A patient with nephrogenic diabetes insipidus is started on hydrochlorothiazide. Despite being a diuretic, it reduces his urine output. The mechanism underlying this paradoxical antidiuretic effect is:
- A Increased ADH secretion from the posterior pituitary
- B Enhanced water permeability in the collecting duct
- C Volume depletion leading to increased proximal tubular reabsorption ✓
- D Direct inhibition of aquaporin-2 channels
Correct answer: C. Volume depletion leading to increased proximal tubular reabsorption
Explanation
Thiazides cause mild volume depletion, which activates the renin-angiotensin system and increases proximal tubular reabsorption of sodium and water. This reduces fluid delivery to the diluting segments, decreasing urine output. This paradoxical effect is useful in nephrogenic diabetes insipidus where ADH is ineffective.
Reference: Katzung Basic & Clinical Pharmacology, 14th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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