A 55-year-old man with syndrome of inappropriate ADH secretion is given demeclocycline to manage his hyponatremia. The pharmacological action that makes demeclocycline useful here is:

• A It increases free water reabsorption by upregulating aquaporin-2 channels
• B It enhances hypothalamic osmoreceptor sensitivity and suppresses ADH release
• C It antagonizes vasopressin V2 receptors in the collecting duct, producing nephrogenic diabetes insipidus ✓
• D It inhibits renin release, reducing angiotensin-mediated thirst

Explanation

Demeclocycline induces a state of nephrogenic diabetes insipidus by blocking the antidiuretic action of ADH at the collecting duct, reducing water reabsorption and correcting dilutional hyponatremia in SIADH. It acts distally at the tubular response level rather than on ADH secretion itself. Its slow onset of several days limits clinical use compared with vaptans, but it remains the classic textbook answer. Upregulating aquaporin-2 would worsen hyponatremia, which eliminates option A.

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

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