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Etomidate and Etomidate Analogues: Molecular Pharmacology and Behavioral Actions

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Total Intravenous Anesthesia and Target Controlled Infusions

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Abstract

Etomidate is an imidazole-based anesthetic induction agent that is highly valued for its ability to maintain respiratory drive and hemodynamic stability even in critically ill patients. However, its ability to potently suppress adrenocortical steroid synthesis significantly limits its clinical use. This suppression is long-lived, lasting for many hours or even days following a single etomidate bolus dose. Two molecular design strategies have been developed to produce etomidate analogues with reduced ability to suppress adrenocortical function.  One strategy is pharmacokinetic in nature: to append a metabolically-labile ester moiety to etomidate’s structure so that it is ultra-rapidly metabolized by non-specific esterases. The other strategy is pharmacodynamic in nature: to modify etomidate’s molecular structure to selectively and substantially reduce its binding to 11ß-hydroxylase, a critical enzyme in the steroid biosynthetic pathway that is very potently inhibited by etomidate.  The goal of this chapter is to review the pharmacology of etomidate and to present recently published data obtained using novel etomidate analogues that were designed to have reduced impact on adrenocortical function.

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Acknowledgment

This is supported by grant R01-GM087316 from the National Institutes of Health, Bethesda, MD, and the Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital, Boston, Massachusetts.

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  1. Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital, 55 Fruit Street, GRB444, Boston, MA, 02114, USA

    Douglas E. Raines MD

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  1. Douglas E. Raines MD
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Correspondence to Douglas E. Raines MD .

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  1. Department of Anesthesiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands

    Anthony R. Absalom

  2. Department of Anesthesia, Harvard Medical School, Department of Anesthesiology, Perioperative and Pain Medicine, Boston Children’s Hospital, Boston, Massachusetts, USA

    Keira P. Mason

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Raines, D.E. (2017). Etomidate and Etomidate Analogues: Molecular Pharmacology and Behavioral Actions. In: Absalom, A., Mason, K. (eds) Total Intravenous Anesthesia and Target Controlled Infusions. Springer, Cham. https://doi.org/10.1007/978-3-319-47609-4_12

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  • DOI: https://doi.org/10.1007/978-3-319-47609-4_12

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