A 55-year-old man with small cell carcinoma and persistent hyponatraemia from syndrome of inappropriate ADH secretion fails fluid restriction. Which tetracycline derivative is used to manage his hyponatraemia, and what is its mechanism?

• A Minocycline, which blocks ADH release from the posterior pituitary
• B Tigecycline, which downregulates vasopressin V2 receptor expression
• C Doxycycline, which increases free water excretion by inhibiting aquaporin synthesis selectively
• D Demeclocycline, which induces nephrogenic diabetes insipidus by antagonising ADH action on the collecting duct ✓

Explanation

Demeclocycline produces a dose-dependent nephrogenic diabetes insipidus by blunting the ADH-driven insertion and action of aquaporin channels in the collecting duct. This undesirable property is exploited therapeutically in chronic SIADH when fluid restriction fails. It acts peripherally on the kidney rather than on pituitary ADH release, and no other tetracycline shares this effect to a clinically useful degree.

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

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Written and medically reviewed by the StethoPrep medical team.