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Chapter 13: Etomidate

The principal mechanism of action of etomidate is best described as:

(A) potentiation of GABA-mediated chloride currents

(B) stimulation of μ- and κ-opioid receptors

(C) stimulation of α2-adrenergic receptors

(D) inhibition of NMDA receptors

(E) blockade of CNS sodium channels

The answer is A. Etomidate is an imidazole-containing anesthetic that is structurally unlike other intravenous anesthetics (Figure 13-1).


FIG. 13-1. Structural formula of etomidate showing imidazole ring with two nitrogen atoms.

The mechanisms by which etomidate produce unconsciousness are somewhat unclear, but appear to primarily involve activation of GABAA receptor, increasing transmembrane chloride conductance. This hyperpolarizes the postsynaptic cell membrane and results in inhibition of postsynaptic neuron. While the GABAA receptor is made up of a combination of five subunits, the β2- and β3-subunits appear to be most important for its effect, and etomidate will selectively potentiate receptors containing these subunits. Etomidate has no analgesic activity.

Ref: Miller RD. Miller's Anesthesia. 8th ed. Philadelphia, PA: Elsevier; 2015.

In order to increase its water solubility, etomidate is formulated with which of the following compounds?

(A) glycerol

(B) benzyl alcohol

(C) sodium bisulfite

(D) propylene glycol

(E) methylparaben

The answer is D. Glycerol is one component of the aqueous emulsion used to carry propofol (the other being soy oil and egg phosphatide). Benzyl alcohol and methylparaben are both preservative agents used in intravenous medications. Sodium bisulfite is a reducing agent used to prevent oxidation of drugs.

In the United States, etomidate is supplied as a 2 mg/mL solution in 35% propylene glycol. It has a pH of 6.9 and, unlike sodium thiopental, does not precipitate when mixed with other drugs. Propylene glycol is associated with pain on injection, and the incidence of pain with this formulation of etomidate is up to 50%. A lipid formulation available in Europe may decrease this side effect.

Ref: Miller RD. Miller's Anesthesia. 8th ed. Philadelphia, PA: Elsevier; 2015.

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