(A) Metyrapone [?]METYRAPONE is an inhibitor of endogenous adrenal corticosteroid synthesis used in the treatment of hypercortocolism.oMechanism of action: Selectively inhibits11-b-hydroxylase, which converts 11-deoxycortisol to cortisol in the terminal reaction of the glucocorticoid biosynthetic pathway.oBecause of this inhibition, the biosynthesis of cortisol is markedly Impaired, and the levels of steroid precursors (e.g., 11- deoxycortisol) are markedly increased which can be used as a diagnostic test to assess hypothalamic-pituitary ACTH function.oMetyrapone is used: To treat the hypercorticism resulting from either adrenal neoplasms or tumors producing ACTH ectopically. As adjunctive therapy in patients who have received pituitary irradiation or in combination with other agents that inhibit steroidogenesis.oChronic administration of metyrapone can cause hirsutism (due to increased synthesis of adrenal androgens upstream from the enzymatic block) and hypertension, which results from elevated levels of 11-deoxycortisol.oOther side effects include nausea, headache, sedation, and rash.[?]Glucocorticoids antagonistsoMitotane: Structure similar to DDT, used in inoperable adrenal cancer.oMetyrapone: Inhibit 11 b-hydroxylaseoAminoglutethamide: Inhibit conversion of cholesterol to pregnolone, medical adrenelectomyoTrilostane: Inhibit conversion, of pregnolone to progesterone; used in Cushing's syndromeoKetoconazole: Anti-fungal, inhibit CYP450 enzymes, inhibit steroid synthesis in adrenal cortex and testis; used in Cushing's syndrome and carcinoma prostate.oMifepristone: Glucocorticoid receptor antagonists; anti-progesterone, used in Cushing's syndrome