A 30-year-old woman on lithium carbonate for bipolar disorder presents with polyuria of 6 litres/day. Urine osmolality fails to rise adequately after water deprivation, and serum sodium is 148 mEq/L. Which single drug best targets the defect while preserving lithium therapy?
- A Amiloride ✓
- B Desmopressin
- C Furosemide
- D Hydrochlorothiazide alone without any other adjustment
Correct answer: A. Amiloride
Explanation
Lithium accumulates in collecting duct principal cells through ENaC-mediated sodium entry and antagonises vasopressin signalling, causing nephrogenic diabetes insipidus. Amiloride blocks the epithelial sodium channel, reducing lithium entry into these cells and directly reversing polyuria even during continued lithium use, making it the preferred targeted therapy. Desmopressin is ineffective because the receptor pathway is refractory, and thiazides work indirectly by volume depletion and are not the specific antidote.
Reference: Harrison Principles of Internal Medicine, 21st ed.
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