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The role of ascorbic acid in etomidate toxicity.
European Journal of Anaesthesiology
|September 1, 1986
Summary
Etomidate, an anesthetic, blocks steroidogenesis by inhibiting cytochrome P450 and depleting ascorbic acid (vitamin C) in humans and guinea pigs. Ascorbic acid supplementation can reverse these effects, suggesting a link between vitamin C metabolism and etomidate
Area of Science:
- Biochemistry
- Pharmacology
- Endocrinology
Background:
- Etomidate is a short-acting hypnotic anesthetic.
- Etomidate blocks steroidogenesis in humans.
- Serious side effects are observed in humans and guinea pigs.
Purpose of the Study:
- To investigate the mechanism by which etomidate blocks steroidogenesis.
- To explore the role of ascorbic acid in etomidate-induced side effects.
Main Methods:
- Review of existing literature on etomidate's effects.
- Analysis of the interaction between etomidate, cytochrome P450, and ascorbic acid metabolism.
Main Results:
- Etomidate's imidazole radical binds to cytochrome P450, inhibiting steroidogenesis.
- Humans and guinea pigs, unlike other species, rely on dietary vitamin C and resynthesis.
- Ascorbic acid, not ACTH, increased cortisol during etomidate infusion and restored the ACTH/cortisol ratio.
Conclusions:
- Etomidate likely blocks ascorbic acid metabolism by inhibiting cytochrome P450-dependent resynthesis.
- Depletion of ascorbic acid pools leads to inhibited steroidogenesis in humans and guinea pigs.
- Species that can synthesize ascorbic acid are less susceptible to these effects.