A patient on chronic lithium therapy develops polyuria and polydipsia with urine specific gravity 1.003 that persists after lithium withdrawal. Which drug directly addresses the tubular defect caused by lithium?

• A Desmopressin
• B Amiloride ✓
• C Furosemide
• D Hydrochlorothiazide plus salt restriction only

Explanation

Lithium enters collecting duct principal cells through the epithelial sodium channel (ENaC) and downregulates aquaporin-2 expression, producing nephrogenic diabetes insipidus that is unresponsive to vasopressin. Amiloride blocks ENaC, preventing further lithium entry and partially restoring water handling, so it is the specific pharmacologic therapy. Desmopressin fails precisely because the defect is post-receptor. Thiazides help by volume contraction but do not reverse the channel defect.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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