A 70-year-old man on famotidine for dyspepsia is switched to cimetidine by mistake. Within weeks he reports gynecomastia, and his warfarin INR rises sharply. These two problems are explained by cimetidine's:

• A Antiandrogenic activity and strong inhibition of cytochrome P450 enzymes including CYP3A4 and CYP2C9 ✓
• B Blockade of histamine H2 receptors in breast tissue and induction of CYP2C9
• C Competitive displacement of warfarin from albumin and estrogen receptor agonism
• D Renal tubular secretion competition with warfarin and prolactin elevation

Explanation

Cimetidine binds peripheral androgen receptors weakly and inhibits testosterone dihydrotestosterone effects, producing gynecomastia and impotence with prolonged use. It is also a potent nonselective inhibitor of multiple CYP450 isoforms, markedly raising levels of narrow-index drugs such as warfarin, phenytoin, and theophylline. Famotidine and ranitidine lack both properties, which is why they replaced cimetidine clinically.

Reference: Katzung's Basic and Clinical Pharmacology, 15th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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