Clinical and Molecular Pharmacology of Etomidate

• Published in: Anesthesiology (Philadelphia) 2011-03, Vol.114 (3), p.695-707
• Main Author: FORMAN, Stuart A
• Format: Article
• Language: English
• Subjects: Adrenal Cortex Hormones - antagonists & inhibitors; Anesthesia; Anesthesia, Intravenous; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Anesthetics, Intravenous - administration & dosage; Anesthetics, Intravenous - pharmacology; Anesthetics, Intravenous - therapeutic use; Animals; Animals, Genetically Modified - physiology; Biological and medical sciences; Etomidate - administration & dosage; Etomidate - adverse effects; Etomidate - pharmacology; Etomidate - therapeutic use; Hemodynamics - drug effects; Humans; Hypnotics and Sedatives - administration & dosage; Hypnotics and Sedatives - adverse effects; Hypnotics and Sedatives - pharmacology; Hypnotics and Sedatives - therapeutic use; Medical sciences; Mutation - physiology; Receptors, Adrenergic - drug effects; Receptors, GABA-A - drug effects; Receptors, GABA-A - genetics; Receptors, GABA-A - physiology; Steroids - biosynthesis
• ISSN: 0003-3022; 1528-1175
• DOI: 10.1097/ALN.0b013e3181ff72b5

This review focuses on the unique clinical and molecular pharmacologic features of etomidate. Among general anesthesia induction drugs, etomidate is the only imidazole, and it has the most favorable therapeutic index for single-bolus administration. It also produces a unique toxicity among anesthetic drugs: inhibition of adrenal steroid synthesis that far outlasts its hypnotic action and that may reduce survival of critically ill patients. The major molecular targets mediating anesthetic effects of etomidate in the central nervous system are specific γ-aminobutyric acid type A receptor subtypes. Amino acids forming etomidate binding sites have been identified in transmembrane domains of these proteins. Etomidate binding site structure models for the main enzyme mediating etomidate adrenotoxicity have also been developed. Based on this deepening understanding of molecular targets and actions, new etomidate derivatives are being investigated as potentially improved sedative-hypnotics or for use as highly selective inhibitors of adrenal steroid synthesis.