A 40-year-old man on lithium develops polyuria of 6 L/day unresponsive to desmopressin, consistent with nephrogenic diabetes insipidus. The drug that directly targets the underlying mechanism is:

• A Hydrochlorothiazide
• B Indomethacin
• C Chlorpropamide
• D Amiloride ✓

Explanation

Lithium enters collecting duct principal cells through ENaC sodium channels and impairs vasopressin-mediated aquaporin-2 expression. Amiloride blocks ENaC, reducing intracellular lithium entry and directly reversing the concentrating defect, making it the specific antidote-like therapy. Thiazides produce mild volume contraction that secondarily reduces urine volume but do not address the mechanism, and NSAIDs only blunt prostaglandin-mediated dilution. Desmopressin fails because the post-receptor pathway itself is impaired.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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