Pharmacology · Corticosteroids and Sex Hormones (OCPs, Androgens)

Ketoconazole was formerly used orally in Cushing syndrome before hepatotoxicity limited its use. Its endocrine action is best described as:

  • A Inhibition of cytochrome P450-dependent enzymes of steroidogenesis, including CYP17A1
  • B Competitive antagonist at the glucocorticoid receptor
  • C Blockade of ACTH receptors on zona fasciculata cells
  • D Irreversible inhibition of 5-alpha reductase
Correct answer: A. Inhibition of cytochrome P450-dependent enzymes of steroidogenesis, including CYP17A1

Explanation

Ketoconazole inhibits several cytochrome P450 steroidogenic enzymes, notably CYP17B1 (17-alpha-hydroxylase and 17,20-lyase) and also cholesterol side-chain cleavage, thereby reducing cortisol and androgen synthesis. This is a blockade of hormone production, not receptor antagonism, which distinguishes it from mifepristone at the glucocorticoid receptor.

Reference: Goodman and Gilman's The Pharmacological Basis of Therapeutics, 13th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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