Effect of etomidate on cortisol biosynthesis: site of action after induction of anaesthesia.
To determine the site of inhibition of etomidate on cortisol biosynthesis, plasma cortisol, aldosterone, 17 alpha-hydroxyprogesterone, 11-deoxycortisol and ACTH levels were measured in healthy women before and after the administration of a single dose of either 0.20 mg kg-1 etomidate (mean value, n = 10) or 3.15 mg kg-1 thiopental (n = 9) for induction of anaesthesia in a randomized trial. Etomidate produced a smaller increase in plasma cortisol and had a later onset of action than thiopental. Plasma ACTH levels, however, rose higher in the etomidate-induced patients to reach peak levels 6 h after drug administration. In the same group, plasma aldosterone remained below the control levels but still within the normal range, whereas it rose about 2-fold in the thiopental group. Plasma levels of 17 alpha-hydroxyprogesterone and 11 beta-deoxycortisol were hardly modified after thiopental but increased significantly and remained high for 6 h after etomidate injection. This marked rise in precursors together with a blunted and delayed cortisol response to high ACTH levels, and slightly lowered plasma aldosterone concentration indicates a blockage of 11 beta-hydroxylation in adrenal cortisol synthesis after induction of anaesthesia with etomidate.
D019326:17-alpha-Hydroxyprogesterone; D000311:Adrenal Glands / Q000187:drug effects* / Q000378:metabolism; D000324:Adrenocorticotropic Hormone / Q000097:blood; D000328:Adult; D000368:Aged; D000450:Aldosterone / Q000097:blood; D000771:Anesthesia, Intravenous; D002986:Clinical Trials as Topic; D003350:Cortodoxone / Q000097:blood; D005045:Etomidate / Q000494:pharmacology*; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000096:biosynthesis* / Q000097:blood; D006908:Hydroxyprogesterones / Q000097:blood; D008875:Middle Aged; D011897:Random Allocation; D013874:Thiopental / Q000494:pharmacology
D006908:Hydroxyprogesterones; D000450:Aldosterone; D019326:17-alpha-Hydroxyprogesterone; D000324:Adrenocorticotropic Hormone; D013874:Thiopental; D003350:Cortodoxone; D006854:Hydrocortisone; D005045:Etomidate