A 55-year-old man on cimetidine for peptic ulcer disease develops gynaecomastia, and his steady-state plasma concentration of warfarin rises above the therapeutic range. Both findings are explained by which properties of cimetidine?

• A Competitive displacement of warfarin from albumin and direct estrogen receptor stimulation
• B Induction of cytochrome P450 enzymes and prolactin excess
• C Blockade of gastric H2 receptors leading to malabsorption of vitamin K
• D Antiandrogenic activity and inhibition of hepatic cytochrome P450 enzymes ✓

Explanation

Cimetidine binds androgen receptors and has weak antiandrogenic effects, producing gynaecomastia, impotence and reduced libido, particularly with prolonged use or in elderly men. It is also a non-selective inhibitor of several cytochrome P450 isoforms, reducing clearance of drugs such as warfarin, phenytoin, theophylline and diazepam. Ranitidine and famotidine lack both properties, which is why they replaced cimetidine. Options B, C and A describe mechanisms cimetidine does not possess.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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