A 34-year-old man on long-term lithium for bipolar disorder develops polyuria with serum sodium of 148 mEq/L. Urine osmolality fails to rise after desmopressin administration. Which drug addresses the underlying tubular defect?
- A Hydrochlorothiazide alone
- B Indomethacin
- C Amiloride ✓
- D Demeclocycline
Correct answer: C. Amiloride
Explanation
Lithium enters principal cells through ENaC sodium channels and impairs vasopressin-mediated aquaporin-2 insertion, producing nephrogenic diabetes insipidus. Amiloride blocks ENaC, preventing lithium entry into the tubular cell and allowing partial recovery of concentrating ability, so it treats the cause rather than just the symptom. HCTZ induces mild volume contraction that reduces free water excretion but does not correct the defect. Demeclocycline worsens it by inducing further resistance to vasopressin.
Reference: Katzung Basic and Clinical Pharmacology, 15th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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