ETOMIDATE

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mechanism of action
structure-activity relationships
pharmacokinetic
effects on organ systems
drug interactions

MECHAMISM OF ACTION
-depresses reticular activating system (RAS)
-mimics the inhibitory effects of GABA primarily binding to GABA type A receptor
-associated with myoclonus incidence of 30-60% due to disinhibitory effects on the extrapyramidal motor system

STRUCTURE-ACTIVITY RELATIONSHIPS

-carboxylated imidazole ring
-lipid solubility at physiologic pH
-water soluable at acidic pH
-usually pain on injection due to propylene glycol in which etomidate is dissolved in

PHARMACOKINETICS

Absorption
-only in intravenous form
-used primarily for induction of general anesthesia

Distribution
-very rapid onset of action due to high lipid solubility and high nonionized fraction at physiologic pH
-rapid emergence is due to redistribution leading to decreasing plasma concentrations

Biotransformation
-rapid hydrolysis of etomidate to inactive metabolites by the hepatic microsomal enzymes and plasma esterases
-rate of biotransformation of etomidate is five times more rapid than for thiopenthal

Excretion
-primarily excreted in the urine

PHARMACODYNAMICS

Effects on Organ Systems

Central nervous system
-decreases CMR02
-decreases CBF
-decreases ICP
-generally well maintained CePP due to minimal CVS effects
-enhances somatosensory evoked potentials (SSEP)
-naseau and vomitting more common with etomidate than other induction agents

Cardiovascular system
-minimal effects on CVS
-may have a slight decline in MAP due to mild reduction in the peripheral vascular resistance
-myocardial contractility and cardiac output generally well maintained
-not associated with histamine release

Respiratory system
-less effect on ventilation than other induction agents (ex. barbiturates,benzodiazepines and propofol)
-often induction doses of etomidate when used alone may still not result in apnea

Endocrine system
-enzymes involved in cortisol and aldosterone synthesis may transiently inhibited with induction doses of etomidate
-adrenocortical suppresion may occur with long term infusion of etomidate

Drug Interactions

Fentanyl: increases both plasma levels and half life of etomidate
Opiods: decreases myoclonus of etomidate induction