FINAL REVIEW

I. PHARMACOKINETICS
- derived from two Greek words: pharmakon = drug or poison kinesis =
motion
- what the body does to drugs, includes metabolism and drug excretion

A. PROCESSES
1. absorption – movement of a drug from its site of administration into the
blood
2. distribution – drug movement from the blood to the interstitial space of
tissues and from
there into cells
3. metabolism – (biotransformation) enzymatically mediated alteration of
drug structure 4. excretion – movement of drugs and their
metabolites out of the body
elimination – combination of metabolism plus excretion

All four processes acting in concert determine the concentration of a drug

at its sites of action.

B. COMMONLY USED ROUTES OF ADMINISTRATION

1. ENTERAL – via the gastrointestinal tract

a. Oral (PO)- per os = Latin phrase meaning by way of mouth

i. Advantages:
- easy, convenient, and inexpensive
- safer than injection: inducing either emesis (vomiting) or
catharsis (rapid emptying of the
small intestine and bowel) or both before there has been
sufficient time for absorption
in the case of inappropriate administration
- administering activated charcoal (compound that absorbs drugs
while they are still in the GI
tract) is another safeguard

ii. Disadvantages:
- Variability makes it difficult to control the concentration of a
drug at its sites of action,
therefore making it difficult to control the onset, intensity and
duration of responses
- Inactivation can occur because the drug is destroyed by stomach
acid, destroyed by
digestive enzymes or undergo rapid inactivation by hepatic
enzymes as they pass
through the liver on their way from the GI tract to the general
circulation
- Patient Requirements = conscious, cooperative patients
- Local Irritation of the GI tract can result in discomfort, nausea,
and vomiting
2. PARENTERAL – outside the gastrointestinal tract
- by injection
- pattern of all routes is unique because the barriers to absorption
associated with each route are
different

a. Intravenous (IV)
i. Advantages:
- Rapid Onset which is beneficial in emergencies
- Control over levels of drug in the blood
- Use of Large Fluid Volumes are permitted only through IV routes
(some drugs are poorly
soluble in water and must be dissolved in a large volume)
- Use of Irritant Drugs can be administered only by IV route; when
administered through a
freely flowing IV line, these drugs are rapidly diluted in the
blood, thereby minimizing
the risk of injury
ii. Disadvantages:
- High Cost, Difficulty (set up takes time and special training;
dependent on a healthcare
professional), and Inconvenience (tethered to lines and
bottles limits mobility)
- Irreversibility can be dangerous: once the drug is in the body, it
cannot be retrieved
- to minimize this risk, IV drugs should be injected slowly in order for
it to dilute in the largest
volume of blood possible and concentrations that are
unnecessary or even dangerous
can be avoided
- slow injection reduces the risk of toxicity to the central nervous
system also
- Fluid Overload
- Infection
- Embolism (blood vessel blockage at a site distant from the point
of administration)
- insertion of an IV needle can injure the venous wall, leading
to formation of a
thrombus (clot); embolism can result if the clot breaks
loose and becomes
lodged in another vessel
- injection of hypotonic or hypertonic fluids can destroy red
blood cells and the debris
from these cells can produce embolism
- injection of drugs that are not fully dissolved can cause
embolism
- Importance of Reading Labels before giving an IV drug, whereas
solutions intended for
subcutaneous administration are concentrated, solutions
intended for intravenous use
 are dilute; giving the right drug is not sufficient, you must also
be sure that the
formulation and concentration are appropriate for the intended
route

b. Intramuscular (IM)
i. Advantages:
- can be used for administration of poorly soluble drugs
- can be used to administer depot preparations (preparations from
which the drug is absorbed
slowly over an extended time) greatly reducing the number of
injections required during
long-term therapy

ii. Disadvantages:
- discomfort and inconvenience
- can cause local tissue injury and possible nerve damage (if the
injection is done improperly)
- less convenient than oral administration

c. Subcutaneous (SC or SQ)

- no significant barriers to absorption
- readily enters the blood by passing through the spaces between
cells of the capillary walls
- blood flow and drug solubility are the major determinants of how
fast absorption takes place
- advantages: suitability for poorly soluble drugs and depot
preparations
- disadvantages: discomfort, inconvenience, potential for injury
- only real difference is the length of the needle – meds stay in
circulation longer

C. EXITING THE VASCULAR SYSTEM

Blood Brain Barrier – refers to the unique anatomy of capillaries in the CNS
- tight junctions between the cells that compose the walls of most
capillaries in the CNS are so
tight that they prevent drug passage
- a drug must be able to pass through cells of the capillary wall
- only drugs that are lipid soluble or have a transport system can
cross the blood brain
barrier to a significant degree
- barrier protects the brain from injury by potentially toxic
substances
- barrier can be a significant obstacle to therapy of CNS disorders
- barrier is not fully developed at birth

D. SPECIAL CONSIDERATIONS IN DRUG METABOLISM

First Pass Effect – refers to the rapid hepatic inactivation of certain oral drugs
that are then carried through the
small intestines through the liver and to the heart (nitroglycerine, insulin)
 - when administered orally, drugs are absorbed from the GI tract and
carried directly to the liver via the
hepatic portal circulation
- if the capacity of the liver to metabolize a drug is extremely high, that
drug can be completely
inactivated on its first pass through the liver
- to circumvent the first pass effect, a drug that undergoes rapid hepatic
metabolism is often
administered parenterally
- this permits the drug to temporarily bypass the liver, thereby allowing it
to reach therapeutic levels in
the systemic blood
- once in the circulation, the drug is carried to its sites of action prior to
passage through the liver; hence,
therapeutic action can be exerted before the drug is exposed to
hepatic enzymes

Age - drug metabolizing capacity of infants is limited

- the liver does not develop its full capacity to metabolize drugs until about
1 yr. after birth
- the elderly can easily overdose because they don’t have the same liver
function anymore

II. PHARMACODYNAMICS

Pharmacodynamics – study of the biochemical and physiologic effects of drugs and

the molecular mechanisms by
which those effects are produced (study of what drugs do to the body and how
they do it)

Maximal Efficacy – largest effect that a drug can produce

- indicated by the height of the dose-response curve
- a drug with very high maximal efficacy is not always more desirable than a
drug with lower efficacy

Relative Potency – potency refers to the amount of drug we must give to elicit an
effect
- a potent drug is one that produces its effects at low doses

affinity – the strength of the attraction between a drug and its receptor
- drugs with high affinity can bind to receptor when present in low
concentrations, therefore, are effective in low
doses
- very potent

intrinsic activity – the ability of a drug to activate the receptor following binding and
is reflected in its maximal efficacy

agonists – drugs that mimic the body’s own regulatory molecules

- molecules that activate receptors
 - neurotransmitters, hormones, and all other endogenous regulators of receptor
functions
- in terms of modified occupancy theory, these drugs have both affinity and
high intrinsic activity
affinity allows the agonist to bind to receptors
intrinsic activity allows the bound agonist to “activate” or “turn on”
receptor function

antagonists – drugs that block the actions of endogenous regulators

- employed most commonly in the treatment of overdose
- have virtually no effects on their own on receptor function
- in terms of modified occupancy theory, these drugs have affinity for a receptor
but with no intrinsic activity

Classes:
a. Noncompetitive (Insurmountable) Antagonists – bind irreversibly to
receptors and inhibition of these
agents cannot be overcome – no matter how much agonist may be
available
-irreversibility does not mean effects last forever; effects wear off as
the receptors to which they
are bound are replaced (life cycle)
- intensity of response is proportional to the total number of
receptors occupied
- if sufficient antagonist is present, agonist effects will be blocked
completely
- rarely used therapeutically

b. Competitive (Surmountable) Antagonists – bind reversibly to

receptors and the inhibition they cause
is surmountable
- produce receptor blockade by competing with agonists for receptor
binding
- if competitive antagonist and an agonist have equal affinity for a
particular receptor, the
receptor will be occupied by whichever agent is present in the
highest concentration

III. ORIENTATION TO PHARMACOLOGY

DRUG – defined as any chemical that can affect living processes and have therapeutic
applications

PHARMACOLOGY - defined as the study of drugs and their interactions with living systems
- encompasses the study of the physical and chemical properties of drugs as
well as their biochemical and
physiologic effects

THERAPEUTICS – also known as pharmacotherapeutics

 - defined as the use of drugs to diagnose, prevent, or treat disease or to prevent
pregnancy
- medical use of drugs

A. PROPERTIES OF AN IDEAL DRUG: - there is no such thing as a perfect drug

1. Effectiveness – an effective drug is one that elicits the responses for
which it is given.
- effectiveness is the most important property a drug can have
***IF A DRUG IS NOT EFFECTIVE, IT SHOULD NOT BE USED***
2. Safety – a safe drug is one that cannot produce harmful effects – even is
administered in very high
doses and for a very long time
- there is no such thing as a safe drug
- pharmakon – Greek word meaning poison
3. Selectivity – one that elicits only the response for which it is given
- there is no such thing as a selective drug: All medications cause
side effects

4. Reversible Action – it is important that effects be reversible

- we want drug actions to subside within an appropriate time
5. Predictability – since each patient is unique, the accuracy of
certain predictions cannot be
guaranteed
6. Ease of Administration – an ideal drug should be simple to
administer, the route should be
convenient, and the number of doses per day should be low
a. Benefits:
- it can enhance patient adherence
- it can decrease errors in drug administration
4. Freedom from Drug Interactions – when taking two or more
drugs, those drugs can interact
with one another in that they either augment or reduce drug
responses
- possible impact of drug interactions must be considered
5. Low Cost – an ideal drug would be easy to afford
6. Chemical Stability – some drugs lose effectiveness during storage;
others which are stable on
a shelf can rapidly lose effectiveness when put into a solution
- losses in efficacy result from chemical instability
7. Possession of a Simple Generic Name – generic names are
usually complex and difficult to
remember and pronounce
- as a rule, the trade name for a drug is simpler than its
generic name

IV. ADVERSE DRUG REACTIONS (ADR)

- any noxious, unintended, and undesired effect that occurs at normal drug
doses, excludes undesired
effects that occur when dosage is excessive (defined by the World
Health Organization)
 - can range in intensity from annoying to life threatening
- when drugs are used properly, many ADR can be avoided or at least kept
to a minimum
- adverse effects are most common in the elderly and very young
- adverse events are more common in patients receiving multiple drugs

Side Effect – a nearly unavoidable secondary drug effect produced at therapeutic

doses
- intensity is dose dependent and generally predictable
- response can develop soon after the onset of the drug use or as long as weeks
or months later
- ex. Antihistamines causing drowsiness

Toxicity – an adverse drug reaction caused by excessive dosing

Allergic Reaction – an immune response

- once the immune system has been sensitized to a drug, re-exposure to that
drug can trigger an allergic
response
- intensity is largely independent of dosage
- very few medications cause severe allergic reactions; in fact, the most serious
reactions are
caused by just one drug family -- penicillins
- reactions can range from mild itching to sever rash to anaphylaxis
- reactions are determined primarily by the degree of sensitization of the
immune system – not by drug
dosage

anaphylaxis – a life-threatening response characterized by

bronchospasm, laryngeal edema, and a
precipitous drop in blood pressure

Idiosyncratic Effect – an uncommon drug response resulting from a genetic

predisposition

Iatrogenic Disease – a disease produced by a physician

- derived from the Greek word iatros = physician and –genic = to produce
- also used to denote a disease produced by drugs
- nearly identical to idiopathic (naturally occurring) diseases
- ex. Patients taking certain antipsychotic drugs may develop a
syndrome whose symptoms
closely resemble those of Parkinson’s disease

Physical Dependence – a state in which the body has adapted to prolonged drug
exposure in such a way that an
abstinence syndrome will result if drug use is discontinued
- develops during long term use
- precise nature of the abstinence syndrome is determined by the drug involved
- usually associated with “narcotics” (heroin, morphine, and other opioids);
however, these are not the only
dependence-inducing drugs
 - patients should be warned against abrupt discontinuation of any medication
without first consulting a
knowledgeable health professional
- people heal better when not in pain – DO NOT WITHHOLD MEDICATIONS
DUE TO PHYSICAL
DEPENDENCY

Carcinogenic Effect – ability of certain medications and environmental chemicals to

cause cancers - several drugs used to treat cancer are among the drugs
with the greatest carcinogenic potential
- unlikely that carcinogenic potential will be detected during preclinical and
clinical drug trials
- ex. Diethylstilbestrol (DES) – synthetic hormone with actions similar to
estrogen was at one time used
to prevent spontaneous abortion during high-risk pregnancies. It
wasn’t until years later when
vaginal and uterine cancers developed in females who had been
exposed to this drug in utero.

Teratogenic Effect – a drug-induced birth defect

- capable of causing birth defects
- ex. Accutane for acne

V. INDIVIDUAL VARIATION IN DRUG RESPONSES

A. BODY WEIGHT AND COMPOSITION

- the absence of adjustments in dosage, body size can be a significant
determinant of drug effects
- response to a drug is determined in large part by the concentration of the
drug at its sites of action
- the higher the concentration, the more intense the response
- when adjusting dosage to account for body weight, the clinician may
base the adjustment on body
surface area rather than on weight per se
- surface area determinations account not only for the patient’s
weight but also for how fat or
lean the patient may be
- dosage adjustments based on body surface area provide a more
precise means of controlling
drug responses than do adjustments based on weight alone

B. AGE - infants and elderly are especially sensitive to drugs

- the very young have heightened drug sensitivity as a result of organ
immaturity
- the elderly have a heightened drug sensitivity due to organ degeneration
- the elderly also have an increased severity of illness, the presence of
multiple pathologies,
and treatment with multiple drugs
C. GENDER - for most drugs, we don’t know much about gender-related
differences because, until recently,
essentially all drug research was done in men
- clinicians must keep in mind that the information currently available may
fail to accurately predict
responses in female patients

D. PATHOPHYSIOLOGY - abnormal physiology (someone that is sick) can alter responses

to drugs

E. TOLERANCE - decreased responsiveness to a drug as a result of repeated drug

administration
1. Pharmacodynamic Tolerance - refers to the familiar type of tolerance
associated with long-term
administration of drugs such as morphine and heroin
- requires increased drug levels to produce effects that could
formerly be elicited at lower drug
levels
- MEC of a drug is abnormally high
- thought to result from adaptive processes that occur in response to
chronic receptor
occupation

2. Metabolic Tolerance - tolerance resulting from accelerated drug

metabolism
- brought about by the ability of certain drugs (e.g., barbiturates) to
induce synthesis of hepatic
drug-metabolizing enzymes, thereby causing rates of drug
metabolism to increase
- because of increased metabolism, dosage must be increased to
maintain therapeutic drug
levels

3. Tachyphylaxis - form of tolerance that is a reduction in drug

responsiveness brought on by repeated
dosing over a short time
- occurs quickly
- not a common mechanism of drug tolerance
- ex. Transdermal nitroglycerin – using a transdermal patch, effects
are lost in less than 24
hours

VI. PATIENT EDUCATION & COMPLIANCE PROMOTION

Issues to Address:
• dosage size and timing
• route and technique of administrations
• duration of treatment
• drug storage
 • nature and time course of desired and adverse responses

- techniques of administration that are difficult, a demonstration should be made,

after which the parents should
repeat the procedure to ensure they understand
- with young children, spills and spitting out are common causes of inaccurate
dosage
- parents should be instructed to complete the full treatment

Additional Compliance Promotional Tools:

• selecting the most convenient dosage form and dosing schedule
• suggesting mixing oral drugs with food or juice (when allowed) to improve
palatability
• providing a calibrated medicine spoon or syringe for measuring liquid
formulations
• taking extra time with young or disadvantaged parents to help ensure
conscientious and skilled participation