THE IDEAL PROPERTIES OF INTRAVENOUS ANAESTHETICS

A. Physical properties
Water soluble
Stable in solution (to light & heat)
Long shelf life
Non-irritant to veins or subcutaneous tissues
Small volume of distribution
Painless on injection
Not absorbed into plastic or glass

B. Pharmacokinetics
Action in one arm-brain circulation
Effective both IM & IV
Rapid recovery by redistribution
Rapid metabolism-no cumulative effects
No drug interaction
No active metabolites

C. Pharmacodynamics
Smooth induction without excitatory phenomena
Not antanalgesia – preferably analgesic
No cardio-respiratory depression
High therapeutic index
No histamine release
Smooth recovery without hang-over effects
No emergence delirium or hallucinations
No nausea @ vomiting
No hypersensitivity reactions
Not inducing Malignant Hyperthermia
Non teratogenic
No interaction with neuromuscular blocking agents
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No effect on endocrine function

Not hepato / nephrotoxic

Classification
Barbiturate e.g. Thiopentone, Methohexitone
Phencyclidine e.g. Ketamine
Imidazole e.g. Etomidate
Phenol e.g. Propofol
Steroid e.g. Althesin, Eltanolone
Euglenol e.g. Propanidid

BARBITURATES
2,4,6-trioxohexahydropyrimidine
the condensation of malonic acid and urea
carbonyl group at position 2 takes on acidic character because of lactam (keto) -
lactim (enol) tautomerization

Structure Activity Relationship: C5

barbituric acid itself lacks central depressant activity, but the presence of alkyl or
aryl groups at position C5 confers sedative-hypnotic activity
the presence of a phenyl group at C5, or on one of the ring nitrogens confers
anticonvulsant activity (eg. phenobarbital)
increases in the length of one, or both the alkyl side chains at C 5 increases
hypnotic potency up to 5-6 carbon atoms, above this potency is reduced and
convulsant properties may result
branch chain confers greater hypnotic activity with shorter duration of action
the presence of a methyl radical at C5 confers convulsant activity

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Structure Activity Relationship: C2

subclassified according to C2 substitution
C2 = O oxybarbiturates
C2 = S thiobarbiturates
thiobarbiturates have higher lipid solubilities than the corresponding
oxybarbiturate resulting in rapid smooth onset and recovery

Structure Activity Relationship: Lipid Solubility

in general, structural changes which increase lipophilicity,
- decrease the latency of onset
- decrease the duration of action
- accelerate metabolic degradation
- often increase hypnotic potency

Structure Activity Relationship: N1

methyl or ethyl substitution at the N1 position increases lipid solubility and
shortens duration of action
subsequent demethylation may occur resulting in a longer acting metabolite
these compound have a high incidence of excitatory phenomena

Structure Activity Relationship: Stereospecificity

agents possessing asymmetrical carbon atoms
pentobarbital, secobarbital, thiopental, thiamylal and methohexital (all side
chains)
l-isomers are ~ 2x as potent
despite similar access to the CNS c.f. the d-isomers

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methohexital has four stereoisomers due to an asymmetric centre at C5

the -l-isomer ~ 4 times as potent as the -l-isomer
however also produces excessive motor activity, and the marketed solution is a
racemic mixture of the -isomers

Mechanism Of Action
the GABAA receptor complex is the most likely site of barbiturate action
enhance and mimic the action of GABA, by binding to the receptor they,
- rate of GABA dissociation
- duration of GABA activated Cl- channel opening
- at higher concentrations directly activate Cl- channel
effects are similar to the benzodiazepines
but there are significant differences,
Barbiturates duration of channel opening
Benzodiazepines frequency of channel opening
both classes Cl- flux
however, the benzodiazepines act only in the presence of GABA

Pharmacokinetics: Degree Of Ionization

barbiturates are weak acids
- pKA slightly above 7.4
thiopentone has a pKA ~ 7.6
~ 60% unionised at physiological pH
methohexital has a pKA ~ 7.9
~ 75% unionised at physiological pH
acidosis unionised fraction, and
transfer into brain (ECF pH = 7.36)
ionization also affects renal excretion
- ionization back-diffusion
- basis of forced alkaline diuresis in the management of overdosage with
phenobarbitone

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Pharmacokinetics: Lipid Solubility

rapidly acting agents are relatively unionised at plasma pH and are absorbed
according to their lipid solubility
thiopentone, being highly lipid soluble, equilibrates with the brain rapidly
phenobarbital, with relatively low lipid solubility, may take over 15 mins to achieve
unconsciousness when given IV

Pharmacokinetics: Placental Transfer

the factors determining access to the foetus are identical to those determining
access to the brain
thiopentone and the other highly lipid soluble agents readily cross the placenta
maximum foetal blood thiopentone concentrations being seen within 3 mins of IV
administration of thiopentone

Pharmacokinetics: Uptake & Redistribution

duration of action is the sum of redistribution, metabolism and renal excretion
for thiopentone, metabolism is too slow to account for its short duration of action
the return of consciousness is governed by two factors,
- the bolus mixing with circulating blood volume
- redistribution from the brain (VRG)

Pharmacokinetics: Compartment Kinetics

Group Blood Flow Body Mass Equilibration

% CO % time
VC STP 100 ~ 38 0.5 min
VRG 75 < 10 3-10 min
MG 18-20 45-50 1-4 hrs
FG 5 15-20 5 days

NB: the relative rates at which various tissue groups take up thiopentone will depend
upon their blood flow and the tissue solubility

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After a rapid intravenous injection, the percentage of thiopental remaining in the blood
rapidly decreases as drug moves from the blood to tissues. Time to achievement of peak
levels is a direct function of tissue capacity for barbiturate relative to blood flow. Initially,
most thiopental is taken up by the vessel-rich group tissues because of their high blood
flow. Subsequently, drug is redistributed to skeletal muscles and, to a lesser extent, to fat.
The rate of metabolism equals the early rate of removal by fat, and the sum of these two
events is similar to uptake of drug by skeletal muscles.

Cerebral Uptake
peak plasma concentrations of STP ~ 175 mg/l are achieved within 30 secs of IV
administration of 350 mg
internal jugular concentrations are much lower ~ 75 mg/l
equates to a brain extraction ratio ~ 60%

Redistribution
VRG includes the heart, liver, kidney and brain
high myocardial blood flow, ~ 70 ml/100g/min, accounts for the rapidity of CVS
depression
muscle blood flow (20% of CO)
~ 15-30 mins are required for equilibration
despite high lipid solubility, blood flow to fat is so low the equilibrium time for STP
is prolonged
thus, redistribution of thiopentone within the first 30 mins after IV bolus is mainly
to the muscle group

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Elimination
most members have high lipid:water partition coefficients and are significantly
protein bound, therefore,
- they are poorly filtered at the glomerulus
- they readily back-diffuse in the late tubular segments
- excretion is largely dependent upon prior metabolism which occurs in the
liver

Metabolism
biotransformation is usually via oxidation of radicals at the ring C 5 to alcohols,
ketones, phenols or carboxylic acids
these are then conjugated with glucuronic acid and excreted
other biotransformations occur, such as N-hydroxylation, N-dealkylation etc.,
however side chain oxidation is the most important
Metabolism is more rapid for methohexitone as compared to thiopentone
because both side chains on C5 are unsaturated
Metabolism of thiopentone is 10-15% per hour

Sodium Thiopentone: Presentation

presented as a sodium salt to ensure total solution of the drug, pale yellow
powder
mixed with anhydrous sodium carbonate 6% (not HCO3-)
ampoule atmosphere is N2 at 0.8 bar
2.5% solution has a pH = 10.6
the solution not stable and should be used within 24-48 hrs

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Comparative Pharmacokinetics

Thiopentone Methohexitone
Rapid distribution T1/2 (mins) 8.5 5.6
Slow distribution T1/2 (mins) 62.7 58.3
Elimination T1/2 (hours) 11.6 3.9
Clearance (ml/kg/min) 3.4 11.9
Volume of distribution 2.5 22
Protein Binding % 75-80 75-80
Hepatic Extraction Ratio 0.1-0.2 0.5-0.6

Incidence of Severe Hypersensitivity Reaction

Thiopentone 1 : 14000
Methohexitone 1 : 7000
Propanidid 1 : 1500
Althesin 1 : 1000

Porphyria

Br J Anaesth 2000; 85: 143–

53

Metabolic pathways of haem

synthesis. The enzymes involved
at each step are listed on the left,
and the type of porphyria
associated with a deficiency of
each enzyme is shown on the
right. The conditions highlighted
in boxes are the acute
porphyrias.

Clinical Features
Pain
Paraesthesia
Paralysis
Psychosis
Photosensitivity
Purple Urine

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BENZODIAZEPINE
the term benzodiazepine refers to the portion of the
structure composed of the following,
a. a benzene ring, fused to
b. a seven member diazepine ring

NB: however, since all of the important members of the group contain a 5-aryl
substituent and a 1,4-diazepine ring, the term has come to refer to the
5-aryl-1,4-benzodiazepines

the 5-aryl ring greatly enhances potency

diazepam and lorazepam have quite similar structures, while midazolam
contains an imidazole ring bridging R1 and R2
both diazepam and lorazepam are insoluble in water, therefore require
solubilizing agents, while the imidazole ring renders midazolam water soluble

Benzodiazepine Receptor

this receptor is a tetramer composed

of two protein subunits with a central
Cl- channel, in an 2 2 configuration
these proteins contain the ligand
binding sites for the benzodiazepines,
barbiturates and GABA

the benzodiazepine site is located on the -subunit, while that for GABA is on
the -subunit
there are three subclasses of receptor ligands for the benzodiazepine portion of
the GABAA receptor,
i) agonists - benzodiazepines & barbiturates
ii) antagonists - flumazenil
iii) inverse agonists - Propyl -carboline-3-carboxylate

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Benzodiazepine
Agonist
-
Antagonist Cl
Inverse Agonist
GABA A
Barbiturate, Alcohol

Extracellular

Membrane

Intracellular

Schematic Diagram of GABA Receptor

Advantages Of Benzodiazepine As Compared To Other Sedatives

1. benzodiazepines have less tendency to produce tolerance
2. less potential for abuse
3. a greater margin of safety after an overdose
4. elicit fewer and less serious drug interactions
5. benzodiazepines do not induce hepatic microsomal enzymes
6. intrinsically far less addicting than opioids, cocaine, amphetamines, or
barbiturates
7. availability of antagonist

Diazepam: Commercial Preparation

Dissolved in propylene glycol & sodium benzoate, for IV and IM
Dilution with water or saline causes cloudiness but does not alter the potency
Diazemul: in soybean formulation, for IV only; less painful

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Midazolam: Commercial Preparation

Midazolam is a water-soluble benzodiazepine with an imidazole ring in its
structure that accounts for stability in aqueous solutions and rapid metabolism
Midazolam is characterized by a pH-dependent ring-opening phenomenon in
which the ring remains open at pH values of <4, thus maintaining water solubility
of the drug
The ring closes at pH values of >4, as when the drug is exposed to physiologic
pH, thus converting midazolam to a highly lipid-soluble drug.

Comparative Pharmacokinetics Of Benzodiazepines

Equivalent Vd (L/kg) Protein Clearance Elimination
dose (mg) binding (%) (ml/kg/min) T1/2 (hrs)
Midazolam 0.15–0.3 1.0–1.5 96–98 6–8 1–4
Diazepam 0.3–0.5 1.0–1.5 96–98 0.2–0.5 21–37
Lorazepam 0.05 0.8–1.3 96–98 0.7–1.0 10–20

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Metabolism of Diazepam and Midazolam

The principal metabolites of diazepam are

desmethyldiazepam and oxazepam. A lesser amount of
diazepam is metabolized to temazepam. T1/2 of diazepam is
20-40 hours and T1/2 of desmethyldiazepam is 48-96 hours.
Desmethyldiazepam is an active metabolite and it is less
potent than diazepam.

The principal metabolite of midazolam is 1-hydroxy-midazolam.

A lesser amount of midazolam is metabolized to 4-
hydroxymidazolam.

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Benzodiazepine: Pharmacologic Effects

1. anxiolysis
2. anticonvulsant
3. Sedation
4. anterograde amnesia
5. spinal cord-mediated skeletal muscle relaxation

Central Nervous System

Dose related CNS depression
Mild sedation to hypnosis
Slow onset and variable
Amnesia: Lorazepam peak at 90 mins, last for 6 hours
Diazepam and Midazolam, last only 20-30 mins
Anti-convulsant: Clonazepam specific
Decrease CBF and CMRO2 but unable to produce an isoelectric EEG
Interaction with alcohol and other CNS depressants
Not analgesic

Respiratory System
Dose related CNS depression
Shift CO2-ventilatory response curve to the right

Cardiovascular System
Decrease SVR by peripheral vasodilatation
Baroreptor reflex slightly depressed
Dependent on dose and speed of injection
Decrease sympathetic tone
CVS depression is worsen if combined with opioid

Musculoskeletal System
Facilitation of brainstem inhibitory interneurons and interference with
interneuronal transmission at the spinal cord level

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No action on neuromuscular junction and does not decrease requirement for

NMBA

Midazolam vs Diazepam
1. Midazolam 3 - 4 times more potent e.g. 3 mg midazolam = 10 mg diazepam
2. Midazolam is much more expensive (TGH data)
3. Midazolam is pharmacokinetically different from diazepam (faster onset and
elimination). Less hangover.
4. Midazolam is water solubility
5. IV injection is painless
6. Can be given IM
7. No postoperative phlebitis
8. Profound amnestic effect (no recall of procedure)

Lorazepam
4 times potency of diazepam
long clinical duration of action (3-4 times that of diazepam) despite shorter half-
life (about 12 hours) [related to volume of distribution]
good for night sedation
Amnesia is of slower onset than its sedative effect (latency about ½ hour)
No correlation between plasma drug levels and amnestic vs sedative effects
2 mg IV yields: 3 hrs sedation, 30 min amnesia
4 mg IV yields: 4 hrs sedation, 4-6 hrs amnesia
Lorazepam is the only benzodiazepine with a significant amnestic effect at low
doses given orally.

Toxicity
1. Excessive drowsiness
2. Muscle weakness
3. Ataxia
4. Nystagmus
5. Dysarthria
6. Respiratory depression

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7. Baby – hyponia, respiratory depression

Flumazenil
a 1,4-imidazobenzodiazepine derivative
benzodiazepine antagonist with a high affinity for benzodiazepine receptors,
minimal agonist activity
reverses, in a dose-dependent manner, in the order of
anaesthesia
muscle relaxation
anterograde amnesia
sedation
anticonvulsant
anxiolysis

Not accompanied by anxiety, hypertension, tachycardia, or neuroendocrine

evidence of a stress response (could be due to intrinsic agonist activity)
Recommended initial dose is 0.2 mg IV (onset within about 2 minute), maximum
of 1 mg
The duration of action of flumazenil is 30 to 60 minutes, and supplemental doses
of the antagonist may be needed to maintain the desired level of consciousness.

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KETAMINE

Phencyclidine derivative that produces “dissociative anesthesia”

Characterized by evidence on the EEG of dissociation between the
thalamocortical and limbic systems
Resembles a cataleptic state in which the eyes remain open with a slow
nystagmic gaze
The patient is noncommunicative, although wakefulness may appear to be
present. The patient is amnesic, and analgesia is intense.
The possibility of emergence delirium may limit the clinical usefulness of
ketamine. Ketamine is considered a drug with abuse potential.

Structure Activity
(+) isomer (a) 3.5X more potent, (b) produces more intense analgesia, (c) more
rapid metabolism and thus recovery, and (d) a lower incidence of emergence
reactions than the (–).
Both isomers of ketamine appear to inhibit uptake of catecholamines back into
postganglionic sympathetic nerve endings

Mechanism of Action
Ketamine is a noncompetitive antagonist of the NMDA. This interaction appears
to be stereoselective, with the positive isomer of ketamine having the greatest
affinity
Also interacts opioid receptors, monoaminergic receptors, muscarinic receptors,
and voltage-sensitive calcium channels

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Recognition site Allosteric site

(glutamate, NMDA) (glycine) Phencyclidine and Ketamine binds here

Extracellular

Ion Resting
Membrane Channel (Channel Closed)

Intracellular

2+ 2+
Mg binds here and blocks Ca channel

Comparative Pharmacology

Elimination Vd (L/kg) Clearance Blood Heart Rate

T1/2 (hrs) (ml/kg/min) Pressure
Propofol 0.5-1.5 3.5-4.5 30-60 Decrease Decrease
Etomidate 2-5 2.2-4.5 10-20 No change No change
Ketamine 2-3 2.5-3.5 16-18 Increase Increase

Ketamine: Pharmacokinetics
pK of 7.5
Water soluble in acidic solution
Ampoule contains Ketamine Hydrochloride and Benzethonium Chloride
Lipid solubility 5X of thiopentone
IM: Therapeutic plasma conc within 5 mins (5-10 mg/kg)
Metabolism: Norketamine 10-30% potency of ketamine

Ketamine: Pharmacodynamics
Analgesia seen with low dose 0.25-0.5 mg/kg
Excellent analgesia for somatic, less for visceral structures
CNS: potent cerebral vasodilator capable of increasing cerebral blood flow by
60% in the presence of normocapnia; increase CMRO2, increase ICP

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Cardiovascular System
Direct stimulation of the CNS leading to increased sympathetic nervous system
outflow leading to increase HR, MAP, CI, PAP, TTI & MvO2.
Critically ill patients occasionally respond to ketamine with unexpected
decreases in systemic blood pressure and cardiac output, which may reflect
depletion of endogenous catecholamine stores and exhaustion of sympathetic
nervous system compensatory mechanisms, leading to an unmasking of
ketamine’s direct myocardial depressant effects
Ketamine has been shown to decrease the need for inotropic support in septic
patients, perhaps reflecting an inhibition of catecholamine reuptake
.
Respiratory System
Does not produce significant respiratory depression
High therapeutic index
Bronchodilatation
Increase mucus gland secretion
Upper airway muscle tone is preserved
Upper airway reflexes remained relatively intact but no guarantee against
aspiration

Emergence Delirium
May be associated with visual, auditory, proprioceptive, and confusional
illusions, which may progress to delirium. Cortical blindness may be transiently
present. Dreams and hallucinations can occur up to 24 hours; frequently have a
morbid content and are often experienced in vivid color.
Dreams and hallucinations usually disappear within a few hours.

Mechanisms
Emergence delirium probably occurs secondary to ketamine-induced depression
of the inferior colliculus and medial geniculate nucleus, leading to
misinterpretation of auditory and visual stimuli.

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The loss of skin and musculoskeletal sensations results in decreased ability to

perceive gravity, thereby producing a sensation of bodily detachment or floating
in space.

Incidence
Ranges from 5% to 30%
More common in (a) age >15 years
(b) female gender
(c) doses of ketamine of > 2 mg/kg IV
(d) a history of personality problems or frequent dreaming
Likewise, no significant long-term personality differences are present in adults
receiving ketamine compared with thiopental
Emergence delirium occurs less frequently when ketamine is used repeatedly.

Prevention
Benzodiazepines have proved the most effective in prevention of this
phenomenon, with midazolam being more effective than diazepam. A common
approach is to administer the benzodiazepine IV about 5 minutes before
induction of anesthesia with ketamine.
Inclusion of thiopental or inhaled anesthetics may decrease the incidence of
emergence delirium attributed to ketamine.
Conversely, the inclusion of atropine or droperidol in the preoperative medication
may increase the incidence of emergence delirium.
Despite contrary opinions, there is no evidence that permitting patients to
awaken from ketamine anesthesia in quiet areas alters the incidence of
emergence delirium.

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PROPOFOL
Called the hindered phenol because the 2 isopropyl side chains protect the
hydroxyl group (phenol is neurotoxic)
Formulation:
- 1% solution in an aqueous solution of
- 10% soybean oil
- 2.25% glycerol
- 1.2% purified egg phosphatide 2,6-diisopropyl-phenol
- sealed under Nitrogen

Pharmacokinetics
Can only be given intravenously
Ripid decline in propofol concentration is due to the extensive distribution and
elimination
High protein binding 98%
T1/2 2-5 mins, T1/2 1-3 hours (~ 54 mins), T1/2 20 -300 mins
Vdi 20-40 L, Vdss 3.5 – 4.5 L/kg
Cl 30-60 ml/kg/min
Metabolism: conjugation with glucuronides and sulphates, inactive metabolites
Clearance of propofol from the plasma exceeds hepatic blood flow, emphasizing
that tissue uptake (possibly into the lungs), as well as metabolism, is important in
removal of this drug from the plasma
No evidence of impaired elimination in patients with cirrhosis of the liver
Renal dysfunction does not influence the clearance of propofol
Patients older than 60 years of age exhibit a decreased rate of plasma clearance
of propofol

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Pharmacodynamics
Central Nervous System
Decreases cerebral metabolic rate for oxygen (CMRO2) ~ 26%, cerebral blood
flow, and intracranial pressure (ICP) 30-50%
Propofol produces cortical EEG changes that are similar to those of thiopental,
including the ability of high doses to produce burst suppression
Produces the same degree of memory impairment as midazolam
Delay in the disappearance of eyelash reflex and loss of verbal contact is a
better endpoint of onset of propofol anaesthesia
Not analgesic

Cardiovascular System
Propofol produces decreases in systemic blood pressure that are greater than
those evoked by comparable doses of thiopental
The relaxation of vascular smooth muscle produced by propofol is primarily due
to inhibition of sympathetic vasoconstrictor nerve activity
Propofol also effectively blunts the hypertensive response to placement of a
laryngeal mask airway.
Heart rate often remains unchanged

Lungs
1. Propofol produces dose-dependent depression of ventilation, with apnea
occurring in 25% to 35% of patients after induction of anesthesia with propofol.
Opioids administered with the preoperative medication may enhance this
ventilatory effect.

Nonhypnotic Therapeutic Applications

1. Antiemetic effects: 10 to 15 mg IV
2. Antipruritic effects: 10 mg IV, is effective in the treatment of pruritus
associated with neuraxial opioids or cholestasis
3. Anticonvulsant activity reflecting GABA-mediated presynaptic and postsynaptic
inhibition

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FANZCA March 1998. NON-ideal features of the current preparation of

propofol.

Pharmaceutical:
complexity of the solution and therefore expense
non-water solubility
susceptibility to bacterial contamination once the ampoule is opened
shelf-life and storage of glass ampoule
incompatibility with other solutions or substances which may go undetected
due to the nature of the presentation of propofol
commonly causes pain on injection.

Pharmacokinetics:
Intravenous preparation only
High volume of distribution and clearance but offset of action due to
redistribution
High protein binding and the potential for displacement reactions
Organ dependent metabolism
Propofol crosses the placenta

Pharmacodynamics:
Mode of action unknown
Not an analgesic
Not amnestic
No antagonists known
Potential for drug abuse

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ETOMIDATE

Carboxylated imidazole
aqueous solution of etomidate is unstable at
physiologic pH and is formulated in a 0.2%
solution, with 35% propylene glycol (pH 6.9)
contributing to a high incidence of pain during
IV injection and occasional venous irritation.

Pharmacokinetics
T1/2 3 mins, T1/2 2-9 hours
Cl 18-25 ml/kg/min
HER 0.5 to 0.9
Protein binding 50%
Metabolism: ester hydrolysis in plasma and liver

Pharmacodynamics
CNS: ICP 30% CBF 30%. Quick recovery. No hangover.
High incidence of excitatory phenomenon
CVS: minimal CVS depression
Resp: less respiratory depression comparatively
Endocrine: Suppression of adrenocortical function. Inhibit 17 - and 11 -hydroxylase

Side-effects
1. Pain on injection 50%
2. Excitatory phenomenon 70%
3. Nausea and vomiting 40-50%
4. Venous thrombosis 8%

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Advantages of Etomidate

1. CVS stability
2. Does not release histamine
3. Rapid recovery, no hangover
4. Decrease CMRO2
5. High Therapeutic Index
In animal studies Etomidate 26.4
Propanidid 6.7
Methohexitone 9.5
Althesin 30.6
Thiopentone 6.9
Ketamine 8.5

NEUROLEPTIC AGENTS
Characterized by trance-like (cataleptic) immobility in an outwardly tranquil
patient who is dissociated and indifferent to the external surroundings
Analgesia is intense, allowing performance of a variety of diagnostic and minor
surgical procedures
The disadvantages of neuro-leptanalgesia are prolonged CNS depression and
failure to depress sympathetic nervous system responses predictably to painful
stimulation
Droperidol combined with fentanyl is administered for the production of
neuroleptanalgesia. A commercially available 50:1 combination of droperidol
with fentanyl is known as Innovar.

Mode of Action
Butyrophenones occupy GABA receptor on post-synaptic membrane
dopamine on intersynaptic cleft.

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Side effects
Very long sedative effect
Agitation
Hallucination
Bizarre sensation and loss of bodily image
Extrapyramindal: Dyskinesia
Oculogyric crisis Rx: Benztropine
Opisthotonus
Akathisia
CVS: -blockade hypotension

PROPANIDID
Euglenol derivatives
Yellow colour
Solvent: Cremophor EL

Pharmacokinetics
50% protein bound
Hydrolysed by plasma cholinesterase, interactions with suxamethonium
Minimal cumulative effects

Pharmacodynamics
Rapid onset and recovery
No hangover
Not antanalgesic
Cardiovascular depression
Initial tachypnoea followed by apnoea
Excitatory phenomenon
Major hypersensitive reaction 1 : 1500

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ALTHESIN

A mixture of 2 steroids: Alphaxalone (potent but insoluble)

Alphadolone (solubilizing)
Solvent: Cremophor EL

Pharmacokinetics
30% protein bound
Glucuronidation in liver
Minimal cumulative effects

Pharmacodynamics
Rapid onset and recovery
No hangover
Excitatory phenomenon
Major hypersensitive reaction 1 : 1000

ELTANOLONE
Eltanolone is a naturally occurring metabolite of progesterone without significant
endocrine effects because of its low water solubility, it is necessary to formulate
eltanolone in an oil-water emulsion (Intralipid) identical to the solvent used for
propofol.
Emergence from anesthesia after ambulatory surgery is slower with eltanolone
compared with propofol
Eltanolone decreases cerebral blood flow and CMRO2
Pain at the injection site does not accompany IV administration of this drug, and
hiccoughs and cough are absent.
Mean arterial pressure decreases about 18%, heart rate increases about 19%
Apnea is infrequent
Safe and potentially useful new IV anesthetic.

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