A 58-year-old man on lithium for bipolar disorder for 12 years reports polyuria of 6 L/day and polydipsia. Serum sodium 146 mEq/L, urine osmolality 110 mOsm/kg, which fails to rise after desmopressin. Which drug is the preferred long-term agent to reduce his urine volume?

• A Hydrochlorothiazide
• B Desmopressin at higher dose
• C Indomethacin
• D Amiloride ✓

Explanation

Lithium enters principal cells through ENaC sodium channels and impairs aquaporin-2 trafficking, causing nephrogenic diabetes insipidus confirmed by absent response to desmopressin. Amiloride blocks ENaC, reducing lithium entry into collecting duct cells, so it treats the cause and is the preferred chronic agent. Thiazides cause volume contraction and compensatory proximal reabsorption and are second line. Desmopressin cannot work because the defect is downstream of the V2 receptor.

Reference: Harrison's Principles of Internal Medicine, 21st ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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