Demeclocycline, an older tetracycline, is used off-label for SIADH because it induces nephrogenic diabetes insipidus. Which site of the nephron does it act on to antagonise ADH?

• A Proximal convoluted tubule
• B Collecting duct principal cells (V2 receptor / aquaporin-2 pathway) ✓
• C Thick ascending limb of the loop of Henle
• D Distal convoluted tubule

Explanation

Demeclocycline inhibits the ADH-V2 receptor-aquaporin-2 signalling cascade in the principal cells of the collecting duct, preventing water reabsorption and producing nephrogenic diabetes insipidus. This is a unique pharmacological use of demeclocycline distinct from its antibacterial properties. It is the tetracycline of choice for SIADH because it reliably causes this effect. Desmopressin resistance at the collecting duct is the mechanism. The other tubular segments are incorrect targets.

Reference: Goodman and Gilman's The Pharmacological Basis of Therapeutics, 14th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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