A 55-year-old man on high-dose cimetidine for peptic ulcer disease develops gynaecomastia and impotence over several weeks. The underlying property of cimetidine responsible is:

• A Accumulation of the drug causing hypothalamic H2 receptor stimulation
• B Direct estrogen agonism at breast tissue receptors
• C Hyperprolactinaemia secondary to dopamine antagonism
• D Antiandrogenic activity at the androgen receptor plus inhibition of hepatic CYP450 enzymes ✓

Explanation

Cimetidine binds peripheral androgen receptors and acts as a weak antiandrogen, producing gynaecomastia, impotence and loss of libido, particularly in older men on high doses or prolonged therapy. It is also a potent inhibitor of multiple hepatic cytochrome P450 enzymes, raising levels of warfarin, phenytoin, theophylline and other drugs. Ranitidine, famotidine and nizatidine lack both the antiandrogen effect and significant CYP inhibition, which is why they replaced cimetidine in practice.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.