agents.



What Is meant by the term "half - lIfe" of a drug:
0raw a concentratIon - tIme curve after an .7. bolus of a drug
What are the basIc processes In pharmacokInetIcs:
How do you determIne the dose of opIoId for analgesIa:
What drugs can be gIven transdermally:
0efIne potency and affInIty
What Is meant by the term "therapeutIc Index":
Factors determInIng uptake of volatIle anaesthetIc agents
What are the uses of nItrous oxIde In anaesthesIa:
CIven a range of analgesIcs how do you determIne speed of onset:
How does heart faIlure affect pharmacokInetIcs:
KInetIcs of propofol
What Is In an ampoule of thIopentone:
How Is nItrous oxIde manufactured:
How do you choose a volatIle anaesthetIc agent:
0raw a Fa/FI curve for Isoflurane
0efIne the term partItIon coeffIcIent

6
|etabolIsm of volatIle agents
How does nItrous oxIde addItIon affect uptake of volatIle agents:
0raw a washout curve
What Is meant by the term "Isomer":
Pharmacology of ketamIne
ClassIfIcatIon of Intravenous anaesthetIc agents
What are the advantages In usIng propofol as an InductIon agent:
0Iscuss the CA8A receptors
0Isadvantages of thIopentone as an InductIon agent
Pharmacology of lIgnocaIne
What Is the fate of an InjectIon of Intrathecal local anaesthetIcs:
ToxIcIty of local anaesthetIcs
E|LA cream
Compare alfentanIl and fentanyl
Advantages of NSA0s
Compare paracetamol and NSA0's
|echanIsm of actIon of opIoIds
How do you defIne paIn:
ClassIfIcatIon of Neuromuscular 8lockIng drugs
What Is meant by the term "margIn of safety" wIth regard to neuromuscular blockIng drugs
What sort of drug Is suxamethonIum:
0epolarIsIng and non depolarIsIng blockade
What sort of drug Is neostIgmIne:
Compare atropIne wIth hyoscIne
0escrIbe drugs used to treat hypertensIon
ToxIcIty of sodIum nItroprussIde
What are the uses of dIgoxIn
|anagement of ventrIcular fIbrIllatIon
0rugs used In cardIac arrest
|anagement of IntraoperatIve hypotensIon
Pharmacology of alpha2 agonIsts
0rugs affectIng seIzure threshold
|etoclopramIde
0rugs affectIng uterIne tone
0Ifferent types of heparIn
AntacIds
0IsInfectants and AntIseptIcs
What are the uses of steroIds:
Prevalence and ncIdence
What are the stages of drug development:
ClInIcal trIals
Forrest plot
|easures of central tendency
0Iscuss 2 x 2 table

7


69 of candIdates achIeved a pass In thIs sectIon of the PhysIology ExamInatIon.


UESTIDN The skIn, the kIdneys, and the carotId bodIes are exampIes of where
specIfIc organ bIood fIow Is far In excess of that organ's metaboIIc
requIrements. For each exampIe, expIaIn what the physIoIogIcaI roIe of
the hIgh organ bIood fIow Is, why thIs hIgh fIow Is an advantage to the
person and a brIef descrIptIon of the mechanIsms InvoIved.


To answer thIs questIon, candIdates had to explaIn the role of the hIgh organ blood flow, the
advantage of thIs hIgh flow, and the mechanIsm creatIng the hIgh flow for all three organs.

SkIn: ThermoregulatIon role wIth heat conservatIon / loss. NormothermIa allows normal enzyme
functIon. HIgh flow vIa superfIcIal arterIole network and arterIovenous anastomosIs wIth
sympathetIc nervous system control. AddItIonal marks for role as a blood reservoIr, correct value of
blood flow, and Importance of sweatIng.

KIdneys: Fole Is to excrete waste products and sodIum / water balance. Advantage Is the
maIntenance of constant Internal envIronment. HIgh flow vIa short large renal arterIes, parallel
Interlobular arterIes and parallel afferent arterIole branches. AddItIonal marks for renal blood flow
value.

CarotId bodIes: HIgh flow means organ oxygen requIrements do not Interfere wIth measurIng PaD
2
.
The advantage Is early detectIon of hypoxIa. HIgh organ flow occurs due to the small sIze of the
organ and flow dIrectly from the carotId artery. AddItIonal marks for organ blood flow rate and lack
of effect from anaemIa or carbon monoxIde poIsonIng.

A common mIstake was to descrIbe In detaIl how blood flow Is controlled or altered, especIally
when referrIng to the kIdney and thIs was not asked for. 0escrIptIons of physIologIcal pathways and
theIr end organ responses were also not asked for. FewrItIng the questIon was not helpful. CarotId
bodIes were often Incorrectly descrIbed as havIng a baroreceptor functIon.

UESTIDN 10 0efIne "thermoneutraI zone". rIefIy expIaIn how the body reguIates
temperature when the ambIent temperature exceeds the thermoneutraI
zone.


|ost candIdates were able to defIne thermoneutral zone and many were able to gIve normal
values for adults and neonates. 8etter answers demonstrated the lInear Increase In metabolIc rate
above and below the thermoneutral zone In graph form.
8
An explanatIon of how temperature Is regulated when the ambIent temperature exceeds the
thermoneutral zone should Include the followIng:

PATHWAYS
Sensors, afferent pathways and IntegratIon were generally well descrIbed but many
candIdates faIled to mentIon that cutaneous vasodIlatatIon was medIated by InhIbItIon of
sympathetIc adrenergIc tone and sweatIng was medIated by sympathetIc cholInergIc
actIvatIon.
8EHA7DUFAL FESPDNSES
CUTANEDUS 7ASD0LATATDN
|aIn poInts expected were, transfer of heat from core to skIn, the role of arterIovenous
shunts and deep venous plexuses and Increases In skIn blood flow up to J0 fold. 8etter
answers explaIned how heat transfer from the skIn by conductIon, radIatIon and convectIon
requIred a temperature gradIent.
SWEATNC
|aIn poInts expected were that evaporatIon of water, does not requIre a temperature
gradIent, Is very effIcIent at heat transfer due to the hIgh latent heat of evaporatIon and Is
the only means avaIlable to transfer heat when ambIent temperature exceeds skIn
temperature.

UESTIDN 11 DutIIne the physIoIogIcaI consequences of dIabetIc keto acIdosIs.


To achIeve a pass, candIdates needed an understandIng that 0KA Is a syndrome IncludIng metabolIc
aspects, fluId and electrolyte abnormalItIes, as well as severe metabolIc acIdosIs. Some mentIon of
InsulIn lack and fat breakdown as the cause of ketoacId overproductIon, of the ensuIng
hyperglycaemIa and osmotIc dIuresIs wIth attendant water and electrolyte (partIcularly potassIum)
derangements, and of the physIologIc consequences of severe metabolIc acIdosIs were requIred.

Extra marks were gIven for more detaIled InformatIon about gluconeogenesIs(CN) from amIno acIds
and glycerol and related aspects of IntermedIary metabolIsm (many answers contaIned Incorrect
InformatIon here); ketone accumulatIon as Krebs cycle entry becomes saturated; realIzIng that
hyperglycaemIa was due both to Increased CN and faIlure of cellular uptake of glucose; for a
summary of the neurohumoral response to hypovolaemIa; for InformatIon about response to acIdosIs
- hyperventIlatIon due to stImulatIon of perIpheral chemoreceptors, bufferIng, renal response and
shIft to the rIght of the HbD2 dIssocIatIon curve; for InformatIon relatIng to osmotIc shIfts IncludIng
cellular dehydratIon and pseudohyponatraemIa; and for the presence In advanced cases of a
secondary lactIc acIdosIs due to decreased tIssue perfusIon.

Common errors. A great many answers focused entIrely on the response to metabolIc acIdosIs only,
omIttIng any reference to hyperglycaemIa and Its effects.
There were many who had scant understandIng of metabolIc processes - for example, ketones are
not produced from glucose or from proteIn; the braIn Is able to utIlIze ketones In states of
starvatIon, but more to the poInt, Is not dependent on InsulIn for glucose uptake, therefore
neuroglycopaenIa Is not a feature of 0KA; oxaloacetate, oketoglutarate and varIous other
IntermedIary metabolItes are not "ketone bodIes"; ketones are not produced as a result of
anaerobIc metabolIsm.

9
|ost omItted all reference to the metabolIc derangements and few IndIcated there was a catabolIc
state wIth Increased Clucagon and other counterregulatory hormones.
A large number of candIdates faIled to mentIon InsulIn lack, and most dId not mentIon
gluconeogenesIs at all. 0KA Is not just severe hyperglycaemIa as many suggested. Nor does It occur
In Type 2 dIabetIcs.

CandIdates should not use terms they do not know the meanIng of e.g. Dsmolar Cap (whIch does
not Increase wIth hyperglycaemIa alone). The osmotIc dIuresIs Is largely due to glucose not ketones
although they may contrIbute somewhat.

0ehydratIon does not cause hyponatraemIa unless there Is concurrent loss of hypernatraemIc fluId
or replacement of sodIumcontaInIng fluId wIth water. n 0KA the commonlyseen abnormalIty Is
pseudohyponatraemIa.

UESTIDN 12 0escrIbe the physIoIogIcaI changes that occur In respIratory functIon
durIng pregnancy.


|aIn PoInts expected for a pass:

A brIef mentIon of reasons for the changes hormonal, mechanIcal and Increases In
metabolIc demand
Changes In lung volume and capacItIes
AlteratIons In ventIlatIon - what causes the Increase, how It Is medIated and what are the
effects (eg. fully compensated respIratory alkalosIs)
ncreased metabolIc demand - the magnItude of the Increase and how the body adapts to
meet the demand
AnatomIcal changes
Some mentIon of the extra stress on the respIratory system resultIng from labour

AddItIonal poInts could be gaIned for:
ClInIcal sIgnIfIcance of the changes
Changes In the hypoxIc ventIlatory response curve and CD
2
ventIlatory response curve
8lood gases In pregnancy
|entIon of changes In extractIon ratIo
0IscussIon of work of breathIng In pregnancy
0ead space changes In pregnancy
Changes to the haemoglobIn oxygen dIssocIatIon curve
0yspnoea of pregnancy

Common problems:
llegIble handwrItIng
Lack of structure when answerIng the questIon
Changes In aIrway resIstance were poorly understood wIth wIde varIatIon In answers
Few candIdates mentIoned the changes that occur durIng labour
The role of relaxIn In medIatIng changes In the respIratory system was often overstated
naccurate terms were common such as 'total lung volume', 'functIonal resIdual volume'
The maIn reason for faIlIng thIs questIon was a faIlure to demonstrate factual knowledge.

10
UESTIDN 13 0escrIbe the productIon of cerebrospInaI fIuId, Its roIe and Its fate.


To pass thIs questIon, candIdates were expected to answer all parts of the questIon: the
productIon, the role, and fInally the fate of CSF. ThIs questIon requIred recall of factual
InformatIon.
|ost candIdates who faIled to pass thIs questIon eIther answered only some parts of the questIon,
or had factual errors In theIr answers.

Dnce the factual InformatIon was demonstrated, further marks were obtaIned for clInIcal
applIcatIons of the physIology of CSF relevant to anaesthesIa and crItIcal care medIcIne.

UESTIDN 14 0escrIbe the pathways whereby myocardIaI IschaemIa may be
experIenced as paIn In the throat or arm regIons.


ThIs questIon was generally very poorly answered. A sIgnIfIcant number of candIdates dIdn't answer
the questIon at all (blank answer booklets) and a number of candIdates wrote only 1 - 2 lInes.
A number of candIdates descrIbed myocardIal work or the components of cardIac output.
Cood candIdates gave a defInItIon, descrIbed the embryologIcal derIvatIon, why paIn Is referred
and descrIbed the correct pathways Involved from stImulus, paIn receptors and the end poInt as
paIn.

Dnly a very few candIdates descrIbed the correct nerve roots Involved. A number descrIbed the
sympathetIc chaIn.

UESTIDN 15 0escrIbe how the kIdney estabIIshes the meduIIary concentratIng
gradIent.


The maIn poInts that needed to be addressed for a pass Include:

1. the Loops of Henle wIth theIr water permeable descendIng part and water Impermeable
ascendIng part whIch actIvely removes solute from the tubule lumen - the counter current
multIplIer system
2. the vasa recta whIch are parallel to the Loops of Henle and permeable to water and solute
wIth low flow, whIch allows the gradIent to be maIntaIned - the counter current exchange
mechanIsm
J. the role of urea whIch Is concentrated In the medulla by mechanIsms whIch Involve changes
In permeabIlIty to urea In dIfferent regIons of the tubules partly Influenced by the effects of
antIdIuretIc hormone.

Areas whIch created problems for a number of candIdates Included (1) the fact that the medullary
gradIent refers to a gradIent down the medulla In the InterstItIal fluId rather than between the
tubules and the InterstItIum (2) The correct use and relevance of the terms "counter current
exchange" and "counter current multIplIer" (J) The role of urea (whIch Is descrIbed wIth some
dIfferences In detaIl In the texts) was often overlooked (4) the detaIls of whIch sectIons of the Loop
of Henle were water permeable and whIch were not and where actIve solute resorptIon occurred.
11
UESTIDN 16 0Iscuss the physIoIogIcaI causes of earIy post-operatIve hypoxaemIa.


For a pass candIdates were expected to defIne hypoxaemIa, IndIcate normal values of PaD2, and
explaIn the sIgnIfIcance of hypoxaemIa. They were expected to dIscuss the PHYSDLDCCAL causes
of hypoxaemIa and thIs Is most easIly done usIng a classIfIcatIon

PhysIologIcal causes of hypoxaemIa can be broken down Into:
1. Low InspIratory oxygen for the needs for the patIent
2. HypoventIlatIon (eg 2 paIn, respIratory depressIon)
J. 7/Q scatter or mIsmatch (areas low ventIlatIon cf perfusIon eg atelectasIs vs loss of areas
wIth hIgh perfusIon cf ventIlatIon eg sIgnIfIcant hypotensIon)
4. ncreased Dxygen consumptIon (eg fever, shIverIng)
5. 0IffusIon barrIer (whIch plays very lIttle part In healthy patIents).

8etter answers Included:
An IndIcatIon of apprecIatIon of the sIgnIfIcance of these values, Ie the begInnIng of
the "slIpperly slope" of the haemoglobIn dIssocIatIon curve.
Common mIstakes / omIssIons:
ThIs was NDT a questIon about tIssue hypoxIa, and no marked were allocated for
dIscussIons regardIng stagnant hypoxIa, etc.

ExplanatIons regardIng 7/Q scatter were often dIsjoInted and Incomplete. Causes of dead space
and shunt were often confused. Pulmonary embolI result In areas of no blood flow and therefore
physIologIcal dead space (not shunt).

Few candIdates IndIcated how the value of PaD2 decreases In healthy agIng.

Few candIdates IndIcated that hypoventIlatIon and 7/Q scatter are the major causes of low PaD2.


PHYSl0L0CY T0PlCS:

Cardovascular
0escrIbe a 7alsalva manoevour
FestIng D
2
consumptIon
C7P and StarlIng's law of the heart
FunctIons of the cIrculatIon
nterpretatIon of PCWP
0etermInants of myocardIal oxygen supply and demand
Coronary sInus oxygen saturatIon
Factors affectIng pulmonary vascular resIstance
FelatIonshIp between electrIcal and mechanIcal events In the heart
Fesponse to an acute 20 blood loss
Substances released by endothelIum
0etermInants of oxygen flux
Compare arterIal waveform centrally and perIpherally
12
Pressurevolume loop for left ventrIcle
0etermInatIon of CD
Causes of InterstItIal oedema
ActIon potentIal for SA and A7 nodes
Effect of sympathetIc blockade on cardIovascular system
0etermInatIon of S7F
FelatIonshIp between C7P trace and ECC
Changes In cardIovascular system wIth agIng
Compare pulmonary and systemIc vasculatures
Effects of PP7 on cardIovascular system

Resratory
Alveolar gas equatIon
Effects of ascent to altItude
ClosIng capacIty
7enous admIxture
0Ifferences between arterIal and venous gases
Compare the apex and base of the lung In standIng patIent
FunctIons of FFC
ComplIance
Flowvolume loops
Control of breathIng
Phases of a capnogram
Dxygen utIlIsatIon In the body
CarrIage of CD
2

|easurement of dead space
|easurement of FFC
|easurement of shunt
Effects of varyIng 7/Q ratIos
HaemoglobInoxygen dIssocIatIon curve

Renal/Flud 8 Electrolytes
Fenal handlIng of metabolIc alkalosIs
Water homeostasIs
Normal values of F8F/CFF
0efIne osmosIs
Fenal compensatIon for respIratory acIdosIs
0efInItIon of pH
0etermInants of capacIty of a buffer

Haematoloyy/lmmunoloyy
Contents of a unIt of packed cells
PreventIon of clottIng In cIrculatIng blood
Control of fIbrInolysIs
ClassIfIcatIon of hypersensItIvIty reactIons
|echanIsm of anaphlaxIs

Castro-ntestnal/Lver
CastrIc acId productIon
0etermInants of gastrIc emptyIng
Factors affectIng lower oesophageal tone
FunctIons of the lIver
13

Metabolsm/Endocrne
0IgestIon/absorptIon of carbohydrate
Effects of 48 hour fast
0efInItIon of basal metabolIc rate
Clucose/fat utIlIsatIon
ClassIfy hormones and theIr mechanIsms of actIon

Measurement
Waveforms of EEC
Pressure measurement devIces
Pulse oxImetry
0ampIng In resonant systems
CalIbratIon of arterIal lInes
Capnography
HumIdIty

Foetal/Placenta/Neonatal
Dxygen delIvery to foetal braIn
FunctIons of the placenta

Muscle
Stretch reflex
0Ifferences between skeletal and smooth muscle

Pan
SpInal modulatIon of paIn
Pathways for perIpheral paIn transmIssIon

0r. C Noonan
ChaIrman, PrImary ExamInatIon CommIttee
10/07 11.1.2.2

Australian and New Zealand College of Anaesthetists
ABN 82 055 042 852

EXAMINATION REPORT


JULY/AUGUST 2007

of training with information about the way in which the performance of candidates in the recent
appropriately for future examinations. The individual reports are not intended to represent
model answers nor imply that all points mentioned are necessary in order to achieve a pass. All
trainees are urged to read the questions carefully and answer the question asked. All teachers
and supervisors of training are encouraged to discuss this report in detail with candidates they





QUESTION 1 Describe the adverse effects that may occur with the administration of
desflurane.


Answers formulated around the adverse effects of desflurane on various organ systems achieved
most marks. Marks were not awarded for provision of pharmacokinetic data and structural
formula. Discussion of the need for a special vaporiser because of desflurane's low boiling point
was correct but did not answer the question.

It was important to mention basic physiological changes and not focus on the unique adverse
effects of desflurane. For instance virtually all answers mentioned desflurane's pungency but
many failed to discuss its respiratory depressant properties. A reduction in minute ventilation is
manifested by reduced tidal volume and increased respiratory rate. Many mentioned tachycardia
with increased inspired concentrations of desflurane but only a minority correctly teased out
cardiovascular changes. Volatile anaesthetic agents typically result in cerebral vasodilaltion with
a rise in ICP. In this regard desflurane is no exception though changes are less significant. Many
answers however stated that ICP falls with desflurane. Carbon monoxide production from carbon
dioxide absorbents was mentioned by most but only half correctly stated that desflurane is a
trigger for malignant hyperthermia.

- 2 -
Other points for a complete answer were hepatotoxicity, minor renal effects, uterine relaxation
and activation of the sympathetic nervous system with rapid increases in desflurane
concentrations.

QUESTION 2 Outline the important pharmacological considerations when stopping
warfarin and commencing prophylactic (low dose) low molecular weight
heparin (LMWH) in the peri-operative period.


Candidates generally performed poorly on this question. Often mainly warfarin or LMWH were
discussed with little discussion of the other drug. Unfractionated heparin was frequently
discussed.

Better answers included an introduction outlining the issues of balancing the risks of thrombo-
embolism Vs bleeding and a summary of the relevant pharmacology of warfarin and LMW
heparins. An outline of the relevant pharmacology is summarised below. This degree of detail
was not required for a pass. The summary is provided to assist candidates with future exam
preparation.

Warfarin
Long acting agent, inhibits Vit K reductase production of Factors 2,7,9,10,Protein C,S
Metabolised in liver, low clearance, T 1/2 40 hrs
Thus clearance of warfarin and resynthesis of new factors 2,7,9,10 required for offset
Approximately 3-5 days required for offset
Warfarin action potentially prolonged in;
Decreased warfarin metabolism- liver impairment, cytochrome inhibition e.g. amiodarone,
fluconazole, metronidazole
Decreased synthesis of clotting factors- liver impairment, Vit K deficiency, cephalosporins
Check INR day before surgery
Small dose Vit K, e.g. 1mg can reverse but potential problems with warfarin effect post op
FFP will reverse but risk with blood products
Recommence after surgery when minimal risk of surgical bleeding
May be initially hyper coagulable due to inhibition of protein C,S (endogenous anticoagulants),
thus continue LMWH until INR therapeutic

LMWH
Activates anti-thrombin 3, inhibits factors 10 and 2 but much greater inhibition of Factor 10
Commence 2-3 days after warfarin ceased
Predictable and reliable, doesnt require monitoring, once daily administration due to longer
T1/2 compared to heparin
S.C admin, high bio-availability, at home administration feasible
Prophylactic dose enoxaparin 40 mg daily, dalteparin 5,000 units daily
Decrease dose in renal impairment, renally excreted
Last prophylactic dose minimum of 12 hours before surgery, neuraxial blockade

QUESTION 3 Outline the important pharmacological considerations concerning
choice of opioid and dosage when converting from intravenous
morphine to oral opioid analgesia in the post-operative period.


The question asked about the science behind our choice and dosage of oral opioids. The other
information in the question was that the patient had been on intravenous morphine in the post-
operative setting.

- 3 -
Good answers covered the rationale of what drugs we use, how and when we use them and why.
Patient factors included the fact that acute pain is usually diminishing, the importance of the
oral route and gut function returning, patient illness, type of surgery, age and previous opioid
use.

Dosage of the drugs can be calculated from intravenous morphine requirements in the previous
period, usually using a prn (as required) dosing schedule and erring on a lower conversion dose
and longer dosing interval for safety. Use of adjuvant drugs such as paracetamol and NSAIDs
reduces the dose of opioid and use of sedative drugs increases the risk of side effects such as
respiratory depression.

Many candidates answered the question using a template; Pharmaceutics / Pharmacokinetics /
Pharmacodynamics. In many cases it was possible to change the word opioid to any other drug
and still have a correct statement. However, if this did not answer the question, no marks were
awarded.

QUESTION 4 A new test called the intubation score has a reported 90% sensitivity
and 70% specificity when used to predict difficult intubation. Describe
how this information and other statistics related to this test can be used
in predicting difficult intubation. How will the incidence of difficult
intubation affect the performance of this test?


This question asks candidates to apply knowledge of statistical analysis related to screening
tests. It guides the candidates to discuss intubation score in relation to reported sensitivity
and specificity and asks how disease incidence effects test performance.

Answers that provided definitions of sensitivity, specificity, positive and negative predictive
values with reference to predicting difficult intubation and described the relationship between
incidence and testing achieved a pass.

This was most easily achieved through reference to a contingency table, which highlighted
possible outcomes of diagnostic testing. Clarification of each cell in the table attracted marks,
for example the situation of positive prediction in the presence of difficult intubation being
described as a true positive. Finally a definition of incidence and its influence on positive and
negative predictive value was needed.

Errors that were evident included confused, incomplete answers and answers that did not make
reference to the scenario of difficult intubation. Some were answered incompletely or the
question was misinterpreted.

QUESTION 5 Describe the factors which increase the risk of systemic toxicity with
amide local anaesthetic agents.


The focus of this question was on CVS and CNS toxicity related to excessive serum plasma levels
of drug.

Successful candidates structured their answers along pharmacokinetic and pharmacodynamic
factors. Concise descriptions of pharmacokinetic factors such as dosage limits, site of
administration and rate of administration vs clearance were expected. There appeared to be
confusion regarding how pH/pKa applied to toxicity. Marks were awarded for describing how
weakly basic drugs with a high pKa would become more ionized and potentially trapped in
- 4 -
acidic environments. This would exacerbate myocardial toxicity in cardiac arrest or other causes
of acidosis.

At times, the role of plasma protein binding was not clearly explained. Reductions in plasma
protein binding via displacement or reduced production would have greater proportional effects
on the unbound levels of highly protein bound drugs. The role of changes in volume of
distribution was commonly omitted. This would apply in situations such as cardiac failure or the
elderly. Succinct descriptions of why certain amides had greater risk of toxicity were expected,
e.g. Na channel affinity, lipid solubility, duration of action, lack of vasoconstrictive properties.
Commonly, there was confusion between amide and ester local anaesthetics.

Marks were awarded for descriptions of a scale of toxicity vs. specific plasma levels and relating
it to CVS:CNS toxicity ratios, but general descriptions of local anaesthetics and their mode of
action did not accrue any marks.

Extra marks were awarded for describing the role of isomers, specific drug interactions, and the
role of various physiological factors (pregnancy, neonate, elderly) and pathological factors
(tachycardia, electrolyte disturbances, hypoxia, hypercarbia).

QUESTION 6 Describe how suxamethonium produces neuromuscular blockade. What
is the mechanism of recovery of neuromuscular function and what
mechanisms may be involved in Phase II block?


In general this question was well answered. In order to gain maximum marks it was important
that candidates specifically answered the three parts of the question i.e. mode of action,
mechanism of termination of effect and the mechanism of Phase II block.

Most candidates explained the salient features of the ion channel comprising the Ach receptor at
the neuromuscular junction (NMJ) and the role of the alpha sub-units. There was some confusion
as to why the post-junctional membrane remained resistant to further depolarization by Ach, but
most correctly stated that this is because it remains in a continual state of suxamethonium
induced inactivation. With regard to termination of action the main error was to suggest
metabolism of suxamethonium by pseudocholinesterase at the NMJ. Pseudocholinesterase is not
found at the NMJ - the main route of termination of action is simple diffusion away from the NMJ
into the plasma following its concentration gradient. With regard to the mechanism of Phase II
block it is acknowledged that this cant be stated with certainty. However, the recommended
texts suggest at least four mechanisms that could be involved and points were awarded for
mentioning any of these. Unfortunately many candidates spent a great deal of time writing
about how a Phase II block can be produced clinically and the means by which it can be
identified using the nerve stimulator.

QUESTION 7 Outline the mechanisms of action and potential adverse effects of the
oral hypoglycaemic agents.


A discussion of the two main groups and their side effects achieved a pass. Sulphonylureas act at
potassium ATPase ion sensitive channels in the beta cells resulting in depolarisation and
increased calcium concentration which causes increased insulin release. The biguanides
decrease hepatic and renal gluconeogenesis, decrease glucose absorption from the gut and
increase glucose uptake.

Side effects were well described. The propensity for hypoglycaemia will vary amongst
sulphonylureas depending on their clearance and site of metabolism along with liver or renal
- 5 -
pathology. The basis of lactic acidosis with biguanides needed some mention of the action of the
drugs at mitochondrial membranes and the increased risk in renal, hepatic impairment and
states of decreased perfusion. Other points worth mentioning relate to the degree of protein
binding with resultant displacement of other highly bound drugs e.g. warfarin and the potential
for altered drug activity, some agents cross the placenta causing fetal hypoglycaemia and the
theoretical potential for inhibition of ischaemic and pharmacological pre-conditioning with
sulphonylureas.

Many candidates outlined the mode of action and side effects of the meglitinindes and
thiazolidinediones. They were rewarded for their knowledge.

QUESTION 8 Write short notes on anti-hypertensive drugs that exert their action via
blocking the effects of angiotensin.


The core answer required a brief account of the two main classes of drugs (angiotensin
converting enzyme inhibitors and angiotensin receptor blockers) that block the effects of
angiotensin, including their mechanism of action, clinical use, side effects and essential
differences between the two classes of drugs.

There was a very broad spread of marks. This was the last question in the exam and a number of
candidates gave very brief answers. Some candidates also gave detailed accounts of the
physiology of the renin-angiotensin system without explaining how or where in the system these
drugs work or what their effects are. Vague statements such as, side effects include electrolyte
disturbances, the drugs decrease BP without explaining how, that the drugs have differing half
lives or the drugs cause ventricular remodelling without explaining when this is useful do not
contribute much to answers. The most frequent omission was any account of when these drugs
are used clinically.


General topics
Pharmaceutics; thiopentone, lignocaine, propofol, solubility, emulsions
Pharmacokinetics; absorption, bioavailability; hepatic clearance; renal drug handling,
pharmacokinetic modelling, clearances, volumes of distribution, context sensitive half
time, variability with age
Tolerance
Hepatic biotransformation
Dose response

Inhalational agents
Induction kinetics
Recovery
Washout curves
Inhalational depth
Measurement of depth
MAC; MAC awake
Structure-activity relationships
CNS effects
Metabolism, toxicity
Physical properties
- 6 -

Local anaesthetics
Structure activity
Physicochemical properties

Induction agents
Factors affecting induction dose and maintenance infusion rate
Propofol pharmaceutics
Propofol pharmacokinetics
Propofol pharmacodynamics
Mechanisms of action
Ketamine, mechanism of action, pharmacodynamics, adverse effects
Neuropharmacology
Anti-convulsants, classification, mechanisms of action, phenytoin, barbiturate,
benzodiazepine pharmacology
Benzodiazepines, midazolam pharmacology

Neuromuscular blocking agents
Factors affecting clinical choice and dose
Compare rocuronium and vecuronium
Neuromuscular monitoring
Inter-individual variability
Factors effecting onset
Non-depolarisers, mechanism of action
Recovery, drug interactions

Anticholinesterase and anticholinergics
Classification
Mechanism of action
Compare anticholinesterases
Compare anticholinergics

Opioid agonists and antagonists
Classification
Mechanism of action
Receptors
Factors effecting clinical choice and dose
Compare fentanyl, alfentanyl, remifentanil
Tramadol

Pain and NSAIDs
NSAIDs, MOA, classification, adverse effects
Aspirin
COX 2 inhibitors
Paracetamol

Cardiovascular drugs
Anti-hypertensive agents
Catecholamines
Vasopressors
Alpha 2 agonists
Antiarrhythmics; classification, amiodarone, digoxin, adenosine, adverse effects
Drug therapy of myocardial ischemia
Anaesthetic agents and cardiac output

- 7 -
Diuretics
Classification
MOA
Loop diuretics

Drugs and coagulation
Anti platelet drugs, MOA, adverse effects
Aspirin
Clopidogrel
Glycoprotein IIb/IIIa receptor antagonists

Statistics
Data type
Power
Drug development and trials
Selection of appropriate statistical tests
Students T test
Correlation
Evidence based medicine

Obstetric pharmacology
Placental drug transfer
Fetal adverse effects
Tocolytics
Oxytocics; adverse effects

Miscellaneous topics
Drugs and gastric acidity
Metoclopramide
Insulin
Intravenous fluids, clinical choice, pharmacokinetics and dynamics
Serotonin and drug action, serotonin syndrome



QUESTION 9 Briefly explain the cardiovascular responses to central neural blockade.


To achieve a pass, candidates were expected to describe the effects of sympathetic blockade on
arterial and venous vessels, how these lead to a drop in cardiac output and blood pressure, and
compensatory reflexes involving the various baroreceptors and atrial naturetic peptide.
Explanations should have included effects of potential and blockade, and the fact that
venodilation (venous side contain 75% of blood volume) and consequent decreased venous return
is more significant than vasodilation. Many candidates failed to explain why hypotension is more
- 8 -
pronounced with ascending block height, and/or effects seen with blockade of cardio-
accelerator fibres (T1 4).

Additional marks were allocated for explaining:
- Effects of sympathetic blockade at different levels e.g.
Sacral blockade alone little effect as parasympathetic fibres involved only;
lumbar blockade vs high thoracic blockade
high block affecting brainstem;
- Mid-thoracic block and renal compensatory mechanism to increase blood flow via JG cells (and
not an increase in sympathetic outflow from brainstem vasomotor centre as described by a
number of candidates);
- Possible contribution of Bezold-Jarisch reflex;
- Afferent/efferent nerves and central control response of high and low pressure baroreceptors;
- Consequences of age, hypovolaemia.

Answers describing vasodilation were read as meaning arterial dilatation alone.

Detailed descriptions of drugs or techniques used to attain an epidural/spinal block did not
attract marks.

QUESTION 10 Briefly describe the factors that affect the partial pressure of carbon
dioxide in mixed venous blood.


The partial pressure of carbon dioxide in mixed venous blood depends on the carbon dioxide
content of the blood and represents a balance between CO
2
production in the tissues and
content in the arterial blood. Good answers demonstrated an understanding of this and provided
details about these aspects

The partial pressure is related to the content by the carbon dioxide dissociation curve the
position of which is determined by the state of oxygenation of haemoglobin, the Haldane effect.
Carbon dioxide is present in the blood in three forms, dissolved, bicarbonate and carbamino
compounds.

Carbon dioxide production is related to aerobic metabolism in cells and the total production is
defined by the metabolic rate. Production may be increased (e.g. exercise, fever, MH,
pregnancy) or decreased (e.g. anaesthesia, hypothermia).

The partial pressure of carbon dioxide in mixed venous blood is related to the pressure or
content in arterial blood. This is determined by alveolar ventilation and normally controlled by
chemoreceptor and the brainstem respiratory centre.

Other relevant material included definitions of mixed venous blood, normal values, the effect of
temperature and cardiac output.

The most common error was discussing PCO2 without making it clear whether it was venous or
arterial. The Fick equation was often used but required solving for CvCO
2
to demonstrate the
factors or importance to this question.

QUESTION 11 Explain the physical principles of ultrasound imaging.

- 9 -

Main points expected:
Definition of ultrasound and range of frequencies.
Principle of ultrasound genesis, tissue passage and reception (piezoelectric crystal
understanding)
Mention of acoustic impedance (density and sound velocity), reflection (intensity related to
degree of differences in tissue density, latency related to depth).
Appreciation of relationship between velocity, frequency and wavelength.
Ability to correctly describe relationship of wavelength (or frequency) regarding penetration
versus resolution.

Extra marks:
for mention of Doppler mode and correct description of Doppler effect. Doppler equation
was awarded points where the values were correctly explained. Ability to calculate cardiac
output was only credited when the principle behind the calculation using Doppler and M
Mode to calculate area of aortic valve was explained. Simple statements such as Doppler
can be used to measure cardiac output scored no marks.
Definition of attenuation and thus need for gel at air/tissue interface
Understanding that 2D pictures require an array of crystals

Common mistakes:
Incorrect formulas
Incorrect statements such as Doppler is used to measure flow followed by the equation which
is solving for velocity.
M mode is used for 2D or 3 D or 4 D! imaging.
Many candidates spent wasted time listing advantages and disadvantages (not asked for and
not worth any marks). Others spent too much time drawing sine waves with amplitude,
wavelength and frequency and not enough time discussing the relationship between these.

QUESTION 12 Outline the mechanisms by which the kidney maintains potassium
homeostasis.


Main points expected for a pass included an outline of how potassium is handled as the
glomerular filtrate passes along the nephron and a brief appreciation of the mechanisms of
secretion and reabsorption of potassium.

Additional marks were allocated for more detail on the actual cellular mechanisms for secretion
and the cellular processes that are influenced by aldosterone.

The most common reason for not passing this question was the lack of any structure and a
paucity of relevant information. Very few candidates appreciated that reabsorption of
potassium is fixed and that altering potassium secretion is the regulatory process.

Credit was not given for elaborate discussions of the determinates of glomerular filtration or for
detailed descriptions of the systemic control of aldosterone secretion.

QUESTION 13 Outline the physiology of blood groupings that allows O negative blood
to be safely transfused to most patients.
- 10 -


Interpretation:
The question specifically asked about physiology of blood groups
Discussion about type, screening or cross-match were not directly relevant.

Points to be covered:
Statement of aims of transfusion and usual problem of previously formed recipient antibodies
reacting against donor cells, and consequences thereof.
Discussion of ABO system and origin of antibodies.
Discussion of Rh system and origin of antibodies.

Better answers:
Mentioned issue of donor antibodies and recipient cells, other potential antigens and antibodies.

Clarity:
The terms antigen and antibody appeared to be frequently confused.
Sources of antigen and antibody were often unclear.

Errors:
Some candidates essays were unclear about whether groups A,B and O have antibodies.
There are no anti-AB antibodies.
Expression of an antigen is associated with tolerance and prevents development of an antibody.
Anti-A and anti-B antibodies are developed in early childhood and do not require blood exposure.

QUESTION 14 Describe the cardiovascular changes in the neonate that occur at birth.


Interpretation:
The question asked for a description of changes; this potentially allows inclusion of a functional
description, mechanism of change (where known), time course and consequences. Discussion of
changes at birth does not include the gradual replacement of HbF with HbA.

Points to include:
A discussion of the changes as above.

Better answers:
Indicated the above and showed the relevance of the changes.
Included comments about the transitional nature of some changes

Clarity:
Diagrams were often of poor quality, and thus unhelpful.
Information in diagrams was often repeated longhand in written form (gaining no extra marks).
Handwriting was sometimes illegible.

Organization:
Ten minute questions probably don't require planning notes in the margin, nor should summaries
be included, as repetition will not gain extra marks. Highlighting of key points is not part of a
traditional SAQ.

Errors:
- 11 -
Terminology was often loose and the sequence of changes and mechanisms was poorly described.
Confusion in the use of the terms; flow, pressure, resistance and volume was common.
The placenta is NOT the reason that the foetal circulation is described as parallel.
The pulmonary circulation initially has high resistance.
The high negative pressure at inspiration is NOT the direct cause of the fall in PVR.
The ductus arteriosus does not connect the right ventricle to the aorta,
neither does the ductus venosus connect the IVC to the brain.

QUESTION 15 Outline the clinical laboratory assessment of liver function.


This question is taken directly from the syllabus objectives and it was important to have a
structured answer to cover all the main points.

Suggested structure.

1. Synthetic function
1.a. Prothrombin ratio (acute injury)
1.b. Albumin (chronic)
1.c. Bilirubin formation (conjugation / jaundice / haemolysis)

2. Hepatocellular injury
2.a. Aminotransaminases (aspartate / alanine)
2.b. Lactate dehydrogenase
2.c. Cell death releases enzymes

3. Cholestatic
3.a. Alkaline phosphatase (ductal cells / T
1/2
7 days / other sources)
3.b. Gamma-glutamyl-transpeptidase (ductal cells / inducible enzyme/alcohol)
3.c. Unconjugated bilirubin / poorly water soluble

4. Higher marks
4.a. Albumin transport of unconjugated bilirubin
4.b. Albumin loss from other causes
4.c. Plasma concentrations of albumin / bilirubin and jaundice
4.d. Glutathione-S-transferase and centrilobular damage
4.e. Ammonia levels in liver failure

Outline does not mean list and there needs to be a connection between what is measured and
how that changes with liver dysfunction. Clarity about increases and decreases is important
for showing understanding. A simple list of tests was not enough to answer the question and
demonstrate knowledge. Normal plasma concentrations of albumin and bilirubin were
infrequently mentioned and enzyme abbreviations without explanations were common.

Information not relevant to the question includes:

Excessive detail on the coagulation pathway
Hepatic blood flow measurement
Clinical signs of liver failure
Functions of the liver and albumin
Explaining how to perform a laboratory test
- 12 -
Ultrasound investigations

QUESTION 16 Draw and label a lead II electrocardiogram (ECG) tracing for one cardiac
cycle, indicating normal values. What is the PR interval and what
factors influence it?


The answer to this question should include:
1) A diagram of a typical lead 2 ECG trace, with axes, and labels on P, QRS, and T waves, PR
and QT intervals, and ST segments.
2) Quantification of the normal values of duration of PR, QRS and QT interval.
3) Definition and explanation of the significance of the PR interval in particular the
importance of the AV node.
4) A list of factors that increased or decreased the PR interval autonomic system, cardiac
abnormalities/disease (WPW, ischaemia), drugs, other physiological derangements
(hypothermia, hypokalemia)

Additional marks were given for detailed description of cellular mechanisms of changes in the PR
interval and an outline of the allowable normal deviation from isoelectric values of the ST
segment, and size of the Q wave.

Common mistakes made by the candidates included:
1) Inability to quantify the time intervals. These values are essential to the clinical
interpretation of the ECG for the rest of an anaesthetists career.
2) Confusion of milliseconds with seconds was very common.
3) The PR interval was not accurately described it is from the start of the P wave to the
start of the QRS complex (which is usually the Q wave, not the R wave).

PHYSIOLOGY TOPICS:

Cardiovascular
Draw the radial artery waveform.
Gross anatomy of the coronary circulation.
Oxygen consumption of the heart.
Draw a flow vs. time curve for the left coronary artery.
Draw a left ventricular pressure vs. time curve.
Function of the microcirculation.
Draw a Swan-Ganz pressure trace as it floats into position.
Role of the balloon in a pulmonary artery catheter.
Definition of contractility.
Changes that occur with aging.
Definition of afterload.

Respiratory
Physiological effect of a pneumothorax.
Determinants of arterial PCO2
Determinants of the work of breathing.
Changes associated with high altitude.
Alveolar gas equation.
Draw the oxygen cascade.
- 13 -
Draw a spirometer trace.
Draw a pressure vs. time curve for a ventilated patent.
Consequences of apnoea.
Definition of compliance.
Draw a capnogram trace.
Draw an expiratory flow-volume curve.

Renal/Acid-base
Definition of GFR.
Definition of an acid.
Renal resorption of bicarbonate.
Range of urine osmolarity.
Functions of the kidney.
Value for renal blood flow.

Measurement
Calibration of an arterial line.
Justify the use of pulse oximetry in anaesthesia.
Difference between heat and temperature.
Definition of pressure.
Units of pressure.

Nervous system
Normal values of ICP.
Normal values of cerebral blood flow.
Examples of excitatory neurotransmitters.
Value of the resting membrane potential.

Haematology
Processing of a unit of donated blood.
Role of platelets in haemostasis.

Pregnancy
Physiological effects of pregnancy.

Endocrine
Iodine utilisation

Pain
Pathways associated with a painful stimulus.

Immunology
Functions of the immune system

Cellular physiology
Role of oxygen in the body.
Process of protein synthesis

Integrated physiology
- 14 -
Physiological effects of obesity

Dr N. Roberts

Chairman, Primary Examination Committee

ABN 82 055 042 852
EXAMINATION REPORT
FEBRUARY/APRIL 2007

supervisors of training with information about the way in which the performance of
candidates in the recent examination was assessed by the examiners, so that candidates
and teachers may prepare appropriately for future examinations. The individual reports
are not intended to represent model answers nor imply that all points mentioned are
necessary in order to achieve a pass. All trainees are urged to read the questions
carefully and answer the question asked. All teachers and supervisors of training are
encouraged to discuss this report in detail with candidates they are preparing for future
examinations.
________________________________________________________________________________

PHARMACOLOGY WRITTEN SECTI ON


QUESTION 1 Describe the potential adverse effects of administering neostigmine post
operatively.


This question examined the pharmacology of neostigmine, a drug that is being used in anaesthesia on a
daily basis. An adequate description of adverse effects was therefore expected for candidates to obtain
a pass mark.

The main points should include a discussion on the accumulation of acetylcholine at muscarinic (at
low dose) and nicotinic (at higher dose) receptor sites after administration of neostigmine. The
muscarinic effects are severe and hence the co-administration of antimuscarinic agent is important.
The most worrying adverse effects are bradyarrhythmia with hypotension. Bronchoconstriction,
salivation, tracheobronchial hypersecretion, postoperative nausea and vomiting, and enhanced
peristalsis (and potential damage on bowel anastomosis) should be mentioned.

- 2 -
Additional marks were awarded for including potential drug interaction with suxamethonium and
mivacurium. Marks were also awarded for depolarizing block after excessive doses of neostigmine. No
credit was given for description of neuromuscular monitoring.

QUESTION 2 After epidural injection in a health term pregnant woman, discuss the
factors influencing the distribution of bupivacaine to (a) the maternal CSF
and spinal cord; (b) the maternal circulation; (c) the foetus.


The main points expected for a pass included a discussion of the factors affecting diffusion as
described in Fick's Law and how these pertained to the three diffusion interfaces outlined in the
question.

Solubility, ionization, tissue and protein binding, amount of drug, and concentration gradient all affect
the distribution of bupivacaine from the epidural space to the CSF and maternal systemic circulation,
and subsequently to the foetus. Demonstration of comprehension that there are physiological
differences between these four compartments and how these determine bupivacaine's distribution was
expected. Additional marks were awarded for the consequences of the addition of adrenaline or
bicarbonate to the bupivacaine solution, a discussion on epidural depot of drug, the biphasic nature of
systemic absorption and foetal acidosis effect on bupivacaine protein binding.

Common errors included discussing elements of bupivacaine that were not requested; such as drawing
its structure or a pharmacodynamic discussion of its toxicity. Also, reproducing factual information,
such as the pKa of the drug, without discussing how this affects its diffusion at the three interfaces, did
not attract marks.

QUESTION 3 Discuss factors contributing to inter-individual variability in the
therapeutic response to opioid analgesic medications.


A structured approach was expected dividing the issues along pharmacokinetic / pharmacodynamic
lines. A patient factors approach or other structure was also acceptable. The discussion was expected
to relate the underlying factors to opioid analgesics. The question was specifically related to inter-
individual variability and a simple discussion of mechanisms of action or side effect profiles for
varying opioid agents scored no additional marks.

Candidates were expected to outline that variability can be seen in areas of absorption, distribution,
metabolism and elimination of these agents. Credit was given to candidates who outlined the potential
impact of liver or renal disease with specific examples. The discussion would also include the impact
of factors such as age, pregnancy, coexisting medical disease or concurrent medication use. Discussion
of genetic influences on enzymes and receptors was expected and was well covered by most
candidates. Discussion of tolerance, prior drug exposures and previous pain experiences in influencing
individual responses attracted extra marks.

QUESTION 4 Discuss the suitability of ketamine as a total intravenous anaesthetic agent
in comparison with propofol.


To reach a pass standard simple, relevant information on the pharmacokinetics and the neurological,
cardiovascular and respiratory pharmacodynamics of both agents was sufficient.

- 3 -
Almost no candidates explained that ketamine is an effective, sole anaesthetic agent used widely in
unsophisticated medical settings, nor the relevance of its particular pharmacodynamic properties in this
situation. Many candidates understanding of total intravenous anaesthesia was limited to the use of
propofol with pharmacokinetic model driven infusion pumps.

Frequently the "comparison" aspect of the answer was not well organized. Answers using parallel
columns for each agent's features were generally more complete in their comparisons. In contrast,
poorly laid out answers were also more likely to focus predominantly on either kinetic or dynamic
features, and to commonly have incomplete comparisons between the two drugs.

QUESTION 5 Classify non-opioid drugs used for the treatment of neuropathic pain and
indicate proposed mechanisms of analgesic action and potential adverse
effects.


The key to successfully dealing with this question was to address each of the three components:
classification, mechanisms, and adverse effects. The main points expected were a classification system
that was coherent; for example: simple analgesics, anticonvulsants, antidepressant, membrane
stabilizers and so on. Proposed mechanisms of action should have included how the drugs work, and
(importantly) why this reduces pain. There are many drugs that can be used and there are many
potential adverse effects. For this component of the question, emphasis on the more specific drugs (e.g.
anticonvulsants and antidepressants), and on specific (e.g. anti-cholinergic effects with
antidepressants) rather that generic (e.g. rash, gastrointestinal upset) adverse effects, were rewarded.

No marks were awarded for a definition of chronic pain, a description of the pathophysiology of
chronic pain, or nonpharmacological therapies as these were not asked.

QUESTION 6 Briefly outline the acute management of malignant hyperthermia (during a
relaxant general anaesthetic). Describe the important aspects of dantrolene
pharmacology relevant to treating malignant hyperthermia.


Equal marks were devoted to each half of the question. Inclusion of the following points would have
scored a good pass mark.

Management: life-threatening emergency, call for help and dantrolene, cease triggers (e.g. volatile
agents), hyperventilate with oxygen, maintain anaesthesia with non-triggering agents, give dantrolene
2.5 mg/kg, repeat up to 10 mg/kg, active cooling to <38 degrees.

Pharmacology: skeletal muscle relaxant presented as orange powder containing dantolene 20 mg,
mannitol 3g and sodium hydroxide to bring pH >9 with 60mls water. Difficult to mix. Metabolized by
liver enzymes, eliminated in urine and bile with a half-life of about 10 hrs. Inhibits calcium release
from sarcoplasmic reticulum. It can cause phlebitis, use of verapamil contraindicated.

Most candidates who did not achieve a pass mark wrote very little on dantrolene pharmacology. Many
candidates gave long, detailed accounts of the etiology and pathology of malignant hyperthermia but
this was not asked in the question and attracted minimal bonus marks.

QUESTION 7 Describe the pharmacology of midazolam including its mechanism of
action.

- 4 -

Better answers were well organized and outlined the important aspects of midazolam pharmacology
including:

Pharmaceutics, pH dependent ring opening, ampoule pH
Pharmacokinetics, administration, oral bio-availability, high lipid solubility and moderately fast
onset, moderate hepatic clearance 7 mls/kg/min approx (cf diazepam), active metabolite, offset
dependent on re-distribution and clearance, relatively short elimination half life
Mechanism of action (MOA), benzodiazepine receptor on alpha subunit of GABAa receptor,
enhanced action of GABA, increased chloride entry and neuronal hyper-polarization
CNS effects, sedation, hypnosis, anxiolysis, amnesia, anti-convulsant, muscle relaxant
CVS effects, hypotension, vaso-dilatation
Respiratory effects, respiratory depression, potential airway obstruction, hypoxemia, interaction
with opioids
Clinical uses, pre-medication, sedation, induction agent, anti-convulsant, antagonized by
flumazenil

Extra marks were awarded for an outline of; kinetics of offset including context sensitive half time,
metabolism and excretion including CYP 3A4 and accumulation of metabolites, the GABA receptor
and alpha sub-unit selectivity, effects on cerebral blood flow, oxygen requirements and the EEG,
factors potentiating CVS and respiratory effects, dosages for particular clinical applications and
clinically important structure activity.
Common errors included; not mentioning MOA, describing MOA as direct activation of GABA
receptor, describing NMDA or cyclic AMP effects, frequent citing of very inaccurate kinetic data with
no mention of clinical implications and frequent omission of adverse effects.

QUESTION 8 List the classes of drugs used clinically to treat chronic left ventricular
failure. Outline their mechanisms of action.


Only 32% of candidates complied with the first part of the question, to LIST the classes of drugs used.
In order to satisfy the requirements of this question, candidates need to relate facts about drugs to their
mechanisms of action. Many answers included a definition of heart failure then attempted to relate the
benefits of classes to this, however since no mention was made of diastolic dysfunction, many
responses were incomplete. It was common for candidates to outline the effects of an agent but not
describe the mechanisms of those effects or their consequences. This information needs to be explicit.
Thus many failed to acknowledge the influence of renin and how its levels are affected by different
agents (eg. beta blockers). Most candidates gave the mechanism of action for the management of
myocardial ischaemia for nitrates and beta blockers; while this is often relevant, it is not the prime
therapeutic goal for these agents in heart failure. Beta blockers are not used to achieve a decrease in
cardiac output. Pre- and after load were frequently confused with few candidates mentioning Starling
curves. Although this question related to chronic failure, many candidates discussed drugs typically
used for acute systolic dysfunction. Credit was given for a description of digoxin and its benefits in
atrial fibrillation and other after-load reducing agents including prazosin and hydralazine.

- 5 -
PHARMACOLOGY TOPICS/INTRODUCTORY QUESTIONS:

General topics
Pharmaceutics; thiopentone, local anaesthetics, benzodiazepines
pharmacokinetic modelling, clearances, volumes of distribution, AUC
Concentration-time curves
Hepatic biotransformation
Mechanism of drug action
Dose response
Pharmacogenetics
Drugs and gastric acidity
Treatment of poisoning
Chemotherapeutic agents, adverse effects, drug interactions

Inhalational agents
Induction kinetics
Recovery
Washout curves
Inhalational depth
Measurement of depth
MAC; MAC awake
CVS effects
Children and adults, kinetic, dynamic differences

Local anaesthetics
Structure activity
Pharmacokinetics
Toxicity, factors affecting toxicity, toxic doses
Cocaine toxicity
Topical anaesthesia

Induction agents
Thiopentone

Neuropharmacology
Anti-convulsants
Phenytoin
Benzodiazepines

Classification
Atracurium, cisatracurium
Isomers
- 6 -
Recovery from neuromuscular blockade
Potency
Suxamethonium; dose response curve, side effects

Mechanism of action
Receptors
Effect site concentration
Tramadol

Classification
Drug interactions and myasthenia gravis
Scopolamine, atropine

Drugs that increase blood pressure
Catecholamines
Vasopressors
Alpha 2 agonists
Antiarrhythmics; classification, lignocaine, amiodarone
Beta blockers
Anaesthetic agents and cardiac output
Nitric oxide
Vasodilators; GTN and SNP

Diuretics
Classification
MOA
Mannitol

Respiratory pharmacology
Anti-asthma drugs
Nitric oxide

Unfractionated heparin, low molecular weight heparin
Warfarin
Antiplatelet drugs
Protamine

Pain
Oral analgesics
Bio-availability
Paracetamol

Statistics
Data
- 7 -
Power
Bias
Regression, correlation
Drug development and trials
Confidence intervals
NNT

Endocrine
Insulin
Corticosteroids

Tocolytics
Magnesium, salbutamol

Antiemetics
Clinical effectiveness
Adverse effects
5HT3 antagonists, ondansetron, tropisetron
Dexamethasone

- 8 -


QUESTION 9 Define Venous Admixture. Briefly explain how venous admixture
influences arterial oxygen tension and how an increase in inspired oxygen
concentration may effect this.


Main points expected for a pass included: definition, sources of venous admixture with brief
description of each, appreciation that venous admixture is a concept which may be expressed by the
shunt equation, statement of effect on PaO2 of venous admixture with reference to the
oxyhaemoglobin dissociation curve (demonstrating relation of oxygen tension to haemoglobin
saturation), and the effect of increased inspired oxygen concentration on venous admixture.
Additional marks were allocated for more detail with respect to sources of venous admixture (e.g.
relative contribution, magnitude effect), demonstration that small and large amounts of venous
admixture affect PaO2 differently, explanation of relative effect of high versus low V/Q units,
reference to isoshunt diagram and quantifying effect of increased inspired oxygen.
Mistakes commonly made included: imprecise or interchangeable use of terms (e.g. oxygen content for
PaO2 and shunt or mixed venous blood for venous admixture); and use of oxyhaemoglobin
dissociation curve to justify arguments regarding the effect of increased PaO2 on oxygen content.
Credit was not given for vague, non-directional statements of effect, or for discussion of carbon
dioxide or factors which affect mixed venous PO2.

QUESTION 10 Explain the mechanisms that prevent blood clotting in intact blood vessels
(do not draw the clotting cascade).


For a pass, an understanding of the balance between pro and anticoagulant processes that occur in the
blood, and a brief outline of the mechanisms that prevent blood from clotting was required. Candidates
who followed the structure of Virchows triad to elucidate these factors tended to score well by
demonstrating understanding.

Many candidates would have benefited by providing a clear introductory statement, outlining the
balance between pro and anticoagulant factors, and then explaining the factors that prevent
coagulation.

As general advice regarding examination technique, candidates may wish to consider that if confronted
by a question that they may not have considered in preparation for the examination, by considering the
basis of everyday clinical practice, they may yet be able to achieve a good score. In this case, common
clinical practices for prevention or perioperative deep venous thrombosis may have provided the key to
an answer.

- 9 -
QUESTION 11 Discuss how the body handles a metabolic acidosis.


The main points to be covered were a definition of a metabolic acidosis, discussion of extracellular and
intracellular buffering systems, respiratory compensation, the renal mechanisms to excrete non-volatile
acids (titratable acidity, ammonium and ammonia), and resorption and regeneration of bicarbonate.

Extra marks were awarded for the mechanism of respiratory compensation, explaining that respiratory
compensation does not lead to acid excretion, description of buffering by long as well as short term
mechanisms, specific details of ammonia and ammonium production and bicarbonate regeneration,
understanding that H
+
ions can not be excreted unbound, the amount of acid that can be excreted by
different renal mechanisms, and aldosterones effect on H
+
excretion.

QUESTION 12 Explain the physiological principles underlying the use of peritoneal dialysis
in a patient with chronic renal failure with this dialysate solution.

Na 132 mEq/L Mg 0.5 mEq/L
K 0 mEq/L Lactate 40 mEq/L
Cl 96 mEq/L glucose 2.5 g%
Ca 3.5 mEq/L


The purpose of this question is to show an understanding of basic physiological principles involved in
peritoneal dialysis and not its clinical applications or indications.

The main points expected for a pass were:
PD takes places across a membrane (peritoneum) by exchange between dialysate and the patients
blood.
The main processes are:
a) Osmosis - movement of solvent from low to high solute concentration
b) Diffusion movement of solute from region of high to low concentration
c) Solvent drag

Definitions of these processes were required. Many candidates showed a lack of understanding of
these basic processes.

The factors which influence these processes are:
a) movement of solvent
tonicity definition, dialysate is hypertonic mainly due to its hight glucose
concentration, osmolarity approx. 400 mmol/L (2[Na]+0.055 [Glucose]+0.36 [BUN]
b) movement of solute
Ficks law of diffusion
Donnan effect due to effect of charged plasma proteins

Many candidates wasted time on detailed description of what happens to individual solutes at the
expense of explaining the basis physiological principles of diffusion and giving an example e.g. K+

Other points which gained marks:
purpose of PD- i.e. achieve balance of fluids, electrolytes, acid-base and excretion of
toxins wastes
osmosis is a relatively fast process compared to diffusion
glucose absorption can cause hyperglycaemia
- 10 -
lactate is provided for conversion to bicarbonate by the liver helping with acid/base
balance
protein transfer into dialysate can result in loss

QUESTION 13 Describe the determinants of Venous Return and the effect general
anaesthesia would have on these.


In general candidates answered the question fairly well, reflecting an understanding of a physiological
variable of major clinical relevance to anaesthetists.

The most successful approach used to answer this question was to address specific physiological and
anatomical factors, which influence venous return (e.g. blood volume, venous tone, posture). The
inclusion of simple formulae (e.g. VR =MSFP-RAP/RVR, Guytonian model) allowed these factors to
be related to an effect on VR, and readily demonstrated a good comprehension of the issues. Whilst
obvious factors (such as venous tone) were usually mentioned, common omissions included
intrathoracic pressures, venous valves and muscle pumps, all important factors both physiologically
and in a clinical anaesthesia setting.

Guyton curves were used by some candidates. They did illustrate some factors quite well, but for
some candidates the time spent with these curves came at the expense of descriptions of either how
some determinants actually affected VR or ommission of specific determinants such as venous valves
or posture.
Most candidates were able to relate the responses to the first part of the question to the second part
(effects of anaesthesia). Major omissions or errors in answering the first part often carried over into
effects of anaesthesia.

A few candidates provided the answer in table form, with each determinant listed along with its effects
on VR and changes with anaesthesia. Whilst this approach provided succinct answers, it sometimes
proved difficult to describe the net effect of individual determinants using this somewhat abbreviated
format.

QUESTION 14 Explain the mechanisms whereby oxygen transfer is facilitated at the
placenta.


Oxygen passes from the mother to the fetus at the placenta by diffusion. This process is facilitated by a
large number of factors including:

1. The placental structure is designed to facilitate diffusion, best summarised by the factors in
the Fick equation.
2. The increased affinity for oxygen of fetal compared to maternal haemoglobin
3. The increased concentration of fetal haemoglobin.
4. The (double) Bohr effect.

Other factors which could be discussed included the potential role for maternal hyperventilation (with
increased maternal PaO
2
and changes in acid base metabolism) associated with pregnancy and the
(double) Haldane effect (relevant due to the increased carbon dioxide flux amplifying the Bohr
effects).

The commonest difficulties with the question arose from taking too narrow a focus. Many candidates
confining themselves to describing the double Bohr effect almost in isolation, perhaps supplemented
with reference to the differences between fetal and adult haemoglobin oxygen affinity. How the
- 11 -
structure of the placenta facilitates diffusion and the role of the high concentration of fetal
haemoglobin were the commonest omissions.

The double Bohr effect was generally well described, but, those that had difficulty mostly
misunderstood the concept that the Bohr effect concerned:

1. The decrease in haemoglobin oxygen affinity from arterial to venous on the maternal side
of the placenta due to increased concentration of carbon dioxide, and
2. Increase haemoglobin oxygen affinity from arterial to venous on the fetal side due to
decreased carbon dioxide concentration.

QUESTION 15 Describe the effects of resonance and damping on an invasive arterial blood
pressure tracing.

21% of candidates passed this question. For a pass, most of the following information was required:
Some attempt at a definition of the concepts
Evidence of understanding that the systems f
0
needs to be several fold the frequency of the
pulse and the consequences for the pressure waveform of not being so
Means whereby the f
0
of the system can be maximised
Effects of under, over and optimal damping on the arterial pressure waveform
Causes of damping in the system

Marks were awarded for other information, including that the measured MAP tends not to be affected
by resonance and inappropriate damping; clear diagrams explaining the waveform changes; correct
explanation of damping co-efficients and the meaning of the term, especially if a correct diagram of
the response to a step change in pressure was included; that the transducers used today have high
natural resonant frequency but the other components of the measuring system are the main cause of
low f
0
in the system; correct use of an equation relating f
0
to mass, elasticity and area and especially if
this could then be related to practical means of increasing f
0
in the measuring system; difference
between optimal and critical damping.

Common problems in the answers were:

Very few answers included a good attempt at defining the concepts especially damping (delay in
response due to frictional resistance, or similar)
Discussion of resonance and damping without any attempt at describing the effects on an arterial
waveform (at least half the candidates)
Wasting time with long descriptions of the components of the measuring system or of zeroing or
of indications for arterial line placement. Zeroing is irrelevant to the question;
Quoting figures for damping coefficients with no evidence of any understanding of the meaning of
the term
Using vague terms like interfere with the trace with no mention of in what way;
Stating that damping is used or added to the transducer in order to combat resonance-damping and
resonance are features of any oscillating system and the measuring systems used must in some
way optimise these inherent features;
Those candidates who attempted a diagram demonstrating response to a step change in pressure in
various damping situations were often wrong
Several dozen answers compared the radial and aortic pressure traces and described the
differences in terms of resonance and damping in the arterial tree. When this information was
correct, marks were given but it was not possible to get a pass mark for this information only.
- 12 -
QUESTION 16 Briefly outline the components of parenteral nutrition, explaining the
rationale for the use of each component.


A good answer would have included a definition of parenteral nutrition and a rationale for its use.
Normal daily requirements should have been described. The components of parenteral nutrition
include water and electrolytes, a common omission in many papers. Most candidates covered well the
caloric components of lipids, carbohydrates and proteins with a rationale for use. Many answers also
included the addition of vitamins, minerals and trace elements, which was pleasing, but the rationale of
to maintain normal levels was insufficient to score marks. Extra marks were awarded for discussing
how the patients requirements alter in normal physiological circumstances, for example age, gender
and pregnancy and in disease states such as sepsis and burns.

PHYSIOLOGY TOPICS/INTRODUCTORY QUESTIONS:

Cardiovascular
Draw LV pressure vs. time curve.
What useful information can be obtained from the ECG?
What is an electrocardiogram?
What are the determinants of cardiac output?
Draw a pressure-volume loop for the LV.
What controls regional circulation?
Draw an LA pressure wave versus time.
Draw a sino-atrial node action potential.
Discuss the determinants of pulmonary blood flow.
What are the assumptions associated with capillary wedge pressure measurement?
What are the determinants of myocardial perfusion?
Discuss the role of arterioles in the CVS.
What does the term "venous capacitance" mean?
What are the determinants of RV function?
What is the coronary sinus blood oxygen level?
Draw a PA catheter tip pressure trace as the device is inserted.
Draw an ECG and an RA pressure trace.
What is the blood supply to the heart?
Factors determining cerebral blood flow.
Changes in the CVS with aging.

Renal
Control of renal blood flow.
Define GFR and discuss its determinants
How is urine diluted?
What is serum osmolarity?
Discuss the renal response to acute haemorrhage.

Respiratory
Discuss the effects of hypercapnea.
Effect of increasing FiO2 on blood gases.
Determinants of arterial oxygen tension.
How is carbon dioxide transported in blood.
- 13 -
Draw the oxygen cascade.
Discuss the control of ventilation.
What is Laplace's law?
Respiratory changes of pregnancy.
What is PEEP?
Discuss FRC and closing capacity.
Discuss the changes that occur with a Valsalva manoeuvre
What is dead space?
Draw a respiratory pressure-volume loop for a paralyzed patient.
Draw a normal capnograph.
Draw an intra-pleural pressure versus time curve during quiet respiration.
Discuss the consequences of a sudden obstruction of the left pulmonary artery.
Discuss the effect of application of CPAP to a spontaneously breathing patient.
Define compliance.
How is diffusing capacity measured?
Define closing capacity.
What are typical values for mixed venous gases?
What is the oxygen tension in fetal umbilical arteries? Veins?
What happens to alveolar ventilation and perfusion as you move from the lung apex to the
base?

Nervous
What is a nerve fibre?
What is sleep?
What is normal cerebral metabolism?
Normal values of cerebral blood flow.
How are membrane resting potentials maintained?
What is the blood brain barrier?
What is CSF?

Measurement
What waves are seen on an EEG?
What is pulse oximetry?
What is saturated vapour pressure?
What is heat? What is temperature?
When will a pulse oximeter give an incorrect reading?
Define humidity.
Principles of measurement of levels of consciousness.

Hormones/Metabolism
Definition of a hormone
How are serum glucose levels maintained during a fast
Consequences of a 24 hour fast.
How does the body handle glucose?

Haematology
Definition of anemia
What are the features of a RBC?
Lifecycle of a platelet
How is a unit of packed cells prepared?
What are blood groups?

- 14 -
GIT
Functions of the liver
What happens when you swallow?
Regulation of gastric pH
Physiological principles of prevention of gastro-oesophageal reflux
Determinants of gastric emptying

Pain
What is pain?
Describe the mechanisms that are associated with acute pain
What happens if you touch something hot?

Temperature
How does an awake subject respond to a decrease in ambient temperature?
Discuss heat loss under anaesthesia.

Acid-base
What is a buffer?

DR NOEL ROBERTS
CHAIRMAN, PRIMARY EXAMINATION COMMITTEE

Australian and New Zealand College of Anaesthetists
ABN 82 055 042 852

EXAMINATION REPORT


JULY/SEPTEMBER 2006

of training with information about the way in which the performance of candidates in the recent
appropriately for future examinations. The individual reports are not intended to represent
model answers nor imply that all points mentioned are necessary in order to achieve a pass. All
trainees are urged to read the questions carefully and answer the question asked. All teachers
and supervisors of training are encouraged to discuss this report in detail with candidates they



81 % of candidates achieved a pass in this section of the Pharmacology Examination.


QUESTION 1 Describe the use of different sympathomimetics to treat hypotension
occurring as a result of subarachnoid block. Outline the advantages and
disadvantages of these agents.


Given the clinical scenario, a brief summary of pertinent issues resulted in less subsequent
repetition.

The hypotension results from a change in tone of resistance vessels (reduced systemic vascular
resistance). This is accompanied by a decrease in venous return to the heart and a lowering of
cardiac output. There may be a lowering of direct sympathetic tone to the heart, leading to a
reduction in heart rate and possibly force of contraction.

Answers should have included discussion of ephedrine and adrenaline (epinephrine). Credit was also
given for discussion of metaraminol, phenylephrine, methoxamine, noradrenaline, dopamine,
dobutamine and vasopressin, even if disadvantages outweighed the advantages of the drug. No
marks were given for naming a drug without other information.

- 2 -
Common features of these agents include:
Pharmaceutical presentation - all require dilution before use.
Agents with strong vasoconstricting effects have a risk of tissue necrosis if extravasation
occurs (including metaraminol).
All the drugs have a risk of causing hypertension.
Many drugs can cause tachycardia via direct effects or reflex bradycardia.

Better answers included a list of relevant patient problems that contribute to the
advantages/disadvantages of the drugs including:
Age/intercurrent illness, particularly cardiovascular disease and antihypertensive
medications.
Pregnancy and childbirth (allowance was made for the differences in prescribed texts
regarding ephedrine and phenylephrine).
Drug interactions - monoamine oxidase inhibitors.

QUESTION 2 Compare and contrast the clinically significant respiratory,
cardiovascular and central nervous system effects of desflurane and
isoflurane.


Cardiovascular effects were well answered with most correctly describing the effects on heart
rate, systemic vascular resistance, contractility and cardiac output; though there were some
incorrect statements such as, hypotension at one MAC is primarily due to impaired contractility.

Better answers discussed the theoretical risk of coronary steal with isoflurane and the practical
risk of increases in catecholamine levels with sudden increased desflurane concentration,
however there was no mention of the secondary effect on the renin angiotensin system.

Common errors in respiratory effects included unqualified comments that both agents could be
used for gaseous induction. Some candidates confused the respiratory effects of these agents
with opioids where tidal volume is maintained or increased and respiratory rate is reduced.

CNS effects were well answered, though only a minority mentioned the faster return to
consciousness with a comparable depth of anaesthesia with desflurane. Some said that these
agents usually decrease cerebral blood flow.

Presentation was of a good standard with most information for the least effort being conveyed
with tables. There were some good answers, though in plain text. Significantly there were no
blank answer papers.

QUESTION 3 Describe the factors which contribute to the inter-individual variability
in drug response seen with intravenous anaesthetic induction agents.


Better answers classified the factors contributing to variability rather than providing a random
list. Factors could be broadly classified as pharmacokinetic and pharmacodynamic in nature.
Then within each class further division into physiological, pathological and pharmacological,
including drug interaction and pharmacogenomic factors. Other schemes that encompassed
these key areas were acceptable. Some indication of the relative importance of these factors in
determining variability of intravenous anaesthetic agents was important.
- 3 -
Key pharmacokinetic factors were those that ultimately influenced the extent or duration of
effect site concentration and included factors increasing the rate of drug distribution to effect
site (e.g. speed of administration, arm-brain circulation time, cardiac output, distribution of
cardiac output, central compartment volume, effect site equilibration time); factors influencing
redistribution, offset of initial effect and body drug stores (e.g. regional blood flow, volume of
distribution, body habitus, age); factors causing variability in metabolism and clearance (e.g.
pharmacogenomic factors; induction, inhibition of enzymes; duration of exposure; age-related
changes in metabolism; hepatic and renal function). Key pharmacodynamic factors included
drug-receptor interaction, receptor numbers and regulation, acute and chronic tolerance,
idiosyncratic reactions.

Higher marks were awarded for comprehensive breadth of cover of the topic including
pharmacogenomic influences and where a clear understanding of the concepts mentioned was
evident. Many candidates did not read the question, and did not relate answers at all to
intravenous anaesthetic agents. Common errors included irrelevant emphasis on differences
between drugs rather than inter-individual variability, confusion over the nomenclature and
roles of the different volumes of distribution, uncertainty regarding the relative roles of
redistribution and clearance in offset of drug effect and confusion over the pharmacokinetic
changes in the very young and elderly patients. A clear knowledge of pharmacological principles
and terminology was expected.

QUESTION 4 Describe the advantages and disadvantages of rocuronium for rapid
sequence induction.


Most candidates failed because they wrote about the pharmacology of rocuronium without
addressing the advantages and disadvantages with regard to rapid sequence induction. It was
noted that the better answers were more focused and usually started by stating that rapid
sequence induction was a technique designed to secure the airway quickly in patients at risk of
aspiration, classically using suxamethonium to cause rapid paralysis.

Rocuronium was usually compared with suxamethonium, but candidates should also have noted
why rocuronium is currently preferred to alternative drugs when suxamethonium is absolutely
contraindicated. Some candidates wasted pages describing all the side effects of
suxamethonium that could be avoided with rocuronium. Answers should have indicated the
likely doses required for rapid sequence induction because this would determine the onset and
offset of neuromuscular block. There was large variation in the times given for onset and offset
of block for both suxamethonium and rocuronium. Some answers did not explain why the long
duration of action with rocuronium could be a disadvantage.

QUESTION 5 Briefly explain the mechanisms responsible for non-steroidal anti-
inflammatory drug (NSAID) induced side effects. Outline the
advantages and disadvantages of selective cyclooxygenase (COX 2)
inhibitors.


This question is in two parts. The first part involves a brief explanation of mechanisms behind
NSAID induced side effects. Candidates listing and briefly explaining the most commonly
discussed effects of peptic ulceration, renal impairment, tendency to bleeding from platelet
inhibition and bronchospasm were able to score most marks allocated from this section. The
mention of specific subtypes of prostaglandins involved attracted marks. Absence of such
information did not stop an answer from scoring well, as long as the discussion of mechanism was
adequate.
- 4 -
The second half of the question called for a brief discussion of advantages and disadvantages of
COX 2 inhibitors. Advantages: reduced peptic ulceration rate, reduced postoperative bleeding,
theoretical advantage of action in inflamed tissues, possible absence of bronchospasm etc.
Disadvantages: expensive, coronary and cerebral thrombosis with chronic use with rofecoxib and
possibly others, similar risk of renal impairment as with undifferentiated COX inhibitors.

Extra marks were scored by those who gave a very brief overview of COX action and the role of
COX 1 and COX 2, as well as discussion of other side effects such as interstitial nephritis,
hypertension, fluid retention, ductus arteriosus closure and sulphur allergy.

QUESTION 6 A new clinical test called the intubation score has a reported 90%
sensitivity and 70% specificity when used to predict difficult intubation.
Describe how the accuracy, predictive value and clinical utility of this
test can be evaluated. How will the incidence of difficult intubation
affect the performance of this test?


To quote from the syllabus (Section C -Statistics [e]), candidates are expected to: "Describe the
features of a diagnostic test, including the concepts of sensitivity, specificity, positive and
negative predictive value and how these are affected by the prevalence of the disease in
question.".

Drawing a 2 x 2 table and defining the terms mentioned in the question obtained a pass mark.
Unfortunately less than half the candidates accomplished this.

The question as to the effect of the incidence of disease on the positive predictive value of a
test is of critical importance. Changing the incidence of a disease does not alter sensitivity or
specificity, as many stated, but as the incidence falls so does the PPV - a restatement of Bayes'
Theorem. This is one of the reasons why all of the predictive tests for failed intubation, a
relatively uncommon event, have such a low PPV.

Some candidates invoked p values, alpha and beta errors, power and even "t-tests" in their
answers, which failed to address the question asked. There were many blank answers.

QUESTION 7 Outline the drug and non-drug treatment of ventricular fibrillation in an
adult. Briefly describe their mechanisms of action. (Do not discuss
basic life support, airway therapies and oxygen)


A similar question was asked in July 2005. The pass mark has improved significantly. Hopefully
knowledge and understanding of this important syllabus topic will continue to improve.

Candidates were expected to describe the current management of ventricular fibrillation with
particular reference to defibrillation, epinephrine and antiarrhythmic therapy. Allowance was
made for both old and new guidelines given their recent introduction. ILCOR published in 2005
(www.erc.edu/index.php/guidelines_download_2005/en/) and Australian guidelines in 2006
(www.resus.org.au/)

- 5 -
The important areas to be addressed were:
Defibrillation, early intervention, effective therapy, biphasic vs. monophasic, energy
settings and mechanism of action.
Epinephrine, dose, emphasis on activation of alpha 1 receptors resulting in
vasoconstriction and improved coronary and cerebral blood flow.
Antiarrhythmic therapy, amiodarone and/or lignocaine with description of dose and
mechanism of action.
Prioritisation, a description of the sequence of these therapies and how they fit into a
cohesive management plan or protocol. This could be implied in description of the
individual therapies.

Extra marks were gained for a description of the possible role of vasopressin, magnesium, sodium
bicarbonate and potassium.

Common problems included; no clear sequence of therapies, the importance of defibrillation and
energy settings omitted, epinephrine not mentioned or dosage and mechanisms incorrect.

QUESTION 8 Describe the pathogenesis and management of paracetamol toxicity.


Most candidates exhibited a sound knowledge of the pathogenesis and toxicity of paracetamol.
Many candidates wrote at length about the general pharmacokinetics of paracetamol. This did
not attract marks.

Marks were given for the following points:
Toxic dose, expressed ideally in mg/kg or a single toxic dose for adults.
Differentiation between a toxic dose and a fatal dose.
Normal metabolic pathway of paracetamol.
Overdose and relationship of minor metabolic pathway with production of toxic
metabolite.
Conditions which may exacerbate toxicity.
Cellular mechanism of hepatic toxicity.
Other features of toxicity e.g. contribution of paracetamol to chronic renal failure.
General management issues of drug overdose.
Role of N-acetyl cysteine and use of normogram.
Monitoring and tests e.g. risk of hypoglycaemia.

It was hard to score very highly without mentioning a toxic dose. When fatal doses were
mentioned, the range given was from 7 to 30g for an adult. No candidate mentioned the
importance of dose/kg reflecting ideal body weight, and precautions in obese patients or
children on long-term paracetamol use. Very few candidates mentioned renal toxicity.

Common errors referred to the metabolism of paracetamol to phenacetin, usefulness of dialysis
and urine pH manipulation in overdose.

- 6 -


General topics
Pharmaceutics; thiopentone, local
anaesthetics, benzodiazepines
Pharmacokinetics; absorption,
bioavailability; hepatic clearance;
renal drug handling, pharmacokinetic
modelling, clearances, volumes of
distribution
Ionisation of drugs
Pharmaco-genetics
Anti-convulsants
Agents that decrease gastric acidity
Drug chirality

Inhalational agents
Induction kinetics
Recovery
Washout curves
Inhalational depth, mechanisms of
action
MAC; MAC awake
Nitrous oxide, advantages and
disadvantages

Tocolytics
Magnesium, salbutamol
Placental transfer of drug

Local anaesthetics
Structure activity
Pharmacokinetics
Toxicity, factors affecting toxicity,
toxic doses

Induction agents
Factors affecting induction dose and
maintenance infusion rate
Cardiovascular effects
Principles of TIVA
Ketamine

Benzodiazepines
Mechanism of action
Pharmacokinetics
Adverse effects
Midazolam
Flumazenil

Factors affecting clinical choice and
dose
Recovery from neuromuscular
blockade
Potency
Suxamethonium; dose response
curve, side effects
Malignant hyperthermia and
dantrolene

Mechanism of action
Structure activity relationship
Pharmacokinetics
Pharmacodynamics
Adverse effects
Morphine, remifentanil
Oxycodone, buprenorphine
Tramadol
Neuraxial opioids

Classification
Muscarinic receptors
Adverse effects
Toxicology

Antiarrhythmics; classification, beta
blockers, digoxin, amiodarone
Anti-hypertensives
Calcium antagonists
Inotropes

- 7 -
Unfractionated heparin, low
molecular weight heparin
Warfarin
Antiplatelet drugs
Protamine

Pain
Oral analgesics
Bio-availability

Statistics
Evidence based medicine
Levels of evidence
Meta-analysis
Selection of appropriate statistical
tests
Confidence intervals
Drug testing
Endocrine
Insulin

Histamine and antihistamines
Histamine receptors
Anaphylaxis, mechanisms, drug
treatment

Antiemetics
Classification
Adverse effects



76 % of candidates achieved a pass in this section of the Physiology Examination.


QUESTION 9 Describe the factors that oppose left ventricular ejection.


A large proportion of candidates misinterpreted this question to be about determinants of left
ventricular ejection fraction and wasted a lot of time on describing pre-load, contractility and
heart rate for which no marks were awarded.

This is essentially a question about determinants of afterload which is the sum of all forces that
oppose left ventricular ejection.

Important points looked for were:
Recognition that the sum of factors which oppose LV ejection is afterload.
Afterload can also be described as ventricular wall tension.

- 8 -
Factors that determine afterload:
Systemic Vascular Resistance. Recognition that this is a major contributor to afterload.
Definition, role of SVR in determining afterload and factors which alter SVR attracted
extra marks.
Left ventricular outflow tract resistance and examples of conditions that change this e.g.
aortic stenosis.
Effect of aortic compliance on afterload.
Ventricular wall factors such as radius and thickness. The relevance of Laplaces law in
relating ventricular wall radius and thickness to wall tension.
Effect of blood viscosity.
Effect of arterial impedance.
Effect of changes in intrathoracic pressure as a result of IPPV or other states. The fact
that IPPV actually reduces afterload by reducing transmural pressure was rarely stated.

QUESTION 10 Describe the determinants of work of breathing in an adult human at
rest.


The main points expected were:
Work is the product of pressure x volume and the SI unit is the Joule.
Inspiratory work has to overcome elastic and resistance forces.
Elastic work consists of deforming elastic tissues and overcoming surface tension.
Resistance work must overcome airway resistance and viscous forces.
Potential energy is acquired during inspiration and stored elastically to provide energy for
passive expiration.
The components of work of breathing are best illustrated on a pressure-volume diagram.

Additional points:
The percentage contributions of the components to work of breathing.
The oxygen cost and efficiency of work of breathing.

Common errors included mislabelling axes and writing detailed descriptions of compliance,
airway resistance and patho-physiological conditions.

QUESTION 11 List the hormones that regulate tubular reabsorption and describe their
action and site of action.


The five principal hormones of relevance to tubular re-absorption are; Angiotensin II,
Aldosterone, ADH, ANP and Parathyroid Hormone. These are hormones affecting the absorption
or excretion of Na+, H2O, Ca ++ and K+. In addition to listing these hormones, marks were
awarded for clearly stating the action and precisely stating the site and mechanism of action.
Many direct effects were relevant but indirect effects were also rewarded where they played a
major part in these hormones actions on tubular re-absorption.

The style of the question suited a highly structured answer. The candidates who used lists,
headings, subheadings, space and columns were able to get many marks with relatively little
writing. This style of answer was easy to understand.

- 9 -
Many candidates wrote a lot about the processes involved in the release of these hormones
which was not asked for and received no marks. Extra-renal effects were not rewarded e.g.
effects of Angiotension II and ADH on systems vasculature. Likewise effects on non-tubular parts
of the nephron e.g. renal bloodflow and glomerular filtration were often not relevant. Some
candidates forgot Parathyroid Hormone and calcium re-absorption.

Overall though, most candidates had a thorough knowledge of the topic, were able to
communicate effectively and many good marks were awarded.

QUESTION 12 Explain the difference between viscosity and density. Outline the
effects of changes in viscosity and density on the flow of gases and
liquids.


Many more candidates were able to adequately define density than viscosity. Few candidates
noted that these are separate properties of gases and liquids and extra marks were awarded for
noting that gases of similar viscosity may have differing densities e.g. helium and oxygen. Extra
marks were also awarded for describing the effects of temperature on the density and viscosity
of gases and liquids.

The second part of this question should have included discussion on how both viscosity and
density effect laminar and turbulent flow. The effects of viscosity on laminar flow, the Hagen-
Poiseuille equation and the Reynolds number were well described by most candidates. Common
omissions were; comment on the effect of density on laminar flow, and comment on the effect of
changing viscosity on turbulent flow. A common mistake was to state that turbulent flow was
directly (rather than inversely) related to density. Many candidates gave detailed descriptions of
the characteristics of laminar and turbulent flow that did not pertain to either viscosity or
density and therefore did not attract any marks.

QUESTION 13 Briefly describe the structure of a mammalian skeletal muscle fibre and
explain how its structure is related to its contractile function. DO NOT
describe excitation-contraction coupling.


There were few high scoring answers. In order to pass this question, a simple outline of the
structural components of the skeletal muscle fibre and their related functions as related to
contraction would suffice. Additional marks were obtained for a more detailed description of
the components of the muscle fibre and for disorders of the fibre structures.

Many candidates confused the muscle fibre with myofibril or myofilaments, and as such were not
able to obtain sufficient marks to pass. Many candidates failed to appreciate that the skeletal
muscle fibre was a cell, and therefore did not mention basic cellular components, especially
those modified to have a specific function in skeletal muscle fibres.

- 10 -
QUESTION 14 Compare and contrast the physiological effects of a six hour fast of
fluids and food with a twenty four hour fast in a healthy adult.


To pass this question, candidates were expected to appreciate that a six hour fast occurs daily
and is thus well tolerated whilst a twenty four hour fast involves a significant mobilisation of
reserves. In doing this, a comparison of the likely water and caloric requirements for each
period, with some mention as to the origin of these calories, was required. An appreciation of
the total fuel reserves available in a healthy adult, along with recognition of the thirst, hunger,
lethargy and other physiological consequences of a twenty four hour fast would round out an
acceptable answer.

Additional marks were awarded to those candidates who were able to more fully quantify the
use of reserves during a short and a longer fast and were able to briefly indicate the pathways
the body utilises for glucose and ketone production.

Few candidates appreciated that the liver is central in the adaptive process whereby the blood
sugar level is maintained by the conversion of fat and amino acids to glucose.

The most frequent reasons for not obtaining a pass mark were; the absence of enough
information to indicate that the key principals were understood, and failing to mention the
actual reserves of energy in the body. Very few candidates mentioned that a twenty four hour
fast would render the patient hungry, thirsty and lethargic. Many candidates incorrectly used
the words glucagon and glycogen interchangeably.

QUESTION 15 Explain how a metabolic acidosis develops in hypovolaemic shock.
Describe the consequences of this metabolic acidosis for the body.


Candidates who scored well answered the question in a structured fashion, with definitions of
the issues at hand and answered both sections. Although an understanding of how metabolic
acidosis develops in hypovolaemic shock was essential, extra credit was earned for
understanding the factors that exacerbate the metabolic acidosis in this situation and for
demonstrated knowledge of the metabolic pathways involved. Some candidates demonstrated
an excellent understanding of these and how they relate to one another.

A common error among candidates was to detail physiological consequences of hypovolaemic
shock at the expense of addressing the physiological consequences of metabolic acidosis. There
was limited information on the cardiovascular effects of a metabolic acidosis. Many candidates
were able to state that a metabolic acidosis results in myocardial depression. Few were able to
outline how a metabolic acidosis effects the response of the cardiovascular system to
sympathetic outflow, or at what pH these effects may occur. Respiratory and renal
compensatory mechanisms, when addressed, were generally well described.

- 11 -
QUESTION 16 Describe the physiological consequences of acute hypoglycaemia.


This was an applied question asking about hypoglycaemia. The physiological response has two
broad components. The first is neurologic because of the brains reliance on glucose. These
symptoms become increasingly serious as the hypoglycaemia worsens and range from confusion
to coma, fitting and death. An early component is significant hunger. Associated with the
neurologic response is the sympathetic response that is responsible for several of the signs of a
hypo. This includes agitation, sweating and pallor. The other component is the endocrine
response. The aim of this is to increase the blood sugar. This response includes decreased
insulin production (if any is usually produced), and increased glucagon, cortisol, and growth
hormone.

Two errors were to include details of diabetic ketoacidosis and focussing on changes in plasma
osmolality based on the equation that includes glucose. A minor point is that the Australian and
New Zealand unit for glucose is mmol/l not mg/dl.


PHYSIOLOGY TOPICS:

Cardiovascular
Determinants of cardiac output
Measurement of cardiac output
ECG
Arterial waveforms, radial and
aortic root
Pulmonary circulation
Pulmonary artery trace and
capillary wedge pressure
Frank-Starling relationship
Contractility
CVP waveform
Pressure-volume loops for ventricles
Myocardial oxygen balance
Blood pressure
Capillary exchange
Effects of IPPV, PEEP

Renal and acid/base
Renal blood flow, regional variations
Glomerular filtration
Clearance
Renal production of concentrated
urine
Response to hypovolaemia
Kidney and acid base balance
Respiratory acidosis
Metabolic alkalosis

Respiratory
Lung volumes
Dead space
Regional lung differences
Alveolar gas equation, universal gas
equation
Oxygen cascade
Respiratory changes at altitude
Spirometry
V/Q mismatch
Mixed venous oxygen tension
Closing capacity, FRC
Respiratory effects of anaesthesia,
positioning
CO
2
carriage
Forced expiratory flow loop
Physiological response to
hypercapnia, hypocapnia

CNS/Pain
Blood brain barrier
CSF, composition, production,
absorption
Cerebral blood flow
Sleep
Response to acute pain
Resting membrane potential

- 12 -
Measurement
Errors in pulse oximetry
Pressure measurement
Arterial pressure monitoring
Damping
Principles of Doppler Ultrasound
Measurement of humidity
Temperature
Capnography
Pneumotachograph

Other
Thermoregulation
Oxygen delivery to the foetus
Principles of parenteral nutrition
Lipid metabolism
CHO metabolism
Amino acid metabolism
The red blood cell
I.V fluids
Immune function
Thyroid function
Anaemia, physiological effects
Diffusion, Ficks law
Gastric contents, emptying
Lower oesophegeal function

Dr. N Roberts

ABN 82 055 042 852

EXAMINATION REPORT


FEBRUARY/APRIL 2006

supervisors of training with information about the way in which the performance of
candidates in the recent examination was assessed by the examiners, so that candidates
and teachers may prepare appropriately for future examinations. The individual reports
are not intended to represent model answers nor imply that all points mentioned are
necessary in order to achieve a pass. All trainees are urged to read the questions
carefully and answer the question asked. All teachers and supervisors of training are
encouraged to discuss this report in detail with candidates they are preparing for future
examinations.





QUESTION 1 Outline the pharmacologic management of bronchoconstriction in acute
severe asthma. Include mechanisms of action and potential adverse effects.


The main points to include were:
A list of classes of drugs used to treat acute severe asthma
Representative examples of drugs
An explanation of how these drugs work
Significant side effects

The most important drugs that should have been included were 2 agonists, steroids, anticholinergics,
volatile agents and methylxanthines. Discussion of leukotriene antagonists, ketamine, magnesium,
oxygen and helium attracted additional marks.

2
Many candidates wrote extensively about the pathophysiology of asthma which could not be credited
any marks. Discussion of the mechanism of action of the drugs was often inadequately dealt with.
Many answers either did not address this part of the question or stated that 2 agonism or muscarinic
antagonism caused bronchodilatation without any discussion of second messengers. Those who did
attempt a more detailed discussion often became confused about the change in cAMP and intracellular
calcium level.

Many answers were dismissive of the use of volatile agents in the treatment of asthma, despite the fact
that they are convenient and readily available to treat bronchoconstriction in the setting of anaesthesia.

QUESTION 2 What is an isomer? Briefly write an account of the types of isomers and
their significance in drugs used in anaesthesia.


The main points to include were a definition, classification and a description of specific drugs and the
implications of isomerism.

Many candidates had incorrect classifications. Some candidates described tautomers as a form of
stereoisomers when in fact they are a subtype of structural (or constitutional) isomers. Similarly, a
large number of candidates confused geometric isomers with structural isomers. Geometric isomers
are stereoisomers that differ in the orientation of groups around a double bond or ring structure. Many
of the diagrams were incorrect.

It is also noted that many candidates neglected to mention the clinical significance of isomers. Better
answers included specific examples such as enhanced analgesia with S-ketamine, lower cardiotoxicity
with levobupivacaine and improved solubility of the enol form of thiopentone.

QUESTION 3 List the non-ideal features of nitrous oxide.


The main points expected for a pass included: the drugs inability to be used as a single agent, diffusion
hypoxia, expansion of gas-filled spaces and cobalt oxidation resulting in reduced activity of vitamin
BB
12
.

Additional marks were obtained for a description of additional adverse effects including, but not
restricted to, non-ideal pharmaceutic properties, post-operative nausea and vomiting, pulmonary
hypertension, increased cerebral blood flow, mild myocardial depression, sympathetic stimulation and
increased homocysteine levels. Some candidates also described the difficulties associated with
interpreting depth of anaesthesia monitoring when administering N
2
O and its potential for abuse.

Forty percent of candidates failed to mention diffusion hypoxia. Also, there was some confusion
regarding the relative solubilities of N
2
O, O
2
and N
2
and how this affects expansion of gas filled
spaces.

3
QUESTION 4 Describe the pharmacodynamic properties of propofol and how this
influences its clinical usage.


It was expected emphasis be placed on the central nervous system effects, followed by the
cardiovascular and respiratory effects and marks were allocated accordingly. The question was
specifically related to pharmacodynamics and a discussion of pharmacokinetic properties scored no
additional marks.

Candidates were expected to outline that Propofol is an intravenous anaesthetic agent used for both the
induction and maintenance of anaesthesia or sedation. Reward was given to candidates who outlined
potential mechanisms of action, the dose dependent nature of effects, the effects on the EEG and on
cerebral metabolism. Further credit was given for describing how this might impact on its clinical use
(e.g. neurosurgery). A description of the cardiovascular effects was expected to include reference to
hypotension, reduced systemic vascular resistance and bradycardia with comment on those patients at
risk. Respiratory effects include alterations in ventilatory response, reduction in airway reflexes and
bronchial tone.

Extra credit was given for discussion of other pharmacodynamic properties including; anti-emetic,
anti-pruritic, non MH triggering, pain on injection, lipid/caloric load, reduction in intraocular pressure
and risk of propofol infusion syndrome.

It was expected that candidates would relate each pharmacodynamic effect to the impact on clinical
use and failing to address this was a common omission (e.g. reduction of airway reflexes is useful for
LMA insertion or airway manipulation). Well organised answers such as those with an ordered list
with subheadings or a table were rewarded.

QUESTION 5 Write short notes on factors affecting the speed of onset and duration of
effect of local anaesthetics when used to produce peripheral nerve block.


This question required candidates to write short notes and candidates who simply wrote a list without
explanation failed to achieve high marks. Likewise the question clearly required candidates to address
the issues of both speed of onset as well as duration of action. Some candidates answered only one
part of this two part question and failed to achieve high marks. Better answers attempted to
differentiate between the factors that affect speed of onset and those that affect duration. Many of the
better answers related the answer to aspects of the Fick Principle.

Patient factors include:
Site of administration
Nerve structure and function
Tissue pH
Pregnancy
Electrolyte disturbances

4
Drug factors include:
pKa and its effect on non ionised fraction
Lipid solubility and its effect on potency and protein binding
Concentration and volume added
Intrinsic vasoactive properties
Effect of local and distant metabolism
Effect of different additives

QUESTION 6 Explain the possible mechanisms for prolonged neuromuscular blockade
after a four hour procedure using a non-depolarising muscle relaxant.


The main mechanisms expected to be addressed were:
Overdose
Pharmacokinetic; hypothermia, hepatic failure, renal failure
Pharmacodynamic
o drug interactions (e.g. volatiles, antibiotics)
o physiological disturbance (hypothermia, acidosis, electrolyte abnormalities)
o neuromuscular abnormality ( e.g. myaesthenia gravis)

Candidates were asked to "Explain..." the mechanisms by which the various mechanisms produced
prolonged neuromuscular blockade. For example, overdosage might be produced by a dose
calculation error, repeated bolus or infusion without neuromuscular monitoring, or a drug swap error
with a long acting agent. The majority of candidates listed some mechanisms that could prolong
neuromuscular block but frequently omitted an adequate explanation.

Few answers considered the potential for a combined effect created by the clinical context of the
question. A four hour case will commonly require repeated doses of neuromuscular blockers, long
exposure to volatile anaesthetic agents, and may result in patient hypothermia and acidosis.

QUESTION 7 Briefly outline the pharmacology of naloxone.


The majority of answers were well organized. The main points to include were:
Pharmaceutics
Pharmacokinetics
o IV and IM administration
o High clearance, short half life
o High lipid solubility
o Clinical implications
5
Pharmacodynamics
o Competitive mu opioid receptor antagonist
o Clinical applications
o Adverse effects

Common problems included; lack of organization, failure to discuss the important pharmacokinetic
properties or the potential serious adverse effects of naloxone.

QUESTION 8 In a clinical trial, why is adequate power important? What factors affect
the determination of an adequate sample size?


Candidates were expected to provide a definition of what Statistical Power is in the context of a
clinical trial and to show a good understanding of the concept. Most candidates were able to identify
why it is important for a trial to have appropriate power. Many demonstrated inadequate
understanding of the relationship between sample size and power.

Although mathematical equations for sample size calculation were not required, an understanding of
the different factors and their significance were expected. Candidates needed to discuss alpha and beta
error, measurement effect and measurement variability.

Very few candidates mentioned that different formulas and nomograms are often used and currently
computer programs make sample size calculations more precise. Many candidates mentioned the main
factors affecting sample size but most failed to give the desired values commonly used for alpha and
beta error or how population variability is estimated.

Candidates who mentioned why meta-analysis increases statistical power, the issues with multiple
outcomes, interim analysis and drop out gained more marks.

6



General topics
Pharmaceutics; thiopentone, local anaesthetics, benzodiazepines
pharmacokinetic modelling, clearances, volume of distribution
Ionization of drug
IV Fluids, properties and kinetics
Agents that decrease gastric acidity
Paracetamol
Oxygen: therapeutic use, side effects, storage, manufacture of gas

Inhalational agents
Induction kinetics
Time to awakening
Washout curves
MAC; MAC awake
Structure-activity relationship
Desflurane vs. isoflurane

Tocolytics
Desirable and adverse effects of magnesium
Placental transfer of drug

Local anaesthetics
Toxicity, factors affecting toxicity
Topical anaesthesia
EMLA cream, amethocaine gel

Induction agents

Benzodiazepines
Mechanism of action
Pharmacokinetics
Toxicology
Antidotes
7
Potency
Suxamethonium; dose response curve, side effects

Opioid agonist and antagonist
Mechanism of action
Structure activity relationship
Pharmacokinetics
Adverse effects

NSAIDS
COX1 and COX2 agents; kinetics, side effects

Classification
Muscarinic receptors
Adverse effects
Toxicology

Antiarrhythmics; classification, beta blockers, digoxin
Clonidine
Vasopressors; metaraminol, ephedrine, phenylephrine; vasopressin
Inotropes
Drugs used for cardiac arrest

Unfractionated heparin, low molecular weight heparin
Antiplatelet drugs
Protamine

Statistics
ANOVA
Nonparametric tests
Diagnostic tests
Relative risk
Odds ratio
Number needed to treat

8
Endocrine
Insulin

Diuretics
Mechanism of action
Toxicology
Dose-response relationship

Histamine and antihistamines
Pharmacodynamic effects
Adverse effects

Chemotherapeutic (including antibiotics) agents
Mechanism of action
Toxicology
Implications in clinical anaesthesia
Allergy

9



71 % of candidates achieved a pass in this section of the Physiology Examination.


QUESTION 9 Outline the systemic cardiovascular response to exercise.


An overall understanding of the systemic CVS response to exercise was looked for.

Very few candidates noted the important difference between isotonic and isometric exercise, with
corresponding differences in total peripheral resistance. Some candidates didnt realise that heart rate
increases in exercise.

Candidates who scored well demonstrated an overall understanding that exercising muscle needs an
increased blood/oxygen/nutrient flow and directed their answers to include all the systems that
combine to do so.

They included redirection of blood from splanchnic circulation, a right shift in the Oxy haemoglobin
curve, 2, 3 DPG, sympathetic and parasympathetic nervous systems, and muscle and thoracic pumps
for example. See Ganong 22
nd
edition pages 632 - 634.

QUESTION 10 List the physiological factors which increase respiratory rate and include a
brief explanation of the mechanism by which each achieves this increase.


Points required for a pass were:
Listing and understanding of the mechanisms by which hypoxia, hypercapnia, and acidosis induce
hyperpnoea plus some of the other common causes of tachypnoea (e.g. exercise, increased BMR,
hypotension, activation of skeletal muscle stretch, various pulmonary conditions/receptors/work of
breathing, CNS causes - voluntary control and in response to pain, age, pregnancy..

Quantitative description of various stimuli, synergistic interactions. Whilst some marks were awarded
for description of the various brain-stem centres that control breathing, the descriptions were often not
directly linked to tachypnoea.

Some candidates wasted time describing factors that slowed respiratory rate, and the definitions of
alveolar ventilation.

10
QUESTION 11 Briefly outline the role of platelets in haemostasis.


In general this question was well answered. To achieve a pass, candidates needed to describe the
involvement of platelets in both primary and secondary haemostasis i.e. platelet adhesion, release
reaction, platelet aggregation and then their involvement in the coagulation cascade.

Some answers were very detailed on particular roles but the candidates failed to cover the range of
actions of platelets. Some candidates focused on pharmacology of anti-platelet agents, which did not
answer this question.

Extra marks were allocated for general information on the production of platelets, their size and
numbers, for explaining contractile elements of platelets, and their involvement in vessel repair.

QUESTION 12 Classify and describe the main cellular and molecular mechanisms by
which chemical neurotransmitters exert their effects. Use examples from
cholinergic and adrenergic neurotransmission to illustrate the answer.


There were a wide range of marks for this question; however there were a few very good answers.

It was important that candidates read the question. The question was based around cellular and
molecular mechanisms, with candidates asked to classify and describe them. Importantly examples
from the cholinergic vs. adrenergic systems were expected and it was notable that many candidates
chose examples from different systems.

In general terms, neuro transmitters can exert their affects on ion channels in cell membranes or
through intracellular affects. Ion channels can be affected by receptor agonists or antagonists, directly
or indirectly (through, for example, G proteins). Intracellular events are usually mediated via G
proteins and second messenger systems.

Most candidates addressed the issue of agonists and antagonists at cell membrane receptors affecting
ion channels well, most usually citing the neuromuscular junction as an example. Most candidates
dealt well with the G protein mediated second messenger system, and cited a number of examples.
The effects of G proteins on ion channels were very rarely mentioned. This is relevant for example,
M1 muscarinic receptors.

Areas such as the relative response times of G protein verses direct ion channel effects, modulation
and/or amplification, and other complex affects such as MRNA transcription or other neuro
modulators were rarely mentioned.
11
QUESTION 13 Describe the factors that influence metabolic rate.


Most candidates provided a reasonable list of factors which influence metabolic rate.

Many candidates incorrectly equated basal metabolic rate (BMR) with metabolic rate. Excessive
focus on BMR sometimes detracted from discussion of more general concepts pertinent to metabolic
rate.

There were significant problems describing the influence of temperature on metabolic rate. Ambient
temperature was not always distinguished from core body temperature. The distinction between the
raised metabolic rate, which accompanies small falls in body temperature versus the lowering of
metabolic rate with more severe hypothermia or when muscle metabolic responses are blocked by
anaesthesia and muscle relaxants was often not made clear.

Few answers provided a good overview and very few demonstrated an understanding of the role of
skeletal muscle as the single largest and most variable source of energy production and thus the origin
of the greatest changes in metabolic rate in an individual.

The effect of consumption of differing food types on metabolic rate was frequently a source of
confusion. The specific dynamic action (SDA) relates to the energy required to assimilate food,
(protein > carbohydrate (1/5 that of protein) > fat (2/3 that of carbohydrate)). SDA is not related to the
respiratory quotient (RQ) which also varies with food type. The RQ may be of importance for
estimating metabolic rate if carbon dioxide production is being measured as a surrogate for metabolic
rate. Neither SDA nor RQ is related to the energy produced per gram of food.

QUESTION 14 Explain the physiological processes which cause oliguria in response to
hypovolaemic shock.


This question has been asked on two previous occasions. The Examiner Reports from then are well
worth reviewing.

The following points and concepts should have been included:
A simple brief definition of hypovolaemic shock and oliguria
The result is to reduce sodium loss and increase water retention
How renal blood flow is reduced and why this is beneficial
Mechanisms for the reduction in glomerular filtration rate (GFR), and the relationship of GFR
to renal artery pressure
Activation of the renin-angiotensin-aldosterone (RAA) system starting with prorenin and
listing the roles of angiotensin II
Effects of aldosterone and anti-diuretic hormone

12
Lack of detail around mechanisms of action was common and many candidates did not mention
autoregulation of renal blood flow or the relationship of renal artery pressure and GFR. Afferent and
efferent glomerular arteriolar effects of angiotensin II and noradrenaline were often confused. A
lengthy description of systemic blood pressure control, the factors comprising Starlings equation, and
the counter-current mechanism was not expected. Details on atrial naturetic peptide were not relevant
to the mechanisms of oliguria.

This question required a well organised answer so that the major points could be covered in enough
detail.

QUESTION 15 Briefly describe the measurement of pH in a blood sample using a pH
electrode.


For a pass, the answer needed to include a description of the apparatus used, including the presence of
pH sensitive glass, two reference electrodes Ag/AgCl and the same, or calomel (Hg/HgCl
2
) although
more modern machines do not use the calomel electrode, a salt bridge to complete the circuit,
connecting the calomel or 2
nd
Ag/AgCl electrode to the test solution, a buffer solution separated from
the sample by pH sensitive glass. The only variable in the circuit, given constant temperature, is the
difference in pH between the buffer and sample. The electrode potential depends on the Hydrogen ion
activity, so the voltage measured in the circuit is proportional to pH. There is a need to calibrate
against two known pH Phosphate solutions, and the system must be temperature controlled to 37
C
.
The device is an example of an ion-sensitive electrode.

A clearly-labelled diagram was a great help, and although not required for a pass, most of the better
answers did include one. In the absence of a diagram, a very clear description was required. Some
answers unfortunately had a diagram at odds with the text, making it very difficult to assess
understanding.

Better answers included detail about how the glass is pH-sensitive, why saturated KCl is used as the
salt bridge, a correct definition of pH, and additional information about minimization of error.
Lengthy discussion of CO
2
control in hypothermia gained little and usually left minimal information
that actually answered the question.

Answers which described the Clarke or Severinghaus electrodes gained no marks. Many answers
included a reasonable diagram but text that inferred a very poor understanding of what was drawn.
The concept of an electrical circuit was absent in most answers that failed. Several dozen answers
defined pH incorrectly, as a variable in the Henderson-Hasselbalch equation. No candidate mentioned
solid-state ion-sensitive field-effect transistors which have been used in pH measurement for 10 or
more years.

13
QUESTION 16 Describe the physiological factors that contribute to the competence and
tone of the lower oesophageal sphincter.


This question has been asked twice before in recent exam history.

The main points sought were:
The anatomical features that maintain the lower oesophageal sphincter, including the
coordination of the diaphragmatic crura and the pinch-cock effect with contraction of the
diaphragm with breathing and coughing. The importance of the lower portion the oesophagus
being intraabdominal. The oblique passage into the stomach allowing the increase in gastric
tone to further enhance closing and push the mucosal folds into the lower oesophagus
contributing the mucosal flap valve.
An understanding of the concept of barrier pressure to reflux of abdominal contents and
normal values for pressures involved.
The neural innervation of both the internal and external portions of the sphincter, i.e. vagal and
phrenic respectively and the part the autonomic nervous system played in maintaining lower
oesophageal tone.
The hormones that alter the tone of the sphincter, including gastrin, secretin, CCK, VIP,
motilin, progesterone, oestrogen, PGE2.
Alteration of tone due to physical factors such as raised intraabdominal pressure, swallowing,
and gastric content acidity.

Marks were given for all of the above as facts and additional marks were given for demonstrating the
mechanism of action of the anatomical features and how changes in physiology (e.g. with pregnancy,
diabetes, vagotomy) or anatomy, (e.g. obesity, pregnancy, hiatus hernia) alter the barrier pressure.

Many candidates did not cover the breadth of this question focusing either on the anatomical features
or the hormonal control and therefore while obtaining a pass not achieving high marks. Unfortunately,
as has occurred with this question in the past, some candidates wasted time writing about
pharmacology that was not asked for in a physiology paper.

14


PHYSIOLOGY TOPICS:

Cardiovascular
Pulmonary capillary wedge pressure
Cardiac Muscle action potential
Determinants of venous return
Cardiovascular effects of aging
ECG
Arterial waveforms-radial and aortic root
Pulmonary circulation
Frank-Starling relationship
Contractility
Cerebral blood flow
CVP waveform
Pressure-volume loops for ventricles
Response to sudden vasodilatation
Myocardial oxygen balance
Blood pressure

Respiratory
Dead Space
FRC
Regional Lung differences
Oxygen cascade
O
2
flux at altitude
Response to sudden occlusion of the pulmonary artery
Spirometry
V/Q mismatch
Surfactant
Compliance
Respiratory changes with aging
Respiratory changes with pregnancy.
CO
2
carriage
Forced expiratory flow loop
PV loop
Physiological response to hypercapnia
Capnography

Renal
15
Renal handling of acid
Renal blood flow
Clearance
Renal production of concentrated urine
Response to hypovolaemia

CNS/Pain
Intracranial waveform
Cerebral blood flow
Sleep
Arousal
CSF
EEG waveforms
Response to acute pain
Response to acute injury

Measurement
Errors in pulse oximetry
Arterial pressure monitoring
Damping
Principles of Doppler Ultrasound
Measurement of humidity
Temperature
Capnography
Pneumotachograph

Other
Thermoregulation
Fasting
Lipid digestion
CHO digestion
The red blood cell
Calcium metabolism
Maternal-foetal oxygen transport
Amino acids
Potassium
Body defence mechanisms
Skeletal muscle
Peripheral nerve
Nerve fibres

16

Dr. N Roberts

ABN 82 055 042 852

EXAMINATION REPORT

PRIMARY EXAMINATION

JULY/AUGUST 2004

PLEASE NOTE THAT THIS REPORT IS PREPARED TO PROVIDE CANDIDATES AND THEIR
TEACHERS AND SUPERVISORS OF TRAINING WITH INFORMATION ABOUT THE WAY IN WHICH
THE PERFORMANCE OF CANDIDATES IN THE RECENT EXAMINATION WAS ASSESSED BY THE
EXAMINERS, SO THAT CANDIDATES AND TEACHERS MAY PREPARE APPROPRIATELY FOR
FUTURE EXAMINATIONS. THE INDIVIDUAL REPORTS ARE NOT INTENDED TO REPRESENT
MODEL ANSWERS NOR IMPLY THAT ALL POINTS MENTIONED ARE NECESSARY IN ORDER TO
ACHIEVE A PASS. ALL TRAINEES ARE URGED TO READ THE QUESTIONS CAREFULLY AND
ANSWER THE QUESTION ASKED. ALL TEACHERS AND SUPERVISORS OF TRAINING ARE
ENCOURAGED TO DISCUSS THIS REPORT IN DETAIL WITH CANDIDATES THEY ARE PREPARING
FOR FUTURE EXAMINATIONS.

PHARMACOLOGY

WRITTEN SECTION




QUESTION 1 Briefly describe how drugs produce their pharmacological effects. Illustrate each
mechanism with examples.


Generally discussion of receptor mediated mechanisms was excellent, with ligand gated, G-protein, tyrosine
kinase & intracellular DNA receptors being well covered with appropriate examples. Non receptor mechanisms
are clearly important also. Some candidates confused local anaesthetics as being ligand gated receptor mediated
when in fact they have direct action on ion channels.

For a complete answer non-receptor mechanisms also include carrier molecules, effects on enzymes, direct
chemical interaction, colligative properties and structural analogues (counterfeiting). Finally mechanisms which
are unknown or not fully elucidated are relevant and received marks (eg volatile anaesthetic agents, placebo
effect).

Some candidates gave erudite discussions on pharmacokinetics but this did not answer the question. Good
answers divided the answer into receptor and non-receptor mechanisms and didnt get bogged down in one area.
A common issue was spending too much discussion on G-protein coupled receptors at the expense of other
areas.

2
QUESTION 2 Write a brief description of the pharmacology of ropivacaine.


The main points that should have been included were correct recognition of the drug and its chemistry and basic
knowledge of the pharmacokinetics (pKa, T
1
/
2
and protein binding). The unique pharmacodynamic features
including differential block, toxicity and the relevance of these to the clinical usage of the drug should have
been mentioned. Additional accurate information about the chemical structure, mode of action and kinetics was
rewarded.

A concise correct answer is preferred; many answers included a large amount of repeated and, at times,
inaccurate information. It was concerning that many answers stated that ropivacaine was suitable for
intravenous regional anaesthesia.

QUESTION 3 List the effects of histamine. Write a brief outline on the pharmacology of the H
1

blocking drugs.


The first part of the question asked for a list of effects. It was not productive to write notes on the chemistry or
distribution of histamine, or discuss its role in anaphylaxis. Less than half the candidates produced a minimal
list that included bronchoconstriction, vasodilatation, increased vascular permeability, acid secretion and one
central nervous system effect. Better answers were able to ascribe the correct receptor subtypes to a
comprehensive list, and also include the effects of histamine at a cellular level.

The second part of the question was also handled poorly, with a significant number of candidates leaving it
unanswered, discussing H
2
blocking drugs, or other drugs that were not antihistamines. Some candidates wrote
about only one antihistamine, but because the H
1
blockers are a diverse group, it was necessary to include other
examples. Specific H
1
blockers are relatively new and used mainly for the management of allergic conditions.
Older antihistamines are not specific, have more diverse indications, and often have a number of side effects.
However, sedation may become a desired effect, as is the case with promethazine that has been used in
premedication. Although several uses were often listed for H
1
blockers, it was important to match these with an
appropriate drug because not every antihistamine is appropriate for every indication.

QUESTION 4 Write short notes on tramadol.


Many candidates handled this question well. A complete answer was helped by organising the essay around sub-
headings such as pharmacodynamics, pharmacokinetics, adverse effects and so on.

While most answers recognised that tramadol is presented as a racemic mixture, only a proportion went on to
say that each isomer had specific effects contributing to the analgesic effect of the drug. Likewise, while the
majority of answers noted that the drug has actions on opioid and non-opioid sites, nobody mentioned that the
drugs analgesic effect is as a result of this somewhat peculiar synergistic activity.

As an analgesic, it is useful to compare it to a standard opioid such as morphine and most did so, noting its
reduced potential for the development of tolerance and dependence and respiratory depression. Pharmacokinetic
aspects were less well handled with many failing to note that tramadol is highly metabolised and that one
metabolite (M1 or O-desmethyl tramadol) has considerable activity at the opioid receptor and may contribute to
the drugs activity. As with codeine, a proportion of patients deficient in the P450 cytochrome CYP2D6 enzyme
will fail to form this product and may exhibit reduced analgesia.

Some candidates noted other interesting features of the drug such as an improvement in oral bioavailability with
multiple dosing; the suggestion that tramadol might increase the risk of awareness under general anaesthesia and
that tramadols analgesic effect might be antagonised by 5HT
3
antagonists.

QUESTION 5 What are the strengths and weaknesses of the randomised controlled trial (RCT)
study design?
3


Answers needed to include the following points.

The RCT is a gold standard, level II evidence clinical trial allocating volunteers or subjects to one of two
groups i.e. a control and a treatment group.

Strengths lie in:
Ability to assign and administer treatment or intervention in a precise, controlled way (avoiding
differing techniques)
Randomisation of subjects or participants aims at decreasing selection bias and minimizing confounders
due to unequal distribution in a chosen population
Measurements, especially parametric data can be chosen precisely making it easier to make
observations consistently
Blinding is easier in RCT improving credibility plus decreasing patient or observer bias
Controlling of group allocations enhance similarity of baseline features so it is easier to form basis for
statistical hypothesis

Weaknesses include:
The increased expense and time consumption, difficult to organize/supervise if multiple sites/locations
Realization that results may not always mimic real life treatment situation
Risk of choosing treatments or subjects whose consent is not valid or unethical treatment is involved

Some other valid points were made:
If a small trial can include very stringent parameters which are somewhat of an academic nature but will
decrease Type I errors as well as test efficacy. Such RCT may lack applicability and be too specific for
a chosen population.
Can make the trial large
o good for detecting small but clinically relevant conclusions
o more expensive yet decreasing Type II errors
RCTs can have subgroup analysis enhancing the usefulness for clinical practice.
A successful RCT with conclusive or inconclusive results is eminently publishable.

QUESTION 6 Compare and contrast neostigmine and the organophosphorus compounds.


The main points expected in the answer in order to pass were considered under three main headings (i)
pharmacokinetics (ii) mode of action and (iii) pharmacological effects, mainly due to increased acetylcholine.
A common mistake was to not discuss the actions of the drugs.

They are both anti-cholinesterases which inhibit both acetylcholinesterase and plasma cholinesterase. There are
important differences in polarity and lipid solubility which contribute to contrasting distribution in the body for
the two compounds. Neostigmine is not distributed to the central nervous system (CNS) whereas
organophosphorus compounds are widely distributed including the CNS. Neostigmine is an ionised water-
soluble compound which has hepatic and renal elimination. Organophosphorus compounds depend on synthesis
of acetylcholinesterase because of the stability of the enzyme-inhibitor complex and a process called aging.

4
The mode of action for neostigmine at the target enzyme is similar to the way acetylcholine is handled, except
the covalent bond of the carbamoylated enzyme is considerably more resistant to hydration and leads to a
prolonged thirty minute duration of effect. Organophosphorus compounds have a half-life of weeks to months
because of phosphorylation of the esteratic site covalent bond. Inhibition of acetylcholinesterase not only
increases the concentration of acetylcholine at the neuromuscular junction but at all other synapses that use
acetylcholine as a transmitter. These include the muscarinic receptors of the parasympathetic nervous system,
the nicotinic receptors of the autonomic ganglia, and the smooth muscles especially of the respiratory and
gastrointestinal tract. Organophosphorus compounds have CNS muscarinic effects that include excitation,
confusion and coma.

QUESTION 7 Outline the factors which influence the elimination half-life of propofol.


This question focused on the application of pharmacokinetics principles to the systemic elimination of propofol.
Therefore, candidates were expected to provide a definition of the determinants of elimination half-life and its
mathematical model with factual data representative of propofol. Factors that affected hepatic clearance of
propofol in particular liver blood flow, severe liver disease, drugs and age should have been mentioned.
Enzymatic activity has little influence in the face of the high hepatic extraction ratio of propofol. Similarly,
factors affecting volume of distribution at steady state like body fat content should have been mentioned.
Many candidates presented irrelevant information such as indications, comparative kinetics with thiopentone
and lengthy description of propofol kinetics by infusion.

Candidates who mentioned the effects of individual patient variability, hypothermia and critical illness on
elimination half-life gained extra marks.

QUESTION 8 List the classes of drugs used clinically to treat chronic left ventricular failure.
Outline their mechanisms of action.


A good answer included information on ACE inhibitors, beta-blockers, diuretics, digoxin and nitrates. Mention
could also be made of calcium channel blockers, orally administered phosphodiesterase inhibitors and new
drugs, but preferably with comments about why they are not often used in the treatment of chronic failure.
Ideally, mechanisms included the cellular or receptor mechanism of drug action and effects of preload,
contractility, afterload and alterations in renal function.

Most candidates omitted one or more of the major drug classes. Many candidates spent a lot of time describing
drugs used in the management of acute or acute-on-chronic failure, such as adrenaline, dobutamine, oxygen,
calcium, glucagon and phosphodiesterase inhibitors. Some discussed drugs used in the treatment of associated
conditions such as hypertension or ischaemic heart disease. Some candidates wrote about drugs that are not used
currently in chronic heart failure such as hydrallazine and sodium nitroprusside.

5
VIVA SECTION

INTRODUCTORY PHARMACOLOGY TOPICS:

General topics
Bio-availability
Pharmaceutics; thiopentone, propofol, local anaesthetics,
Pharmacokinetics; midazolam, propofol
Anaphylaxis
Isomerism
IV fluids, properties and kinetics
Opioids
Mechanism of action
Adverse effects
Remifentanil; kinetics, dynamics
Advantages, disadvantages
Choice of opioid
Cholinergic, anticholinergic drugs
Atropine
Inhalational agents
Speed of induction
Fa/Fi curves
Time to awakening
MAC
Structure activity
Nitrous oxide
CVS and CNS effects of inhalational agents
Desflurane and sevoflurane
Tocolytics and mechanisms of action
Adverse effects of magnesium and salbutamol
Oxytocics
Adverse effects of oxytocics
Local anaesthetics
Factors effecting toxicity
Lignocaine and bupivacaine toxicity
Toxic doses
Management of toxicity
Structure activity
Kinetics
Induction agents
Ketamine; CVS, CNS effects
NMDA receptor
Propofol; CVS, CNS effects
Pharmacokinetics of induction and recovery
Effect site concentration
6
Anti-arrhythmic drugs
Classification
Pharmacological management of ventricular fibrillation
Amiodarone
Lignocaine
Sotalol
Kinetics
Adverse effects
Recovery from non-depolarising relaxants
Assessment of recovery
Cisatracurium and vecuronium
Diuretics
Classify
Mechanism of action
Pain
NSAIDS; classification, kinetics, mechanism of action, adverse effects
Opioids
Anticonvulsants
Classify
Phenytoin
Adrenoceptor blocking agents
Beta blocker pharmacodynamics
Adverse effects
Pharmacology of adrenaline
Vasopressin
Drug therapy of myocardial ischaemia
Calcium channel antagonists
Statistics
Types of data
Parametric and non parametric tests
Anticoagulant and anti-platelet agents
Adverse effects
Heparin and LMWH

PHYSIOLOGY

WRITTEN SECTION




QUESTION 9 Describe how carbon dioxide is produced in the body. How does it move from
the site of production to the pulmonary capillary?


The points required for a pass included
Site of production of carbon dioxide
Amount of carbon dioxide produced
A brief description of the mechanism of production
The transfer of carbon dioxide from its site of production to the blood down its concentration gradient
The mechanisms of carriage of carbon dioxide in the blood
The amounts carried in each form

Additional credit was given for
An explanation of the Haldane effect
The differences in carbon dioxide with different substrates
Situations in which there is greater or less production of carbon dioxide
Normal values for the partial pressure of carbon dioxide in venous blood

Common errors included
Failure to understand that carbon dioxide is produced with aerobic metabolism
A description of the arterial carriage of carbon dioxide rather than venous carriage
Describing the elimination of carbon dioxide, which was not asked for in the question

Common omissions included
The transfer of carbon dioxide from the mitochondria to blood
The presence of a concentration gradient down which carbon dioxide moves

QUESTION 10 List the physiological factors which affect left atrial pressure and explain their
effects.


Candidates were rewarded one mark for each correct factor they listed. The list of factors could be considered
in three categories:
Venous return: influenced by blood volume, posture, venous tone, intrathoracic pressure and
intrapericardial pressure
Left ventricular emptying: influence by contractility and afterload
Left ventricular filling: influenced by the diastolic compliance and mitral valve disease.

Additionally, listing variations in heart rate and obstruction to pulmonary flow were rewarded with additional
marks.

8
For the second part of the question, marks were awarded for a statement as to how the left atrial pressure
(LAP) would be affected by a change in each of the factors listed by the candidate. Whilst a statement of the
range of normal LAP gained further credit, the range of pressures quoted was often incorrect.

Many candidates only listed a few of the factors that affect LAP thus limiting the mark they could expect to
achieve. A common misunderstanding was the effect of an increase in intrathoracic pressure on the LAP with
many candidates concluding that IPPV will increase the LAP.

QUESTION 11 Briefly explain how oximetry can be used to estimate the partial pressure of
oxygen in a blood sample.


This question required integration and application of knowledge about oximetry and the oxygen haemoglobin
dissociation curve. Candidates were expected to briefly cover how an oximeter measured haemoglobin
saturation in a blood sample, the Beer Lambert law either as a formula or as a written description and the link
between haemoglobin saturation and partial pressure of O
2
via the oxygen haemoglobin dissociation curve
with some common values.

Better candidates also described the assumptions and the inaccuracies made in the link between haemoglobin
saturation and partial pressure of O
2
, eg shift of the oxygen haemoglobin curve with changes in pH, pCO
2
,
temperature, 2,3 DPG, the difficulty in deducing pO
2
when haemoglobin is fully saturated due to the flat upper
portion of the oxygen haemoglobin curve.

Common mistakes included writing about the Clark electrode, oxygen content of blood, discussion of pulse
oximetry and its inaccuracies, applying the effects of other types of haemoglobin on pulse oximetry to co-
oximetry of a blood sample and claiming that oximetry measured the oxygen in the blood directly.

QUESTION 12 Briefly describe the secretion and functions of renin and angiotensin.


This question was asked in a slightly different form in July 2002 and attracted a similar pass rate at that time.
The main points that would gain a pass were:
A description of the site of release of renin.
The main stimuli that lead to the release of renin, including a reduction of systemic blood pressure and
extracellular fluid, an increase in sympathetic stimulation and a decreased delivery of solutes to the
macula densa.
The cleaving angiotensin I from angiotensinogen by renin.
The conversion of angiotensin I to angiotensin II by the action of angiotensin converting enzyme,
mainly by contact with pulmonary endothelium.
A description of the main functions of angiotensin II, including vasoconstriction, alteration of
glomerular filtration rate, direct action on the renal tubules and stimulation of aldosterone secretion.
The ability of angiotensin II to inhibit the secretion of renin.
This process leading ultimately to conservation of sodium and water.

Additional information that attracted further marks included:
Detailed information about the process of renin secretion.
Describing other stimuli for renin secretion over and above those described above.
Explaining the site of synthesis of angiotensinogen.
A description of the size, structure and half-lives of renin and the various subtypes of angiotensin.
Other functions of angiotensin II, over and above those described above.
The relative potency of angiotensin III.
More detailed descriptions of the intimate processes and interactions of the system.

Common mistakes or omissions included:
9
Confusion over the exact cells that secrete renin.
Inexact descriptions or omissions of the interrelationship of renin to angiotensin.
Confusion over the way solute load reaching the macula densa affects renin secretion.
Incorrect associations with the process of tubuloglomerular feedback.
Very detailed and often correct descriptions of the actions of aldosterone and vasopressin, at the
expense of the required information.

QUESTION 13 Describe the functions of the gastric secretions.


The question asked about gastric secretions and their actions. Lengthy descriptions of the control of gastric
secretions did not attract marks and would have consumed a significant component of the time available.
Some answers did not go beyond control of gastric secretions and did not answer the question asked.

The constituents needed to be identified, namely HCl, pepsinogen, mucus and bicarbonate, intrinsic factor (IF)
and gastrin. Additional points were attracted for mention of other constituents e.g. gastric lipase and their
functions.

The breakdown of the action of each of these components was useful in an organised answer to the question.

Example: HCI
Main points such as activation of pepsinogen to pepsin by HCl, its direct proteolytic action, its bactericidal
property and its effect on innate immunity. Additional points were attracted for discussion of its effect on
ferric ion to its more soluble ferrous form, and its stimulant action on biliary and pancreatic secretions.

A similar approach could have been adopted for the other products.

QUESTION 14 Briefly describe the difference between a single twitch and a tetanic contraction
in a skeletal muscle fibre. Include in your answer the physiological basis for the
development of a tetanic contraction.


This question required an understanding of the physiological basis of a single twitch versus a tetanic
contraction. In particular, it was expected that the answers made reference to the following concepts with
regards a tetanic contraction:
The requirement for repetitive stimulation
The importance of the frequency of the stimuli
The difference between incomplete tetanic contraction and complete tetanic contraction
The critical frequency required for tetanic contraction and its relationship to the single twitch
duration for that fibre
That the contractile mechanism of skeletal muscle has no refractory period

Candidates also earned marks for outlining the sequence of events from motor nerve action potential to muscle
depolarisation and subsequent contraction. Some candidates included a comparison with cardiac muscle action
potential and its important differences regarding the question of tetanic contraction.

The most common errors related to confusion regarding what is summating or fusing in a tetanic response.
This mainly was in relation to whether it was the action potential or the contractile response or both that were
summating in tetanic type contractions.
10
QUESTION 15 Describe the mechanism of action of G-proteins in the cell.


To achieve a pass mark, it was expected that the answer would include:
An indication of the general concept of G-proteins acting as a kind of transducer, converting an extra-
cellular event (ligand associating with a G-protein coupled receptor (GPCR)) into a series of intra-
cellular events involving 2
nd
messenger systems.
A summary of the sequence of events that occurs in this transduction i.e. ligand binds to receptor,
brings about a conformational change such that the -subunit of the G-protein binds GTP, then
dissociates from the subunits. The -GTP then activates a 2
nd
messenger system, or directly acts
upon an ion channel, in some cases the subunit can also activate ion channels. The intrinsic GTP-
ase of the -subunit acts as a self-limiting step to deactivate and allow recombination of the subunits.
Mention of at least a couple of different kinds of G-proteins e.g. Gs, Gi, Gq, Gt, etc and their
associated 2
nd
messenger systems e.g. adenylate cyclase/cAMP, PLC/IP
3
/DAG, cardiac K-channels,
etc.
Preferably, examples of receptors associated with each of the mentioned G-protein types.

Extra marks were obtained for a detailed description of the mechanism described above, including for
mentioning and understanding such features of the system as amplification, self-regulation, uni-directionality
and sustained duration; for more complete lists of G-protein types and associated 2
nd
messengers; for accurate
description of the structure as currently appreciated; and also for mention of the existence of small G
proteins and their role in intracellular organelle function and gene expression.

Common mistakes, none of which precluded passing the question as a whole, were:
describing the G-protein as either a receptor or as a 2
nd
messenger. Often answers began by saying the
G-protein was a receptor then describing the process outlined above where the GPCR is a separate
entity. ,
stating that G-proteins are guanine nucleotides or similar comments
describing the role of ATP rather than GTP in activation
describing the structure of G-proteins as serpentine, 7-trans-membrane-spanning, or similar

These errors suggest an inability to distinguish between various concepts of signal transduction, receptor
function and intracellular functions. Some answers resembled a lucky-dip of terms and concepts.

Some answers gave great detail on the roles of cAMP, DAG, IP
3
etc which while usually correct was not
relevant and so did not score marks.

QUESTION 16 Explain the physiological processes involved in the development of interstitial
oedema.


The main points were: the variables contributing to Starling forces, lymphatics, and mechanisms changing
these variables. Amongst others, these mechanisms included decreased arteriolar tone, increased venous tone,
and increased permeability and surface area.

Additional points were definitions of oedema and the interstial space, and that as oedema develops changes in
the interstitial Starling variables limit the formation of oedema.

This was an applied physiology question; the most common omission was discussion of how Starling forces
contribute to oedema rather than the normal balance of the forces and many candidates repeated information or
discussed the consequences of oedema rather than the development of oedema.
11
VIVA SECTION

INTRODUCTORY PHYSIOLOGY TOPICS:

Cardiovascular
Radial artery pressure-time waveform
o Comparisons to aortic trace
o Changes with ageing
Define preload and afterload
o Frank Starling relationship
ECG complex
Action potential phases & ion currents in cardiac muscle
Pressure vs. volume loop for left ventricle
Fetal circulation and changes at birth
Cardiac effects of IPPV
Respiratory
Respiratory quotient and respiratory exchange ratio
Effects of breathing low FiO
2

The oxygen cascade
Arterial PO
2
and changes with age
Ventilatory response to raised CO
2

Shunt
Dead space
FRC and its measurement
Closing volume / closing capacity
Normal capnograph tracing
o Changes with disease states and equipment variations
Expiratory volume vs. time graph
Pulmonary blood flow and its measurement
Renal/Acid-Base
Renal handling of glucose
Renal handling of water balance
o Maximal diuresis
Fluid osmotic changes in the loop of Henle
Metabolic acidosis
o Compensation
Metabolic alkalosis
Liver/Metabolic/Endocrine
Hormones released by the thyroid
Changes with fasting
Aerobic vs. anaerobic metabolism
Calcium levels in blood
o Control
12
Thermoregulation
Normal body temperature
o Causes of heat loss
Thermoneutral zone
Body Fluids & Electrolytes
Distribution of body water
o Measurement of compartments
Haematology / Immunology
Anaphylaxis
Classification of hypersensitivity reactions
Contents of a unit of packed cells
Measurement
Defining heat / temperature
Measurement of temperature
Methods of measurement of BP
Define transducer
Nervous System
Normal cerebral blood flow
Factors controlling CBF
Measurement of CBF
Define ICP, normal values
Pathways involved in pain transmission
Sleep
Musculoskeletal / Cellular
Contrast different types of muscle
Describe a sarcomere

D B F COTTEE
CHAIRMAN
PRIMARY EXAMINATION

ABN 82 055 042 852

EXAMINATION REPORT

PRIMARY EXAMINATION

FEBRUARY/MARCH 2004

PLEASE NOTE THAT THIS REPORT IS PREPARED TO PROVIDE CANDIDATES AND
THEIR TEACHERS AND SUPERVISORS OF TRAINING WITH INFORMATION ABOUT THE
WAY IN WHICH THE PERFORMANCE OF CANDIDATES IN THE RECENT EXAMINATION
WAS ASSESSED BY THE EXAMINERS, SO THAT CANDIDATES AND TEACHERS MAY
PREPARE APPROPRIATELY FOR FUTURE EXAMINATIONS. THE INDIVIDUAL REPORTS
ARE NOT INTENDED TO REPRESENT MODEL ANSWERS NOR IMPLY THAT ALL POINTS
MENTIONED ARE NECESSARY IN ORDER TO ACHIEVE A PASS. ALL TRAINEES ARE
URGED TO READ THE QUESTIONS CAREFULLY AND ANSWER THE QUESTION ASKED.
ALL TEACHERS AND SUPERVISORS OF TRAINING ARE ENCOURAGED TO DISCUSS
THIS REPORT IN DETAIL WITH CANDIDATES THEY ARE PREPARING FOR FUTURE
EXAMINATIONS.

PHARMACOLOGY

WRITTEN SECTION




QUESTION 1 Describe the effects of isoflurane on intracranial metabolism, intracranial
haemodynamics, intracranial pressure and the EEG.


This question examined core material relating to a commonly used inhalational anaesthetic agent.

The main points expected included; significant dose-dependent reduction in cerebral metabolism by
isoflurane, indication of direct and indirect influences on cerebral blood flow with cerebral
vasodilatation and increasing cerebral blood flow at 1 MAC, maintenance of autoregulation at low
concentrations, increased intracranial pressure in parallel with increasing cerebral blood flow,
influence of CO
2
on intracranial pressure and EEG features of an initial increase in frequency
followed by decreased frequency and increased amplitude then burst suppression and electrical
silence with increasing MAC.
2
Additional marks were awarded for; demonstrating points with clearly labelled graphs, correlating
effects with MAC values, noting increasing supply:demand of cerebral blood flow with increasing
MAC, noting possible increased reabsorption of CSF with no effect on CSF production and noting
the anticonvulsant action of isoflurane.

Some candidates were unclear about the final balance of the major determinants of cerebral blood
flow and intracranial pressure, indicating that flow and pressure were reduced by isoflurane. Many
did not indicate that the ICP rise could be attenuated by hypocarbia.

No credit was given for irrelevant information about the structure and physicochemical properties of
isoflurane supplied by many candidates.

QUESTION 2 Outline factors determining speed of onset of neuromuscular blocking
agents.


This question had been asked in the 1999 July paper.

The main factors for a pass mark were:
Dose of agent noting that multiples of ED
95
had faster onset of action compared to lower
doses.
Potency of the agent noting that more potent agents have a slower onset of action compared to
equivalent doses of a less potent agent, with an explanation of this effect.
The effect of cardiac output and the perfusion to muscle groups to distribute the agent.
Relevant physicochemical properties of the agents and an explanation of their relevance.

Additional marks were awarded for identifying and explaining the differences in speed of onset
between depolarising muscle relaxants and non-depolarising neuromuscular blocking agents,
discussion of the different speed of onset between different muscle types and groups, the effects of
different routes and sites of administration and the priming principle on speed of onset, the effects of
other drugs and the effects of age and relevant disease states.

Three common mistakes were:
Candidates confused the term dose with the term concentration. The two are significantly
different and are not interchangeable.
Description of Ficks Law without any attempt to interpret or explain its relevance to the
question.
There appeared to be considerable confusion between the term speed of onset and the term
onset time. An increased speed of onset will result in a reduction of the onset time. Great
latitude was given in this matter but candidates are advised to consistently refer to one or the
other to avoid confusion and not use the terms interchangeably

3
QUESTION 3 Briefly describe the factors that determine skin penetration by local
anaesthetics. Briefly describe the formulation and pharmacology of
EMLA cream.


Marks available were divided equally between the two parts of the question.

An understanding of Fick's Law of Diffusion related to i) the structure of the skin, and ii) the
properties of representative local anaesthetic agents.
Defining "eutectic", details of how EMLA is formulated and administered to overcome the
barriers described in the first part of the question, and aspects of the pharmacology of
lignocaine and prilocaine relevant to the use of EMLA.

Candidates achieving high marks presented detailed, integrated information showing a higher degree
of understanding in both parts of the question.

There was confusion about the definition of "eutectic" with a number of candidates writing that it
referred to a lowered boiling point of the mixture. A "eutectic mixture" is the mixture of constituents
at a ratio that produces the lowest temperature melting point.

Candidates and tutors will find relevant information in "Dermatological Pharmacology" in Goodman
& Gilman in addition to texts covering local anaesthetic pharmacology.

QUESTION 4 Outline the effects of an opioid injected into the spinal intrathecal space.


One good approach to this question was to identify the three main mechanisms by which intrathecal
opioids act: (i) local effect at receptors in the dorsal horn of the spinal cord, (ii) higher centres in the
brainstem and via bulk flow of CSF, (iii) central effects following systemic absorption via the
epidural venous plexus.

The main points attracting higher marks included an outline of the spinal opioid receptors and
additional discussion of the mechanisms of spinal analgesia, a brief outline of the relevant
pharmacokinetics (explaining why a small dose is effective), variation in lipid solubility, and major
adverse effects such as pruritis, urinary retention and late respiratory depression. Other points that
attracted marks included the differential effect on A-delta and C pain fibres and unique features of
some opioids (pethidine, remifentanil).

Poorer candidates did not discriminate between the effects of intrathecal and other routes of
administration. Specific treatment of each of the adverse effects was not required.

4
QUESTION 5 Outline the effects of liver failure on drug kinetics and dynamics.


The effects on kinetics to outline included:
Absorption; decreased absorption eg; Vit K
Bioavailability; decreased first pass metabolism
Metabolism and decreased clearance; decreased enzymatic degradation with decreased
clearance of low extraction ratio drugs, decreased hepatic blood flow and decreased clearance
of high extraction ratio drugs, decreased pseudocholinesterase levels, decreased biliary
excretion and potentially decreased renal clearance
Distribution; increased volume of distribution for water soluble drugs, decreased levels of
albumin and acid glycoprotein with decreased protein binding

The effects on dynamics to outline included:
Encephalopathy and potential interaction with CNS depressants
Coagulopathy and potential drug interactions
Potential for increased hepatotoxicity

Candidates frequently did not outline the effects on metabolism, biliary excretion, protein binding
and pharmacodynamics.

QUESTION 6 Outline the circulatory effects of glyceryl trinitrate.


Most candidates understood the drugs mechanism of action. Good answers included not only the
direct effects of glyceryl trinitrate on blood vessels but also how those effects lead to favourable
changes in the myocardial oxygen supply and demand ratio.

Many candidates also gave a brief description of glyceryl trinitrates effects in pathological states,
such as in myocardial ischaemia, cardiac failure and hypovolaemia.

Fewer candidates outlined the effects of glyceryl trinitrate on other organ circulations such as the
pulmonary, uterine and cerebral circulations or possible effects on platelets.

QUESTION 7 Describe the mechanisms of action of inotropes and provide examples.


Main points expected included:
Definition of inotropes
Roles of c-AMP and intracellular Ca
2+
in promoting cardiac contractility
Beta-1 agonists, cardiac glycosides, phosphodiesterase inhibitors (III) and their mechanisms
of action

Credit was given for mention of glucagon and calcium.

5
Common errors included:
Failure to define inotropes or stating that inotropes were agents which increased blood
pressure and discussing alpha agonists at length
Many candidates wrote about sympathomimetic agents or catecholamines including those
which act predominantly by vasoconstriction

QUESTION 8 Describe briefly the side effects and complications of heparin therapy.


The question specifically requested the candidate to address the side effects of heparin therapy.
Detailed accounts of the mode of action of heparin were frequently included however only in those
answers where this information was related to the mechanism of side effects were these of value.

To obtain a pass in this question, it is necessary to recognise that side effects can be predictable and
dose related, e.g. bleeding, or idiosyncratic, such as the heparin induced thrombotic
thrombocytopenic syndrome. Particular reference to intercurrent pathology and drug interactions
was valuable.

Although many candidates commented on APTT measurement, its significance relates to the narrow
therapeutic range and unpredictable effective dose of heparin; few candidates mentioned this.
Differentiating the mechanisms of platelet effects is important in view of therapeutic and prognostic
implications.

Most candidates were aware of alopecia and osteoporosis as side effects, frequently not mentioning
the situations in which these occur. Mention of low molecular weight heparins was appropriate,
however comparisons often were omitted.

Many candidates gave a fairly detailed account of complications of protamine therapy, which was not
asked; the requirement for protamine might better be perceived as a disadvantage of heparinisation,
particularly at high doses.
6
VIVA SECTION

INTRODUCTORY PHARMACOLOGY TOPICS:

General topics
Bio-availability
Adverse drug reactions
Mechanisms of drug action
Anaphylaxis
Drug interactions
Esterases
Drug dose response
Bronchodilators
Isomerism
Poisoning

Opioids
Mechanism of action
Adverse effects
Pharmacokinetics of morphine
Remifentanil
Antagonists

Cholinergic, anticholinergic drugs
Muscarinic cholinergic synapse
Drug actions
Acetylcholine receptors
Donepezil, tacrine
Compare the anticholinesterases
Organophosphate poisoning

Inhalational agents
Speed of induction
Fa/Fi curves
Time to awakening
MAC
Structure activity
Sevoflurane in infants and adults
Sevoflurane compared to halothane
Nitrous oxide

7
Tocolytics and mechanisms of action
Adverse effects of magnesium and salbutamol
Oxytocics
Adverse effects of oxytocics

Local anaesthetics
Factors effecting toxicity
Lignocaine and bupivacaine toxicity
Toxic doses
Management of toxicity
Structure activity
Kinetics

Induction agents
Ketamine; CVS, CNS effects
NMDA receptor
Propofol; CVS, CNS effects
Thiopentone
Pharmacokinetics of induction and recovery

Anti-arrhythmic drugs
Pharmacological management of ventricular fibrillation
Amiodarone
Lignocaine
Sotalol

Kinetics
Adverse effects
Recovery from non-depolarising relaxants
Assessment of recovery
Plasma cholinesterases

Diuretics
Classify
Mechanism of action
Compare frusemide and spironolactone

Pain
NSAIDS; mechanism of action, COX-2, offset of action
Paracetamol toxicity
Tramadol
8
Antidepressants
Classify
Drug interactions

Adrenoceptor blocking agents
Classify beta blockers
Esmolol
Adverse effects

Histamine and serotonin
Classify drugs acting via serotonin effects
Serotonin receptors
Histamine effects and receptors

Vasoactive drugs
Classify vasoactive drugs
Catecholamines
Pharmacology of adrenaline
Vasopressin

Statistics
Drug trials
Types of data
Chi squared

Antiemetics
Adverse effects

PHYSIOLOGY

WRITTEN SECTION




QUESTION 9 Briefly outline the differences between the pulmonary circulation and the
systemic circulation.


The main points expected for a pass were differences in anatomy, function, haemodynamics
(especially pressure, resistance and the affect of lung volume and gravity) regulation of the
circulation and other functions such as filtering.

Common errors were as follows:
to treat this as a compare and contrast question. Many candidates wrote how the pulmonary
circulation was controlled and how the systemic circulation was controlled. Only the
differences were required.
many candidates gave lists of the functions of the pulmonary circulation, not differences eg.
The blood reservoir function of the lung which is also present in the systemic circulation.
to state eg. pulmonary vascular resistance is affected by lung volume and not to say how it
is affected. A statement like this does not receive marks.

The best candidates were well organised, wrote only the differences between the circulations and
gave brief explanations.

QUESTION 10 Describe the vasoactive substances released by the endothelium. Explain
the role they play in regulating blood flow through the peripheral
circulation.


The key vasoactive substances released from the endothelium are nitric oxide, prostacyclin and the
endothelins.

The main points expected for a pass were to describe the formation of these substances and pathways
by which they interacted with vascular smooth muscle. Also required was an understanding that
these paracrine substances are vasoactive regulators, helping match regional perfusion to metabolic
demand. Additional points were awarded for listing the factors which stimulated or inhibited release
of these substances; hormones, local metabolites and changes in wall tension.

Common errors were to describe the role of the endothelium in coagulation in fibrinolysis, and to
describe the physics of blood flow.
10
QUESTION 11 What is 2,3 DPG? How is it produced in the red blood cells and how does
it interact with haemoglobin? What is its relevance in altitude exposure,
anaemia, and stored blood?


Main points expected for a pass included a definition of 2,3 DPG, and a brief description of the
metabolic pathway involved in production. Also required was a description of the interaction with
haemoglobin defining the right shift in the haemoglobin-oxygen dissociation curve, with extra marks
awarded for differences with fetal haemoglobin. The role of pH change in altering the production of
2,3 DPG also attracted additional marks.

Required also were the role of 2,3 DPG in allowing increased oxygen delivery in anaemia and during
altitude exposure, with additional marks awarded when the effects in the lung in the hypoxic
environment were included. The potential deleterious effects of a lack of 2,3 DPG in stored blood
was also required, with additional points given for inclusion of time-scale, and discussion of the
importance of different additives.

Overall the question was answered well by candidates, with problems occurring when parts of the
question were unanswered, or unclear. The use of diagrams aided in the explanations for most
candidates.

QUESTION 12 What are the physiological consequences of decreasing functional residual
capacity by one litre in an adult?


This question was last asked in March 2001.

As described then, to achieve a pass, candidates were expected to cover the majority of the following
points:
Some definition of FRC, being:
The equilibrium point of the lung & chest wall, or
The lung volume at the end of a normal tidal breath, or
Residual volume + Expiratory reserve volume
An approximate normal value: FRC 2.2L, or 30mL/kg.
FRC will fall below closing volume, resulting in:
Airway/alveolar closing with atelectasis
An increase in V/Q mismatch, shunt and arterial hypoxaemia
Increased work of breathing to open airways/alveoli
A decrease in lung compliance.
An increase in airways resistance
Increased work of breathing.
Increased pulmonary vascular resistance.
Decreased store of oxygen.

Additional marks were attained for the following:
11
Quantification of one litre as a significant (~40-50%) decrease.
Increased work of breathing being multifactorial:
compliance, and
airways resistance, and
critical opening pressure for collapsed alveoli
Decreased O
2
store
Increased breath-to-breath variation in PaO
2

Increased risk of hypoxaemia during induction of anaesthesia
Increased pulmonary vascular resistance RV work
Graphs indicating effect of changing volume/FRC on:
Compliance
Airways resistance
Pulmonary vascular resistance

Many candidates duplicated material, first listing the functions of FRC in-depth, and then listing the
consequences of a decrease. While making a short list is a useful aid, repeating several pages of text
gains no additional marks and wastes valuable time. Some candidates wasted time writing about the
measurement of FRC, the respiratory changes in pregnancy, which were not asked. Vague answers,
such as may result in ABG deficits are not considered sufficient in detail.

QUESTION 13 Describe the concept of renal clearance and its use to estimate glomerular
filtration rate.


Renal clearance is a basic physiological concept, and its translation into glomerular filtration rate is a
straight-forward application of this concept.

Candidates were expected to provide some definition of clearance, with some detail on how the
elements of function of the kidney relate to clearance. These include filtration and tubular
reabsorption and secretion. Most candidates were able to provide a reasonable definition of
clearance, although there were a significant number of errors.

The inclusion of any discussion about glomerular filtration and tubular function was a common
omission in a number of answers. In a number of cases, extensive detail was provided on the
mechanisms of filtration at the glomerulus, but this did not attract significant additional marks.

Inclusion of some basic formula about how clearance relates to plasma concentration and urinary
volume and concentration was an important inclusion in the answer. Quite a number of candidates
included an extensive derivation of this formula, but omitted more important facts.

The properties required of a marker, ideal for use in the measurement of glomerular filtration rate
was well described by the majority of candidates, and was an important part of the answer. Most
candidates included discussion of specific examples which can be used, such as inulin and creatinine.
Whilst this was generally done well, an understanding of the relationship between creatinine
concentrations, creatinine clearance, and glomerular filtration rate was not always apparent.

12
QUESTION 14 Briefly describe the difference between laminar and turbulent flow. List
the factors that increase the probability of turbulent flow.


The question most naturally fell into three areas:
A description (and diagrams) of the nature of laminar and turbulent flow and the significance
this might have for passage of fluid through a tube.
A description of the different ways that laminar and turbulent flow are related to pressure,
radius and length of tubing, viscosity and density. These were usually summarized by
equations (+/- graphs) with interpretation.
A description of how diameter, velocity, density and viscosity can be used to predict the
likelihood of turbulent flow, as summarized by the Reynolds number. This section should
also include mention of the geometry of the tube potentially affecting the nature of the flow as
the Reynolds number is for parallel-sided cylindrical tubing. Concepts of critical velocity,
entrance length and transitional or mixed flow types could also reasonably be included.

There were two main areas which created problems with understanding.
The relationship of turbulent flow to driving pressure, tube length and density was often
poorly described even when an acceptable equation was quoted. The meaning of the
equation was often not understood and commonly misrepresented in graphical form. Most of
the confusion arose from difficulties dealing with the flow tending to vary with the square
root of pressure and radius to a power of 2 to 2.5 (i.e. the square root of the power 4 or 5)
depending on which source was quoted.
If these equations are written as driving pressure is proportional to: then flow will be
squared and radius to the 4
th
or 5
th
power. The fact that turbulent flow can not be described
by a simple equation and will vary with the degree of turbulence means that the study sources
will have slightly differing summaries of the relationships. These were all acceptable.
Although the Reynolds number can be incorporated into complex equations for predicting
rate of flow, for the purposes of this question the relevant property of the Reynolds number
was its ability to predict the likelihood of turbulence. This needed to be distinguished from
equations for estimating flow rates such as the Hagen Poiseuille for laminar flow or the
Fanning for turbulent flow. Some candidates tried to apply the Reynolds number equation to
describe factors affecting rate of turbulent flow rather than likelihood of turbulent flow. This
resulted in major errors in describing the factors affecting rate of turbulent flow.

13
QUESTION 15 List the physiological factors that determine intracranial pressure.
Explain briefly how intracranial pressure is regulated.


Main points expected for a pass included the definition, normal value and significance of intracranial
pressure, a description of the nature of the vault and its component contents and the factors that
influence the magnitude of those contents.

Additional points were awarded for discussion of the idea of ICP being non-uniform, the separation
of cerebral blood flow from cerebral blood volume and other physiological factors that can change
ICP (e.g. posture, intra-thoracic pressure)

Common errors included directionless relationships, graphs with unlabelled axes, a misstatement of
the Monro-Kellie hypothesis and the inclusion of details about the effects of pharmacological agents
on ICP.

QUESTION 16 Explain how the kidney handles glucose. Describe the physiological
consequences of glycosuria.


Glucose is freely filtered in the glomerulus and reabsorbed in the proximal tubule.
The mechanisms of re-absorption involve secondary active transport and facilitated diffusion.
The energy for this process is provided by Na/K ATPase.
The amount absorbed depends on the amount filtered (up to a transport maximum).
Glycosuria leads to:
Diuresis and dehydration caused by osmotic effects and medullary dilution
Loss of sodium (and other electrolytes) leading to hypovolaemia and subsequent
homeostatic responses
Loss of energy substrate

Quantification of rate of re-absorption and glycosuria.
Details of (co)-transport mechanisms involved in re-absorption SGLY and GLUT
Heterogeneity of the saturation of reabsorption mechanisms manifest as splay.
Increased chance of urinary infection with glycosuria.
14
VIVA SECTION

INTRODUCTORY PHYSIOLOGY TOPICS:

Cardiovascular
Radial artery pressure-time waveform
LV pressure-time trace
RA (CVP) pressure-time trace
Preload
correlation with PAOP
Determinants of myocardial O
2
supply and demand
Bodys response to haemorrhage (15%BV)
Normal coronary blood flow and measurement
Autoregulation
Contractility
methods for measurement
ECG Complex:
waves, intervals
action potential phases & ion currents
Cardiac function curve
Vascular function curve

Respiratory
Classification and causes of hypoxia
Alveolar gas equation
RQ
Arterial blood gas measurement
Shunt
Dead space
Closing volume / closing capacity / FRC
differences in the neonate & with pregnancy
Work of breathing
influence of changes in resistance and compliance
Resistance to breathing
Static and dynamic compliance of the lung
Normal flow-volume loop
changes with various disease states
Pulmonary surfactant
Normal capnograph tracing
changes with disease states and equipment variations
Intrapleural pressure vs. time
Pneumotachograph
Flow vs. volume during respiratory cycle
15
Oxygen stores in the body
changes breathing X% O
2
for 10 minutes
Physiological consequences of isolated obstruction of:
the left pulmonary artery
the left main bronchus
CO
2
carriage in the blood
Distribution of PO
2
, PCO
2
, pH and V/Q in the upright lung
HbO
2
dissociation curve
normal, pregnant & foetal values

Renal/Acid-Base
Functions of the kidney
Renal handling of water balance
minimum and maximum urine osmolality
Renal maintenance of intra-vascular volume
Renal handling of acid-base balance
titratable acidity vs. renal hydrogen excretion
Renal blood flow and regulation of GFR
Tubular fluid osmotic changes along the nephron
Functions and regulation of ADH release

Liver/Metabolic/Endocrine
Glycolysis, glycogenolysis, gluconeogenesis
Hormones secreted by the pancreas
Hormones released by the thyroid
Metabolic changes of pregnancy

Thermoregulation
Normal body temperature
causes of heat loss

Body Fluids & Electrolytes
Distribution of body water
measurement of compartments

Haematology/Immunology
Anaphylaxis
Classification of hypersensitivity reactions
Immunoglobulins
Haemostasis
Coagulation process and assessment of function
Constituents of fresh frozen plasma
16
Requirements for cross-matching
Changes which occur in stored blood
Fibrinolysis

Measurement
Heat / temperature
Measurement of temperature
Humidity
Principles of pulse oximetry
Principles of end-tidal CO
2
measurement
Methods of measurement of BP
aspects of fidelity for intra-arterial measurement

Nervous System/Cellular
Role of GABA receptors in the CNS
Role of the Nernst equation
Normal cerebral blood flow
Factors controlling CBF
Pathways involved in pain transmission
Normal EEG waveforms

D B COTTEE
CHAIRMAN
PRIMARY EXAMINATION

ABN 82 055 042 852

EXAMINATION REPORT

PRIMARY EXAMINATION

JULY/SEPTEMBER 2003

PLEASE NOTE THAT THIS REPORT IS PREPARED TO PROVIDE CANDIDATES AND THEIR
TEACHERS AND SUPERVISORS OF TRAINING WITH INFORMATION ABOUT THE WAY IN
WHICH THE PERFORMANCE OF CANDIDATES IN THE RECENT EXAMINATION WAS
ASSESSED BY THE EXAMINERS, SO THAT CANDIDATES AND TEACHERS MAY PREPARE
APPROPRIATELY FOR FUTURE EXAMINATIONS. THE INDIVIDUAL REPORTS ARE NOT
INTENDED TO REPRESENT MODEL ANSWERS NOR IMPLY THAT ALL POINTS MENTIONED
ARE NECESSARY IN ORDER TO ACHIEVE A PASS. ALL TRAINEES ARE URGED TO READ
THE QUESTIONS CAREFULLY AND ANSWER THE QUESTION ASKED. ALL TEACHERS AND
SUPERVISORS OF TRAINING ARE ENCOURAGED TO DISCUSS THIS REPORT IN DETAIL
WITH CANDIDATES THEY ARE PREPARING FOR FUTURE EXAMINATIONS.

PHARMACOLOGY

WRITTEN SECTION




QUESTION 1 Draw and label, on the same X Y axis, F
A
/F
I
curves for the following
halothane concentrations in oxygen, showing a 30 minute period from starting
administration.

(a) Halothane 1%, subject breathing spontaneously.
(b) Halothane 6%, subject breathing spontaneously.
(c) Halothane 6%, subject paralysed and ventilated.

With reference to the major factors determining the shape of F
A
/F
I
curves
explain the differences between A and B, and A and C.


Most candidates started the three curves from the origin satisfactorily. However the rise in F
A
F
I
is in fact
more rapid for curve (a) rather than (b) to the end point at thirty minutes.

2
Most candidates recognised the significance of the concentration effect on the rise in alveolar
concentration. However the effect is more modest on the F
A
/F
I
ratio, and textbooks discuss this effect
where ventilation is controlled.

6% halothane is a profound respiratory depressant in the unstimulated patient and this overrides the
concentration effect that most candidates quoted. Some candidates correctly mentioned the mild
reduction in cardiac output which would be seen with 6% halothane which would augment the rise in
F
A
/F
I
. However the effect on ventilation remains paramount.

Most candidates recognised the rapid and sustained rise in the F
A
/F
I
which would occur during controlled
ventilation with 6% halothane. Here the concentration effect and sustained ventilation act together to
produce a rapid rise in the F
A
/F
I
ratio.

Better answers included the effect of IPPV and 6% halothane on cardiac output, which is profoundly
reduced. This further segments the rise in F
A
/F
I
.

Some candidates who clearly had difficulty with the curves went back to first principles, describing the
various factors on F
A
/F
I
which earned valuable marks.

QUESTION 2 Describe the potential interactions of sevoflurane, desflurane and isoflurane
with carbon dioxide absorbents.


Different carbon dioxide absorbents exist and they vary with respect to the potential interactions
described.
A description of the specific interactions: sevoflurane resulting in compounds A E, desflurane and
isoflurane producing carbon monoxide.
Factors that accelerate or minimize these reactions.
The potential toxicity and clinical relevance of the products of these reactions.

Several candidates stated that the same factors increased the production of compound A and carbon
monoxide. This is only partially correct. Low flow and closed circuit techniques have not been implicated
in increased carbon monoxide production from desflurane. Soda lime dehydration actually decreases the
production of compound A from sevoflurane, this detail was known by only a very small number of
candidates.

Credit was also given for mentioning potential absorption and subsequent release of volatile agent by the
carbon dioxide absorbents.

QUESTION 3 Outline GABAs role as a neuro transmitter and indicate how its actions may
be modified by pharmacological agents.

63% of candidates passed this question but there were no outstanding answers. This question was also
asked in March 2001, when the pass rate was lower.

The answer should have recognized the importance of GABA as a major inhibitory neurotransmitter, and
given a description of the distribution and function of GABA and its receptors. Many candidates failed to
mention that there were different GABA receptors. A brief description of the neurophysiology of the
GABA receptors would have facilitated the subsequent description of how different agents modify the
action of GABA at different sites or by different mechanisms. Many answers did not clearly distinguish
3
the effect of benzodiazepines from that of barbiturates on the GABA receptor. A list of drugs acting on
the GABA receptor would not receive credit if the direction of effect was not indicated. Only a few
answers mentioned non-anaesthetic drugs that affected GABA.

QUESTION 4 Describe how a computer-controlled infusion device targets and maintains
constant blood concentrations of propofol.


The main points expected for a pass were:
Device contains microprocessor with algorithms for infusion.
Algorithms based on multi-compartment pharmacokinetic model for propofol.
User enters patients age, weight and desired target concentration. Typical concentrations range are 1
8 mcg/mL depending on the situation.
User adjusts target according to adjuvant drugs, co-morbidities or degree of surgical stimulation.
Computer designs variable-rate infusion.
Loading dose calculated as volume of distribution of central compartment times target concentration.
Maintenance infusion rate includes component for redistribution and component for elimination.

Additional points which attracted higher marks were:
Picture of multi-compartment model.
Graph of infusion rate and target concentration vs. time.
How the infusion rate changes if increased or decreased target entered.
Equation for calculation of maintenance infusion rate (redistribution and elimination).
The fact that the pharmacokinetic data are derived from a small group of volunteers.
Details of device hardware and syringes.
An appreciation of the fact that the Diprifusor calculates compartmental volumes and rate
constants based on the weight of the patient and does not use the age of the patient, the clearance or
the context-sensitive half-life to make its calculations.

Common mistakes and problems included:
Confusion of physiological models (i.e. vessel rich and poor groups) with the mathematical models
used in the current devices.
Confusion of targeting effect-site and blood concentrations.
Failure to appreciate that these devices achieve targets within 30-60 seconds without overshoot and
then maintain constant concentrations. Very few graphs reflected this accurately.
The current devices do not measure the actual blood concentration of propofol.

QUESTION 5 Describe the pharmacological effects of paracetamol. Outline its toxicity and
management.


Paracetamol is a commonly used drug in anaesthetic practise and the majority of candidates displayed a
good understanding of the drugs pharmacology and toxicity.

All candidates noted the analgesic and anti-pyretic actions of the drug, and the fact that it has little or no
anti-inflammatory activity. It is true that there is still some conjecture as to the exact mechanism of action
of paracetamol, but pass marks were given for citing the usual explanation of central cyclo-oxygenase
inhibition. Candidates who showed evidence of more extended reading and listed alternative theories
such as COX-3 inhibition or inhibition of 5HT reuptake at the spinal cord level were given credit.

4
With regard to the drugs toxicity, all candidates had a basic understanding of the mechanisms involved
in its adverse effects on the liver. Most were able to name the reactive intermediate produced (N-acetyl-p-
benzoquinoneimine) although there were a number of inventive spellings.

Hepatic toxicity was the main focus of most respondents, and extra marks were awarded to candidates
who were able to list other (less common) adverse effects, such as allergic reactions, skin rash and renal
impairment.

Again the section on management of paracetamol toxicity was generally well handled with all candidates
aware of the role of N-acetyl cysteine and the use of nomograms to predict the likelihood of liver damage.
In this part, extra marks were awarded for those who remembered that simple strategies can, in some
circumstances, be important in limiting paracetamol toxicity. Such interventions to reduce drug
absorption include the administration of activated charcoal and gastric lavage.

QUESTION 6 List the potential clinical uses of an alpha-2 adrenoceptor agonist and outline
the limitations of clonidine for each.


The list of potential clinical uses for alpha 2 adrenergic receptor agonists should include the following.
Anaesthesia and sedation, pain management, treatment of hypertension, premedication using anti-
sialogogue and anxiolytic properties, haemodynamic stability with a decrease in circulating
catecholamines and the reduction of intraocular pressure. Additional other clinical indications are in post
operative shivering and the treatment of opiate withdrawal syndromes.

The limitations of clonidine in these situations relate to its reduced potency as a partial agonist, and long
elimination half life. Its use is associated with hypotension and bradycardia which can be a disadvantage
in all the previously mentioned clinical uses. Most candidates understood and explained the acute
hypertension with bolus injection and rebound hypertension on withdrawal of clonidine. Sedation and dry
mouth can be a limitation except where desirable in use as a premedication. More selective alpha 2
agonists have greater MAC reducing properties than clonidine. A common omission of many candidates
was to not address the limitations of clonidine for each use, or to instead to explain adrenergic receptor
molecular pharmacology in great detail.

QUESTION 7 Write short notes on factors affecting the speed of onset and duration of effect
of local anaesthetics when used to produce peripheral nerve block.


Patient factors include:
Site of administration.
Nerve structure and function.
Tissue pH.

Drug factors include:
pKa and its effect on non ionised fraction.
Lipid solubility and its effect on potency and protein binding.
Concentration and volume added.
Intrinsic vasoactive properties.
Effect of local and distant metabolism.
Effect of different additives.

5
Common omissions were effect of local metabolism and site of administration. Listing the different
factors without indicating the direction of change and why the change is observed doesnt answer the
question.

Candidates were awarded more marks if they used the Fick principle to illustrate some of the principles,
using examples with correct numbers and if they mentioned physiological or pathological states such as
pregnancy and electrolyte disturbances.

QUESTION 8 Outline the pharmacological differences between neonates and adults with
reference to sevoflurane, vecuronium and morphine.


In order to pass the candidate needed to make a number of correct statements pertaining to the question.

These statements may have included, but are not limited to the following:
definition of neonate.
brief description of sevoflurane, vecuroniun and morphine.
definition of pharmacology-pharmacokinetics/dynamics.
kinetics: key differences between neonate and adult i.e. relativities of TBW, ECFV, comparison of
protein binding, renal and hepatic clearance, different ratios of ventilation and FRC.
dynamics: different sensitivities to drugs, permeability of BBB, sensitivity of resp centre.
morphine: in neonate increased t1/2 increased respiratory depression and apnoea.
sevoflurane: more rapid induction in neonate, reduced blood gas solubility, MAC higher in neonate
than adult.
Vecuronium: increased Vd reduced clearance increased t1/2 in neonate with increased sensitivity of
neuromuscular junction. Net effect dose per kg similar to adult.

Common omissions include widespread lack of definitions e.g. of neonate, drugs. No candidate referred
to the effect of prematurity on neonatal drug effects.

Common errors:
Many candidates were unclear as to the relative sensitivities of neonates to non-depolarising muscle
relaxants NDPMRs. Many stated MAC for sevoflurane is lower in neonates than adults. There was much
confusion over the effect of an increase in Vd for a polar drug. Many candidates stated that morphine
was a highly polar drug. Many stated that neonates have increased TBW and increased fat content
compared to adults.

Many answers appeared incomplete; suggesting that time management may have been an issue.

6
VIVA SECTION

INTRODUCTION TO PHARMACOLOGY QUESTIONS:

How can analgesic drugs be grouped?
What is your induction dose of propofol and why?
Draw a concentration- response curve for isoflurane.
What are some of the cardiovascular responses to spinal local anaesthetic?
What physiological factors affect a dose of propofol.
How do anti-platelet drugs work.
A set of data is presented. Asked to discuss what statistical tests should be used to interpret it.
What is heparin?
Discuss anti-cholinergic drugs.
Compare atropine and glycopyrrolate.
What are the CNS effects of propofol?
What variables are involved in time to wake up after ceasing isoflurane?
Local anaesthetic toxicity.
Contents of an ampoule of thiopentone.
What is meant by the term isomer?
What sort of a drug is neostigmime?
Draw a nephron and discuss where diuretics work.
What is the function of additives in an ampoule of propofol?
What drugs can be used to treat hypotension?
Describe the fate of a 100mg bolus dose of suxamethonium.
What is meant by the term normal distribution?
Discuss where drugs act in the renin-angiotensin system.
What are some of the side effects of nitrous oxide?
What are the differences between rocuronium and vecuronium?
How does theophylline work?
Describe the chemical structure of some inhalational agents.
What is a meta-analysis?
7

PHYSIOLOGY

WRITTEN SECTION




QUESTION 9 Describe the effects of tachycardia on myocardial oxygen supply and demand
in a normal heart.


The determinants of myocardial oxygen supply and demand.
The left ventricle is perfused mainly during diastole.
Tachycardia not only reduces the diastolic time and oxygen delivery to the left ventricle but also
increases oxygen demand.
Comparison of left and right ventricles; including coronary flow versus time graphs; and that flow in
the right ventricle is continuous and little affected by heart rate.
Subendocardium is most susceptible to ischaemia.
Vasodilation via metabolic mechanism increases flow

Extra points were given for detailing coronary blood flow, the high oxygen extraction, and for explaining
that oxygen supply cannot be increased by increasing extraction. Extra marks were also given for
describing pressure differentials in both ventricles in systole and diastole.

Common omissions or errors were:
To not label the diagrams.
To put no units on the axes.
To draw inaccurate traces.
To not list the determinants of myocardial oxygen supply and demand.
To ignore the right ventricle.
To mix up supply and demand.

QUESTION 10 Describe the role of baroreceptors in the control of systemic arterial pressure.


This question was asked in July/August 2000 and at that time the pass rate was 54%.

An overview of the role of baroreceptors in controlling blood pressure was expected. The high pressure
baroreceptors react via a negative feedback arrangement to rapidly regulate blood pressure changes by
changing cardiac output and systemic vascular resistance. The low pressure cardiopulmonary receptors
have a role in long term blood pressure control by regulation of blood volume.

8
Other points expected were:
Afferent pathways.
Central integration, and the reciprocal balance between sympathetic and parasympathetic system
Efferent pathways and effects, including hormonal.

Common omissions were to not describe the low pressure baroreceptors at all, or to describe the
sympathetic response without mention of the parasympathetic.

QUESTION 11 Briefly describe the potential causes of a difference between measured end-
tidal and arterial partial pressure of carbon dioxide.


The answer required consideration of both patient factors, and those errors and limitations of the
equipment and techniques used to monitor carbon dioxide both in the expired gas and arterial blood.

The effect of alveolar dead space on the difference between end-tidal and arterial CO
2
was recognised by
most candidates, and many included satisfactory explanations of the causes and potential underlying
pathologies, gaining extra marks. The commonly observed clinical effect of delayed alveolar emptying
with slow rise in expired CO
2
, leading to failure to obtain a true plateau, was usually overlooked, but
attracted extra marks when included.

Equipment problems expected to be included were leaks and occlusions, effect of sampling site and other
gases, and calibration errors. This area was overlooked completely by many candidates, leading to the
low pass rate. Most candidates that addressed both the patient and equipment components obtained a
good pass.

QUESTION 12 Explain the difference between perfusion limitation and diffusion limitation in
the transfer of gas between alveolus and pulmonary capillary. Outline the
factors that determine whether gas transfer is perfusion or diffusion limited.


The main points expected were a definition and explanation of both perfusion limitation and diffusion
limitation, as well as a description of the factors included in Fick's law of diffusion. It was expected that
candidates would provide some indication that diffusion limitation implies that that equilibration of gas
between alveolus and pulmonary capillary is incomplete. The factors affecting whether a gas is perfusion
or diffusion limited include the solubility of the gas, its partial pressure gradient, and the transit time of
blood through alveoli. It was expected that examples would be given, and that carbon dioxide and oxygen
transfer would be correctly categorised.

Additional marks were given for explaining the significance of the binding of the gas to haemoglobin,
and for discussing the effects of increased cardiac output and increased altitude on the transfer of oxygen.
A graph comparing the changes in red blood cell partial pressures of carbon dioxide and oxygen during
its transit through the pulmonary capillary attracted extra marks. Marks were given also for commenting
on the transfer of carbon monoxide, and for explaining that this is used to measure gas transfer.

Many candidates failed to provide definitions for perfusion and diffusion limitation, or provided incorrect
or opposite definitions. Others incorrectly categorised carbon dioxide and oxygen. Many candidates
commented on nitrous oxide or carbon monoxide transfer, without discussing carbon dioxide or oxygen.
Others failed to mention the factors included in Fick's law, thereby reducing the total marks possible.

QUESTION 13 Describe the factors that affect airways resistance.
9

64% of candidates passed this question and there were quite a number of excellent answers.

Better answers included a definition of Airways Resistance (AWR), invoking a version of Ohms law and
correctly ascribing units (either SI units or more commonly cmH
2
O/L/sec) and giving some idea of a
normal value. Also expected was an outline of the relative contributions of the upper and lower
respiratory tracts, the relationship between lung volume and AWR (best demonstrated graphically), the
concept of laminar and turbulent airflows and their effect on AWR (including a version of the Hagen-
Poiseuille equation and Reynolds number), the differing relationships between AWR, driving pressure,
flow and airway calibre in both turbulent and laminar flow states, and examples of physiological factors
that effect AWR (e.g. bronchomotor tone, respiratory rate, dynamic airways compression).

Common errors included:
Not mentioning units or wrong units (e.g. mmHg/L/min).
Incorrectly stating that the driving pressure is intrapleural-alveolar gradient rather than mouth-
alveolar.
Incorrect versions of the Hagen-Poiseuille equations or Reynolds number.
Not explaining the relationship between airway calibre, turbulent flow and AWR.
Discussing lung compliance instead.
Confusing the Lung Volume-AWR relationship with the Lung Volume-PVR relationship and stating
therefore that AWR is lowest at FRC than at TLC.
Ignoring the role of the upper airway in AWR.
Wasting time on an exhaustive classification of all Pathological and Pharmacological factors which
effect airway calibre.

QUESTION 14 Outline the role of the kidney in the regulation of body water.


Important concepts expected were:
The identification and separation of discussion about sodium chloride and associated water (i.e.
saline) and "pure" water regulation.
Description of the ability and associated mechanisms for production of either hypo- or hyper tonic
urine relative to plasma.
Identification and discussion of the role of ADH within this process.

Common errors or omissions included:
Many answers failed to address the question as asked.
Terms such as water, volume and fluid depletion were used in ambiguous ways.
Directionless relationships e.g. a change in X causes a change in Y.
Failure to discuss how dilute urine is produced.

Better answers:
Discussed the threshold and gain for hypo-osmolarity vs. hypo volemia.
Set the role of the kidney within the broader scope of water homeostasis.

10

QUESTION 15 Briefly describe the NMDA (N-methyl d-aspartate) receptor and its
physiological role in the central nervous system.


For a pass mark, candidates needed to provide a general description of the receptor e.g. one of a family of
excitatory amino acid receptors, widespread throughout CNS especially in spinal cord and hippocampus,
it is a ligand-gated, voltage-dependent, receptor, the naturally-occurring ligand for which is glutamate
(not NMDA as several candidates suggested); it is a transmembrane multi-unit structure with a central
cation ionophore. It is associated with but not part of AMPA receptor and neurokinin-1 receptor,
stimulation of which causes partial depolarisation of the cell membrane which allows an Mg
2+
plug to
leave the central ionophore. Glycine is also required. Not all of this information was required to pass, but
an indication of the general structure and method of activation was.

Mention of the roles played by the receptor in chronic pain states, with sensitization and hyperexcitability
caused by persistent input from sites of tissue or nerve injury; in the phenomenon of wind-up, likely
due to changes in spinal cord expression of the c-fos protooncogene; and proposed in learning and
memory were expected and in most cases provided. Other proposed roles such as in excitotoxicity,
ischaemic cell death, and CNS plasticity attracted extra marks, but a more detailed discussion of the role
in pain states scored more heavily. Mention of antagonists e.g. ketamine and phencyclidine scored but
was not essential.

A diagram of the receptor and its associated structures and interactions was not essential, but generally-
speaking; the better answers included such a diagram, clearly labelled. Few answers mentioned the need
for AMPA receptor stimulation to partially depolarize the cell membrane, thus releasing the Mg plug.
Many answers gave detailed descriptions of structure and activation but scant information on role, or vice
versa; and did not score as well.

QUESTION 16 Outline the mechanism of secretion of hydrochloric acid by the stomach.
Briefly describe how secretion of hydrochloric acid by the stomach is
controlled.


The answers to the second part on control were often better than the first part on mechanism. Some
candidates only answered the second part.

There were several important points that were often best dealt with by appropriate diagrams.
The central role of the hydrogen/potassium ATPase.
Receptors for gastrin, acetylcholine, and histamine.
The role of the vagus.
Multiple stimuli both enhancing and inhibiting acid secretion that many divided into cephalic,
gastric, and intestinal factors.

Other issues included detailed descriptions of hydrogen ion formation using carbonic anhydrase and
associated ion movements in and out of the parietal cells. Points attracting higher marks included a clear
understanding that the stomach fluid is extremely acidic and that the parietal cells must actively secrete
hydrogen ions against a considerable concentration gradient. Very few mentioned the role of canaliculi in
inserting proton pumps into the cellular membrane when the parietal cells are stimulated.
11
VIVA SECTION

INTRODUCTION TO PHYSIOLOGY QUESTIONS:

Cardiovascular
Left ventricle pressure volume loop
Estimation of myocardial contractility
Foetal circulation
Thermodilution
Autoregulation
Cardiovascular changes at birth
Cardiovascular effects of IPPV
Determinants of net fluid flux across a capillary
Normal pulmonary artery pressure
Total peripheral resistance
Pressure vs time curves for aortic root and radial artery
Definitions of systolic, diastolic, and mean arterial pressures

Respiratory
Alveolar gas Equation
Normal expired wave capnogram
Compliance and the respiratory system
Lung volumes
Closing volume
Functional residual capacity
Control of breathing
Chemoreceptors
Determinants of tissue oxygen delivery
Haemoglobin oxygen dissociation curve
Mixed venous PO
2

Coronary sinus PO
2

Carbon monoxide poisoning
Causes of a low PaO
2

Difference between shunt and V/Q inequality
Respiratory quotient
CO
2
carriage
Effects of altitude

Blood
Effects of haemorrhage
Water division within body compartments
Haemoglobin molecule
Production and breakdown of haemoglobin
Foetal haemoglobin

Renal
Mechanisms for producing concentrated and dilute urine
Antidiuretic hormone
Filtration and absorption of bicarbonate

12
Neuro
Blood brain barrier
Cerebral blood flow
Intracranial pressure
Monro-Kellie doctrine

GI
Role of vitamin K
Role of liver in glucose homeostasis
Immunological functions of the liver
Constituents and functions of bile
Urea cycle

Measurement and physics
Colligative properties
Heat and temperature
Humidity
Measurement of blood pressure
Wheatstone bridge
Osmolality
Osmotic pressure
Flow and resistance
Blood pressure measurement

Effects of insulin and glucagons
Regulation of blood glucose
Insulin and glucose interaction

Other
Respiratory acidosis
Metabolic alkalosis
Nernst equation
Sodium potassium ATPase pumps
Primary active transport
Temperature control

N.M. GIBBS
CHAIRMAN
PRIMARY EXAMINATION

ABN 82 055 042 852

EXAMINATION REPORT

PRIMARY EXAMINATION

MARCH/APRIL 2003

EXAMINATIONS.

PHARMACOLOGY

WRITTEN SECTION




QUESTION 1 Briefly outline the effects of isoflurane on skeletal, smooth and cardiac muscle
tissues. Indicate how these effects are mediated and their clinical significance.

Although the pass rate for this question was 74%, many answers were borderline and few candidates
(<10%) provided a clear well-considered answer directly addressing all aspects of the question.
Knowledge of the potential pharmacological and pathological actions of isoflurane on each type of
muscle, the clinical significance and a general concept of the postulated mechanisms of action was
expected. Candidates were required to know that isoflurane causes dose-dependent skeletal muscle
relaxation and potentiation of neuromuscular blockers, with increased skeletal muscle blood flow and
drug delivery. The relaxant effects of isoflurane on vascular smooth muscle including coronary and
cerebral circulations and the actions on bronchial, pulmonary and uterine smooth muscle should have
been considered. Many were unclear of the mechanism of coronary steal and of the controversy over
its clinical significance. Actions on cardiac contractility and conduction should have been included.
Possible mechanisms of action including CNS effects, postjunctional effects, effects on calcium
channels and intracellular calcium, atypical ryanodine receptors in MH, nitric oxide production and G-
protein linked receptors were often not outlined.

QUESTION 2 Outline the neuropharmacology of thiopentone, covering only its site of action,
EEG changes, effects on cerebral blood flow and intracranial pressure.

The pass rate for this question was 80%. The question was asked in appreciably the same format on the
March 1999 paper. The marking parameters as set out in that Examiners Report were still appropriate
for this sitting. Candidates are directed to read that Examiners Report. Virtually all candidates
2
appreciated the question had four sub-sections and ensured that they answered all four sections.
Despite the question specifying that only the four sections needed to be answered many candidates
gave detailed, additional information on packaging, dosing and the structure of thiopentone without in
any way attempting to relate these facts to the question asked. No credit was given for this. Also vague
answers such as EEG changes are dose related or thiopentone has an inhibitory affect on the brain
via GABA receptors were deemed inadequate to answer the question satisfactorily without more
detailed explanation.

QUESTION 3 Explain how lignocaine prevents the conduction of a nerve action potential.

The pass rate was 37%.
The content areas where marks were available could be split as follows.
a) How lignocaine reached the site of action which might include differences between routes of
delivery, nerve sites (e.g. peripheral vs. intrathecal), pH/pKa/ionisation relationships and principles
of diffusion.
b) Details of voltage gated sodium channel binding site and function, and lignocaines interaction
with it.
c) Channels/nodes blocked to prevent action potential propagation. Differential nerve fibre block and
why it occurs
Common problem areas were
i) An almost universal belief that only ionised axoplasmic lignocaine gains access to the channel
(refer Miller 5
th
Ed: Ch 13, Cousins & Bridenbaugh 3
rd
Ed: Ch 2, Rang, Dale & Ritter 4
th
Ed:
Ch 40).
ii) The relationship between pH/pKa/drug ionisation with some candidates producing correct
diagrams but incorrectly interpreting them, suggesting rote learning but a lack of
understanding.
iii) Lignocaine binding to the various channel states.
iv) Unlabelled/inaccurate time axes on action potential diagrams.
v) A small, but significant, group stated that lignocaine primarily acted at ligand gated sodium
channels in synapses.
Candidates who included correct material on anti-arrhythmic and toxic effects of lignocaine gained no
extra marks because the material was not relevant to the question asked.

QUESTION 4 Outline the potential problems associated with additives used to make
medicines suitable for intravenous injection.

The pass rate was about 43%. Many candidates made no mention of anaphylactic/anaphylactoid
reactions, pain on injection, thrombophlebitis, physicochemical inactivation (and crystallization) and
manufacturing costs. A pass required a brief description of (at least) four additives found in drug
preparations used in anaesthesia, and their potential adverse effects. Good answers named the drug and
additive and outlined its problems. Higher marks were obtained if consideration was given to dose-
response, actual versus theoretical problems and pharmaceutics (complexity, cost, shelf-life). No
marks were given for additives found in halothane, EMLA cream, spinal local anaesthetic solutions or
blood. It was not accepted that the mannitol found in vecuronium leads to an osmotic diuresis. The
statement "causes toxicity", was considered to be non-specific and did not gain marks.

QUESTION 5 Outline the important statistical issues in designing a study to compare the
duration of analgesia of two drugs given for post-operative pain relief.

The pass rate for this question was 38%. The principal points expected to pass would have included
the following. The setting of the study should be a randomised controlled clinical trial. A statement
defining the Null Hypothesis to answer the question raised, for example that the drug has no
3
significant effect on post-operative duration of pain relief. Discussion regarding the appropriate
determination of sample size including power analysis and the setting of threshold for type one and
two error. Power is only one of the issues in sample size estimation and a common mistake was to
give too much emphasis to this point in candidates answers. The surgical procedure and anaesthetic
technique must be standardised to reduce bias. Other methods to reduce bias include blinding the
person responsible for data collection. The definitions of inclusion criteria for endpoints of analgesic
effect are important and pain severity scores were mentioned by many candidates. Higher marks were
given to answers which addressed which statistical test would be suitable and the reasons why it would
be appropriate. The data may not be normally distributed so a non parametric test such as a Mann-
Whitney U test might be preferred. Other tests were acceptable provided potential limitations were
identified and data suitability was included.

QUESTION 6 Explain how differences in the pharmacokinetics of alfentanil and
fentanyl can influence the way they are administered intravenously.

The pass rate was 51%. Candidates were expected to provide a pharmacokinetic explanation to the
differences in the way fentanyl and alfentanil behave when given intravenously. The differences in
onset time, effect site equilibration, pka and diffusible fraction should have been discussed. The
differences in offset time (bolus and infusion), context sensitive half time and the kinetics underlying
this should have been outlined. Many candidates presented a comparative table of kinetic data of both
drugs without any further explanation. Similarly, many candidates presented context sensitive half-
time graphs with inaccurate indication of the behaviour of the two drugs.
Candidates who provided representative figures on kinetics with their answer and made comments on
administration of a single small dose bolus, high dose, repeated bolus and infusion gained extra marks.

QUESTION 7 Classify diuretics, briefly explaining their mode of action.

88% of candidates passed this question, and many demonstrated a high level of understanding of this
group of drugs. Almost all candidates successfully classified the main groups of diuretics according to
their mode of action. Better marks were achieved by candidates that not only mentioned their cellular
mechanisms of action but also the net effect of this on electrolyte shifts and therefore how diuresis is
actually achieved.

QUESTION 8 Describe the onset and offset of neuromuscular block at the diaphragm, larynx
and adductor pollicis after administration of 2.5 x ED95 dose of vecuronium.
Comment on the differences observed. What are the clinical implications of
these differences?

The pass rate for this question was 50%. In this question the candidate was expected to address the
issues of the kinetics of onset and offset of neuromuscular block (NMB) and the known different
levels of sensitivity of the muscles mentioned. It was important to mention that although the
diaphragm (D) and larynx (Lx) are relatively resistant to competitive NMB with respect to the
adductor pollicis (AP), the major determinant of onset under these circumstances is blood flow. Thus
onset is more rapid in the Lx and D and slowest in the AP. Candidates needed to define ED95 and that
the ED95 referred to is that for the AP. At the time of AP twitch disappearance both the D and Lx may
have been maximally blocked and may be beginning to recover. Thus it is also critical to mention that
the order of recovery is D, Lx and then AP. Clinical implications that should have been discussed
included onset of block and intubating conditions, offset of block and adequacy of recovery and
monitoring of block at AP, orbicularis oculi and prediction of block at AP, Lx and D. Useful diagrams
(as are found in both Miller and Stoelting) to explain these phenomena were used by some candidates
to their advantage.
4
VIVA SECTION

Common Introductory Pharmacology Questions

Introductory topics for Pharmacology:
* Volatile agent FA/FI curves
* Recovery from volatile agent anaesthesia
* Cardiovascular pharmacodynamics of volatile agents
* Nitrous oxide
* Propofol plasma concentration vs. time curves
* Thiopentone
* Onset and recovery from neuromuscular blockade
* Monitoring neuromuscular blockade
* Local anaesthetic toxicity
* Local anaesthetic pharmacokinetics
* Inotropic agents
* Pressor agents
* Antiarrhythmics
* Intravenous fluid pharmacology
* Isomers
* Drugs altering uterine tone
* Meta-analysis
* Inherited conditions causing variation in drug response
5

PHYSIOLOGY

WRITTEN SECTION




QUESTION 9 Explain the role of haemoglobin as a buffer.

Only 38% of candidates passed this question. A definition of a buffer was required, and also
that buffering capacity or effectiveness depends on the concentration of the buffer relative to the
ambient pH of the solution. Haemoglobin, although intracellular (within the erythrocyte), functions
mainly as an extracellular buffer for CO
2
(volatile acid) formed from aerobic metabolism. The
solubility of CO
2
, the presence of carbonic anhydrase within the erythrocyte and the buffering capacity
of haemoglobin all contribute to make the haemoglobin buffering system extremely efficient.

Haemoglobin is a quantitatively important buffer because there is a large amount present in blood
150gm/L. Also the imidazole groups of the histidine residues of the globin chains are an effective
buffer as their pKa of 6.8 is close to the pH within the erythrocyte. The buffering capacity of
haemoglobin is greatest when it is needed most, that is when haemoglobin is deoxygenated in venous
blood with a higher CO
2
content. Deoxygenated haemoglobin is a better buffer than oxyhaemoglobin
as it is a weaker acid, and the pK
a
of its imidazole groups are higher at 7.9. This information was
deficient in most answers. The increased buffering capacity of deoxygenated haemoglobin contributes
approximately 30% of the Haldane effect.

Many candidates incorrectly stated that haemoglobin functioned as a buffer by the formation of
carbamino compounds. The dissociation of carbamino compounds within the erythrocyte actually
adds hydrogen ions that need to be buffered by haemoglobin and other buffers. Better answers
mentioned the fact that the bicarbonate buffer system cannot buffer carbonic acid (CO
2
) as they form
part of the same weak acid conjugate base pair.

QUESTION 10 Describe the factors influencing hepatic blood flow.

55% passed this question. Less than 9% scored well.

Candidates are expected to provide anatomical information stating that hepatic blood flow has a dual
blood supply: (i) the hepatic artery (25%) and (ii) the portal vein (75%). Normal values of flow and
pressure are expected.

One is expected to discuss the factors that affect the respective pressures and hepatic vascular
resistance,

Hepatic arterial flow = [mean arterial pressure hepatic venous pressure]
Hepatic vascular resistance

Portal venous flow = [portal venous pressure hepatic venous pressure]
Hepatic vascular resistance

6
Some better answers stated that there is an inverse relationship between the hepatic arterial and portal
venous flow with autoregulation occurring in the hepatic artery and not in the portal system. A few
mentioned that metabolic regulation can cause the hepatic artery to supply up to 50% of the hepatic
blood flow.

Many recognised that factors such as sympathetic stimulation, anaesthetic agents, surgical factors and
pathological states will affect blood flow by their effects on arterial pressure or cardiac output as well
as their effects on hepatic vascular resistance.

However, a number of candidates answered the question only from first principle, discussing the
Hagen-Poiseuille equation in some detail without making specific reference to hepatic blood flow. A
large number of candidates did not give any normal values or had them wrongly stated.

Measurement of hepatic blood flow and functions of the liver were not required

QUESTION 11 Define the thermoneutral zone. Briefly explain how the body regulates
temperature when the ambient temperature exceeds thermoneutral zone.


A satisfactory answer would have included the following points:
Definition of the thermoneutral zone (TNZ) including some reference to oxygen
consumption at rest being minimal. Also acceptable was the recognition that body
temperature is able to be maintained by changes in skin blood flow alone. Normal values
for adults (22 28C) and neonates (32 34C) were required.
A brief mention of the neural mechanisms involved.
Mention of the means for losing heat; ie, conduction, convection and radiation with
emphasis on the paramount importance of sweating in the absence of a thermal gradient.
A brief mention on the role of behavioural responses (seeking a cooler environment,
removing clothing and increasing fluid intake).

Information that was rewarded with additional marks included:
A well labelled graph.
Relationship of TNZ to body surface area and age.
Relative importance (in percentage terms) of the modalities of heat loss as the ambient
temperature climbs.
Rates of sweating that can be achieved.
The effect of humidity on sweating.

QUESTION 12 Explain the mechanisms that maintain cerebral blood flow on moving from a
supine to a standing position.

The past rate for this question was 60%.

There was a broad range of marks, with some candidates doing very well, and a large number doing
very poorly. In general, an appreciation of both systemic and cerebral factors relevant to cerebral
blood flow changes on changing posture were required.

From the systemic aspect, an explanation of the hydrostatic effects of a changing posture, and the
mechanical and cardiovascular reflex responses to these effects was required. This was included in
most answers, though was the only aspect discussed in quite a number.

7
From the cerebral perspective, some appreciation of the key determinants of cerebral blood flow was
required, and in particular some mention of the factors affecting cerebral perfusion pressure and
cerebral vascular resistance. It was noted that whilst many candidates had an appreciation of the
changes in the arterial side of cerebral perfusion with changes in posture, many candidates failed to
appreciate the importance of a concomitant decrease in cerebral venous pressure. This is a significant
contributor to minimising the hydrostatic effects of direct position on cerebral blood flow.

Some mention of pressure autoregulation was an important component of the answer and many
candidates did not mention this aspect at all. There was sometimes confusion between pressure
autoregulation and metabolic-cerebral blood flow coupling. The term autoregulation is sometimes
used interchangeably in the literature, and this creates confusion in published texts. In reality, both
responses may share common mechanisms.

It was interesting to note that almost no candidates discussed the time course of cerebral blood flow
changes. The figure of a 20 percent reduction in cerebral blood flow was commonly quoted, however,
it was not often appreciated that this is a temporary change.

QUESTION 13 Briefly describe the principles and sources of error in the measurement of
systemic arterial blood pressure using an automated oscillometric non-invasive
monitor.


Most candidates demonstrated a good understanding of the principles of the device and the strengths
and weaknesses in detection of systolic, diastolic and mean pressures.

Some candidates presented their answer as if this device was synonymous with a particular brand. It is
very reasonable to present the specifications of a particular brand as an example of such a device but
not to imply that there is only one type.

Some descriptions of the equipment were problematic.

The concept of the bladder within the cuff was often not clear and lead to confusion about describing
the positioning and size of the bladder. Descriptions of the recommended dimensions of the cuff (and
bladder) often did not specify whether length or width were being presented.
There were some instances of confusion between historical two tube and two cuff equipment
(particularly oscillotonometry cf oscillometry) and current single cuff and tube equipment. Occasional
candidates also confused detection of oscillations with detection of Korotkoff sounds. Modern
oscillometry devices have the transducer in the control box not in the cuff.

Formulas presented for calculating the diastolic pressure were often presented as variations of Mean
Arterial Pressure = Diastolic Arterial Pressure + 1/3 pulse pressure. These were usually technically
correct but would be better presented as Diastolic Arterial Pressure = a formula related to directly
measured parameters (or other algorithm related to change in percentage size of oscillations detected).

QUESTION 14 Describe the factors that affect lung compliance.

A pass rate of 39% was achieved for this question. Irrelevancies were uncommon on this occasion,
however some basic mistakes and omissions did occur.

The answer is best introduced with a definition. Marks were allocated for a value with the correct units

*the compliance equation relating the total lung, to chest wall and lung compliance.
8
*Surfactant and its role on surface tension.
*Laplaces law and its applicability.
*The importance of elastic forces and their role in disease states.
*Lung size.
*Lung volume and its relationship (to FRC) on compliance.
*Effect of gravity on the lung and hence on compliance.

Mention of various compliances like dynamic, static and specific with their definitions attracted extra
marks as did diagrams showing a pressure volume loop, hysteresis, or a compliance curve, with
explanations.

Clinical relevance is also important and mention of restrictive lung disease, obstructive lung disease:
pulmonary emphysema, pleural effusions, or at least some of those was appropriate. Differentiating the
effects of emphysema on dynamic vs. static compliance also attracted extra marks.

QUESTION 15 Describe the physiological actions of thyroid hormones.


The question asked the physiological actions of thyroid hormones, not the synthesis of thyroid
hormones. There is a lot to cover by way of physiological actions. Some candidates spent time
detailing their synthesis

Marks were awarded for noting the forms of thyroid hormones, the relative amounts in the
bloodstream and relative activities. An account of their mechanism of action at a cellular level was
considered important. An understanding of the implication of this mechanism of action to the time for
onset of action and duration of effect scored extra marks.

An account of end-organ effects was present in some form in most answers, with a system by system
approach often used. Most candidates were able to state that thyroid hormone increases metabolic rate.
Many of these were able to go on to state that thyroid hormone had some catabolic effects. Some
briefly mentioned the role of thyroid hormone in growth and development. Few picked up on the
apparent contradiction between catabolic and anabolic effects, and described that the effects of thyroid
hormones can be dose and age dependent. The effect of thyroid hormone to provide a negative
feedback on its own synthesis was not often mentioned.

QUESTION 16 Describe the functions of the loop of Henle, including the physiological
mechanisms involved.

The pass rate for this question was 64%.


The main function of the loop of Henle is to establish a concentration gradient in the renal medulla,
which allows the collecting duct to regulate water excretion.

This is achieved by active ionic transport (associated with impermeability to water diffusion) from the
tubular lumen in the thick ascending segment of the loop to the interstitium, coupled with water
permeability of the descending part of the loop.

Some quantification of osmolalities in various parts of the loop, and mention of counter current
mechanisms was also required.

9
Additional marks were given for comparison of the effects of short and long loops (the physiology of
desert rats was popularly mentioned!), the role of urea, and role of the loop of Henle in excretion of
other ions. Because there is disagreement between texts as to whether the macula densa is part of the
ascending loop of Henle - rather than the DCT - marks were given to candidates who described
function of the juxta-glomerular apparatus.

VIVA SECTION

Common Introductory Physiology Questions
CVS
Left ventricular pressure/volume curves
Coronary artery flow curves
Afterload and Guytons curves
Cerebral blood flow
Left ventricular volume curves
Myocardial contractility
Draw a Lead II ECG complex and label waves and intervals
Valsalva manoeuvre
Frank-Starling curve
Factors determining feto-maternal exchange
Wedge pressure and preload
Wiggers diagram
Resp
Lung volumes and capacities
Closing capacity
Respiratory compliance
Dead space
A-a gradient
Effects of altitude on PO
2

Arterial blood gases
Types of hypoxia
Airways resistance
Work of breathing
Effects of lung volume on pulmonary vascular resistance
Peripheral chemoreceptors
Shunt and venous admixture
Effect of occluding the left main bronchus in a ventilated patient
Effect of adding 5cmH
2
O PEEP to a circuit
Effect of occluding the left pulmonary artery
ETCO
2
waveforms
Effect of changes in minute ventilation on CO
2

Effect of changes in inspired pressure on CO
2

CNS
Control of intracranial pressure
Head down tilt effects on ICP
Monro-Kellie doctrine
Formation and flow of CSF
Renal
Range of urine osmolalities
10
Excretion of fixed acids
Forces acting across a glomerular capillary
Free water clearance
ADH effects
Renal response to hypovolaemia
Renal blood flow
Renal handling of potassium
Blood
Haemoglobin-oxygen dissociation curve
Buffers
Difference between plasma and serum
Carriage of CO
2
in blood
Crossmatching of Blood
Carriage of oxygen in the blood
GI
Gastric acid secretion
Carbohydrate handling in the gut
Measurement
Humidity
Pulse oximetry mechanism of measurement
ETCO
2
measurement
Temperature
Invasive measurement of blood pressure
Pneumotachograph
Other
Iodine metabolism
Lactate production
Aerobic versus anaerobic metabolism
Factors affecting heat loss in a hot environment
Pain pathways
Determinants of the resting membrane potential
Morbid obesity

N.M. GIBBS
CHAIRMAN
PRIMARY EXAMINATION

ABN 82 055 042 852

EXAMINATION REPORT

PRIMARY EXAMINATION

JULY/SEPTEMBER 2002

EXAMINATIONS.

PHARMACOLOGY

WRITTEN SECTION


QUESTION 1 Outline the influences of pregnancy on pharmacokinetics.

The pass rate for this question was 39%. Answers framed around the structure of absorption, distribution,
metabolism and excretion performed better. It was clear from a large number of answers that candidates
who structured their answers around the physiological changes of pregnancy, a more familiar topic,
performed poorly. This was not because of factual errors, but rather omission of important areas of
pharmacokinetics (eg absorption). The effects of pregnancy on oral absorption should have included a
discussion of gastrointestinal motility, nausea and vomiting and gut blood flow.

The opposing effects of the changes in ventilation and cardiac output on the uptake of volatile agents
should have been presented. The effects of increased cardiac output on transdermal and intra muscular
routes of administration were infrequently discussed. Volume of distribution is increased in keeping with
the increase in total body water and plasma volume. Distribution of drugs is also affected by the changes in
cardiac output and plasma protein binding. Hepatic blood flow is generally stable or slightly increased. The
differential effects of oestrogen and progesterone on liver enzyme activity were discussed by some.

Most candidates discussed the reduction in pseudocholinesterase with pregnancy but few mentioned that
this has minimal effect on the dose of suxamethonium because of the increased volume of distribution.
Candidates generally mentioned the effect of increased renal blood flow and renal clearance on drug
elimination.

QUESTION 2 Briefly describe the factors affecting the uptake of orally administered
medicines.

The pass rate for this question was 67%. Factors affecting uptake of orally administered drugs can be
related either to the drug itself or to the patient. Subsequent pharmacokinetics including the first pass effect
or bioavailability should not have been part of the description of uptake and were not awarded any marks.
2
The answer should demonstrate an understanding that drug uptake is usually dependent on a lipid soluble,
un-ionised compound moving down a concentration gradient.
Drug factors affecting uptake include formulation, pKa and ionised state in the gut and ability to resist
degradation.
Patient factors include blood flow to mucosa, compliance, altered gut motility or transit times, absorptive
surface area, effects of disease and chemical or microbiological contents of the bowel that may degrade the
drug. Ficks Law of Diffusion relates concentration gradient, surface area and permeability coefficient for
the passive flux of a drug molecule. This illustrates many of the important principles in oral drug uptake.

QUESTION 3 Draw a graph comparing the ratio of inspired to alveolar concentrations
during the first half hour of administration for nitrous oxide, isoflurane, and
halothane. Outline reasons for observed differences between the agents and
indicate the effects of increases in alveolar ventilation and cardiac output.

This question was passed by 73% of candidates, including a borderline pass in 20%. The wording of the
question created some confusion, as inhaled anaesthetic uptake is dependent upon the rate at which the
alveolar approaches the inspired concentration, graphically represented as the time-course of the ratio of
alveolar to inspired concentrations. Most candidates drew this latter graph, correctly labelling the axes,
that was accepted as the correct response to the question. A single candidate inverted the ratio and
accurately plotted the equivalent time-course of inspired to alveolar concentrations, gaining full marks.
Candidates gained marks for accurate representation of the uptake of each of the specified anaesthetic
agents. Reasons for the observed differences between the specified agents include the influences of
different concentrations, blood/gas partition coefficients and the effects of the agents on alveolar
ventilation and cardiac output. For all agents, increased alveolar ventilation results in more rapid rise of the
alveolar to inspired concentration ratio, whereas increased cardiac output reduces the rate of rise of alveolar
concentration.

QUESTION 4 Briefly outline the potential interactions between volatile agents and carbon dioxide
absorbents.

This question was passed by 52 % of candidates.

The main points expected in the answer were:
The different types of carbon dioxide absorbent with differing likelihoods of interaction with
volatile agents.
Specific interactions with:
- sevoflurane, producing compounds A E
- desflurane, enflurane and isoflurane, producing carbon monoxide
- trichloroethylene, producing dichloracetylene, phosgene
- halothane, producing difluorovinyl compound
The influence on these reactions of:
- temperature
- hydration of the absorbent
- concentration of the volatile agent
The potential toxicity of the various products of the interactions
The practical relevance of these interactions in clinical anaesthesia

Credit was also given to those who mentioned the ability of carbon dioxide absorbents to absorb volatile
agents, with the possible consequences of:
Slowing of anaesthesia induction
Release of absorbed volatile agent to a subsequent case.

3
QUESTION 5 Outline the possible reasons for prolongation of paralysis induced by an
intravenous dose of 1 mg.kg
-1
of suxamethonium. Briefly indicate the
consequences of such a prolonged block.

The pass rate for this question was 60%. The main points were as follows:
Suxamethonium 1 mg/kg is a routine dose. Phase 2 block from overdose therefore is unlikely
Suxamethonium is metabolised by pseudocholinesterase. Alterations in the concentration or
activity of this enzyme can cause prolongation of suxamethonium action.
A discussion of acquired alterations in concentration or activity (i.e. liver disease, pregnancy, drug
interactions etc). Note that these do not often result in clinically signficant prolongations in
suxamethonium action.
A discussion of the inherited alterations in concentration or activity, including the genetics,
incidence, effect on duration of action, investigation with dibucaine number and other tests
The duration of action of suxamethonium can also be altered by other agents or diseases with
pharmacodynamic effects.
Consequences including the need for ventilation and sedation in a suitable environment, monitoring
of neuromuscular function, possible treatments, investigation of patient and family and implications
for future anaesthesia.

Common mistakes included discussion of the clinical indications and other side-effects of suxamethonium
and omission of information about consequences of prolonged block. Many candidates omitted to discuss
one of the three main causes (i.e. inherited, acquired or pharmacodynamic interactions).

QUESTION 6 Write brief notes on tolerance and dependence in relation to opioid analgesics.

The key elements of a successful answer were clear definitions of each term and a discussion of their
features and mechanisms. Decreased potency rather than decreased efficacy is generally seen with opioid
tolerance. Many candidates described a lack of tolerance to respiratory depression when tolerance to
analgesia occurs. This was in contradiction to the common finding of tolerance to analgesia, euphoria and
respiratory depression being much more marked than that for constipation and pupillary constriction.
While the majority highlighted the relevance of tolerance and dependence in heroin addicts few highlighted
the similar importance in chronic pain patients on oral opioids. Overall those who stuck to the topic and
provided brief notes on both tolerance and dependence achieved a good mark.

QUESTION 7 Outline the potential pharmacological advantages and disadvantages of intra-
operative beta-blockade.
76% of candidates passed this question, although there were few high marks achieved. Good answers
included an explanation of how improved myocardial oxygen balance was achieved rather than merely
mentioning the fact and distinguished between the normal heart and that with coronary artery disease.
Many candidates also distinguished between the physiological explanation of how improved myocardial
oxygen balance is achieved and the epidemiological studies that have shown that the theoretical advantages
translate into improved outcomes in relevant patients. In general candidates were much stronger on the
disadvantages of intra-operative beta-blockade than its advantages. Few candidates mentioned interactions
with other aspects of anaesthesia, such as their MAC sparing effects, problems with resistance to
vasopressors and their possibly masking cardiovascular signs of inadequate anaesthesia.

QUESTION 8 Outline the pharmacological effects of vasopressin.


The question asked for a description of the pharmacological uses of vasopressin. Information relating to
these aspects rather than physiological characteristics of the endogenous ligand was therefore given
preferential weighting. Candidates should have mentioned the peptide nature of vasopressin and hopefully
4
comment on the implications for administration. Peptides typically have extremely low oral
bioavailability due to intestinal proteases. Details relating to receptor subtypes and specific effects were
frequently mentioned. Generally there was a good standard of explanation of sub-cellular events and
mediators. Candidates should have discussed the different clinical effects and indications for vasopressin
and DDAVP. Commonly omitted was the synergistic activity with catecholamines. Although vasopressin
will afford water retention in diabetes insipidus it is preferable to use DDAVP to avoid vasoconstriction.

VIVA SECTION


Adenosine
Atenolol
Amiodarone
Assessment of neuromuscular blockade
Central nervous system effects of volatile
agents
Compare atropine and hyoscine
Contrast atracurium and rocuronium
Calcium channel blocking drugs
Cardiovascular effects of volatile
anaesthetics
Clearance
Changes in pharmacokinetics and
pharmacodynamics with age
Drugs affecting the renin-angiotensin
system
Define drug synergy
Dose response curves
Drug disposition in the neonate
Define sensitivity and specificity
Drugs causing amnesia

Drugs that affect serotonin receptors
Digoxin
Describe statistical tests you would use
for a variety of data types
Formulations of propofol
Hepatic clearance of drugs
Hepatotoxicity of volatile agents
Local Anaesthetic toxicity
Lignocaine metabolism
Lignocaine infusion
Mechanism of action of benzodiazepines
Nitrous oxide elimination
Nitroprusside
Paracetamol
Renal toxicity of volatile agents
Remifentanil infusion
Tramadol
The effects of a combination of propofol
and fentanyl

PHYSIOLOGY

WRITTEN SECTION




QUESTION 9 Draw a pressure volume loop for the left ventricle in a normal adult. Outline
the information that can be obtained from such a loop.


The main points expected were an accurate pressure volume loop, with the phases named and the points of
valve opening and closing marked. In addition, an outline of the information gained from the loop was
expected, such as stroke volume, ejection fraction, left ventricular end diastolic volume (as a measure of
preload), left ventricular diastolic pressure/volume relationship (as a measure of elastance), left ventricular
5
end systolic pressure/volume line (as an indicator of contractility), and area within the pressure/volume
loop (as a measure of stroke work).

A common omission was not including simple information eg. naming the phases of the loop and
indicating where the valves open and close. Stroke volume and ejection fraction were often forgotten in
favour of complicated elastance lines. A common mistake in the loop was to mark the aortic valve opening
at a higher pressure than at which it closed. Also, the diastolic curve often had correct volumes but
incorrect pressures.

QUESTION 10 List the physiological factors which increase respiratory rate. Include a brief
explanation of the mechanism by which each achieves this increase.


The question was quite specific in requiring a list of physiological factors followed by a brief explanation
of each factor. It was expected that the effects of hypoxia, hypercapnoea, and acidosis would receive most
attention. In addition it was expected that at least two other factors would be mentioned (eg exercise,
voluntary control, depression of respiratory centre, pulmonary stretch reflexes). Most candidates neglected
to mention that hypoxia and hypercapnoea are synergistic in their effect on increasing respiratory rate.
Others made vague statements linking the effects of PaO
2
, PaCO
2
and pH. Some candidates produced
detailed descriptions of respiratory control mechanisms which were not required. Many candidates were
confused about pulmonary stretch reflexes, which act primarily to limit or prevent hyperinflation, and are
less important for controlling respiratory rate.

QUESTION 11 Outline the factors that determine coronary vascular resistance.


The main points expected were a clear understanding of the link between myocardial oxygen utilisation
and blood flow, as well as the effect of systolic extravascular compression of coronary blood vessels, and
the role of the autonomic nervous system in controlling coronary vascular tone. Inclusion of the myogenic
mechanisms that regulate coronary vascular resistance to maintain flow across a range of perfusion
pressures gained extra marks, as did mention of the putative mechanisms involved in metabolic regulation.
Additional marks were also gained by illustrating the differences between right and left ventricular systolic
and diastolic flow patterns.

Some candidates began the answer with an explanation of Ohm's Law, but then were unclear about the
relationship of flow to pressure, as determined by the coronary vascular resistance. Many also began with
Poiseuille's equation, but did not follow this with a clear explanation of the major role of vessel radius as
the primary determinant of resistance. Mention of blood viscosity as a determinant increased the score if
included in a relevant context.

QUESTION 12 Briefly explain the changes that occur in stored whole blood.


Candidates who scored well addressed each of the components of whole blood (red cells, Hb, 2,3-DPG,
white cells, platelets, plasma proteins/coagulation factors, electrolytes/acid-base, dissolved gases,
additives). They explained rather than listed the changes, and provided detail of the magnitude and time
course. A number drew tables showing the changes during each week of storage, then explained the
underlying causes of these changes.

6
Candidates who failed did so because they omitted major components of whole blood. Several candidates
wasted valuable time writing about the effects of massive transfusion, which was not required. Others did
not answer the question, preferring to state that whole blood is no longer used and then to describe the
storage of packed cells, fresh-frozen plasma and platelets.

QUESTION 13 Briefly describe the functions of renin and angiotensin.


The function of renin is to convert angiotensinogen to angiotensin I. Angiotensin I is converted to the
active angiotensin II by angiotensin converting enzyme (which is found principally in pulmonary
endothelium, but also in many other organs). Angiotensin II has direct vasocontrictor and direct renal
effects, and also stimulates thirst, as well the release of antidiuretic hormone and aldosterone. The overall
effect is to retain salt and water. Additional marks were awarded for a more detailed information on the
structure of renin and angiotensin I and II, where and how they are produced, and where and how they
produce their effects.

Some answers included a discussion of antidiuretic hormone and aldosterone physiology which was not
relevant. The most common weakness in answers was the omission of basic aspects of the renin-
angiotensin system.

QUESTION 14 Explain the physical principles of ultrasound imaging.


The main points expected were how ultrasound waves are generated; their passage through tissues (eg.
conduction velocity, reflection, attenuation); recording of reflected waves and processing (eg signal noise
ratio, gain, modes of display); and the Doppler effect. Extra marks were awarded for factors affecting
resolution (frequency, wavelength, attenuation, artifacts), and the role of transoesophageal
echocardiography in avoiding technical limitations in transthoracic imaging. Common errors included
stating that ultrasound is electromagnetic radiation, and that increasing amplitude always improves
resolution.

QUESTION 15 Give a brief account of the mechanisms which regulate gastric secretion.

Gastric secretions include water, hydrochloric acid, intrinsic factor, pepsin, and alkaline mucus. In
addition gastrin is secreted by cells in the stomach antrum. Some candidates chose to pursue the control of
each individual component, while others took a more global approach. Both approaches were equally
acceptable.

The main points expected included the contents of gastric fluid, and the three phases of gastric secretion
(cephalic, gastric, and intestinal), including the nervous and hormonal mechanisms involved (eg. vagus,
acetylcholine, histamine, gastrin, prostaglandins). Additional marks were awarded for detail of the afferent
and efferent pathways, the effect of various food types, stimulatory and inhibitory processes, and the
control of the content of gastric secretion (eg. volume, pH).

7
QUESTION 16 Explain the Bohr and Haldane effects in trans-placental gas exchange.


The main points expected were a definition of the Bohr and Haldane effects, a description of their
molecular basis, a description of placental gas transfer, and mention of the double Bohr and Haldane
effects for both the foetal and maternal placental/uterine circulations. Diagrams were useful in efficiently
conveying information. Additional marks were awarded for some quantification of the size of the effects
(eg. values of foetal and maternal blood gases), the relative importance of the two effects, and the effects of
maternal factors (eg. hyperventilation).

VIVA SECTION


What is a buffer?
Define pH
Regulation of pH
Renal bicarbonate management
Sources of acid in the body / renal
handling of acid
Consequences of acid loss
Functions of the kidney / water balance
Determinants of renal blood flow
Forces acting across a glomerular
capillary
Renal clearance
Carriage of CO
2

Oxyhaemoglobin dissociation curve
Interpretation of arterial blood gas
analysis
Venous admixture.
The pulmonary circulation
Non-respiratory functions of the lung
Dead space
Surfactant
Calculation of alveolar-arterial O
2

gradient
Types of cellular hypoxia
Oxygen cascade
Respiratory system compliance
The physiological effects of IPPV
Peripheral chemoreceptors
Closing volume / closing capacity /
measurement
Resistance to breathing / components /
measurement
Autoregulation
Diffusion / osmosis / osmotic pressure /
colligative properties
Determinants of the resting membrane
potential
Cardiovascular responses to exercise
Effects of intravenous 2 litre saline load
Physiological changes with exercise
Cardiac function curve / vascular function
curve
Left ventricular pressure curve
Determinants of cardiac output /
contractility / measurement
Draw a radial artery pressure wave /
determinants of mean, systolic, and
diastolic pressures
Draw a Lead II ECG complex & label
waves and intervals
Cardiac action potential
Pulmonary artery pressure trace
Actions of insulin
Blood glucose regulation
Functions of calcium / balance /
regulation
Gastric secretions
Dietary carbohydrate and fat
Effects of prolonged vomiting
Functions of liver / complement
Fat metabolism
Content of a unit of fresh frozen plasma
Cerebral blood flow control
Formation and functions of CSF
Cerebral blood flow/cerebral perfusion
pressure
Classification of neurotransmitters
Foetal circulation
Changes in the foetal circulation at birth
Respiratory changes in pregnancy
Cardiovascular changes in pregnancy
Thermodilution cardiac output
measurement
Pulmonary artery pressure measurement
Thermistors
Measurement of gas flow
8
Pulse oximetry - mechanism of
measurement
ETCO
2
- measurement / A-aCO
2
gradient
Temperature measurement
Gas laws

N.M. GIBBS
CHAIRMAN
PRIMARY EXAMINATION

ABN 82 055 042 852

EXAMINATION REPORT

PRIMARY EXAMINATION

MARCH/ APRIL 2002

THEIR TEACHERS AND SUPERVISORS OF TRAINING WITH INFORMATION
ABOUT THE WAY IN WHICH THE PERFORMANCE OF CANDIDATES IN THE
RECENT EXAMINATION WAS ASSESSED BY THE EXAMINERS, SO THAT
CANDIDATES AND TEACHERS MAY PREPARE APPROPRIATELY FOR FUTURE
EXAMINATIONS. THE INDIVIDUAL REPORTS ARE NOT INTENDED TO
REPRESENT MODEL ANSWERS NOR IMPLY THAT ALL POINTS MENTIONED ARE
NECESSARY IN ORDER TO ACHIEVE A PASS. ALL TRAINEES ARE URGED TO
READ THE QUESTIONS CAREFULLY AND ANSWER THE QUESTION ASKED. ALL
TEACHERS AND SUPERVISORS OF TRAINING ARE ENCOURAGED TO DISCUSS
THIS REPORT IN DETAIL WITH CANDIDATES THEY ARE PREPARING FOR
FUTURE EXAMINATIONS.

PHYSIOLOGY

WRITTEN SECTION




QUESTION 1 Explain how oxygen supply of organs is maintained during isovolaemic
haemodilution.

45% of candidates passed this question. A satisfactory answer should have indicated that although
haemodilution decreases oxygen carrying capacity (by a decrease in arterial oxygen content),
oxygen delivery is usually maintained by an increase in cardiac output. These variables are
quantified by the oxygen flux equation. The decrease in blood viscosity as a result of
haemodilution causes many of the cardiovascular changes that occur. This was not mentioned by
over half the candidates. Decreased blood viscosity simultaneously increases venous return and
stroke volume and decreases systemic vascular resistance and afterload, all of which increase
cardiac output. From Poiseuilles law we note that flow resistance is directly proportional to blood
viscosity. Other relevant areas include the vasodilation that occurs in organ beds and the
mechanisms involved. Also important is the increase in oxygen extraction by most organs and
possible changes in the oxyhaemoglobin dissociation curve that enhance tissue oxygenation.

Some candidates wrongly indicated that anaerobic metabolism and lactic acidosis (as seen in
hypovolaemic shock) occur in moderate isovolaemic haemodilution. Many answers described
clinical methods of increasing arterial oxygenation or reducing oxygen consumption which were
not relevant to the question asked. Erythropoiesis secondary to increased erythropoietin levels (as
occurs in chronic anaemia) was mentioned by many candidates but again has no relevance to this
question.
2
QUESTION 2 Draw a labelled diagram of a cardiac muscle action potential
highlighting the sequence of changes in ionic conductances. Explain the
terms threshold, excitability, and irritability with the aid of the
diagram.

56% of candidates passed this question. The first part of this question required a diagram of a
cardiac muscle action potential with labelled axes, normal values, and phases 0, 1, 2, 3, and 4
identified. An explanation of the ionic fluxes involved with each phase was expected. Additional
marks were awarded for drawing a diagram showing changes in conductances of Na
+
, Ca
++
, and K
+
.

Threshold, the level of depolarisation at which a self propagating action potential is generated, was
well described and illustrated.

Excitability and irritability were often confused. Excitability refers to the increased slope and
conduction velocity of phase 0 as action potentials are initiated at different stages of the relative
refractory period of the preceding excitation. Irritability refers to the diminished potential between
resting and threshold. Extra marks were awarded for mentioning that as irritability increases,
depolarisation is easier, but there is a decreased gradient and reduced conduction velocity of phase
0.

A common omission was to describe the ionic fluxes only in terms of membrane permeability, with
no explanation of the electro-chemical forces acting on the various ions during the five phases.
Few candidates mentioned the effect of K
+
on resting membrane potential.

QUESTION 3 Define Venous Admixture. Briefly explain how venous admixture
influences arterial oxygen tension and how an increase in inspired
oxygen concentration may affect this.

46% of candidates passed this question. The main points expected in the answer were:

1. An adequate definition
2. A brief discussion of shunt and V/Q inequality, both physiological and pathological
3. A brief discussion of the contribution of V/Q inequality and shunt to changes in PaO2
4. A differentiation between true shunt and V/Q inequality
5. An explanation of the effect of cardiac output on venous admixture
6. An explanation of the effects of increased FiO2 on true shunt and on venous admixture due
to V/Q inequality

Points that gained extra marks included mention of sources of physiological and pathological shunt
and V/Q inequality, the effect of the shape of the Hb saturation curve on the response to increasing
FiO2, and mention of extra-pulmonary shunts (normal and abnormal). A correctly labelled iso-
shunt diagram or description of the shunt equation also received extra marks.

Common mistakes included omission of all mention of V/Q inequality. The axes of the iso-shunt
diagram were often incorrectly labelled.

3
QUESTION 4 Outline the physiological factors that influence pulmonary vascular
resistance.


The main points expected included the following:- Approximate normal values (and normal range)
with correct units. The relationship between pulmonary vascular resistance (PVR), pulmonary
perfusion pressure, and cardiac output. The effects of cardiac output and pulmonary artery pressure
on PVR by distension and recruitment of vessels. The influence of lung volume on PVR by its
effect on the diameter of extra- and intra-alveolar vessels, with the lowest PVR being at functional
residual capacity. The influence of alveolar oxygen tension on regional and global PVR.
Candidates who discussed the mechanism of these effects scored higher marks.

Additional marks were awarded for describing the role of nitric oxide, the effect of blood viscosity,
the effect of autonomic factors, the effect of hormones such as serotonin and histamine, and the
effect of changes in posture. Candidates who indicated that PVR was better described as pulmonary
vascular impedance, giving reasons, also gained extra marks.

Several candidates wasted time providing unnecessary information such as detailed descriptions of
West's zones of the lung, the benefits of hypoxic pulmonary vasoconstriction, or the difference
between laminar and turbulent flow.

QUESTION 5 Outline the factors contributing to the generation and maintenance of
the resting membrane potential.

77% of candidates passed this question. Key concepts expected included the semi-permeable
nature of the cell membrane, the uneven distribution of ions/charge across the membrane, the
equilibrium (Nernst) potential for each ion (with an explanation of what it means). Some version of
the Goldman Field Equation (or similar), emphasizing the importance of permeability, with a brief
explanation of the role of Na/K ATPase in both maintenance of, and a contribution to, the RMP,
was also expected. It was also anticipated that some mention of the Donnan effect and its minor
contribution to RMP would be made.

Answers were enhanced by including typical resting membrane potentials of various cells (eg
Myelinated Axon, Skeletal Muscle, Ventricular Myocyte, Smooth Muscle or Erythrocyte). A few
candidates wasted time on a discussion of Action Potentials, which was not required.

QUESTION 6 Explain the physiological processes which cause oliguria in response to
hypovolaemic shock

72% of candidates passed this question. The following areas could have been included: Definition
of oliguria and hypovolaemic shock; The way that hypovolaemia is detected (role of low and high
pressure baroreceptors); The consequent neuro-endocrine responses which affect the kidney, such
as activation of the sympathetic nervous system, the role of the renin-angiotensin system and
aldosterone, and release of antidiuretic hormone; Influences on glomerular filtration such as renal
blood flow, arterial blood pressure, glomerular permeability; Distribution of blood flow within the
kidney, intra-renal factors effecting glomerular and tubular function, and the role of the medulla in
concentrating urine; Some over-view of the physiological advantage in producing concentrated
urine in response to hypovolaemia; Some indication of the relative importance of the concentration
process compared to the other factors. Given that the word shock was included in the question it
was reasonable to include comment about pathophysiology relating to shock and oliguria.
4
The challenge of this type of question is to succinctly provide a broad overview. Difficulty in
achieving high marks generally related to the problem of going into too much detail in part of the
answer and omitting other major areas or explanation of concepts.

QUESTION 7 Outline the principles of a pneumotachograph. What factors affect the
accuracy of this device?

44% of candidates passed this question

Several candidates wrote answers on different pieces of equipment, e.g body plethysmograph,
capnograph, Bourdon gauge, or others. No matter how correct that information, no marks could be
given. Eight candidates wrote nothing at all.

For a pass, an answer should have included most of the following points :
Fixed-orifice device i.e. measurement of pressure drop across a fixed resistance
Design with either a mesh screen or capillaries to encourage laminar flow
With laminar flow there is a linear relationship between flow and P, according to
Poiseuille's equation.
Accuracy is affected by the following factors,
Humidity and condensation
Temperature
Flow greater than maximum recommended for the particular device
Viscosity of gas measured versus calibrated for

Extra marks were awarded for additional relevant information e.g. design features; the low pressure
drop (< 1 - 2 cmH
2
O); the Fleisch screen can incorporate a heater to prevent condensation; There is
a range of sizes available (eg suitable for children and adults); if flow is too large for the device
chosen then turbulence will result in which case there is no longer a linear relationship between P
and Flow; if flow is too low the P may be too small for the transducer to detect.

Common errors included listing changes in gas density rather than viscosity as important without
mentioning that this was only of relevance to calculation of Reynolds' number.

QUESTION 8 Describe the physiological factors that contribute to the competence and
tone of the lower oesophageal sphincter.

42% of the candidates passed this question. The main points expected included the following:- The
lower oesophageal sphincter (LOS) at the terminal 4 cm of the oesophagus is characterised by an
increased number of nerve cells. It consists of smooth muscle (intrinsic sphincter); which is
tonically active, and is under neural control. Acetylcholine leads to contraction of the intrinsic
sphincter. The crura of the diaphragm constitute the external sphincter, and are under control of the
phrenic nerve. Contraction is coordinated with ventilation and contraction of the chest and
abdominal muscles. On swallowing, the LOS relaxes temporarily. The oesophagus enters the
stomach at an oblique angle and the diaphragm maintains this angle which forms a pinch valve. The
lower oesophagus is in the abdomen and is thus exposed to intra abdominal pressure. Some
description of hormonal influences was expected (eg. gastrin, motilin, prostaglandin E2, glucagon,
secretin, cholecystokinin, VIP).

5
Additional marks were awarded for including the following points: The oblique fibres of the
stomach wall functions as a flap valve. There is a pressure differential between the stomach and the
oesophagus. Barrier pressure is the difference between the LOS pressure and the intra-gastric
pressure. The latter is about 10 cm H
2
O. Normal barrier pressure is about 26 cm H
2
O (reflux can
occur when this pressure falls below 13 cm H
2
O).

Some candidates listed the hormones without stating how they affect the LOS tone. Most
mentioned barrier pressure but some did not state any values. Others discussed pharmacology
which was not required.

VIVA SECTION

Introductory Physiology Questions

CVS
Guyton's Curves. Effect of haemorrhage
Left ventricular pressure volume loops
Myocardial oxygen supply and demand; Coronary sinus PO
2

Valsalva manoeuvre.
Effects of IPPV and PEEP
Preload and Frank-Starling curve
Autoregulation
Fluid flux across capillary; Lymph formation and flow
Haemodynamic changes during pregnancy
Foetal circulation and changes at birth
Cerebral blood flow
Head-down tilt - effects on ICP
Resp
Effects of supine position
Closing capacity
Regional variations in ventilation
Static compliance
A-a gradient
Effects of lung volume on pulmonary vascular resistance
Effects of breathing high inspired CO
2

Alveolar air equation
Effects of increasing altitude on PO
2

Work of breathing
Blood
Changes in stored blood
Effects of massive transfusion
Prevention of blood clotting in normal blood vessels
Difference between plasma and serum
Blood Groups
Structure and synthesis of Hb
O
2
carriage in plasma
Hb-oxygen dissociation curve
6
Renal
Range of urine osmolalities
Mechanisms of concentration/dilution
Excretion of fixed acids
ADH effects
Total body water and its measurement
Effects of increasing renal blood flow on GFR
What is in 1L of Hartmann's solution?

GI
What factors prevent gastro-oesophageal reflux?
Lower oesophageal sphincter

Measurement
Cardiac output: invasive and non-invasive
Invasive measurement of blood pressure
Humidity
Osmolality
Lung compliance: dynamic vs static

Other
Thermoregulation
Effects of 48 hour fast
Lactate production
Buffers

PHARMACOLOGY

WRITTEN SECTION




QUESTION 9 Outline the toxicity of local anaesthetics.

57% of candidates passed this question

Toxicity is defined as the deleterious side effects of a drug. Toxicity may be reversible or
irreversible and is usually dose related over a range. It may be systemic or local. The main points
expected in the answer were:

Local anaesthetics vary in their toxicity, toxicity correlates with intrinsic potency.
Systemic toxicity relates to the blood level of local anaesthetic.
Blood levels depend on site, dose and rate administered and other factors such as metabolism.
A description of the sequence of events that occurs with increasing blood levels, the CC:CNS
ratio.
Specific examples including a brief discussion of the mechanism of toxicity eg. bupivacaine,
cocaine.

Other information that was rewarded included a discussion of factors that predispose to toxicity,
maximum dosages, local toxicity and anaphylaxis. A common error was to imply that toxicity was
the same for all local anaesthetics, eg, 'arrhythmias caused by local anaesthetics are difficult to
treat'. Serum levels were sometimes listed without reference to a particular agent. Cousins and
Bridenbaughs Neural blockade in clinical anaesthesia and pain management is an excellent
reference for this topic.

QUESTION 10 Outline the factors that determine recovery (offset of action) after
ceasing a drug infusion.

The pass rate for this question was 43%. This question was also asked in 1999, 1998 and 1995.

The effect of most drugs is related to the drug concentration at the effect site. Thus recovery is
dependent on all the factors that influence the concentration at the end of the infusion, the rate of
decline in concentration, and the final concentration that no longer has an effect.

The concentration at the end of the infusion will be dependent on the dosing regimen up to that time
and the drug pharmacokinetics. Diffusion of drug between the blood and the effect site will be
affected by the concentration gradient and the physicochemical characteristics of the drug.
Although a few drugs may be metabolised at the effect site, most drugs will have to diffuse back to
the blood before elimination. The decline in blood concentrations will be determined by drug
clearance and distribution (and factors that alter clearance and volumes of distribution). Many
answers listed potential factors without indicating whether recovery would be prolonged or
shortened.

8
Many answers elaborated on the context sensitive half time (CSHT) as an example of the balance
between distribution and elimination. The CSHT does not determine recovery (although it is better
than the elimination half-life as an indicator); it just predicts a defined specific decline in
concentration. It is unlikely that exactly a 50% decrease in concentration is required for recovery,
and the CSHT can not be simply scaled for other decrement times. Many answers were confused
about the effect of volume of distribution (Vd). A larger peripheral Vd may hasten the decline in
plasma concentration if the infusion is relatively short. An increase in lipid solubility does not
necessarily mean an increase in Vd. A comparison of the opioid data will illustrate the inter-
relationships among all the pharmacokinetic variables.

The effect site drug concentration required for recovery may be affected by factors such as
individual variability, tolerance and drug interactions. Other factors that may influence actual
recovery include active metabolites and patient status. A few drugs bind irreversibly to receptors or
inactivate them so that the effect long outlasts their measured blood concentration.

QUESTION 11 Briefly outline the effects of thiopentone and ketamine not mediated via
the central nervous system.


Passing required attention to both the cardiovascular and respiratory peripheral effect of
thiopentone and ketamine. Mention of anaphylactic and anaphylactoid reactions; tissue irritation;
enzyme induction and porphyria also gained points.

Some candidates were unable to clearly differentiate the central and peripheral direct effects of the
drugs. However some were very lucid and described both the peripheral effect and the alteration
superadded with central system input.

QUESTION 12 Outline the mechanism of action of non-steroidal anti-inflammatory
drugs and their potential adverse effects.

The pass rate was 72%. The "mechanism of action" and "adverse effects" parts had equal marks
available. A bare pass answer in each part could have included -
Mechanism of Action: The inhibition of metabolism of arachidonate by cyclooxygenase (COX) to
subsequent prostaglandins, together with detail about COX-I & II differences, explaining why these
might be exploited with selective COX-II inhibitors.
Adverse Effects: Gastric haemorrhage, inhibition of platelet aggregation and renal impairment
together with detail about how and when these occur

Extra marks were given for greater detail of how the analgesic, anti-pyretic, and anti-inflammatory
actions are produced and for non-COX inhibition mediated mechanisms of action. Anti-platelet
actions were accepted in either part of the answer but marked only once.

NSAIDs, including aspirin and paracetamol, have many other adverse effects. These include
general CNS disturbances, Reye's syndrome, elevation of LFTs & hepatitis, PDA closure, inhibition
of uterine contraction, displacement of plasma protein bound medications, haematopoietic problems
including aplastic anaemia, and overdose toxicity of paracetamol and aspirin.

9
Candidates frequently stated that "NSAIDs cause asthma" without further qualification. A subgroup
of asthmatic patients (20% to 25% of middle-aged patients with asthma, nasal polyps, or chronic
urticaria) show hypersensitivity to even small doses of aspirin, and most other NSAIDs. This is
thought to be due to diversion of arachidonic acid to the 5-lipooxygenase pathway and leukotriene
production. Lipooxygenase blockade appears to be effective in preventing the problem. (Goodman
& Gilman 10
th
Ed, Ch 27).

QUESTION 13 What are the side effects of amiodarone and what problems may develop
during concurrent anaesthesia.

44% of candidates passed this question. The main points expected included the following:
Pulmonary fibrosis and/or alveolitis is a common serious toxicity estimated to occur in 5 to 15% of
patients on chronic therapy. The cause is not known but it has a high associated mortality. There
are two presentations progressive dyspnoea with infiltrates on chest X-ray or an acute onset
cough, hypoxia, and dyspnoea that mimics infectious pneumonia. Postoperative patients are at risk
of developing adult respiratory distress syndrome particularly if they have been on cardiopulmonary
bypass. Additional marks were awarded for mentioning the potential role of inspired oxygen levels
in this postoperative complication.

Amiodarone is an antiarrhythmic agent with side effects relating to its multiple sites of action in the
cardiovascular system. As a non-competitive blocker of - and - adrenergic receptors IV
administration induces arteriolar vasodilation resulting in hypotension. General anaesthesia may
exacerbate these antiadrenergic effects leading to sinus arrest, AV conduction block, peripheral
dilation, hypotension and low cardiac output. Direct myocardial depressive effects are minimal.
Bradycardia can occur with chronic therapy and the additive effect of volatile anaesthetics in
suppressing myocardial conduction may enhance this effect. Amiodarone prolongs the cardiac
action potential, and hence the QT interval, through its suppression of outward K channels. This
may lead to life threatening ventricular arrhythmias including torsades de pointes, although the
incidence is less than with other class III agents.

Hypothyroidism or hyperthyroidism occurs in 2-4% of patients, and is related to the iodine content
of amiodarone. Corneal microdeposits occur in almost all patients receiving long term therapy.
Photosensitive skin reactions are quite common, slate grey pigmentation that persists after
discontinuation of the drug is more rare. Dose dependent mild increases in liver transaminases are
common. Peripheral neuropathy can occur in patients on long term high dosage. Additional credit
was given for mentioning the pharmacokinetic implications of displacement of drugs such as
digoxin from protein binding sites and the potentiation of warfarin.

QUESTION 14 Briefly outline pharmacological methods of reducing gastric acidity.
Indicate the mechanisms of action and the advantages and disadvantages
of each method.

There was a 59% pass rate for this question. Good answers included discussion of antacids (non-
particulate and particulate), histamine-2 antagonists, proton pump inhibitors, prostaglandin
analogues (misoprostol) and anticholinergic agents. Areas that were often inadequately discussed
were antacids, perioperative reduction of acidity and advantages/disadvantages of the methods
outlined.

10
QUESTION 15 Describe the mechanism of the anticoagulant effect of coumarin
derivatives and what determines the onset and offset of effect.

45 % of candidates achieved a pass. Most candidates indicated that the anticoagulant effect of
coumarins is mediated via vitamin K antagonism and inhibition. However, most candidates failed to
describe the nature of this antagonism (competitive) at therapeutic levels and also to mention the
coumarin sensitive step in the recycling of vitamin K and its role in the carboxylation of glutamic
acid residues to produce biologically competent factors.

An understanding of the different half-life of vitamin K dependent factors, II, VII, IX, X and
protein C and S, was essential to explain the delayed onset of action of coumarins. The time to peak
plasma levels and its relation to biological effect were often omitted. Coumarin appears in the
plasma after 1 hour and peaks in 4 to 8 hours after an oral dose but the biological effect takes 3 to 5
days to manifest.

Important and clinically relevant determinants of onset were rarely mentioned. The effect of loading
dose, age sensitivity, postoperative relative vitamin K deficiency, level of coagulation factors and
albumin levels should have been included. The effect of congenitally high levels of coagulation
factors, disease states, enzyme induction, ingestion of vitamin K rich food could have been included
but were rarely mentioned. Most candidates however, identified external supplementation of
vitamin K and fresh plasma as ways of accelerating offset of coumarin effect.

Most candidates mentioned INR as a monitor for warfarin therapy; some gave unnecessary details
of INR levels needed for different indications.

QUESTION 16 Briefly outline the pharmacology of flumazenil.

The pass rate for this question was 45%. The question asked for straightforward factual
information. To pass, the candidate needed to describe the chemical identity, presentation,
pharmacokinetics (briefly) and pharmacodynamics of the drug. It was difficult to score enough
points to pass without at least a brief mention of each of these points. Many candidates gave lengthy
and often incorrect descriptions of the kinetics of the drug.

More complete answers usually gave a dose or dosage range for the drug and referred to the clinical
problem of re-sedation, due to the longer half-lives of the most commonly used benzodiazepines-
compared with flumazenil.

VIVA SECTION

Introductory Pharmacology Questions

Draw a concentration/time curve after an IV bolus of propofol
How do you calculate volume of distribution
What is the induction dose of propofol and what is its disposition in elderly patients?
Describe the structure/function relationships of local anaesthetics
Correlate the pKa of local anaesthetics and their activity
Describe the site of action of local anaesthetics
What is your recommended dose of paracetamol?
What is the toxic dose of paracetamol?
How do you express drug safety? What is therapeutic index?
What is an emulsion?
Outline a chi-squared test
11
Draw a wash-in curve for your choice of inhalational agent
Draw or describe the concentration/response curve for an inhalational agent
Describe the uptake of volatile agents
Classify diuretics by their site of action
What drugs affect uterine motility?
Compare/contrast pancuronium and vecuronium
Account for a case of delayed recovery from vecuronium
How do you assess reversal of muscle relaxants?
Describe the anti-platelet agents
Discuss factors affecting awakening from isoflurane
Cardiovascular effects of remifentanil
Classify inotropes
Compare propofol and midazolam as induction agents
Discuss the brain concentration of bupivacaine after an epidural dose
Discuss the principles of drug interactions using opioids and MAOIs as examples
Describe tolerance to opioids
Describe the metabolism of morphine
Why infuse a drug?
Describe the mechanism of action of anti-convulsants
Compare neostigmine and edrophonium
Describe the distribution of histamine receptors
What drugs are used in cardiac arrest?
What are some sources of bias
Heparin-effects, metabolism
Serotonin receptors
Pharmacokinetics in heart failure
Renal failure and drug metabolism
Classify drugs used in cardiac failure

N.M. GIBBS
CHAIRMAN
PRIMARY EXAMINATION

ABN 82 055 042 852

EXAMINATION REPORT

PRIMARY EXAMINATION

AUGUST/ SEPTEMBER 2001


PHYSIOLOGY

WRITTEN SECTION




QUESTION 1 Explain the effects of intermittent positive pressure ventilation on left
ventricular output.

55% of candidates passed this question The main points expected for a pass were outlined in
previous Examiners' reports, August 1996 and March 1998. In brief they are:-

On inspiration;

1. An initial increase in left ventricular stroke volume as the increased intra-thoracic
pressure squeezes blood into the left atrium, increasing LV preload.
2. Then a decrease in left ventricular stroke volume as the venous return to the right
ventricle decreases and the afterload of the right ventricle increases.

On expiration;

1. The decrease in intrathoracic pressure and increase in pulmonary vascular compliance
initially allows blood from the right to collect in the lungs before it crosses to improve
the left ventricular stroke volume
2. The venous return to the right ventricle improves as the intrathoracic pressure
decreases.

2
Additional marks were given for comments on the left ventricular afterload, compliance and
ventricular interdependence, and also for the exaggerated drop in blood pressure seen with
hypovolaemia and PEEP.

Common mistakes were

1. Failure to organise the information.
2. Ignoring expiration.
3. Writing too much on normal ventilation or reasons for positive pressure ventilation.
4. Writing too much on the long-term responses (hormonal) to positive pressure
ventilation and the baroreceptor reflexes.

QUESTION 2 Describe the determinants of work of breathing in an adult human at
rest.

The pass rate for this question was 72%. This question was asked in similar form in March/April
2000, when the pass rate was slightly less than 50%.

The main points expected were-

* that the S.I. unit of work is the Joule, and an explanation of how work is derived (eg. Pressure
times Volume)
* a breakup of inspiratory work into elastic and non-elastic components
* that elastic work consists of deforming elastic tissue, and overcoming surface tension
* that non-elastic work consists of overcoming airway resistance and viscous forces
* that resistance work is performed during inspiration and expiration, but that the energy for
expiration is acquired during inspiration
* the effects on work of breathing due to changes in compliance, airway resistance, and
respiratory rate

Additional marks were awarded for-

* correctly labelled pressure-volume diagrams with percentage contributions
* the oxygen cost and efficiency of work of breathing
* mentioning that energy is also lost as heat

Common mistakes were to write detailed answers on compliance, airway resistance, and patho-
physiological conditions. A common omission was to describe expiration as passive, without stating
that potential energy is acquired during inspiration and stored elastically to provide energy for
expiration.

QUESTION 3 Describe the fuel sources used during early and sustained fasting in man.

51% of candidates passed this question. A large number of the candidates who did not achieve a
pass were borderline fails.

The main points expected for a pass included a definition of early and sustained fasting. A wide
range of definitions was accepted so long as early fasting was considered less than 24h. A brief
description of the conversion of liver glycogen stores to glucose during early fasting was required
as was the importance of glucose as a source of energy. Similarly, a brief description of the role of
gluconeogenesis, lipolysis, and the production of ketone bodies during sustained fasting was
3
expected. The fuel sources could be considered as either the substrates (ie glycogen, protein and
fat), or their breakdown products (ie glucose, amino acids, free fatty acids, glycerol, and ketone
bodies). The reliance of the brain on glucose or ketone bodies was considered core knowledge.

Additional marks were awarded for (1) providing quantitative information, (2) a description of the
Cori and alanine cycles, (3) the fuel sources used by individual organs (eg brain, heart, muscle etc),
(4) the initial sparing of protein during sustained fasting (due to preferential breakdown of
triglycerides), and (5) the time course of changes in fuel utilisation. Candidates who mentioned the
continued absorption of food remaining in the gut during early fasting received credit.

Common mistakes were to consider ATP or creatine phosphate as 'fuel' sources, to discuss the
effects of water deprivation (while the question asked for a description of fuel sources), or to
consider other aspects of starvation. Common omissions were to overlook the importance of
glucose, especially in early fasting, and free fatty acids in sustained fasting.

QUESTION 4 Describe the physiological changes that occur in respiratory function
during pregnancy.

Although almost 60% of candidates passed this question few achieved high marks. Key points
expected included changes to the various lung volumes, pattern of respiration, minute ventilation,
and the resultant arterial blood gases. Additional marks were gained for outlining the various
anatomical changes that occur, explaining the physiological implications, and outlining the changes
to oxygen flux. Demonstrating understanding of the ramifications of the various changes enhanced
answers. For example the reduction in FRC (and therefore the lung O
2
stores), coupled with the
increased O
2
utilization, increases the rapidity of onset of hypoxaemia. Also the arterial gas tension
changes enhance placental gas transfer to the benefit of the foetus.

Common misconceptions included tidal volume decreasing or remaining unchanged, significant
rises in ventilatory rate, elevation of PaCO
2
, reduction of PaO
2
, increased shunt, and significant
reduction in vital capacity.

A number of candidates wrote in some detail on the clinical anaesthetic implications of the airway
and ventilatory changes. This only gained additional marks where clear understanding of the
underlying physiology was demonstrated.

Candidates are referred to Nunns Applied Respiratory Physiology 5
th
edition Chapter 13 and to the
5
th
edition of Anaesthesia. Miller R. D (ed). Chapter 57.

QUESTION 5 Describe the structure and function of voltage gated ion channels.

59% passed this question. This question asked for a description of both structure and function of
voltage gated ion channels specifically. General information on ion channels which did not pertain
to voltage gated ion channels did not score marks. 'Structure' was generally covered adequately,
with inclusion of the basic concept of a transmembrane protein channel. The inclusion of detail on
the subunit components and gating mechanisms was variable, and was often restricted to sodium
channels alone. Some candidates provided excessive detail at the expense of other areas. The
answers to the 'function' component of the question were much more variable.

What was sought was evidence of comprehension of the basic functioning of voltage-gated
channels. This included knowledge of their dependence on voltage changes for configurational
changes, a resulting alteration in specific ion conductance, and awareness of the concept of channel
4
activation and inactivation. Further marks were gained by relating this to specific roles in excitable
membranes and organs. Again, quite a few candidates focused solely on sodium channels, but this
was accepted if comprehension of the concepts of voltage-gated channels was displayed. Inclusion
of details of other channels (e.g. potassium and calcium channels), however, scored additional
marks. Some candidates included detail on modulation of receptor function over time, and changes
in functioning with drugs/toxins, which gained extra marks.


47% of candidates achieved a pass mark.

The kidney freely filters glucose and almost completely reabsorbs it in the proximal convoluted
tubule. This is an active process, utilising a Na
+
co-transport system. Energy for this process
comes from Na
+
/K+ ATPase on the basement membrane, pumping Na+ out of the renal tubular cell.
This co-transport system is saturable. Extra marks where attracted for discussion of the SGLT 1
and GLUT 2 transporters and their role. A description of the T
M
and how glycosuria occurs at a
level below the theoretical T
M
also received extra marks.

Glycosuria causes an osmotic diuresis, and details of the mechanism were expected. Candidates
who explained the effect on the medullary osmotic gradient and the subsequent failure to
concentrate urine received extra marks. Some mention of the systemic implications of these effects
was also expected.

QUESTION 7 Explain the main difference between the intrinsic and extrinsic pathways
of coagulation.

41% of candidates passed this question. The main points expected in the answer included an
account of the coagulation factors involved, a sketch of the pathways demonstrating the cascades of
factor activation, and the co-factors involved. Also required was an account of what initiates or
triggers the pathways of coagulation, the relative importance of the pathways in vivo, and how
blood may coagulate in other settings, such as in a test tube. Additional marks were awarded for
information regarding the relative speed of the pathways, interaction between the pathways,
implications of specific factor deficiencies, the tests used to measure the activity of the pathways
(including how these tests are performed), and where anticoagulants such as heparin and warfarin
act. The few candidates who described how sepsis and inflammation activate coagulation received
additional marks.

Common errors were confusion about what the intrinsic and extrinsic pathways of coagulation are,
the triggering mechanisms involved, and the relative importance of the pathways in vivo. Some
candidates spent time giving accounts of other aspects of haemostasis at the expense of providing
information about the intrinsic and extrinsic pathways of coagulation.

5
QUESTION 8 Explain the physiological processes involved in the development of
interstitial oedema.


Interstitial oedema occurs when the volume of fluid leaving the capillaries and entering the
interstitial space is increased, and/or the lymphatic drainage is reduced, and/or the total ECF
volume is increased. Many candidates discussed only the Starling forces acting across the capillary
and failed to mention the role of impaired lymphatics. No candidate mentioned the effect of
increasing total ECF volume.

To achieve a pass, candidates were expected to include in their answer

Starlings equation (or the main components of the equation), with approximate normal
values
Examples of causes of raised capillary hydrostatic pressure, reduced plasma oncotic
pressure, increased permeability, and/or decreased reflection coefficient;
The role of lymphatics with an example of impaired function.

Additional marks were awarded for including the following points: explaining the concept of
oncotic pressure (ie osmotic pressure due to non-diffusable particles); giving examples of reduced
interstitial hydrostatic pressure leading to oedema (e.g. negative pressure pulmonary oedema);
explaining that the pressure and permeability vary between capillary beds; indicating that
hydrostatic pressure

can increase by venoconstriction or arteriolar dilation; mentioning that protein
leak into interstitium increases
i
, thus favouring water movement.

Common mistakes made were:

60% of candidates stated that increased blood pressure leads to increased capillary
pressure. However, this is not alway the case, because most of the pressure drop in the
arterial circulation occurs before the capillaries. In fact, arteriolar dilation increases
capillary pressure. This reflects a basic misunderstanding of the nature of pressure drops
along the circulation.
Many candidates stated that oedema occurs when net filtration exceeds net reabsorption in
the capillary, whereas this occurs in many capillary beds without formation of oedema.

A few candidates restricted their answer to pulmonary oedema, but they were not penalized if the
other required information was present. No candidate mentioned that oedema may be localized or
generalized.

6
VIVA SECTION


Atrial pressure waveform
Factors affecting stroke volume
Coronary blood flow
Preload, contractility, afterload
Pressure volume loops of the heart
Aortic and radial artery pressure waveforms
Draw the cardiac cycle
Pressure waveforms during pulmonary artery catheter insertion
ECG Origin of waveform
Pulmonary blood flow
Effects of age on lung function
Ventilation / perfusion matching
Causes of tissue hypoxia
Causes of arterial hypoxaemia
Carbon dioxide carriage in the blood
Respiratory acidosis; alkalosis
Causes of an A-a gradient
Alveolar pressure
Shunt and V/Q mismatch
Functions of liver
Effects of vomiting
The effects of insulin
Control of blood glucose
Response to lack of insulin
Absorption of carbohydrate load
Active transport
Facilitated diffusion
Resting cell membrane potential
Osmolality
Blood gas analysis
Spirometry
Pneumotachograph
Oximetry; pulse oximetry
Measurement of arterial pressure
Humidity
Intracranial pressure
Control of cerebral blood flow
Renal handling of acid load
Renal clearance
Effects of drinking 2 litres of water
Excretion of dilute and concentrated urine
Countercurrent exchange in the kidney
Factors affecting GFR
7
Regulation of potassium
Temperature regulation
Changes in pregnancy
Oxygen delivery to the foetus
Foetal circulation
Structure of haemoglobin
Blood groups
Haemostasis after finger laceration
Haemoglobin dissociation curve
Loading / unloading of haemoglobin

PHARMACOLOGY

WRITTEN SECTION




QUESTION 9 What do you understand by the term clearance. Using propofol as an
example, explain briefly the importance of clearance.

77% of candidates passed this question. It was expected that candidates should provide a definition
of clearance including units. Some mention of total body clearance being the sum of individual
organ clearances was also expected. The most common mistakes made were to define the
elimination rate rather than clearance and/or not to provide units. Some candidates entered into
erudite discussion of renal clearance, which was more a discussion of renal physiology than drug
pharmacology.
Propofol is a general anaesthetic agent with a high clearance (30ml.kg
-1
.min
-1
). This is in fact
greater than liver blood flow suggesting extra-hepatic sites of elimination. Whilst redistribution is
important in drug offset in bolus doses, clearance becomes increasingly relevant with infusions.
Clearance is also important in determining steady state infusion rates. Most candidates understood
these concepts. Equations were a time efficient method of explaining concepts however this
occasionally led to confusion. For example volume of distribution and clearance are independent
variables and in effect the half life is a proportionality constant. Answers of a higher standard
mentioned context-sensitive half time, compartment model infusion regimens and compared
propofol to thiopentone.

QUESTION 10 Briefly describe the adverse effects of nitrous oxide.

76% candidates passed this question. To achieve a pass mark, candidates were expected to describe
the adverse effects of nitrous oxide resulting from expansion of air-containing spaces, diffusion
hypoxia and decreased activity of vitamin B
12
and methionine synthetase. Additional marks were
obtained for comprehensive descriptions of the aforementioned effects, and for description of
additional adverse effects including but not restricted to post-operative nausea and vomiting,
pulmonary hypertension, increased cerebral blood flow, mild myocardial depression and
sympathetic stimulation. Many candidates also described the potential for adverse effects of
impurities in manufacture.

QUESTION 11 Describe the required pharmacological characteristics of local
anaesthetic formulations intended for topical use.

41% of candidates passed this question. It was expected that there would be a description of the
characteristics of the formulations applied at the different sites where topical local anaesthesia is
used.

9
The main points expected for a pass were concerned with characteristics common to all topical
anaesthetics including those incorporated in Ficks law of diffusion. However there should have
been mention of various possible sites of application (eg skin and mucous membranes) in order to
illustrate the differing relative importance of characteristics which could subsequently have been
divided into pharmaceutical, pharmacokinetic and pharmacodynamic properties.

Pharmaceutical
Presentation, (eg aerosol, solution, gel, cream, lozenges), stability during storage, concentration of
active component, possible additives including those required to optimise kinetics (eg pH
adjustment and/or vasoconstrictors), lack of local toxicity.

Pharmacokinetic
Molecular weight, pKa and intrinsic lipid solubility, rapid onset, appropriate duration, high
systemic clearance, no active or toxic metabolites.

Pharmacodynamic
Effective block of nerve transmission, relevance of intrinsic vasoconstrictor activity, high
therapeutic ratio.

Additional marks were awarded for explanation of the relevance of the above characteristics, eg
buffering of formulation to ensure low ionisation thus further enhancing intrinsic lipid solubility or
why vasoconstriction, despite the limits it places on systemic uptake, may be undesirable if venous
cannulation is planned. Mention of other characteristics (eg ease and economy of production,
preservatives, protein binding and common side effects) could also gain additional marks.

The question did not relate only to cutaneous application and EMLA. Unnecessary detail about this
formulation, to the exclusion of other information, was the most common reason not to gain marks.
Similarly extensive discussion of non-pharmacological topics such as the thickness of the cutaneous
barrier or area of application did not gain marks unless in relation to kinetics or dynamics (eg onset
times and systemic toxicity). Occasional confusion seemed to exist between potency and
concentration. The former is a comparison of the mass of one drug, compared to another, to bring
about an effect. In this context potency is of little importance so long as the concentration of the
formulation is far enough above the effective concentration to ensure a high concentration gradient.
Despite the fundamental nature of the relationship between pH, pKa, ionisation and transmembrane
passage of molecules, some candidates still appear not to understand this topic.

QUESTION 12 Outline the effects of an opioid injected into the spinal intrathecal space.

The pass rate for this question was 18%. Intrathecal opioids act initially on spinal opioid receptors,
causing presynaptic and postsynaptic effects at a cellular level such as decreased release of
substance P. The resultant analgesia is greater for dull pain mediated by C fibres than sharp pain
mediated by A-delta fibres. Urinary retention, pruritis, nausea and delayed respiratory depression
are important side effects but few candidates mentioned their expected incidence. Better answers
compared different opioids, gave some indication of the duration of analgesia and gave more detail
on the different side effects.

Some candidates appeared to list the effects of spinal local anaesthetics and stated that intrathecal
opioids would cause significant cardiovascular disturbance. Although meperidine has been used as
a sole intrathecal anaesthetic and large doses of other opioids such as sufentanil may have
significant local anaesthetic effect, this is not usually the case after small doses of intrathecal
opioids. Secondary haemodynamic or other effects occurring because of adequate analgesia were
not rewarded. However candidates should note there has been concern about intrathecal opioids in
labour and fetal bradycardia. Some candidates discussed epidural opioids, and gave unnecessary
10
detail about transfer of opioids across the dura and systemic absorption. Many candidates wasted
time on a detailed comparison of the pharmacology of different opioids. Candidates scored few
marks when they listed all the possible effects of opioids without taking into account the intrathecal
route and consequent small dose used.

QUESTION 13 Compare and contrast neostigmine and the organophosphorus
compounds.

The pass rate for this question was 64 %. The question asked for a comparison and contrast
between two drugs and it was essential for candidates to have addressed both agents to achieve
a pass mark and not discuss only one of the agents.
It was imperative to define the actions of these drugs and describe the mode of binding with some
explanation of their durations of action. An explanation of their actions, clinical effects and the fact
that neostigmine does not cross the blood brain barrier unlike organophosphates was considered
important to the answer. Candidates who were able to give detailed explanation of the binding
characteristics of these agents and how that influenced their duration of action, pharmacodynamic
profile and clinical applications attained higher marks. It was considered that a general comment
such as neostigmine being short acting and organophosphates being long acting, without detailed
explanation, was inadequate to pass

QUESTION 14 Outline the direct effects of endogenously released histamine.

All candidates attempted to answer this question; the pass rate was 49%. The main points expected
were a brief description of histamines usual roles, including gastric acid production, central
neurotransmission, and vascular tone; and its role in inflammation and allergic reactions. A specific
mention of drug allergy was rarely included. Many candidates provided an unnecessary amount of
detail about the synthesis and G-protein mediated mechanism of action of histamine, but minimal
information about its effects. The specific cardiovascular, respiratory and local effects (eg. skin
wheal and flare response, pain), specific identification of H
1
, H
2
(& H
3
) actions, and gastric acid
secretion were the main points required.

QUESTION 15 Outline the potential benefits and disadvantages of peri-operative
beta-blockade.

The pass rate for this question was 47%. To achieve a pass candidates needed to include the
following main points. The potential benefits including: lower incidence of ischaemia secondary to
improved myocardial oxygen balance, antihypertensive effects particularly during sympathetic
nervous system hyperactivity for example during endotracheal intubation and antiarrhythmic
actions in catecholamine induced arrhythmias. Extra marks were given for correctly quoting long-
term studies where mortality has been reduced. The concept of how beta-blockers improved
myocardial supply and demand by decreased heart rate and decreased contractility should have
been included.

The disadvantages that should have been mentioned were: negative inotropic effects, especially in
patients with cardiomyopathies or when combined with inhalational agents or calcium blockers,
bradycardia and possible heart block, perioperative hypotension, bronchoconstriction, and
hypoglycemia and delayed recognition in diabetes. The incidence of cardiovascular side effects is
generally low.

11
A common mistake made by candidates was to discuss at length the pharmacology of individual
agents or to describe beta receptors and their actions.

QUESTION 16 Briefly describe correlation and simple linear regression, and explain
their differences. What assumptions are common to both?

This question has previously been asked in this form. A pass rate of 82% indicates that much of the
required information had been identified by reference to previous reports. In order to pass in this
question, the answer needed to convey the concept that correlation attempts to assess the degree of
association between variables, and that linear regression is a process by which a linear relationship
could be examined. In reality, linear regression is simply a modelling process, for which the
goodness of fit of the model (a straight line relationship) to the data is given by the correlation
coefficient. Most candidates could name the Pearson and Spearman coefficients and their
respective data requirements. Most candidates also stressed the lack of implied causality with
correlation and the danger of extrapolating beyond the data range with regression equations.
Commenting on the meaning of various values of r from 1 to +1 and particularly zero was
essential. A useful diagram showing a scattergram with data points, a regression line and 95%
Confidence Interval lines was included occasionally, being an efficient mode of expressing several
important concepts. The coefficient of determination was seldom mentioned, as was the problem of
the inevitable correlation (when y is, in fact, necessarily determined by or a product of x).
Although most candidates mentioned the term "method of least squares", few attempted to expand
the concept and most were incorrect.

VIVA SECTION


1. Effects of isoflurane, propofol, fentanyl on blood pressure, in healthy adults
2. What is meant by loading dose?
3. Mechanisms of drug-induced histamine release
4. Effects of lignocaine on nerve conduction
5. Factors affecting onset of muscle relaxants
6. Measurement of muscle relaxant effect
7. Effect of isoflurane on respiration
8. The pharmacology of clonidine
9. Early phase (I-II) drug testing
10. Glyceryl trinitrate and sodium nitroprusside
11. Risk ratio
12. Meta-analysis
13. Bias
14. Offset of action of propofol
15. Propofol bolus concentration-time curve
16. Utility of MAC
17. Choice of drugs to treat hypotension after spinal anaesthesia
18. Volume of distribution
19. Factors that alter induction dose
20. Volatile anaesthetic concentration-response curves
21. Characteristics of intravenous induction agents
22. What is a receptor?
23. Comparison of thiopentone and propofol induction
24. Drug effects on skeletal muscle tone
25. Describe events during onset of depolarising / non-depolarising neuromuscular block
12
26. Classification of local anaesthetics
27. Cardiotoxicity of local anaesthetic
28. Stereoisomerism
29. Mechanism of action of benzodiazepines
30. Structure of midazolam
31. Metabolism of midazolam vs diazepam
32. Gas uptake from lungs
33. Types of data
34. Structure-activity relationship of barbiturates
35. Mechanism of action of local anaesthetics
36. Types of vasoconstrictors
37. Determination of, and factors influencing, oral bioavailability
38. Conversion to oral opioids
39. Toxicity of sodium nitroprusside
40. Analgesic actions of ketamine
41. DNA and RNA, and recombinant drugs
42. Drugs influencing ligand-gated vs voltage-gated ion channels
43. G-protein-linked receptors
44. Metabolism of sevoflurane

N.M. GIBBS
CHAIRMAN
PRIMARY EXAMINATION

DISTRIBUTION College Council Supervisors of Training
Regional Education Officers Panel of Examiners
Registered Trainees
ABN 82 055 042 852

EXAMINATION REPORT

PRIMARY EXAMINATION

MARCH/APRIL 2001


PHYSIOLOGY

WRITTEN SECTION




QUESTION 1 Outline the determinants and regulation of extracellular fluid volume.


The volume of ECF is primarily determined by the total amount of osmotically active solute present
in this fluid compartment which is predominantly sodium and chloride. Changes in the amount of
chloride are to a large extent secondary to changes in sodium. Hence the amount of sodium in the
ECF is the most important determinant of ECF volume. This was not mentioned by 46% of the
candidates. These candidates were then less likely to go on and describe the mechanisms that
control sodium balance and hence determine ECF volume. The factors that regulate ECF volume
include angiotensin (which stimulates aldosterone and ADH secretion), aldosterone which causes
renal sodium and chloride reabsorption, and ADH which promotes water retention by the kidneys.
Changes in GFR alter the amount of sodium filtered. However, the fraction of sodium reabsorbed
is held constant by glomerulotubular balance. This is different to tubuloglomerular feedback (the
mechanism by which delivery of sodium and chloride to the macula densa feeds back to alter GFR).
These two processes were often confused with each other. Stimulation of osmoreceptors in the
hypothalamus cause thirst and also increase ADH secretion. Atrial natriuretic peptide secreted by
the atria in response to increased intravascular volume causes natriuresis. Sodium is also lost in
sweat. Volume stimuli override the osmotic regulation of ADH secretion and hence water
excretion. Those candidates who over-emphasised one area at the expense of others, or who
produced irrelevant information gained less marks. For example many candidates offered lengthy
2
and irrelevant descriptions of the Starling forces across the capillary and the Gibbs-Donnan effect.
The location of the volume receptors and osmoreceptors was incorrect in many answers.

QUESTION 2 Briefly describe the effect of resting muscle length and load conditions
on the tension generated by a skeletal muscle. How do these factors
affect the velocity of shortening?

19% of candidates achieved a pass in this question.

The main points expected for a pass were the relationship of resting muscle length to tension
development, and the components of active and passive tension which contribute to total tension as
length is increased. The inverse relationship of load to velocity of shortening was also expected.
High scoring candidates made effective use of correctly labelled graphs to illustrate points, and
explained that developed tension was maximal at resting length. Most candidates were able to
illustrate the role of actin/myosin cross-bridge formation in the development of tension, but there
was often confusion with cardiac muscle, and a Frank-Starling mechanism was often invoked for
skeletal muscle. Diagrams frequently referred to left ventricular haemodynamics rather than
skeletal muscle. Muscle spindle control and Golgi tendon organ involvement were not required in
the answer and did not attract marks.

QUESTION 3 Briefly describe the measurement of pH in a blood sample using a pH
electrode

The main points expected for a pass included:-

the definition of pH
use of an ion-specific electrode, based upon the use of H
+
-ion sensitive glass
the presence of a buffer solution to maintain a gradient for H
+
-ion
the generation of a potential difference, in proportion to H
+
-ion concentration
the presence of a reference electrode, completing an electrical circuit through a salt bridge,
allowing measurement of this potential with a voltmeter or galvanometer
the requirement for regular calibration

The use of a clearly labelled diagram was beneficial in answering this question, but not essential for
a pass. A number of candidates described the electrode based upon "half-cells", c.f. the classical
description of ion-specific and reference electrodes. On average, candidates using this approach
scored well as they appeared to have a clearer understanding of the underlying principles involved.
Many candidates confused measurement of H
+
-ion concentration with arterial PCO
2
, or the Clark
PO
2
electrode. Many candidates went into lengthy discussions of the Henderson-Hasselbalch
equation, which was not required. A large number expressed that "the pH electrode produced a
current flow which was then measured as pH".

Additional marks were awarded for including further details. Examples of additional information
presented by candidates are listed below. It was not expected that candidates would include more
than a few of these examples in the time available.

the dependence of H
+
-ion concentration on temperature and the requirement for temperature
control
3
common sources of error.
the measurement of thermodynamic activity, c.f. concentration
the physical structure pH sensitive glass and the basis of the potential difference generated
the magnitude of voltage produced and calibration to H
+
-ion concentration
the variation of pH with temperature and Rosenthal's correction factor
the principles of "pH-stat" and "alpha-stat" measurement
the composition and concentrations of buffer and salt solutions used
the standard calibration solutions used
the use of a thermistor to compensate for temperature changes
the use of either a differential voltage amplifier or "null deflection circuit" to measure the
small voltages produced

QUESTION 4 Indicate the sequence of the physiological changes to the fetal circulation
at birth and briefly describe the mechanisms which account for these
changes.


The main points expected were a description of the physiological changes occurring at birth,
including closure of umbilical vessels and ductus venosus, reduction in pulmonary vascular
resistance, reduced right atrial pressure, increased left atrial pressure, increased systemic vascular
resistance, closure of the foramen ovale, and closure of the ductus arteriosus. Some explanation of
the mechanisms involved was required. Additional marks were given for more detailed
explanations of (1) the role of lung inflation and loss of hypoxic pulmonary vasoconstriction in the
reduction in pulmonary vascular resistance, (2) the loss of the low pressure placental circulation in
the increase in systemic vascular resistance, and (3) the effect of pressure changes, increased
oxygen tensions, and reduced prostaglandin activity in the closure of the ductus arteriosus.
Similarly, additional marks were given for indicating a physiological sequence for the changes,
although a temporal sequence was not required. Credit was given for mentioning the change from
parallel to a series circuit, and for mentioning that the initial changes are dynamic and potentially
reversible (transitional).

Many candidates provided detailed descriptions of the fetal circulation, the stimuli to breathing, or
the physiology of the first breath. These were not required. Similarly, detailed descriptions of
pathological states were not required. Common errors were ignoring the changes in pulmonary
vascular resistance, systemic vascular resistance, or both, or listing the changes without describing
the sequence or mechanism. Many candidates incorrectly stated that prostaglandins were
responsible for closure of the ductus arteriosus.

4
QUESTION 5 Explain briefly the role of the skin in maintaining a normal body
temperature.


It is important to note that this question specifically asked for an explanation of the role of the skin
in maintaining normal body temperature. It was expected that candidates briefly mentioned the
general concept of a reflex pathway to maintain temperature through a balance of heat production
and loss. It was not expected that there be a long and detailed discussion of this reflex system.
Similarly, it was valuable to include the sensory function of the skin in maintaining body
temperature. However, a detailed description was not expected.

The control of skin blood flow, with its role in heat loss as well as conservation, was an important
part of this question. Rather than simply listing the responses of skin blood flow, inclusion of how
changes in this flow related to the mechanics of thermal exchange added significantly to the answer.
For example, the inclusion of the concept that heat exchange via radiation/conduction/convection
requires a heat gradient, and that skin blood flow changes can facilitate or impair that exchange,
demonstrated a clearer understanding of the issues of the skin in the maintenance of body
temperature.

Most candidates included comments about sweat production. Very few candidates, however,
recognised its increasing importance as ambient temperature increases, or the relevance of ambient
humidity to its effectiveness. Credit was given for mentioning piloerection as a means of
conserving heat, despite its minimal relevance in man. It was interesting to note, however, that
almost every answer included piloerection even when other, and much more important, areas
related to the skin and body temperature were omitted.

QUESTION 6 Describe the substances released by the endothelium. Explain the role
they play in regulating blood flow through the peripheral circulation.


The key vasoactive substances released from the endothelium are nitric oxide, prostacyclin, and
endothelins. Factors affecting coagulation and fibrinolysis should have been included, although
some of these substances are not so much released as expressed on the surface of the endothelium.
Factors relating to tissue metabolism were accepted (adenosine, hydrogen ion, carbon dioxide and
others), although the endothelium would commonly not be the primary source of these substances.

The second part of the question primarily required a discussion of role of the vasoactive substances
on the peripheral circulation. A discussion of substances which do not affect the peripheral
circulation was not required in this part of the answer. The fact that many vasoactive substances
such as thromboxane A
2
, bradykinin, histamine and serotonin do not primarily arise from
endothelial cells was commonly either not understood or poorly expressed.

5
QUESTION 7 Describe how the body detects and responds to water deficit.


Main points expected were the implications of a water deficit, how this is sensed (emphasising
hypothalamic osmoreceptors), and the central role of ADH including its structure, synthesis,
transport, release and actions. Other points that attracted additional marks included the distribution
of body water (including normal values), the sensitivity of osmoreceptors vs. volume sensors, and
the effects of severe water deficit sufficient to cause intravascular depletion. A common mistake
was to concentrate solely on hyperosmolarity and contraction of the ECF or hyperosmolarity and
hypotension. Many candidates failed to indicate that a water deficit involves contraction of both
intracellular and extracellular compartments. Pure water deficit does not include Na
+
loss, nor does
pure water deficit occur in haemorrhage. Thirst is not a "backup system" in water deprivation.
High pressure baroreceptors do not respond to hypovolaemia. There was little appreciation that in
pure water deficit, a 10% reduction in intravascular volume would be associated with a water deficit
of over 4 litres.

QUESTION 8 What are the physiological consequences of decreasing functional
residual capacity by one litre in an adult?

62% candidates passed this question

To achieve a pass, candidates were expected to define FRC (ie. equilibrium volume of the lung and
chest wall; residual volume plus expiratory reserve volume) and give normal values, such that the
physiological effects of a decrease of one litre in FRC could be put in perspective. The main points
expected were a decrease in compliance, increase in airway resistance, increase in pulmonary
vascular resistance, and small airway closure below closing volume leading to increased work of
breathing and V/Q mismatch. The increased work of breathing is due to the additional pressure
(positive or negative) required to open airways/alveoli as well as the decreased compliance at low
lung volumes. Low V/Q leads to arterial hypoxaemia. Candidates who provided appropriately
labelled diagrams attracted higher marks.

Additional marks were given to candidates who described functions of FRC and the common
causes that lead to a decrease, provided that they continued to discuss how the normal functions are
disturbed by the fall in FRC. The common errors were not answering the question (eg providing
information about FRC without mentioning the effects with a fall in FRC of 1L, confusing shunt
with dead space, mislabelling diagrams, confusing the diagram of lung volumes vs airway
resistance and lung volumes vs pulmonary vascular resistance. Some candidates discussed at length
the effects of hypoxaemia which was not required.

VIVA SECTION

Alveolar-arterial gradient for oxygen
Anaphylaxis
Aortic vs. radial pressure traces
Autoregulation
Blood gas interpretation
Blood groups
Blood-brain barrier
BMR / MRO
2

6
Calcium: functions, regulation
Calibration of arterial lines
Capnography
Cardiac function curves
Causes of low PaO
2

Central chemoreceptors
Cerebral blood flow
Changes in stored blood
CO
2
carriage in blood
Colligative properties of solutions
Colloid osmotic pressure
Comparison of pulmonary and systemic vascular resistances
Complement cascade
Control of blood glucose
Continuous positive airways pressure
CSF composition, functions
CSF production and absorption
Differences between static and dynamic compliance
Diffusion
Diffusion abnormalities in the lung
Factors affecting O
2
transfer from mother to fetus
Frank-Starling mechanism
Gastric emptying
Gastric secretions
Glomerular filtration rate
Haemoglobin structure
Haldane effect
Heat and temperature
Henderson-Hasselbalch equation
Humidity
Hypersensitivity
Hypoxia - definition, causes, effects
Impedance
Iron distribution in body
La Place's law
Lung volumes
LV pressure-time curves
LV pressure-volume loop
Measurement of blood pressure (invasive/non-invasive)
Measurement of osmolality
Myocardial action potential / ionic fluxes
Myocardial O2 supply and demand
Neuromodulation of pain sensation
Occluded left main bronchus
Occluded left pulmonary artery
7
Osmosis
Oxygen stores
PCWP as an estimate of LV preload
Placental O
2
transfer
Pregnancy - cardiovascular changes
Pregnancy - respiratory changes
Preload
Pulmonary compliance
Pulse oximetry
Renal concentrating ability
Renal response in metabolic alkalosis
Resistance in fluid systems
Resistance to breathing
Resistors
Respiratory dead space
Respiratory effects of morbid obesity
Respiratory flow-volume loops
Respiratory quotient
Shunt
Surface tension
Surfactant
Temperature regulation
Temporal response to haemorrhage
Thyroid hormone synthesis, action
Titratable acidity
V/Q mismatch
Venous admixture
Venous return curves
Water homeostasis
PHARMACOLOGY

WRITTEN SECTION




QUESTION 9 Briefly describe how drugs may produce their pharmacological effects.
Illustrate each mechanism with examples.

75% of candidates passed this question. To obtain a pass, a brief explanation of the following was
required.

1 Receptors - at least two types with correct examples of agonists or antagonists
Ion channel linked (atracurium)
G-protein coupled (adrenaline)
Kinase linked (insulin)
Cytosolic or nuclear receptors that regulate gene transcription (steroids)
2 Direct Ion channel actions (local anaesthetics)
3 Enzyme inhibition (neostigmine)

Other mechanisms of action, with examples, such as those listed below earned additional marks.
Carrier molecules (diuretics, digoxin)
Colligative properties (mannitol)
Structural analogues / counterfeiting (acyclovir, chemotherapeutic agents)
Chemical reactions (heparin/protamine, antacids)
Chelation (penicillamine, desferrioxamine)
Structural proteins (colchicine)
Mention of differing effects as a result of the stereospecificity of interaction was also noted.

A common mistake was the description of voltage sensitive ion channels such as calcium and
sodium as ligand gated receptors. The mechanism of interaction between heparin and protamine
was often incorrectly used as an example of chelation, rather than a simple physicochemical
interaction. The lipid theory of the mechanism of action of inhalational agents was often used as an
example of a colligative action. This was used as an example in the Examiners Report of this same
question in August/September 1996. However, there is now good evidence that the mechanism of
action of inhalational agents is via stereospecific protein interaction in the lipid membrane. It is
expected that the best answers would integrate relevant current knowledge.

9
QUESTION 10 Outline GABAs role as a neurotransmitter and indicate how its actions
may be modified by pharmacological agents.

53% of candidates passed this question. The major points expected in the answer were mention of:

the distribution and function of GABA as a major inhibitory neurotransmitter
the distribution and function of GABA
A
, GABA
B
(and GABA non
A
, non
B
) receptors
GABA
A
is

predominantly a postsynaptic ligand gated chloride ion channel. Binding of
the GABA
A
receptor increases chloride flux and hyperpolarises the cell. Drugs that
influence GABA
A
receptor function include the benzodiazepines, barbiturates,
propofol, etomidate, steroidal anaesthetics, ethanol, and possibly volatile anaesthetic
agents.
GABA
B
is a G-protein coupled receptor influencing calcium ion and potassium ion
fluxes Baclofen is the best known agonist at GABA
B

QUESTION 11 Define the term context-sensitive half time. How does this differ from
the elimination half life? Illustrate your answer by comparing
thiopentone vs. propofol and fentanyl vs. remifentanil.

The pass rate for this question was 64%. To obtain a pass mark, candidates needed to accurately
define context-sensitive half-time, explaining the context and the reliance of the half time on
both drug distribution and elimination. Candidates had to show that they understood the limitations
of the elimination half-life in predicting the duration of action of infused drugs, in contrast to the
context-sensitive half time. When comparing thiopentone vs. propofol and remifentanil vs. fentanyl,
candidates were required to detail the influence of the duration of infusion on the context-sensitive
half times of the contrasting drugs, and to discuss factors influencing the distribution and
elimination of the drugs, and hence their rate of decline in the central compartment after infusion.
Extra marks were obtained for including graphs with appropriate axes and discussing their clinical
importance with respect to drug suitability for infusion, and for discussing further details of drug
infusion modelling used to determine context-sensitive half time. Mention of the tendency for the
value of the context-sensitive half time to approach the elimination half life after prolonged
infusions, depending on the individual drug disposition, indicated an understanding of the terms
that earned further marks.

Relatively few candidates demonstrated a clear understanding of the clinical uses and limitations of
the two terms. Some confusion was evident between effect-site decrement times and the context-
sensitive half time applicable to the central, or plasma, concentration. Definitions and discussions of
elimination half life were frequently imprecise, and some candidates were confused by various uses
of the term T1/2
.

QUESTION 12 Briefly describe the respiratory effects of the volatile agents.

58% of candidates passed this question. Three key points were required to pass this question.

1 control of ventilation and the altered response to hypercarbia and hypoxia. The use of
graphs was a quick and effective way of presenting this information. However an
inaccurately drawn graph indicated a lack of understanding in some cases.
2 change in respiratory pattern, with tachypnoea initially.
3 reduction in airway reflexes and upper airway tone.
10
Differences among the volatile agents should be mentioned. Other useful points included reduced
hypoxic pulmonary vasoconstriction, reversal of bronchospasm, airway irritation, increased
secretions, reduced ciliary activity, and reduced gas exchange efficiency.

A common error was to state there was a global reduction in respiratory rate in spite of the daily
observation of the reverse even in the presence of opioids.

QUESTION 13 Outline the NON-ideal features as an intravenous induction agent of the
current formulations of propofol.

The pass rate was 55%. Good answers included discussion of:
1. Pharmaceutics; complex formulation, possible bacterial growth, incompatibilities and
difficulty of detection, glass packaging, expense
2. Pharmacokinetics; hepatic (mostly) organ dependent clearance, offset of effect mostly
dependent on redistribution, high lipid solubility with consequent easy transfer across
placenta
3. Pharmacodynamics; a) Central nervous system; decreased cerebral perfusion pressure,
excitatory phenomenon, controversial association with epilepsy, not analgesic, mechanism
of action not fully understood, no antidote. b) Cardiovascular system; vasodilation, negative
inotrope with higher levels, hypotension, depression of baroreceptor response, bradycardia.
c) Respiratory system; decreased CO
2
and hypoxic response, depressed minute ventilation
with possible apnea, depressed airway reflexes/tone with possible aspiration and/or
obstruction. d) other; pain on injection with occasional thrombophlebitis, very rarely
anaphylaxis.
Many candidates wasted time by describing all the ideal characteristics of propofol.

QUESTION 14 Give examples of drugs that enhance the action of the non-depolarising
neuromuscular blocking agents at the neuromuscular junction. Briefly
describe the mechanism of these interactions.

36 % of candidates achieved a pass.

Inhalational agents such as isoflurane produce CNS depression and reduction in muscle tone, and
decrease the sensitivity of the post-junctional membrane to depolarisation. A comparison of the
effects of different agents attracted more marks. Local anaesthetics such as lignocaine interfere with
acetylcholine release, reduce Na
+
conductance, reduce the action potential in neighbouring areas to
the motor end plate (producing stabilisation of the post-junctional membrane) and cause direct
muscle depression. Antibiotics such as the aminoglycosides decrease the release of ACh and
decrease the sensitivity of post-synaptic membrane to ACh. Drugs that could have been included
were diuretics, magnesium, quinidine, trimetaphan, cyclosporine, calcium channel blocking agents
and others.

Many candidates incorrectly mentioned physiological effects (like temperature and acidosis) and
pathological effects like renal and liver impairment. Although an understanding of neuromuscular
physiology was essential to answer the question, there was no need for a detailed account of the
physiology of the neuromuscular junction with diagrams.

11
QUESTION 15 Compare and contrast the pharmacology of esmolol and propranolol


Those candidates who took a systematic approach to the answer scored better marks and missed
fewer important points. It was not adequate to state that a drug was a
1
selective, or a non-selective
-blocker, without describing what this meant in terms of effects on vital organs. Many candidates
scored well in describing the contrasting pharmacokinetics of the two agents, but then gave little or
no detail on the pharmacodynamic effects of the drugs, particularly their cardiovascular effects that
are the main therapeutic target. Important side effects and contraindications to their use were also
frequently omitted. A number of candidates stated that esmolol causes no bronchoconstriction in
asthmatics because of its selectivity for
1
receptors. The drug is only selective for
1
receptors at
low doses. Few candidates mentioned the exaggerated responses that may occur when sympathetic
tone is high.

QUESTION 16 Describe the use of the null hypothesis and the P-value in a drug trial.

In a drug trial the null hypothesis reflects the supposition that the drug has no effect compared with
a control or other drug. Thus the null hypothesis states there is no difference (in the variable of
interest) in the populations from which the samples are drawn. Most candidates adorned this
definition with unnecessary statements of random chance differences. When we examine our
statistical analysis of a data set, we can neither prove nor disprove the null hypothesis in the
strict sense that these terms are used in logic. The null hypothesis is rejected or retained on the basis
of likelihood. Although the null (or alternative) hypothesis is commonly said to be accepted, this
terminology has been criticised as misleading because it may imply that the hypothesis is true.
Failure to reject the null hypothesis does not necessarily mean that the study groups are truly the
same, only that a difference could not be detected. Although this appears to be a semantic
discussion, much of the confusion with answers was due to candidates difficulties with these
concepts. It was important that candidates clearly differentiated likelihood from truth.

The explanation of P-values was less confused. Most candidates stated the notional origins of
P<0.05, commenting on the limitations of the application of this expression. The majority of
answers included some useful explanation of alpha and beta errors, with many discussing the
methods by which P is determined for comparison with alpha. The importance of power calculation
was commonly mentioned correctly with marks also being awarded for comparisons with
confidence intervals and clinical vs. statistical significance. Frequent mention was made of
increasing sample size to improve power. It is also possible (although not always) to improve power
by increasing the resolution of the measurement being made. Many candidates included diagrams of
distributions to illustrate regions and these were helpful.

12
VIVA SECTION


Bioavailability
Volume of distribution, clearance and half-life
Difference between plasma and biophase concentrations
Pharmacokinetics of propofol infusions
Potency, dose response curves and use of log dose
Definitions of ED
95

Mechanisms of anaesthesia
Changes of induction dose in different patient groups
Induction and recovery with inhalational agents
Kinetics of drugs in the epidural space
Pharmacology in pregnancy
Pharmacology in neonates

General topics
Definition and clinical utility of MAC, MAC
awake
, MAC
BAR

Effects of anaesthetic agents on CNS
Adverse effects of nitrous oxide; diffusion hypoxia
Topical use of local anaesthetics
Local anaesthetic toxicity, toxic dose, blood levels
Opioid metabolism
Catecholamines: structure-activity relationships
Metabolism of catecholamines, MAO inhibitors
Acetylcholine, Histamine
Non-steroidal anti inflammatory drugs
Diuretics
Inotropic drugs
Antihypertensive agents
Drugs that affect the uterus

Pharmacology of specific drugs:
Isoflurane, Sevoflurane, Halothane
Vecuronium, Pancuronium, Suxamethonium
Codeine, Morphine, Fentanyl, Alfentanil, Remifentanil, Tramadol
Paracetamol
Heparin, Protamine, Antiplatelet agents
Ropivacaine, Lignocaine, Bupivacaine, Prilocaine, Cocaine
Adrenaline, Clonidine
Atropine, Glycopyrrolate, Neostigmine
Sodium nitroprusside, Glyceryl trinitrate, Nitric oxide
Adenosine, Amiodarone
Ketamine, Propofol, Thiopentone
Dantrolene
13
Statistics:
Clinical trials
Sample size
Sensitivity and specificity
Normal distribution, Measures of central tendency
Parametric and non-parametric data
Odds ratio

N.M. GIBBS
CHAIRMAN
PRIMARY EXAMINATION

Registered Trainees

EXAMINATION REPORT

PRIMARY EXAMINATION

JULY/AUGUST 2000


PHYSIOLOGY

WRITTEN SECTION




QUESTION 1 Describe the role of baroreceptors in the control of arterial pressure.

54% of candidates passed this question. The main points expected were an overall view of a
negative feedback system to maintain the blood pressure constant including the following:-

High pressure baroreceptors
Role in beat to beat control (eg. changes in posture)
Afferent pathways
Response to a change in blood pressure (ie sympathetic and parasympathetic)
Low pressure baroreceptors
Role in long term regulation of intravascular volume.

Additional marks were awarded for mentioning that baroreceptors respond to both sustained and
changing pressures, respond primarily to stretch, can be reset in hypertensive patients, and can be
tested clinically (eg Valsalva manoeuvre).

Common omissions were failure to describe the relationship between the blood pressure and the
rate of firing in the afferent nerves (and the inhibitory effect this has on the vasomotor centre), and
the parasympathetic response. Some candidates gave a detailed account of the response to both an
increased and decreased blood pressure, essentially duplicating information. Others spent too much
time describing intra-renal mechanisms and hormonal responses.
2

QUESTION 2 Briefly describe the principles and sources of error in the measurement
of arterial blood pressure using an automated oscillometric non-invasive
monitor.

70% of candidates passed this question. The main points expected were a description of the
components of an oscillometric system (eg. cuff, tubing, device for inflating the cuff, a method to
gradually deflate the cuff, a transducer for measurement of pressure and oscillations in pressure in
the cuff, and a display), as well as an indication of how systolic, diastolic and mean pressures are
determined using this system. Explaining that the maximum oscillation corresponded to the mean
arterial pressure was considered fundamental. The main sources of error expected included
inappropriate cuff size, irregular heart rhythms (particularly atrial fibrillation), patient movement
including shivering, low output states, and inaccurate calibration. Some explanation of how these
factors introduced error was required.

Additional marks were awarded for commenting on the relative accuracy of systolic, diastolic and
mean pressures, the limited accuracy in certain clinical scenarios, patient factors that affect
accuracy, the use of algorithms to calculate systolic and diastolic pressures, and methods for
reducing artifact. Similarly, additional marks were awarded for describing the optimal cuff size.

Common mistakes were incomplete descriptions of the technique, or descriptions of different
techniques such as detection of pressure changes using audible signals, ultrasonic methods, or
oscillotonometry. Many candidates commented on the relative advantages and disadvantages of the
technique, or the hazards of the technique. This was not required and no marks were awarded for
this information.

QUESTION 3 Draw an expiratory flow volume curve for a forced expiration from total
lung capacity. Describe its characteristics in people with normal lungs,
as well as those with obstructive and restrictive lung disease.

77% of candidates passed this question. The question asked for a diagram of a forced expiratory
flow volume curve and it was expected that this would be done reasonably accurately with correctly
labelled axes and values. Additional marks were awarded for description of the effort dependent
and independent portions of the curve, as well as for some explanation about effort dependent and
independent flow. It was also expected that the candidate would draw the patterns in obstructive
and restrictive lung diseases and describe the characteristics in these conditions. The common
errors were inaccurately shaped curves, inaccurately labelled axes, or incorrect values.

QUESTION 4 Outline the principles of compatibility testing of allogeneic (homologous)
blood for transfusions.

27% of candidates passed this question. Principles of compatibility testing requires:-

Blood grouping. Determination of the recipient's blood group for ABO and Rh antigens.
This is achieved by adding a reagent known to contain a specific antibody and observing for
agglutination
Screening for the presence of antibodies in the recipient to other red cell antigens. This is
achieved by adding a panel of red cells of the same ABO and Rh group, which are known to
express other antigens, and observing for agglutination.
Selection of a probably compatible unit grouped by techniques as described above.
3
Crossmatching: Mixing a sample of the potential donor red blood cells from this unit with
the recipients serum and observing for agglutination:

Additional marks were awarded for information on IgM/IgG (and the difference in techniques for
detection), the importance of attention to patient and sample identification, and why some
antigen:antibody reactions are more important than others.

Common mistakes were to confuse or misuse the following terms:-

Haemolysis and haemagglutination
Autologous and homologous
Direct and indirect Coombs test
Haemolysis and anaphylaxis
Universal Donor
IgM and IgG antibodies
Immediate and delayed transfusion reactions

A common incorrect statement was that group O red blood cells have no antigens. Several
candidates stated that 98% compatibility could be achieved using an abbreviated (and cheaper)
testing procedure. While this may be true, it is important to state that a 2% incompatibility rate is
unacceptable. 12 candidates wrote on autologous not allogeneic transfusion.

QUESTION 5 Briefly discuss the relationship between structure and function in
skeletal muscle.

52% of candidates passed this question. The main points expected were a brief description of the
macroscopic, microscopic, and molecular structure of skeletal muscle and how these structures
relate to the function of skeletal muscle (isometric contraction, isotonic contraction, movement,
maintenance of posture). Some discussion of the molecular contractile elements was required as
well as some explanation of how the structure of muscle relates to shortening or the generation of
tension.

Additional marks were awarded for description of different types of muscle (red/white fibres) with
different functions, oxidative capacities and mitochondrial numbers; the concept of motor units
with increasing size (depending on the function of the muscle); and how shortening of muscle
results in movement of body structures.

A common error was to describe the structure of muscle OR the function of muscle, but not to relate
the two. Many candidates also concentrated on the contractile elements without covering the other
aspects involved.

QUESTION 6 Briefly outline the physiological control of intraocular pressure.

30% percent of candidates passed this question. Intraocular pressure depends on the production and
drainage of aqueous humour and the volume of blood within the globe, particularly in choroidal
vessels. Small changes in these compartments with variable volume can have major effects on
intraocular pressure, as the globe has relatively low compliance. Contraction of muscles external to
the globe also may cause a rise in intraocular pressure.

Description of the normal mechanisms of production and drainage of aqueous humour and the
causes of changes in intraocular blood volume were expected. Additional marks were awarded for
4
commenting on the physiological importance of maintaining intraocular pressure (to maintain the
optical properties of the cornea), for briefly mentioning pharmacological and pathological causes of
abnormalities, and the problems associated with excessive intraocular pressure.

The anatomy of the eye (and physiology of aqueous flow) was a frequent source of error. The
terms orbit and globe, the anterior and posterior chambers, the aqueous and vitreous humours,
the position of the canal of Schlemm, and the mechanism of the potential adverse effects of
mydriasis on aqueous drainage were often incorrect. Although there is a relationship between
intracranial pressure and intraocular pressure, it was not adequate to state that the factors would be
the same and focus the answer on factors effecting intracranial pressure.

QUESTION 7 Outline the actions of insulin that affect fat metabolism.

28% of candidates passed this question. Main points expected were:-

Decreased fat utilisation due to increased intracellular availability of glucose
Increased production of fat which occurs mostly in the liver
Increased uptake of free fatty acids by fat cells
Increased storage of fat
Decreased breakdown of fat.

Some details of these processes were required. For example, in the liver, increased glucose uptake
by hepatic cells via activation of glucokinase leads to glucose phosphorylation and glucose trapping
in the liver. Initially, glucose is utilised in glycogen production, but excess glucose is broken down
via the glycolytic pathway to form pyruvate which is converted to acetylCoA, the substrate for free
fatty acids. Free fatty acids are transported in the blood as triglyceride, incorporated in lipoprotein
complexes. Insulin increases activity of endothelial lipoprotein lipase, thereby increasing the
absorption of free fatty acids into fat cells. Insulin also inhibits hormone sensitive lipase, inhibiting
the breakdown of triglyceride in fat cells. Insulin promotes uptake of glucose into fat cells where it
is utilised for glycerol synthesis.

Additional marks were awarded for greater detail and for some quantification of the processes
involved. Similarly, additional marks were given for mention of insulins effect on citrate,
isocitrate and carboxylase.

QUESTION 8 Describe the factors governing glomerular filtration rate.

52% of candidates passed this question. The main points could be covered by a description of the
following equation:-

GFR = Kf[(P
GC
-P
T
) - (
GC
-
T
)] where
Kf = glomerular ultrafiltration coefficient
P
GC
= capillary hydrostatic pressure
P
T
= tubular hydrostatic pressure

GC
= plasma osmotic pressure

T
= tubular osmotic pressure
= reflection coefficient

A short description of how each of these factors affected GFR was required. A description of Kf,
was expected; i.e. the product of the glomerular capillary wall hydraulic conductivity (its
permeability) and the effective filtration area.
5

Additional marks were awarded for stating normal values, and for more detail on how GFR is
affected by:

Changes in blood pressure; autoregulation
Tubuloglomerular feedback
Changes in the afferent and efferent arteriolar vascular tone of the glomerular capillaries
Factors affecting afferent and efferent arteriolar vascular tone
Changes in hydrostatic pressure in Bowman's capsule
Effects of oedema within renal capsule
Changes in plasma protein concentration
Permeability of glomerular capillaries in pathological states

The major errors or omissions were to "list" rather than "describe" factors affecting GFR, and to
not state the direction in which GFR was affected, i.e. an increase or a decrease.

VIVA SECTION


Determinants of intracranial pressure
Control of cerebral blood flow
Composition of cerebrospinal fluid
Potassium distribution in body
Sodium intake/absorption
Total body water distribution
Donnan effect
Nernst equation
Osmolality
Differences between heat and temperature
Osmotic pressure
Active transport
Carbon dioxide and oxygen measurement
Clot formation
Natural inhibitors of coagulation
Platelet contents and function
Determination of cardiac output
Compensatory effects in chronic anemia
Effects of blood loss
Normal electrocardiograph
Left ventricular pressure wave forms
Arterial pressure waveforms
Coronary perfusion pressure
Pulmonary vascular resistance
Effects of body immersion
Role of baroreceptors
6
Aldosterone
Anti-diuretic hormone
Insulin and insulin receptors
Hormones produced by the kidney
Acid-base changes and buffers
Renal elimination of acid
Renal excretion of potassium
Production of a concentrated urine
Functions of the nose
Lung volumes
Lung compliance
Non-respiratory functions of lung
Causes of hypoxemia
Alveolar air equation
Ventilation/perfusion mismatch
A-a gradient
Causes of hypercapnoea
Effects of hypercapnoea
Closing capacity
Work of breathing
Liver blood flow
Liver function
Gastric secretions
Lower oesophageal sphincter function
Mechanisms of pain

7
PHARMACOLOGY
WRITTEN SECTION




QUESTION 9 What is an isomer? Briefly write an account of the types of isomers and
significance in drugs used in anaesthesia.

67% of candidates achieved a pass in this question. A correct definition of an isomer and an
explanation of the main types of isomers were expected. Structural isomers are also known as
constitutional isomers and they include the tautomers or dynamic isomers such as the keto/enol
transformations of thiopentone. Stereoisomers can be classified into enantiomers and
diastereoisomers. The commonest error was to define a stereoisomer as a molecule having a chiral
centre. Stereoisomers are molecules with identical formulae having a different spatial arrangement,
and the geometric isomers need not have a chiral centre. Marks were also given for explaining the
nomenclature of chiral centres although this was a common source of confusion. Classification by
any of the following systems is completely independent of the others: absolute configuration of a
chiral centre [R- and S- by the Cahn Ingold Prelog convention]; optical rotation of polarised light
[(+) and (-) or (d-) ,and (l-)]; and relative configuration of simple sugars and amino acids [D- and L ].

Few papers explained clearly that isomers may have different pharmacokinetic and
pharmacodynamic properties. Some isomers also have different physicochemical characteristics.
Examples of isomeric forms of anaesthetic drugs with correct explanations of the resultant variation
in physicochemistry, kinetics, and dynamics were awarded additional marks. Common examples
discussed included isoflurane and enflurane, keto and enol forms of thiopentone, bupivacaine,
ropivacaine, atracurium and cisatracurium.

QUESTION 10 Classify diuretics giving examples and briefly explaining their action.

79% of candidates achieved a pass for this question. While possible to classify diuretics in a
uniform way by their site of action (action on proximal tubule, loop of Henle, etc.) or mechanism
(osmotic, inhibitor of ion exchange, etc.), the majority of standard texts use a mixture of these. Thus
acceptable answers for this question could include any of the above, as long as all major types of
diuretics were mentioned. The commonest classifications used were: action in proximal tubule
(carbonic anhydrase inhibitor); loop of Henle (loop diuretics); distal tubule (thiazide compounds);
collecting ducts (potassium sparing agents); osmotic agents.

A specific example was expected for each of the other major classes (e.g. acetazolamide,
frusemide, chlorothiazide, spironolactone, mannitol).

A brief but clear explanation of the mechanism of action was expected. It was commonly assumed
that a description of altered ion flux alone was an explanation of diuresis. This was particularly
apparent in descriptions of inhibition of carbonic anhydrase. Few answers mentioned the effect of
osmotic diuretics on the renal medullas concentration gradient or the difference between the site of
action of spironolactone and other potassium sparing diuretics such as triamterene. Mention of
diuresis secondary to increases in cardiac output, renal blood flow and glomerular filtration, or to
antagonism of the effects of antidiuretic hormone, also received credit.

Details of the therapeutic uses of diuretics gained no credit.

8
QUESTION 11 Describe the structure and function of G proteins.

50% of candidates achieved a pass for this question. G proteins are so named because they are
guanine nucleotide binding proteins (and thus bind GDP and GTP, not ADP and ATP as suggested
by some candidates). The most common error was to confuse the structure of the G protein with
that of the receptor to which the G protein is coupled. Otherwise the heterotrimeric structure of the
G protein and the sequence of events from activation of the receptor to activation of the effector
mechanism was well described. Some candidates mistakenly referred to the G protein itself as the
second messenger. Better answers were able to give several examples of G protein linked receptors
along with the corresponding enzyme systems or ion channels that were the effectors for the
different G proteins (e.g. adrenoreceptor linked to Gs to stimulate adenylyl cyclase to increase
cAMP; opioid receptor linked to an inhibitory G protein that opens K+ channels, etc.). Many
candidates gave unnecessary information on the structure of the G protein linked receptor itself or
wasted time describing a long cascade of effects caused by different second messengers. Most
candidates knew that G proteins are responsible for transduction and amplification of the original
signal but very few mentioned how changes in G protein coupling are involved in the regulation of
receptors.

QUESTION 12 Explain how differences in the pharmacokinetics of alfentanil and
fentanyl can influence the way they are administered intravenously.

54% of candidates passed this question. It was not sufficient to list the pharmacokinetic parameters
of these two drugs without reference to the core of the question, which was to explain how these
characteristics influence the way the drugs are administered intravenously. Relative comparisons of
the pharmacokinetic values were satisfactory and given the same credence as exact kinetic values.

Marks were given for a description of how data such as pKa, lipid solubility, protein binding,
volume of distribution and clearance influenced the drugs relative potency, onset, and duration of
action. The time to peak effect and context sensitive half time of the two drugs could also be
compared. All these factors in turn could influence the choice of drug, timing of administration,
dose, dosing intervals and dosing regimens that are used in clinical practice.

QUESTION 13 Write short notes on factors affecting the speed of onset and duration of
local anaesthetics when used to produce peripheral nerve block.

54% of candidates passed this question. In order to achieve a pass, the following factors should
have been mentioned:

Drug factors
pKa and its effect on non-ionised fraction
lipid solubility and its effect on potency (and therefore dose) and protein binding
concentration and volume administered
intrinsic vasoconstrictor properties
effect of local and distant metabolism
effect of additives
Patient factors
site of administration including its vascularity
structure and function of nerve
pH of tissues

Candidates were awarded more marks if they used the Fick equation to illustrate some of the
principles, if they used examples with numbers, such as a comparison between lignocaine and
bupivacaine, and if they mentioned other patient factors such as pregnancy or electrolyte
9
disturbance. High marks were achieved if the candidates addressed some of the complexities, such
as that relating to the effect of lipid solubility on the onset of action.

Common mistakes included listing the factors which influence onset and duration without
describing the actual direction of effect, confusing tissue binding with plasma protein binding, and
the use of trade names instead of generic names.

QUESTION 14 Write short notes contrasting the cardiovascular effects of propofol and
ketamine seen clinically.

46% of candidates achieved a pass for this question. Key words in the question were contrasting
and seen clinically.

Marks were awarded for answers structured to clearly contrast the two drugs. Some candidates used
tables while others used headings of the various clinically seen effects followed by a discussion of
the two drugs in relation to that effect. Candidates describing all the effects of one drug in isolation,
followed by the other, gained no marks for contrasting.

Effects seen clinically are those seen during anaesthesia or intensive care, i.e. heart rate, blood
pressure. In patients monitored with pulmonary artery catheters, changes in cardiac output and
haemodynamic variables can also be seen. A correct description of the direction of most of these
clinical effects, and an explanation of why they occurred, achieved a pass in this question.
Additional marks were given for noting the differences in dose dependency of effects, cerebral
blood flow changes, the differences expected in a range of disease states (e.g. the elderly,
hypovolaemia, ischaemic heart disease), and clearly identified in vitro findings relevant to the
clinical cardiovascular effects.

A number of candidates provided correct, but irrelevant, information about the chemistry and
anaesthetic effects of the two drugs.

QUESTION 15 Write brief notes on latex allergy.

44% of candidates passed this question. In a previous paper two years ago, the pass rate was 30%.
The majority of candidates who failed chose to write extensively on the basic immunology of type 1
hypersensitivity reactions with specific reference to latex. Better answers included information
relevant to latex allergy in the perioperative period. This included brief comments on what latex is,
identifying ubiquitous sources of latex, methods to reduce exposure, consequences of exposure to
latex, and the investigation of latex allergy.

QUESTION 16 Compare and contrast the pharmacology of atracurium and cis-
atracurium.
26% of candidates passed this question. This question was best answered in tabular form using a
standard pharmacological approach starting with physicochemistry and moving to
pharmacokinetics and pharmacodynamics.

It was incorrect to write that cisatracurium is the cis isomer of atracurium. Atracurium is a mixture
of 10 isomers, 15% by weight being cisatracurium which provides 50% of the relaxant activity.
Cisatracurium is the R-cis, R'-cis isomer, where R designates the stereochemistry of the
tetrahydropapaverine rings and cis represents the dimethoxy and 2 alkyl ester groups at C1 and N2.

10
Pharmacokinetic parameters were poorly presented and many answers stated incorrectly that the
drugs have identical kinetics. The effects of age, temperature, pH and advanced liver and renal
failure were rarely presented. Metabolic pathways of cisatracurium were a source of confusion in
many answers. Cisatracurium is 77% metabolised by Hoffman elimination, with 16% cleared by the
kidneys. Atracurium is mainly metabolized by ester hydrolysis.

The drugs are not pharmacodynamically similar and it is important to compare the two drugs at
ED
95
equivalent doses. In fact ED
95
, duration of action, and recovery times from bolus and infusion
regimens were rarely mentioned.

VIVA SECTION


Bioavailability
Volume of distribution, clearance and half-life
Difference between plasma and biophase concentrations
Pharmacokinetics of propofol infusions
Enzyme substrate interactions
Esterases
Potency, dose response curves and use of log dose
Definitions of ED
95

Mechanisms of anaesthesia
Changes of induction dose in different patient groups
General topics
Drug delivery systems
Drugs that affect gastric acidity
Drugs that affect the uterus
Opioids: cardiovascular effects; receptors; duration of action
Definition and clinical utility of MAC and MACawake
Adverse effects of nitrous oxide; diffusion hypoxia
Adverse effects of suxamethonium
Barbiturate structure-activity relationships
Metabolism of catecholamines
Choosing between ephedrine and metaraminol
Interaction of chemotherapeutic agents and anaesthesia
Differences within the penicillin class of drugs
Serotonin and antagonists
Colloids; mannitol
Non steroidal anti inflammatory drugs
Pharmacology of specific drugs:
Sevoflurane Cisatracurium
Codeine Tramadol
Heparin Protamine
Ropivacaine Lignocaine
Clonidine Milrinone
Atropine Glycopyrrolate
Adenosine Sodium bicarbonate
Statistics:
11
Clinical trials
Sample size
Sensitivity and specificity
Normal distribution
Parametric and non parametric data

N.M. GIBBS
CHAIRMAN
PRIMARY EXAMINATION

Registered Trainees

EXAMINATION REPORT

PRIMARY EXAMINATION

MARCH/APRIL 2000


PHYSIOLOGY

WRITTEN SECTION




QUESTION 1 Explain how cardiac output is measured using a thermodilution
technique?

Half of the candidates passed this question. Main points required included a definition of cardiac
output, a definition and description of the Fick principle, an accurate description of the technique, a
description of the temperature/time curve generated, advantages and disadvantages, and errors in
the technique. Common omissions were failure to describe the Fick principle, the site of injection,
to accurately draw the temperature/time curve, or appreciate that the area under the
temperature/time curve is inversely proportional to the cardiac output. Many candidates also did
not state advantages and disadvantages of the technique.

QUESTION 2 Briefly describe the factors that influence the partial pressure of oxygen
in mixed venous blood?

56% of candidates passed this question. It was apparent that candidates had difficulty in sourcing
from the relevant areas of respiratory and cardiovascular physiology to present an adequate answer.
The following areas were explored in the better answers. A definition of mixed venous including
sampling site. The relationship between PO
2
and O
2
content in mixed venous blood. For any
mixed venous O
2
content the mixed venous PO
2
is dependant on the shape of the haemoglobin-
2
oxygen dissociation curve. A right shifted HbO
2
curve increases mixed venous PO
2
. Most
candidates wrongly stated the reverse. Some candidates interpreted this as a question on the HbO
2

dissociation curve and the factors that shift it. This was only a small part of the answer.
Also expected was the relationship between mixed venous O
2
content, arterial O
2
content, oxygen
consumption and cardiac output. All are related by modification of the Fick equation:CvO
2
=CaO
2
-
VO2/Q. Any factor which affects CaO
2
, VO
2
or Q will ultimately affect mixed venous PO
2
. Of
note is the reciprocal relationship between oxygen extraction and cardiac output. As cardiac output
falls, O
2
extraction increases and mixed venous PO
2
falls. Arterial O
2
content is also an important
determinant of mixed venous PO
2
. However, some candidates produced a lengthy description of all
the factors affecting PaO
2
or even drew the oxygen cascade which was not required. A common
error was to relate the factors described to the mixed venous O
2
content or saturation rather than
partial pressure. Terms such as content and concentration were often confused with each other, as
were tension and saturation.

QUESTION 3 What is a normal value for pulmonary vascular resistance? Outline
physiological factors that influence pulmonary resistance.

49% of candidates passed this question. The first part of the question specifically asked for the
normal range of pulmonary vascular resistance (PVR). Common mistakes included presenting only
a single value instead of normal range, and using incorrect units. Some candidates completely
ignored this section. The units and the normal range are best considered by referring to the
relationship between PVR, cardiac output, and the pressure drop across the pulmonary circulation
(mean pulmonary artery pulmonary capillary wedge pressure). In this way the units mmHg/L/min
(also known as Wood units) are obtained. Values using dyne/sec/cm
5
were also accepted. Even if
exact values were not known, it was important to indicate that PVR is much less (1/8-1/10) than
systemic vascular resistance.

The factors that influence PVR are those that affect resistance to flow anywhere in the body, as well
as factors particular to the lung. ie. Resistance is directly proportional to blood viscosity (which is
influenced by haematocrit) and inversely proportional to the fourth power of the radius (given that
flow is laminar and that length is constant). Most candidates ignored the effects of blood viscosity.
Factors particular to the lung that affect radius include lung volume, distension and recruitment of
pulmonary vessels (secondary to changes in pulmonary artery pressure), and hypoxic pulmonary
vasoconstriction. An outline of at least two of these factors was required for a pass. Additional
marks were given for more detail on the mechanism of these effects. Detailed discussion of Wests
zones was not required. Credit was given for mentioning the lesser effects of carbon dioxide, pH,
and endogenous vasodilators and vasoconstrictors. Few candidates explained that pulmonary
vascular impedance is a more appropriate term for the pulmonary circulation due to the relatively
greater pulsatility.

QUESTION 4 Briefly describe the difference between a single twitch and tetanic
contraction in a skeletal muscle fibre. Include in your answer the
physiological basis for the development of a tetanic contraction.

53% of candidates passed this question. The main points expected in the answer were:-

A Single twitch is the response to a single stimulus, whereas a tetanic contraction is the
response to repetitive stimulation above a critical frequency.
The critical frequency depends on the single twitch duration in that muscle fibre.
Repetitive stimulation before complete relaxation causes summation of contractions, and
repetitive stimulation before any relaxation causes tetanic contraction.
3
The physiological basis of tetanic contraction is the maintenance of a high Ca
++
concentration in
the myoplasm, as repetitive sarcolemmal depolarisation causes Ca
++
to enter the myoplasm
faster than it is pumped out into the sarcoplasmic reticulum.
The contractile mechanism has no refractory period.
The tetanic force is up to 4 times greater than that of a single twitch.
Tetanic contraction continues until the repetitive depolarisation ceases or until fatigue occurs.

Other points which gained marks included:

A description of the mechanism by which sarcolemmal depolarisation causes Ca
++
to enter the
myoplasm.
Mention of high ATP consumption during tetanus.
A brief description of the role of Ca
++
in electromechanical coupling.
Actin-myosin bridge formation (and hence shortening) continue as long as the Ca
++
concentration in the myoplasm is high.

Several candidates mis-read the question, assuming it to be about the response to use of a peripheral
nerve stimulator in the operating theatre, while in fact the question was about normal
neuromuscular physiology in the intact human. Failure to discuss the role of calcium was a
stumbling block for some candidates.

QUESTION 5 Describe the important determinants of work of breathing in an adult
human at rest. Explain how to minimise work of breathing.

Slightly less than 50% of candidates passed this question. A number of candidates appeared to be
unaware of the work of breathing' as a concept. Better answers defined the work of breathing and
gave correct SI units (Joules). A well-labelled pressure-volume graph was an ideal way to clearly
and concisely demonstrate an understanding of elastic and non-elastic/resistance work, potential
energy stored elastically for passive expiration, and energy dissipated as heat. Percentage
contributions to overall work on overcoming elastic forces, airway resistance and tissue viscous
resistance enhanced answers. A figure for O
2
consumption by the respiratory muscles was
expected. The second part of the question related to minimising the work of breathing and was
particularly poorly done. Better answers used graphic representation of the work and respiratory
rate relationship for elastic work, resistance work and overall work. Comparing work of breathing
and optimal respiratory rate in situations of increased resistance work and increased elastic work
enhanced answers. A number of candidates wrote very clinical answers emphasising patho-
physiology, ICU management principles and lists of drugs useful to treat increased airways
resistance. This was not required. Simply writing down Poiseiulles equation or Reynolds number
with no effort to relate them to work of breathing was also unhelpful. Mentioning FRC and the role
of surfactant was useful but not to the exclusion of a discussion of other factors.

QUESTION 6 Describe the control of gastric emptying.

Just over 50% of the candidates achieved a pass in this question. The main points should have
included a discussion of the neural and hormonal factors, both local (gastric and duodenal), as well
as extrinsic factors. Many candidates appeared not to know the structure and function of the
nervous supply of the stomach and duodenum. The hormonal control of gastric emptying was
either not mentioned or was wrong in several answers. The inter-relationship between the stomach
and duodenum in the control of gastric emptying was mentioned by only a few candidates.

4
QUESTION 7 List the hormones that regulate renal tubular reabsorption and describe
their action and site of action.

70% of candidates passed this question. The question required listing the hormones that act directly
on the tubule cells to regulate reabsorption of the glomerular filtrate ie. aldosterone, angiotensin 2,
atrial natriuretic hormone, antidiuretic hormone, and parathyroid hormone. Locally released
hormones, and hormones that indirectly affect reabsorption by, for example, affecting renal
perfusion, were listed by some and were accepted if their action was appropriately explained.
Calcitonin was accepted, even though its physiological role in the kidney is unclear. There were
generally good descriptions of actions, particularly of aldosterone and antidiuretic hormone, at the
cellular level. There was less certainty and accuracy in describing site of action within the tubule
(eg proximal vs distal tubule vs collecting duct). Parathyroid hormone, when listed, was correctly
described by few candidates. There was confusion between it and 25-hydoxyvitamin D, calcitriol
and calcitonin, by many candidates.

QUESTION 8 Briefly describe the breakdown of haemoglobin after red cell lysis.

Overall this question was done poorly, with only 17% passing. Another 20% were close to passing
but there were no excellent answers. The main points expected were a discussion of the structure of
haemoglobin and the fate of all three of its constituents ie; iron, haem and globin. Details about
haemoglobin's survival time and the mechanisms of breakdown of the constituents were required, as
well as the relevant transport proteins, and enzymes involved in key reactions. Some comments
about the fate of bilirubin should also have been included, such as its secretion into bile, and its
enterohepatic circulation. A common misconception was that globin is directly reincorporated into
haemoglobin. In addition, the enterohepatic circulation was often incorrectly described. However,
the main error was failure to discuss all three of haemoglobin's constituents, or to describe the
breakdown processes in sufficient detail.

VIVA SECTION

Cardiovascular
Determinants of myocardial O
2
demand and supply
Myocordial contractility
CVP / RAP trace
LV pressure time curve
LV pressure volume loop
Coronary artery blood flow
Oxygen flux
Circulatory charges at birth
Pressure trace right atrium to wedge
Afterload
Myocyte Action Potential
Storlings law of the heart
Radial artery vs Aortic waveform

Respiratory
Surfactant
Dead space, types and measurement
Hypoxia, definition and classification
5
Compliance
Capnogram
Spirograph
PEFR
Airways Resistance
Flow Volume loops
Blood gases; acute respiratory acidosis
Shunt / Venous admixture
CO
2
carriage

Fluid & Electrolytes / Renal / Acid Base
Countercurrent systems
GFR; Starling forcers
Atrial Natriuretic Peptide
Mole / Osmole / Osmolality measurement
Colligative properties
1/3 Blood Volume loss
Renal handling of bicarbonate

Mass spectrometer
Transducers
Wheatstone bridge
SI units
Flowmeters; types & principles
Impedance
Pneumotacograph
Humidity
Boiling Point
Heat vs Temperature

Cellular
Krebs cycle
Trans membrane transport

Gastrointestinal
Dietary fat handling
Bile and its loss
Gastric secretions
Pancreatic secretions
Effects of Insulin

Blood
Coagulation
What stops blood clotting ?
Blood groups
Von Willebrands factor

6
Other
Effect of Tourniquet release
Effect of Steep trendelenberg position
Hormones. Definition. Classification. Secretion
Reflexes

7

PHARMACOLOGY

WRITTEN SECTION




QUESTION 9 Compare and contrast the effects of halothane and isoflurane on the
heart.

65% of candidates passed this question. Effects on the heart refers to changes in heart rate, stroke
volume and rhythm. A good approach was to divide the effects into direct and indirect. Changes in
systemic or pulmonary vascular resistance were relevant to the question provided it was indicated
that these would influence stroke volume. Although halothane is not often used in adult anaesthesia
practice, it provides a contrast with isoflurane, and is well covered in the standard texts.

Important points required for a pass answer were that cardiac output is better maintained with
isoflurane (normocapnic ventilated patient) and heart rate is lower during halothane anaesthesia.
Good answers had detail of the probable mechanisms of the differences in vascular resistance
changes, baroreceptor depression, SA and AV nodes and cardiac conduction, and myocardial
depression. Where standard texts and current literature are still conflicting or vague, such as the
degree of direct myocardial depression at various concentrations of these agents, any plausible
explanation of clinical observations was accepted.

Interactions with other drugs could also be included and most candidates compared the agents with
reference to adrenaline-induced arrythmias. Some even mentioned malignant hyperrexia, which is
a valid interaction.

QUESTION 10 Briefly describe the pharmacological effects of paracetamol. Outline the
mechanisms of its toxicity.

70% of candidates passed this question. The better answers were structured into sections on
kinetics, dynamics, and toxicity. This was a pharmacology question, not a question about the
physiology and biochemistry of pain. Nevertheless, many candidates gave unnecessarily elaborate
details of arachidonic acid metabolism and cyclooxygenase inhibition. Although these answers
were not penalised for this additional information, many easy marks were lost because basic
pharmacological details such as onset and offset of action, and dosage were not included. Many
candidates mentioned that paracetamol has a mild antiinflammatory action, yet then wrote
extensively about peripheral inhibition of prostaglandin. Explanations of paracetamol toxicity were
generally good. Some candidates incorrectly attributed the renal toxicity of paracetamol to the
same mechanism to that associated with NSAIDs.

8
QUESTION 11 Outline the main biochemical events involved in noradrenergic
transmission, and how these may be altered by the use of MAO (mono
amine oxidase) inhibitors ?

This question was passed by 57% of candidates. The main points covered in the better answers
included:-

The structure of noradrenaline.
A concise outline of the synthesis of noradrenaline from phenylalanine via tyrosine, dopa and
dopamine, including the sites of these processes and the enzymes involved.
The storage function of the granulated vesicles and the calcium ion dependent mechanism(s) of
noradrenaline release via exocytosis into the synaptic cleft in response to an action potential.
The interaction between noradrenaline and post-synaptic receptors.
The breakdown in the synaptic cleft (and elsewhere) or noradrenaline by catechol-o-methyl-
transferase (COMT) to form normetanephrine.
The presynaptic and post-synaptic uptake of noradrenaline, most of the noradrenaline from the
presynaptic uptake being reincorporated into the granulated vesicles.
Metabolism by mono-amine-oxidase(MAO) within the nerve terminal to form 3,4
dihydroxymandelic acid, which is converted by COMT to 3 methoxy-4-hydroxy-mandelic acid
(vanillymandelic acid,VMA).
Inhibition of MAO results in reduced breakdown and increased activity of adrenaline,
noradrenaline and serotonin at relevant sites throughout the nervous system.
The differentiation of sites and functions of MAO A and MOA B, and their specific inhibitors.
Reversible (eg moclobemide) and irreversible inhibition of MAO.
The biomechanical events underlying the various adverse reactions to MAOIs precipitated by
eg. Sympathomimetics, amphetamines, tricyclics, pethidine, and tyramine rich foods.
The blood pressure lowering effected of a MAOI-induced false transmitter (octopamine).
Comments on the putative basis for the antidepressant effects of MAOIs.

Several answers included extensive accounts of the physiological functions subserved by
noradrenergic transmission but made little or no reference to the relevant biochemical events.

QUESTION 12 Outline the pharmacology of oxytocin.

There was a high pass rate (77%) with few poor answers, which might reflect the fact that
candidates had made good use of examiners' reports from previous years.

Oxytocin is an endogenous polypeptide hormone released from the posterior pituitary and is
available for clinical use in a synthetic form. In the literature there is some dispute as to whether it
is an octapeptide or a nonapeptide and either statement was acceptable. The primary actions of
oxytocin are on the gravid uterus and breast milk ducts. It has very poor oral bioavailabilty due to
inactivation by chymotrypsin as a first pass effect, and must be administered parenterally but can
also be used intranasally. Indications for use are augmentation of labour, uterine contraction post
delivery, and as aid in lactation.

The common side effect seen is vasodilation resulting in flushing and a drop in systemic vascular
resistance that produces hypotension and a reflex tachycardia that elicits a net increase in cardiac
output. This hypotension can augment that seen with anaesthetic agents and techniques that
produce hypotension. Synthetic oxytocin has very little antidiuretic hormone effect and the
syndrome of water intoxication, whilst relevant and important is not a common side effect. It is
usually seen after prolonged high dose infusions with significant water infusion, usually in the from
9
of 5% dextrose. There are real risks to foetal well being if the full dose of oxytocin is administered
prior to delivery.

It is stated in texts that oxytocin infusions antagonise the effect of suxamethonium and that it is
inactivated if co-administered with blood transfusion.

QUESTION 13 Briefly describe correlation and simple linear regression, and explain
their differences. What assumptions are common to both?

70% of candidates passed this question. Many candidates successfully used a set of scatter plots to
aid their description of these two concepts. The formula for a straight line [y= a + bx] was noted
along with the phrase least squares method in describing simple linear regression. The slope of
this line [b] which is called the regression coefficient was however commonly confused with the
Pearsons correlation coefficient [r]. While r describes the strength of the association, b does not.
They will have the same sign for a given data set but are otherwise completely separate concepts.

While discussing the assumptions common to both, most candidates mentioned that data must be
normally distributed. Additional marks were given to the few candidates who indicated that a
distribution free correlation coefficient, the Spearmans rank correlation, is applicable to non-
parametric data.

The examiners' expectation was for an explanation of the concepts rather than detailed knowledge
of the statistical equations and their derivations. However, in many cases the use of an equation is
most appropriate in quickly explaining the 'concept'.

QUESTION 14 Discuss the roles of plasma esterases on drugs used in anaesthesia.

67% of candidates passed this question. Good answers included an overview of the unique
properties of the esterases and their pharmacological implications followed by a discussion of
pseudocholinesterase (butyrylcholinesterase) and non-specific plasma and red cell esterases. ie.

Overview;
Hydrolysis of ester bonds with drug inactivation by esterases
High capacity/clearance enzymes produced in liver and red cells
Non organ dependent drug metabolism with generally inactive metabolites
Exceptions including laudanosine and salicylic acid
Pseudocholinesterase;
Metabolism of succinylcholine, mivacurium, and ester local anaesthetics
Potential problems with congenital and acquired dysfunction
Common congenital pseudocholinesterase variants and clinical implications
Acquired dysfunction including physiological, pathological and drug interactions
Non specific plasma esterases;
Metabolism of remifentanil, atracurium
High capacity systems little effected by hepatic metabolism
High clearance of remifentanil with infusion and independent short context sensitive t1/2
Atracurium and laudanosine
Red Cell esterases;
Metabolism of esmolol and possibly remifentanil
High clearance of esmolol with short duration, titratable

Some problems with answers included; extensive discussion of acetylcholinesterase and detailed
discussion of pseudocholinesterase with none of plasma and red cell esterases.
10

QUESTION 15 Describe the effects of opioids on the respiratory system.

75% of candidates passed this question, although very few achieved a high mark.

The question required a description of the centrally mediated effects of opioids, including site of
action, receptors, effects on respiratory rate, tidal volume, responsiveness to carbon dioxide and
oxygen concentrations in the blood, and that the drug can cause apnoea. Mention of truncal
rigidity, mast cell degranulation, and depression of cough reflex and cilial motility were expected.

Better answers included some differentiation of effects of different opioids such as morphine,
pethidine, phenylpiperidines and partial agonists. How pharmacokinetics of the drugs and route of
administration alter the likelihood and timing of effects, and how other sedative drugs, sleep,
disease (such as sleep apnoea), extremes of age, hypothermia and the degree of pain affect the
responses in individuals could have been included. Secondary effects of sedation and loss of upper
airway reflexes were rarely mentioned.

Extremely few candidates mentioned the therapeutic ratio of these effects, the fact that they occur in
the dose range of desirable analgesia, that tolerance does not always develop to the respiratory
depression, or that the respiratory depression may be fatal.

QUESTION 16 Briefly describe the factors that determine skin penetration by local
anaesthetics. What is an eutectic mixture? Briefly describe the
formulation and pharmacology of EMLA cream.

73% of candidates passed this question. However, a large number of answers included a list only,
without further explanation, thus scoring poorly on this section. Although most candidates
correctly referred to the fick equation, simply writing it down without explanation did not constitute
adequate coverage. Furthermore, very few noted that a large surface area was not needed if a small
area of anaesthesia was desired. In fact, some comments about uptake and blood flow suggested
that many candidates felt that EMLA cream was intended to achieve therapeutic systemic
concentrations (this was not a question about trans-dermal opiates; fentanyl in particular). Many
candidates referred to protein binding without indicating which proteins were they referring to.
Plasma protein binding plays little, if any role in the trans-cutaneous action of EMLA. No
candidate made use of the structure-solubility relationship of local anaesthetics (2 mentioned
amethocaine or benzocaine, but failed to qualify these inclusions adequately), nor did many explain
non-ionised fractions well, several suggesting that ionisation increases with increasing pH. Please
note that potency correlates with lipid solubility (and toxicity), but is not an independent
determinant of absorption. Generally, it appeared that few candidates understood much of the
chemistry of these drugs or the definition of an eutectic mixture. Local anaesthetics are not the only
compounds to form eutectic mixtures. In fact only 2 candidates correctly defined the mixture as
being the composition at the eutectic point. EMLA cream is a CREAM (as written in the question),
not an ointment, etc. Knowledge of the constituents, the droplet formation, and the free base
content were required to score highly. Most candidates mentioned metHb formation from
prilocaine and the low systemic toxicity potential for this preparation. Several candidates confused
basic concepts such as melting and boiling points. Details of onset and duration were also poorly
covered.

11
VIVA SECTION

What are the side effects of opioids ?
What drug factors influence the side effects of opioids ?
Plasma concentration time graph of morphine.
Change of etCO
2
with time after an IV bolus of morphine.
What factors influence the onset of action of volatile agent ?
Why is N
2
O used ?
Side effects of N
2
O.
Recognition of structure of lignocaine. Metabolism and protein binding of lignocaine.
Define therapeutic index.
Toxicity lignocaine vs bupivacaine (R + S).
How does liver disease affect the way the body handles drugs.
Side effects of Suxamethonium

2
agonists pharmcodynamics.
Isoflurane and brain.
Isomerisation of isoflurane.
Isoflurane vs sevoflurane
Structure/activity of sevoflurane.
Classification of vasodilators.
How does GTN work ?
Structure activity relations of catecholamines.
Draw and explain the F
A
F
1
curve. Does the curve reach unity at infinity ?
Differences between midazolam & diazepam.
Diazepam metabolism.
Differences between morphine and fentanyl.
What agents can be used to decrease gastric acidity ?
Discuss one parenteral antihypertensive.
Sodium nitroprusside mechanisms of action and metabolic toxicity.
Margin of safety of neuromuscular function.
Assessment of neuromuscular block.
Dibucaine number.
Suxamethonium apnoea.
Types of anticholinesterase.
Recognise 5-hydroxy typamine. What drugs interact with 5HT ?
Discuss digoxin
Contents of ampoule thiopentone, role of each adjuvent.
Draw barbituric acid nucleus. What are the keto and enol forms ?
pH & pKa, Henderson Hasselbach equation.
What are the effects of cocaine on the heart ?
What is the effect of B
2
agonist drugs, how do they work ?
What is in an ampoule of propofol ?
Draw the plasma concentration time curve of propofol and the effect site (brain)
concentration time curve.
How would it vary with age ?
Discuss the pharmacodynamics of atropine.
Dose-response curves of neuromuscular blocking agents.
Define ED95.
Statistical classification of data relating to trial of antiemetic drug and test that may be used to
analyse the data.
12
Statistical classification of data relating to trial to assess potency of inhalational agent and
appropriate statistical test.
Information from confidence intervals versus P-value
Define nonparametric data ?
Pharmacodynamics of tramadol.
Define the term an Hypnotic drug.
Classify muscle relaxants.
What is phosphodiesterase. What drugs affect it ?
What is muscle relaxation and how can it be achieved.
Side effects nonsteroidal anti-inflammatory drugs.
Types of anti-cholinesterase drugs.
Catecholamine structure and effects of ephedrine.
Comparision of Thiopentone and Methohexitone.
Actions of adenosine.
Actions of diuretics, comparision of thiazide & loop diuretics ?
Pharmacogenetics examples related to anaesthesia.
Fate of I.V. bolus of morphine.
Onset of action of Fentanyl.

N.M. GIBBS
CHAIRMAN
PRIMARY EXAMINATION

Registered Trainees

EXAMINATION REPORT

PRIMARY EXAMINATION

JULY/AUGUST 1999


PHYSIOLOGY

WRITTEN SECTION




QUESTION 1 How does a fall in temperature influence blood gas solubility and acid
base values?

28% of candidates passed this question. This question was asked in the March/April examination in
1998, and most of the Examiner's comments from that time apply to this 1999 exam. When
temperature is lowered, the solubility of a gas in a liquid increases, since the decreased kinetic
energy of the gas particles reduces the partial pressure exerted by a given amount of the gas in the
solution. When in equilibrium with a liquid/gas interface, a larger amount of gas will be dissolved
at a lower temperature, hence the solubility is greater. Henry's Law defines the proportional
relationship of amount of gas in solution, to its partial pressure. The solubility coefficient is
inversely proportional to temperature (Ostwald) or defined at a fixed temperature (Bunsen). There
was considerable confusion about the basic physical principles involved, in particular concerning
Henry's Law. Effects of temperature on haemoglobin/oxygen affinity were also mentioned, and
were generally well understood by candidates.

pH increases as temperature falls, due to decreased ionic disassociation. The increase in pH in
blood follows closely the change seen in neutral water. Decreased temperature also affects pH,
which was generally overlooked by candidates when attempting to apply the Henderson-Hasselbach
equation to explain this effect. Alpha-stat and pH-stat strategies of blood gas interpretation were
again often misunderstood.
2
Candidates need to remember that this is primarily an examination of physical and physiological
principles, often in the context of patient management, rather than of pathophysiology.

Refer to Nunn, Blitt & Hines, and Scurr & Feldman.

QUESTION 2 What physiological factors contribute to the competence and tone of the
lower oesophageal sphincter?

42% of candidates passed this question. The standard of answer for this question was relatively
poor considering it's importance to anaesthesia. The main points sought were that the area is
anatomically indistinguishable from other portions of the oesophagus, although containing an
increased number of nerve cells. It is however able to maintain a higher pressure.

A discussion of the anatomical factors contributing to the competency was expected. These
include:
A functional flap valve of gastric mucosa
Oblique entry into the stomach
Effect of diaphragm
Lower oesophagus exposed to intra abdominal pressure
Increased tone of circular muscle in sphincter

A description of the concept of barrier pressure, with the inclusion of physiological pressures
encountered was expected. Describing other factors including the hormones that may alter tone of
the sphincter e.g. Gastrin, motilin, PGE2, oestrogen, progesterone, glucagon, secretin,
cholecystokinin & VIP, gained additional marks. Physical factors such as elevated intra abdominal
pressure and reduced gastric pH, should have been mentioned.

Many candidates gave excellent papers on the anatomical contributing factors and failed to mention
the hormonal or physical factors. The reverse was also the case. Although scoring well on the
aspect that they discussed, they often only managed a borderline pass. Some candidates discussed
pharmacological manipulation of the sphincter. This was not asked in the question and although
done very well in many instances, was not rewarded with additional marks.

QUESTION 3 Describe the factors that affect airway resistance.

60% of candidates passed this question. This was a straightforward question that required little
more than repetition of textbook material. Although the majority of candidates passed the question,
few achieved high marks.

The examiners expected a brief description of the following factors which contribute to airway
resistance:
The upper airway
The calibre of the lower airways.
This can be varied by factors in the lumen, the tone of the bronchi, factors in the wall of the
airway, and factors external to the airway such as dynamic compression.
Examples of these factors were expected.
Whether the airflow is laminar or turbulent.
The likelihood of turbulent flow is determined by Reynold's number. A description of the
factors (preferably with formulas) affecting the resistance to laminar and turbulent flow was
expected.
The volume of the lung.
3
A hyperbolic relationship exists between lung volume and airway resistance.

Many candidates wasted time through poor technique. Repeating the question, or writing an
introductory paragraph does not answer the question and wastes valuable time.

This was a broad topic. Many candidates focused in detail on some parts of the topic but ignored
others. This scored full marks for part of the question but no marks for unmentioned parts of the
topic. Many candidates gave detailed and impressive accounts of the resistance to laminar and
turbulent flow, but ignored other factors contributing to airway resistance, such as lung volume.

Some candidates confused factors contributing to lung compliance with airway resistance. Others
confused factors affecting pulmonary vascular resistance with airway resistance. Measurement of
airway resistance was not asked, and was not required in an answer.

QUESTION 4 Outline the role of the kidneys in the regulation of body water.

66% of candidates passed this question. The difficulty in presenting the wide range of pertinent
material that could be discussed meant that high marks were difficult to achieve.

The key concept was that the kidney is usually the major effector of body water regulation based on
the large renal blood flow and glomerular filtration and its capacity to excrete either dilute or
concentrated urine in response to the requirements of maintenance of body water volume and
osmolality. Most candidates focussed on either the details of renal tubular handling of water, or on
how the kidneys function in relation to the body's sensors of intravascular volume and osmolality
and how the hypothalamus has a key role in integrating this process. Either approach done well,
with reference to the importance of regulation of urine volume and osmolality achieved a pass.

Discussion on other sites of water loss and their potential for regulation compared with the kidneys
and the effect of various situations which may disturb the kidney's ability to perform its role in
regulation of body water were included by some candidates. If integrated with discussion of the
kidney's role in body water regulation, these were also considered pertinent material.

QUESTION 5 Describe the ways in which CO
2
is carried in the blood.

55% of candidates passed this question. The carriage of gases in blood is an area where a good
understanding is expected and indeed, some of the answers were outstanding. The relative
importance of the ways in which carbon dioxide is carried in arterial and in venous blood, and an
account of why the percentages differ on the venous side was expected. A good account of the
factors making up the Haldane effect and their relative importance was a feature of the better
answers. Many candidates gave an adequate account of carbon dioxide carriage as bicarbonate
ions. Fewer discussed the chloride shift and very few went on to mention the implications on
venous blood haematocrit. Carriage of carbon dioxide as carbamino compounds was generally not
as well accounted for as the other forms of carbon dioxide carriage. Candidates are reminded that
carboxyhaemoglobin (carbonmonoxyhaemoglobin) refers to the carriage of carbon monoxide on
haemoglobin. A discussion of carboxyhaemoglobin was not requested.

QUESTION 6 Explain the mechanisms that maintain cerebral blood flow on moving
from a supine to a standing position.

51% of candidates passed this question. This question explores a topic that is clinically important,
the maintenance of cerebral perfusion. The answer should have divided the mechanisms into
4
global and local. Since a significant amount of the answer revolves around pressures, its
relationship to flow and resistance should have been highlighted. The global response revolves
around restoring MAP via baroreceptors. The venous pump and valves minimising the pooling
effect is also relevant. Again this needs to be tied in with the question, i.e. CPP=MAP-CVP (ICP).
The local factors have to include the autoregulation of cerebral blood flow, with the myogenic and
local metabolic theories quickly outlined. The Munroe-Kellie doctrine along with the relationship
of the perfusion pressure to ICP and CVP, also helps to explain the postural effect on venous
pressure and intracranial pressure favouring flow. This all leaves us with a final balance of about a
20% decrease in cerebral blood flow.

QUESTION 7 Describe how the partial pressure of oxygen in a blood sample is
measured using a Clark electrode.

28% of candidates passed this question on basic measurement. There were some good answers, but
the results overall indicate that many candidates do not have a satisfactory working knowledge of
the principles underlying blood gas analysis. This may be the result of a "black box" approach to
automated blood gas analysis. Candidates are again reminded that the theory underlying
measurement techniques remains an important component of the syllabus and will continue to be
examined. Most candidates included a diagram in their answer illustrating the components and
configuration of the Clark electrode. The use of diagrams is encouraged, but candidates are
reminded to apply clear and correct labelling. A diagram on its own is not sufficient to achieve a
pass. Additional detail is required to demonstrate an understanding of the function of each of the
components of the diagram. Some of the common errors that cost valuable marks included the
following: the incorrect assignment of materials to the anode and cathode; chemical reactions
incorrectly assigned to anode and cathode; unbalanced or incorrect chemical equations outlining the
reactions at the anode and cathode; confusion as to the role of current and voltage; the voltage and
current relationship plotted with current as the independent variable. Many candidates omitted a
description of methods of calibration and factors affecting accuracy and limitations. These included
the effects of temperature, consumption of oxygen by the electrode, problems with the membrane
(e.g. holes, proteins), non-linearity of voltage and current.

QUESTION 8 Draw both aortic root and a radial artery pressure wave forms on the
same axes. Explain the differences between them.

50% of the candidates passed this question. There were very few good answers. Candidates were
expected to draw waveforms on appropriately labelled axes. The curves should show the peak and
pulse pressures of the radial artery pressure wave to be greater than the aortic root pressure wave
(with correct normal values). Furthermore, the radial wave pressure should show a steeper upstroke
and a shorter duration than the aortic trace, and with a delay in the time of onset of the initial
pressure rise.

The differences between the waves are due to the decreased compliance which gave rise to the
steeper upstroke in the radial wave form. The higher systolic radial arterial pressure is due to
reflection and summation, tapering and faster transmission of pressure waves. Whilst damping in
the radial wave causes the loss of anacrotic and dicrotic notches; whereas reflection and resonance
lead to a diastolic hump on the radial wave form.

In elderly patients, pulse wave may be transmitted unchanged from the ascending aorta to the
periphery because of the less compliant vessels.

The common errors in the answers were unlabelled axes and a lack of normal values. 16% of the
candidates drew wave forms on 2 separate sets of graphs using identical axes rather than one graph
5
with superimposed wave forms on the same axes. They were not penalised if the above mentioned
points were illustrated. Some showed a grossly exaggerated delay of the radial wave. There was a
general lack of understanding of the reasons for the differences in the wave forms.

VIVA SECTION

Cardiovascular
Determinants of myocardial oxygen demand and supply
Relationship of pulmonary artery occlusion pressure to left ventricular preload
ECG principles
Pressure traces from right atrium to pulmonary artery
Left ventricular pressure-volume loop
Vascular function curves
Origins of arterial blood pressure
Compare and contrast muscle capillary with glomerular capillary
Circulation to muscle
Red blood cell production, structure and metabolism
Haemoglobin structure and metabolism

Respiratory
Changes in gas exchange due to induction of intravenous anaesthesia
Ventilation perfusion changes from apex to base of lung when upright
Functional residual capacity, role and measurement
Spirometry and lung volumes
The single breath nitrogen washout test (Dead space and closing volume measurement)
Shunt and venous admixture
Shunt equation
Ideal gas equation
The oxygen cascade
Dead space
Oxygen stores, effect of preoxygenation
Effect of occlusion of left main bronchus
Effect of occlusion of left pulmonary artery

Fluid and electrolytes / Renal / Acid Base
Distribution of body water including compartments and content.
Effect of intravenous administration of one litre of 3% saline
Fate of one litre of 0.9% saline given intravenously
What is a buffer?
Factors effecting glomerular filtration rate
Starling forces in the capillary
Antidiuretic hormone
Small bowel cutaneous fistula
renal handling of bicarbonate
pH homeostasis

6
Measurement
Pulse oximeters: principles and sources of errors
Intra-arterial pressure measurement
Measurement of anaesthesia circuit gases and vapours
Humidity and its measurement
What is an exponential function?

Other
Gastric emptying
Thyroid hormone synthesis
Physiological modulators of the pain pathway
Inducible enzyme systems

7

PHARMACOLOGY

WRITTEN SECTION




QUESTION 9 What is meant by "95% confidence interval"? Explain the practical
applications of confidence intervals and indicate why they may be
preferred to P-values?

This identical question has been asked in August 1995 and March 1997 (see previous reports). The
pass rate of 48% this time was poor albeit better than in the previous papers. Many answers
showed poor understanding not just of confidence intervals (CI) but also the principles of statistical
inference concerning samples and populations. Comments from the previous examiners' reports are
still applicable. In addition, it was surprising that many answers referred to the 95% CI as a single
value, or neglected to mention 95% in their definition. Many statements did not make sense
grammatically or logically e.g. "95% certain that the sample mean lies within the population mean".
The use of the term "sample population" prevented marks from being awarded because it was not
certain whether the candidate meant sample or population. Other common errors were statements
such as "95% CI has a 95% probability of containing the sample mean"; and the incorrect formula
that 95% CI = 1.96SEM. There was confusion regarding the significance of a CI containing zero.
This depends on what the particular CI is providing an estimate for. Many candidates wrote
unnecessary information about P values without comparing them to CI, and many thought
incorrectly that CI could not be used for hypothesis testing.

QUESTION 10 Outline factors determining speed of onset of neuromuscular blocking
agents.

58% of candidates passed this question. This was a question essentially addressing
pharmacokinetics and pharmacodynamcis involved with drug delivery, distribution to the effector
site and interaction at the effector site. As a result the better answers presented a balanced
understanding of drug and patient related factors.

The candidate should be able to provide information regarding:
1. Drug factors: physicochemical properties, dose and potency concepts
2. Patient factors: rate and site of injection, cardiac output and muscle blood flow and receptor
kinetics
3. Other factors: the differences in responses different muscle group that are monitored and the
effect of the priming principle

QUESTION 11 Outline the toxicity of local anaesthetics.

This basic question was passed by 36% of candidates. Essential features expected in an answer
were the causative factors and manifestations of toxicity in both the central nervous system and the
cardiovascular system, together with a comparison of the blood levels (e.g. for lignocaine)
8
associated with CNS and CVS toxicity. Mention was also expected of the particular risks
associated with the use of bupivacaine. A number of answers omitted any reference to CVS
toxicity, and some made no reference to CNS toxicity. A few made no mention of either.

In addition to an outline of CNS and CVS toxicity good answers included some of the following:

A definition of "toxicity" (needle-induced nerve damage and CSF leak do not fall within any
standard definition)
Kinetic factors influencing toxic plasma levels (e.g. dose, rate and site of administration, lipid
solubility, protein binding, clearance)
Effects on toxicity of both acidosis and elevated PCO
2

Direct toxicity to nerves
Toxic effects at autonomic ganglia
Toxic effects at the neuromuscular junction
Special features of prilocaine
Special features of cocaine
Stereoisomers and the relevant features of ropivacaine and S and R bupivacaine
Toxicity in association with pregnancy
Toxicity in the foetus
Effects of additives (e.g. adrenaline, metabisulfite)
Effects of metabolites (e.g. of esters and of lignocaine)
Immune-based reactions

QUESTION 12 Briefly describe the mechanism and treatment of the toxicity of sodium
nitroprusside.

48% of candidates passed this question. A complete answer required not only the description of the
primary mechanism of cyanide toxicity but also toxicity associated with thiocyanate,
methaemaglobinaemia and excessive hypotension associated with nitric oxide. An indication of the
dosage at which this might occur and the relationship of this to metabolic pathways of excretion
was appropriate.

Treatment was best covered by an explanation of the cessation of infusion of nitroprusside in the
presence of warning signs (elevated mixed venous PO
2
, metabolic acidosis and tachyphylaxis).
Further explanation of the use of sodium nitrate to convert haemoglobin to methaemoglobin in
severe toxicity and the use of sodium thiosulphate and the use of sodium thiosulphate and
hydroxycobalamine in less severe toxicity was necessary.

There was considerable confusion amongst candidates as to the structure (and activity) of
nitroprusside with many unaware of the presence of a nitric oxide group or iron. Many candidates
did not understand the role of methaemaglobin and often had an incorrect understanding of the
action of methylene blue believing it to form rather than reverse methaemaglobinaemia. A
significant number of candidates made no valid attempt at the question.

9
QUESTION 13 Using opioids as an example describe and illustrate with graphs what you
understand by the terms "potency", "efficacy", "partial agonist",
"competitive antagonist", and "therapeutic index".

77% of candidates passed this question. This question was a challenge to provide a meticulous and
systematic explanation of five basic pharmacological concepts. To gain a pass it was expected that
a description would be provided for every part of the question.

Attention to the phrasing of the question was neglected by candidates who performed poorly.
Examples of other substances were not relevant and were ignored during the examiners
assessment. A graphical illustration of each concept was considered essential. Each of the terms is
in common use and well described in any of the standard references.

This question was a straight forward memory exercise that enabled well organised candidates to
achieve high marks.

QUESTION 14 Briefly outline the effects of intravenous induction agents not mediated
via the central nervous system.

24% of candidates passed this question. This question was badly answered, lack of time might have
been a factor. Many candidates wasted time on irrelevant details like:

1. Effects of inhalational agents.
2. Centrally mediated effects, mainly respiratory effects.
3. Contraindications of intravenous induction agents

Candidates should be able to provide a systematic answer of the effects of the different agents on
different systems.

The cardiovascular effects of Ketamine were poorly understood. Ketamine can produce a direct
reduction in myocardial contractility especially at high doses while producing a dilator effect on
vascular smooth muscle. It also causes a direct increase in coronary blood flow that is unmatched
to the central effect of tachycardia, hypertension and increased contractility. The net effect is an
unfavourable increase in myocardial oxygen demand and little change in systemic vascular
resistance. Similarly the role of nitric oxide in vascular smooth muscle relaxation due to
thiopentone and propofol was seldom mentioned.

The respiratory effects should include effects on laryngeal reflexes (relatively maintained with
thiopentone and depressed with propofol ) as well as effects on bronchial secretions and bronchial
smooth muscle.

The local effects of pain on injection, local thrombosis, skin necrosis and the effects of intra arterial
injection of agents like thiopentone should also be mentioned. Other important effects like allergic
reactions, histamine release, metabolic, endocrine, gastrointestinal and uterine effects were not
mentioned by many candidates.

10
QUESTION 15 Briefly describe the preparation of oxygen for medical use. List the
physical properties of oxygen. Outline the potential adverse effects
associated with its medical use.

50% of candidates passed this question. Many answers only addressed one part of the question.
Preparation, physical properties and toxicity should all have been covered. Better answers covered
the following points:

Preparation
1. Fractional distillation of liquid air. Based on different boiling pints of oxygen and nitrogen.
Used for commercial production.
2. Oxygen concentrators. Absorption of nitrogen by "artificial zeolite". Used for home use and
remote locations.

Physical properties
Colourless, odourless gas. Molecular weight 32. Critical temperature 119
o
C. Supports
combustion.

Potential adverse effects
Acute pulmonary toxicity, absorption atelectasis, decreased hypoxic respiratory drive in patients
with hypercarbic respiratory failure, retrolental fibroplasia, hyperbaric effects including convulsions
and pulmonary toxicity.

QUESTION 16 Outline the factors that determine recovery (offset of action) after
ceasing a drug infusion.

The pass rate for this question was 55%. As always, it was disappointing to see that several
candidates had failed to plan the examination, and had left little or no time to answer the final
question.

An ideal answer would have considered the offset of infusion effects in terms of both
pharmacokinetics and pharmacodynamics. Kinetic parameters of importance include re-distribution
and clearance. Pharmacodynamic effects would have led to a consideration of the interactions with
other drugs. Good answers used several examples, the commonest used being propofol,
remifentanil and non-depolarizing muscle relaxants. Answers (and there were many) which
concentrated purely on the issue of context-sensitive half time and remifentanil attested more to
successful marketing by drug companies, rather than a clear understanding by candidates of the
issues raised by this question.

VIVA SECTION


Pharmacokinetics and Pharmacodynamics:
Receptor theory
Functional properties of receptors
Halflife and time-constant
First order and second order kinetics
Spare receptors
Kinetics of Inhalational agents
Storage of drugs and potency
Tolerance
11
Therapeutic Index
ED 90

Inhalational agents
Structure-activity relationship
MAC uses and shortcomings
Occupational hazards
System effects of different agents
CVS effects
Respiratory effects
Endocrine and Metabolic effects
N
2
O properties and contra indications
Uptake and wash-out curves

Intravenous agents
Barbiturates, structure-activity relationship
Propofol uptake and distribution
Ketamine, mechanism of action
Metabolism of different agents
Determinants of an induction dose
Benzodiazepine receptors

Muscle relaxants
Principles of neuromuscular monitoring
Characteristics of depolarising and non depolarising block
Contraindications and side-effects of suxamethonium,
Cis-atracurium vs atracurium
Dose-response curve of different muscle group

Narcotics
Morphine vs fentanyl vs alfentanil
Epidural and subarachnoid narcotics
Remifentanil, kinetics and cardiovascular effects
Tramadol, kinetics and effects
NMDA receptors

Local anaesthetics
Additives to local anaesthetics
EMLA
Foetal LA toxicity
Structural-activity relationships
Comparative toxicity of bupivacaine vs ropivacaine
Systemic toxicity

Miscellaneous
Bias in clinical research
specificity / sensitivity / predictive value
Study design and clinical trials
Antiemetics
Dopamine
Serotonin and antagonists
Histamine and antagonists
Bradykinins
12
Prostaglandins, synthesis and inhibition
Renin-Angiotensin system
Alpha blockers
Beta blockers
Antibiotics mechanisms of action
Structure activity relationships of catecholamines
NSAIDs, mechanisms of action
Compare and contrast Paracetamol and Acetylsalicylic acid.
Mechanism of action of antiepiliptic drugs
Kinetics and side effects of phenytion
Uterine relaxants
DDAVP, mechanism of action
Side effects of sodium bicarbonate
Atropine vs glycopyrolate
Neostigmine like drugs
Anticoagulants
Heparin vs LMW heparin
Side effects of Protamine
Classification and clinical indications of phosphodiesterase inhibitors ,
Dose response curve for diuretics
Mechanism of action of mannitol
Dextrose vs dextran
Clinical toxicity of Mg
Sterioisomers
Antihypertensives in pregnancy
Nitric Oxide

A.W. Quail
CHAIRMAN
PRIMARY EXAMINATION

Registered Trainees

EXAMINATION REPORT

PRIMARY EXAMINATION

MARCH/APRIL 1999


PHYSIOLOGY

WRITTEN SECTION




QUESTION 1 Explain the Bohr and Haldane effects in trans-placental gas exchange.

Approximately 42% of candidates passed this question.

The Bohr and Haldane effects were defined accurately by nearly all candidates and most confined
themselves to the question including little irrelevant information. Good answers also included the
PO
2
, PCO
2
and pH values in the maternal and fetal circulations before and after the placenta. The
best way to describe the transfer of oxygen and carbon dioxide was in a narrative form, explaining
each effect eg. the Bohr effect on the maternal side then on the foetal side.

This answer required precision with terms. Many candidates did not make it clear whether they
were discussing maternal or foetal haemoglobin, or maternal or foetal haemoglobin oxygen
dissociation curves. Uterine and umbilical vessels, when included in diagrams were often wrongly
labelled or not labelled at all.

The most common mistake was to try and draw the double Bohr effect diagram. This diagram is
very complicated and takes a lot of time. Very few candidates drew it accurately or labelled the
axes with both numbers and units. Often the diagram was drawn and no attempt made to explain it.
The diagram alone is not an adequate explanation.
2

QUESTION 2 Explain the mechanisms that prevent blood clotting in intact blood
vessels (do not draw the clotting cascade).

42% of candidates passed this question and there were few good answers. Most candidates failed
to appreciate that blood clotting (haemostasis) depends on a fine balance between procoagulant and
anticoagulant processes. The activation of platelets and coagulation is minimal in intact blood
vessels with normal blood flow. Even minor activation of the clotting mechanism results in a rapid
escalation of procoagulant processes (positive feedback or amplification). This can result in
uncontrolled clotting unless anticoagulant processes are simultaneously activated to limit clot
formation.

The mechanisms preventing clot formation can be considered under the following headings:

1. Endothelial surface factors include the smooth endothelial surface and glycocalyx layer, which
prevents contact activation of coagulation factors and platelet activation. Thrombomodulin
binds thrombin thus slowing the clotting process and the thrombomodulin - thrombin complex
activates protein C. PGI 2 inhibits platelet aggregation.
2. Blood flow dilutes and removes activated clotting factors, which are then inactivated by the
RES. Laminar flow causes axial streaming of platelets which minimises endothelial contact and
hence activation
3. Natural anticoagulants are present in concentrations, which exceed that of procoagulants.
Heparin combines with antithrombin III increasing its activity up to a thousand fold.
Antithrombin III inactivates factors IIa, IXa, Xa, XIa and XIIa. Protein C inactivates factors Va
and VIIIa and plasminogen activator inhibitor-1 which stimulates fibrinolysis.
2
-
macroglobulin inhibits thrombin.
4. Limitation of clot size due to fibrin binding thrombin in the clot and fibrinolysis breaking down
formed clot.

Whilst antithrombin III and protein C were mentioned by most, few could correctly describe their
activation or mechanism of action. Many answers wrongly stated that the natural anticoagulants
inhibited the inactive form of the coagulation factors.

QUESTION 3 Describe the factors that affect the transport of oxygen and carbon
dioxide from the alveolus to blood.

Overall this question was well answered with 44% of candidates achieving a pass.

The factors that affect transport of oxygen and carbon dioxide between alveolus and blood can be
described by Ficks Law of simple diffusion ie. Diffusion constant, surface area, membrane
thickness, and concentration gradient (or more correctly partial pressure gradient). Marks were
awarded for relating these factors to the alveolus and lung. The influence of solubility and
molecular weight on the diffusion constant for individual gases should have been described, with
comparisons for oxygen and carbon dioxide. Additional marks were awarded for describing the
influence of cardiac output and the rate of combination of oxygen with haemoglobin. Oxygen
diffusion is normally perfusion limited. Increases in cardiac output (eg. with exercise) normally
result in recruitment of alveoli thereby increasing the surface area for diffusion. However, in the
presence of disease or a low partial pressure gradient (eg. at high altitudes), an increased cardiac
output may reduce red blood cell transit time resulting in insufficient time for equilibration of
oxygen, making oxygen, unlike carbon dioxide, diffusion limited. The combination of oxygen with
3
haemoglobin is important because it ensures a low capillary partial pressure of oxygen and
maintains a gradient for oxygen diffusion despite a higher oxygen concentration in the blood. In
this way haemoglobin concentration, the affinity of haemoglobin for oxygen, and capillary blood
volume influence the rate of oxygen diffusion.

Many candidates wasted time providing detailed descriptions of oxygen and carbon dioxide
transport in the blood, the haemoglobin-oxygen dissociation curve, alveolar ventilation, or
ventilation-perfusion mismatch. Failure to address the question led to a reduction in scores.


49% of candidates passed this question. To answer the question adequately, candidates should
point out that glucose is filtered at the glomerulus and reabsorbed in the proximal tubule by a
secondary active transport mechanism, using energy supplied by Na/K ATPase. Reabsorption
increases as glucose filtration increases up to a transport maximum (Tm), above which glucose
appears in the urine. They should also mention that glycosuria causes an osmotic diuresis, as
glucose holds water and sodium in the proximal tubule, causing urinary loss of water, sodium and
other electrolytes and consequent hypovolaemia and electrolyte and osmotic imbalance. High fluid
flow in the nephron washes out the medullary osmotic gradient, impairing the kidneys ability to
concentrate urine. Loss of glucose represents a loss of nutrient and energy.

Other points, which gained marks, included discussion of the link between sodium and glucose
absorption, and of the reason for Tm limitation. Discussion of the mechanism of potassium loss
and mention of the bodys response to osmotic effects of glycosuria on the circulation and
extracellular fluid also gained marks.

Common errors included the assumption that glycosuria equals diabetes mellitus, and consequent
irrelevant discussion of ketoacidosis and its consequences. Several candidates incorrectly stated
that glucose was secreted by the nephron. Others repeated, more or less verbatim, the account of
renal glucose handling given in Ganong, with little evidence of understanding.

Exact statements are more likely to gain marks than vague, imprecise ones. Undefined
abbreviations and forms of shorthand (eg c) which clearly have some meaning to the candidate,
but not to the examiner, should be avoided.

QUESTION 5 Differentiate between the terms heat and temperature. Explain
briefly the principles of a mercury thermometer, indicating its
advantages and disadvantages.

82% of candidates passed this question. Most passed well and there were a number of very good
answers. There was a reasonable amount of confusion about the difference between Heat and
Temperature. Mentioning S.I. units and relating the entities via Specific Heat Capacity enhanced
definitions and gained extra marks.

Most candidates gave a reasonable explanation of the physical principles of the mercury
thermometer, although many omitted calibration principles and did not mention the importance of
the relative volumes of the Mercury Reservoir in the bulb and the capillary column. It is also
critical that the capillary tube is evacuated.

4
The concept of a time constant was often mentioned but also often misunderstood. In general,
advantages and disadvantages were well done with a number of candidates having prepared
exemplary lists.

QUESTION 6 Describe the factors influencing hepatic blood flow.

Although the pass rate for this question was 73%, very few candidates scored well. A good answer
should have included a discussion of:

a) anatomical considerations of hepatic blood flow
b) normal values and the autoregulation of hepatic artery flow
c) the difference in perfusion pressures of the hepatic artery and portal vein
d) factors that affect the hepatic vascular resistance, including changes in blood gases,
sympathetic stimulation, anaesthetic agents and hepatic diseases
e) other factors including cardiac output, blood pressure and ventilation.

Although most candidates discussed the anatomical factors and perfusion pressures, very few
included in their answer the factors that change the hepatic blood flow.

QUESTION 7 Describe the autonomic innervation of the heart, and the direct effect of
autonomic stimulation on cardiac function.


Anatomical knowledge was required of the neural innervation of the heart, site of ganglia, pathways
to the heart and differences between the left and right sides of the body. The identity of the
neurotransmitters was relevant as well as the receptors activated. Many answers were more suited
to a question on the effects, on the heart, of adrenergic and cholinergic receptors without
distinguishing between the effects of neural stimulation and blood borne agonists.

The cardiac tissues are specialised and the effect of neural stimulation differs on sinoatrial node,
atria, atrioventricular node, Purkinje cells and ventricular myocytes. Many of the better answers
used this information to structure their answer and succinctly present a large amount of information
on the effects of stimulation.

The sequence of events following receptor activation was well handled.

5
QUESTION 8 Explain the significance of plasma oncotic pressure in capillary fluid
dynamics.

This question was successfully answered by 75% of candidates, with some excellent answers.

The osmotic pressure exerted by the unfiltered proteins obviously required definition in relation to
the other Starling forces acting across the capillary membranes. This was successfully done by
those who passed, usually with the aid of the Starling pressures equation common to the standard
texts.

Answers that scored well used some or all of the following, to explain the significance of the
plasma osmotic pressure.

Comparison of forces in different capillary beds
Quantification of forces. Allowance was made for the different values by different authors in
the standard texts
Explanation of significance of filtration and reflection coefficients
Effects of altered osmotic and hydrostatic pressures
Lymphatic function

Candidates who failed either did not answer the question, or made significant errors, demonstrating
limited understanding of plasma protein osmotic pressure and its function in capillaries.

VIVA SECTION


What is the effect of a sustained increase in sodium intake?
Describe how the kidney concentrates urine.
How can one measure liver blood flow?
What are the effects of a biliary fistula?
What are the changes in blood volume in pregnancy?
Draw a muscle spindle
What blood groups are there?
What is a buffer?
What are the effects on the body of tipping the body steeply head down?
What factors determine the glomerular filtration rate?
What is complement?
What is an exponential process?
What forces are overcome by muscle activity during a tidal breath?
What is lung compliance?
What is the resting membrane potential of skeletal muscle?
How can one measure intravascular pressure?
What are the effects of releasing a tourniquet?
What are the effects of a Valsalva manoeuvre?
What is colloid osmotic pressure?
What are the causes of hypoxaemia?
What is meant by the term basal metabolic rate?
6

What is Starlings law of the capillary?
Draw a pressure trace obtained from the root of the aorta.
What is the effect of right atrial pressure on venous return?
What is the meaning of the term resistance?
What is the oxygen cascade?
What is the structure of the haemoglobin molecule?
How is pain sensation transmitted in the spinal cord?
What is the Nernst equation?
What is the origin of the resting membrane potential?
What is the difference between resistance and impedance?
What is the effect of unconsciousness on temperature control?
What are the constituents of cerebrospinal fluid?
How can one measure gas flow?
What respiratory changes occur during pregnancy?
What is closing capacity?
What are the actions of thyroxine?
How can one measure dead space?
What types of hormone receptor are there?
How does one calibrate a pressure transducer?
What types of muscle fibre are there?
What factors influence pulmonary vascular resistance?
What is the circulating blood volume of a 70 kg adult?
What are the effects of acute loss of one third of the blood volume?
What are the effects of transfusion of 2 litres of whole blood?
What are the effects of lying supine from a standing position?
What is Von Willebrands factor?
How does the kidney handle bicarbonate?
What is absolute humidity?
Interpret a set of blood gases
What is the lower oesophageal sphincter?

7

PHARMACOLOGY

WRITTEN SECTION




QUESTION 9 In a clinical trial, why is adequate power important? What factors affect
the determination of an adequate sample size?


There was a wide range of marks for this relatively straightforward question, probably indicating
that some candidates do not consider the statistical component of the syllabus worth serious study
time. The majority gave an adequate definition of statistical power, but not many really addressed
the question why is it important? The answer is simply related to the ethics of clinical research,
the efficient use of resources and the need to obtain a correct result to the research question.
The provision of actual formulae to calculate sample size was not required, but several candidates
made very creditable efforts. Most correctly defined alpha and beta errors and indicated how the
values chosen influence sample size. Having done that many omitted to mention the effect of
population variability and the need to estimate it in some way. Other made no reference to the size
of the difference that the study hoped to detect. A few good answers also commented on the
possibility of a number of different outcomes being studied in the one trial and the need to consider
sample size for these individually.

QUESTION 10 Write a brief outline on the pharmacology of remifentanil.

47% of candidates obtained a pass mark in this question.

This was a straightforward question that required an overview of information found in any standard
text, with an emphasis on unique properties. Credit was given for information as outlined below,
although it should be emphasised that this represents an exceptionally good answer that would have
gained near full marks.

Introduction - Remifentanil is a relatively potent, selective mu agonist with a short
duration of action.
Pharmacy - A phenyl piperidine derivative, containing two ester bonds which is a
weak base with a pKa of about 7.1 Presented as a powder mixed with
glycine it can be reconstituted with water.
Pharmacokinetics Predominantly ionised at body pH, with moderately low lipid solubility (cf
fentanyl) and 70-90% plasma protein bound. It has a rapid onset (about
1min.) and a modest distribution volume (about 0.5l/kg). High clearance
(5l/min) rather than redistribution is responsible for its speed of offset
(beta half-life about 10min.). Notable is a context sensitive half-life of
about 4min, independent of the infusion time. Clearance is almost
8
exclusively by hydrolysis of one of the ester bonds by non specific
blood and tissue esterases (not by red cell esterase alone and not by
pseudocholinesterase) producing an almost inactive carboxylic acid
derivative
Pharmacodynamics Typical of a mu agonist.
CNS analgesia, sedation, depresses some brain stem regulatory centres
(respiratory/cardiovascular), excites others (causing nausea, pupillary
constriction, truncal rigidity).
CVS minimal direct effects on myocardium or vasculature, normally no
histamine release (cf. morphine). Bradycardia and decreased vascular
resistance secondary to effects on vagal nuclei and vasomotor centres.
Resp.- decreased airway reflexes and respiratory rate possibly with
increased volume leading to apnoea; decreased response to hypercapnia
and hypoxia.
GI/GU increased tone (biliary tree and ureter) and/or decreased activity
(stomach and bowel) probably of little clinical significance because rarely
used long term post operatively.
Adverse effects bradycardia, decrease in blood pressure, truncal rigidity with high
dose/rapid administration; neurotoxicity due to glycine and immune
mediated histamine release; nausea/vomiting and severe pain after
cessation of administration in awake patients.
Clinical use Intraoperative analgesia of rapid onset/offset (0.1- 1.0 microgm/kg/min)
with optional preceding bolus of 1-2 microgm/kg. Need to make provision
for postoperative analgesia before cessation of remifentanil.

Relatively common mistakes included: failure to appreciate mu selectivity; lack of familiarity with
presentation; confusion concerning enzymes responsible for metabolism; inability to work out
degree of ionisation in vivo when agent has already been identified as a weak base and pKa has
been stated; pharmacodynamics that were simply described as being fentanyl-like ( the examiner
has no way of knowing if the candidate knows what fentanyls properties are); confusion
concerning cause of depressant cardiovascular effects.

QUESTION 11 Briefly compare and contrast the clinical pharmacology of atropine,
hyoscine (scopolamine) and glycopyrrolate.

Many candidates struggled with this question with 42% passing. There were two main problems:

1. Inadequate attempts to compare and contrast the pharmacology of the three drugs; and
2. Consideration of only one aspect of the pharmacology (eg. pharmacodynamics)

Remarkably, only about half the candidates stated that these drugs act at muscarinic receptors.
Very few identified the drugs as competitive antagonists. The candidates should be very careful not
to omit core information such as this - planning would help.

Historical aspects were not well covered. Some candidates mentioned the sources of atropine and
hyoscine in nature, but very few mentioned the use of atropine with ether or hyoscine with
Omnopon. As far as structure-activity relationships went, most candidates identified the
fundamental differences between atropine and hyoscine, and glycopyrrolate. However, very few
talked about isomers and the relationship of the drugs to the ionic site on the receptor. Only three
candidates attempted to draw the structures.

9
Pharmacodynamic and pharmacokinetic differences were discussed fairly well. Toxicity was also
frequently discussed, however, many candidates incorrectly stated that central cholinergic
syndrome was a problem. Many candidates failed to mention doses and a surprisingly large
number did not mention the use of these drugs in antagonising neuromuscular blockade.

QUESTION 12 Explain the phenomena known as fade and post tetanic facilitation
associated with the use of neuromuscular blocking agents.

The overall pass rate for this question was about 43%. Most candidates seemed to appreciate that
this question required an explanation of the mechanism of Fade and Post Tetanic Facilitation (PTF)
as seen with the non-depolarising class of neuromuscular blocking drugs. The question clearly did
not call for any discussion about how these phenomena are elicited in clinical practice nor the
clinical relevance or usefulness of the elicitation of these phenomena. A few candidates indicated
that Fade and PTF are restricted to the adductor pollcius muscle alone. Quite a few candidates
ignored the term PTF and wrote entirely on Post Tetanic Count. The two are different and
candidates must be careful to answer the question.

Most candidates furnished a definition of Fade and PTF and whilst this was not explicitly called for,
it did appear to provide a good starting point to their answers. Fade exists when, during a partial
non-depolarising block, administration of frequent repeated stimuli eg. Train of Four, results in a
reduction of twitch height with each of the subsequent stimuli. Post Tetanic Facilitation is seen
during partial non-depolarising blockade when after a tetanic stimulation is applied to a nerve-
muscle unit there is seen after a delay, of classically three seconds, a potentiation of twitch height
with a subsequently applied single supra maximal stimulus.

The explanation of Fade should have included discussion of pre-junctional nicotinic receptors
involved in a positive feedback loop with Acetylcholine (ACh) being blocked by the non-
depolarising neuromuscular blocking agent resulting in reduced production of ACh vesicles and
therefore less vesicles available for release. The explanation of Post Tetanic Facilitation required
some discussion of temporarily increased mobilisation of ACh vesicles into the pre-junctional area
for ready release as a result of tetanus.

QUESTION 13 Describe the neuropharmacology of thiopentone covering its site of
action, EEG changes, effects on cerebral blood flow and intracranial
pressure.

This question was generally well answered with a pass rate of 78%. Many candidates showed
detailed knowledge of the site of action, but there was considerable confusion about the
mechanisms reducing cerebral blood flow and intracranial pressure. Candidates describing other
areas of thiopentones neuropharmacology were awarded marks but the emphasis in marking was
on the required content. A number of candidates produced answers similar to the following model -

Site of action:
Thiopentones actions are thought to occur at the -amino butyric acid (GABA)
A
receptor complex.
GABA
A
receptors are ligand gated chloride ion channels, have up to five subunits, and have
benzodiazepine and picrotoxin binding sites. GABA is the principal inhibitory neurotransmitter in
the central nervous system. Barbiturates decrease the rate of dissociation of GABA from the
receptor and increase the duration of GABA mediated channel opening. At higher concentrations
barbiturates directly activate the channels even in the absence of GABA. Channel opening causes
membrane hyperpolarisation and thereby inhibits action potential transmission.
10

EEG Changes:
Thiopentone produces a dose-related depression of the electroencephalogram (EEG). The awake
alpha pattern progresses to higher amplitude and slower frequency delta- and theta-waves until
there is burst suppression and finally a flat EEG.

Effect on cerebral blood flow and intracranial pressure:
There is a dose-dependent reduction in cerebral metabolism of oxygen (CMRO
2
) which reaches a
maximum of 55% with a flat EEG. Note this is due to reduced neuronal, not metabolic, oxygen
consumption. This produces a parallel reduction in cerebral blood flow, cerebral blood volume,
intracranial pressure (ICP), and increased cerebral vasoconstriction, provided that CMRO
2
and
blood flow remain coupled. Cerebral perfusion pressure is maintained if the fall in mean arterial
pressure produced by thiopentone infusion is less than the fall in ICP.

QUESTION 14 Briefly outline the pharmacological effects of the volatile anaesthetic
agents on the kidneys.

This question was generally well answered with 64% of candidates passing this question. The most
important aspects were that all volatile agents decrease renal blood flow to some extent, and this
associated with a reduction in glomerular filtration rate and urine flow. These effects are usually
minimal and can be largely negated by maintaining intravascular hydration. The stress response
of major surgery may compound these effects.

The metabolism of some agents results in free fluoride ions, which have been associated with
tubular damage and high output renal failure. This is related to the amount and duration of
exposure, as well as their solubility (rate of excretion) and extent of metabolism - this is why
methoxyflurane is particularly nephrotoxic; the critical level for methoxyflurane is about 2 MAC-
hours, and this is usually associated with a plasma fluoride level of 50 mol/litre.

Sevoflurane metabolism also produces fluoride ions, but there is no clinical evidence that this is
associated with renal damage. This has been attributed to its rapid excretion and low rate of intra-
renal production of fluoride ion. Sevoflurane is also broken down in soda lime (& Baralyme) to
compound A; this is increased at low fresh gas flows. Compound A is nephrotoxic in rats, but
probably not in humans (though this remains controversial).

QUESTION 15 List the drugs used clinically as anticoagulants and antithrombotics.
Write short notes on their mechanisms of actions.

The pass rate for this question was 65%. The majority of the candidates were able to list the
required anticoagulants and antithrombotics namely heparin, the coumarin derivatives and aspirin.
Many received additional credit for discussing dextran 70, dipyridamole, hirudin, ticlopidine, and
abciximab. However many of the answers failed to demonstrate a clear understanding of their
mechanisms of action, and were lacking in precise details. Unfortunately most candidates devoted
a large part of their answer to discussing thrombolytic therapeutic agents such as tissue
plasminogen activator and streptokinase. No credit could be given for such discussion, as this was
not asked in the question.

The references for information on this subject are the relevant section of Katzung and Stoelting 2
nd

edition, p467, 472, 474.

11

QUESTION 16 Describe the effects of the alpha-2 adrenoceptor agonists relevant to
anaesthesia.


Alpha-2 adrenoceptor agonists have been in use as antihypertensives, as adjuncts and
investigational agents in both human and veterinary anaesthesia for over 20 years. It is therefore
reasonable to expect that the candidates should have some knowledge of which agents are included,
their effects (both specific to anaesthesia and in general), and the likely physiological consequences
following their administration. Areas in which difficulties were encountered included identification
of the relevant drugs (eg. clonidine and dexmedetomidine), the sites of significant action (central
post-synaptic, peripheral pre-synaptic, spinal cord) and the assignment of anaesthesia utility to
various actions and characteristics. The listing of drug effects does not constitute a description, as
the effects may not be clinically useful. Similarly, while the assertion of the high oral availability
of clonidine was frequently made, the significance of this to anaesthesia was seldom encountered.
Better responses were typically legible, well organised with sites and mechanisms clearly stated,
and the effects listed with appropriate comment. Only a few candidates mentioned the problem of
prolonged hypotension after clonidine, although many mentioned the transient hypertension with
intravenous (IV) bolus dosing. No one mentioned the relatively slow onset of central activity of
clonidine or that any of these properties might actually be undesirable for an IV anaesthetic agent.
The frequent assertion that bolus dosing with clonidine produces hypertension with tachycardia was
disconcerting, as it suggested scant regard for baroreflex responses and little awareness of the effect
of alpha-1 receptor stimulation in an intact subject. One further difficulty in interpreting
candidates answers was the tendency to use personalised (or local) abbreviations, often without
translation; this also was less frequent in the better responses.

VIVA SECTION


What volatile agent are you most familiar with and can you tell me about that agent?
Please describe the site of action of neuromuscular blocking agents.
What are the contents of an ampoule of Sodium Thiopentone?
Tell me about Aminophylline.
Can you classify and list the side effects of Suxamethonium administration?
Can you explain the offset of non-depolarising muscle relaxants?
Can you describe the effects of Isoflurane on respiration?
Explain the techniques used to monitor neuromuscular block.
Tell me about the effects of Morphine on the cardiovascular system.
Tell me about the effects of Fentanyl on the cardiovascular system.
Can you explain the concentrating and second gas effects?
What determines uptake of volatile anaesthetic agents from the alveolus?
Describe the production of adrenalin in the body.
Can you define standard deviation and explain confidence levels?
How is nitrous oxide produced?
Tell me about the cardiac effects of Adenosine.
How do benzodiazepines exert their effects in the body?
Tell me about factors effecting MAC.
Discuss the clinical uses of long acting opioids.
12

What factors determine variation in doses of induction agents, for example with age and shock?
Tell me about pharmacogenetic disorders.
Can you tell me about Phenytoin?
What do you understand by the term context sensitive half-life?
How does one determine sample size in statistics?
Can you tell me about Ergometrine?
What can you tell me about Esmolol?
Tell me about agents that are used to lower blood pressure.
Explain the mechanism of action of anticholinesterases.
Classify drugs that affect the gastric acidity.
Draw a set of wash in curves versus time for commonly used volatile anaesthetic agents.
Give a classification of non-opioid analgesic drugs.
What is meant by the term volume of distribution?
Tell me about the formulation of Propofol.
What is meant by the Therapeutic Index?
Explain how Heparin exerts its anticoagulant effect.
What is meant by meta-analysis?
Please explain the second gas effect.
Tell me about neuroleptic malignant syndrome.
Tell me about the structure-activity relationships of volatile anaesthetic agents.
Classify the drugs used in the treatment of asthma.

A.W. Quail
CHAIRMAN
PRIMARY EXAMINATION

Registered Trainees

Primary Exam Reports 2011 To 1999

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AUSTRALIAN AND NEW ZEALAND COLLEGE OF ANAESTHETISTS

ABN 82 055 042 852

65 of candIdates achIeved a pass In thIs sectIon of the Pharmacology ExamInatIon.

70 of candIdates achIeved a pass In thIs sectIon of the PhysIology ExamInatIon.

6J of candIdates achIeved a pass In thIs sectIon of the Pharmacology ExamInatIon.

69 of candIdates achIeved a pass In thIs sectIon of the PhysIology ExamInatIon.

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