Tolvaptan is used in hyponatremia associated with SIADH and in ADPKD. Its mechanism of action is best described as:

• A Osmotic diuretic that increases tubular fluid osmolality in the proximal tubule and descending loop, promoting water excretion
• B Inhibitor of aquaporin-2 (AQP2) channel synthesis by blocking gene transcription in collecting duct cells
• C V1 vasopressin receptor antagonist that reduces systemic vascular resistance and promotes free water excretion
• D Selective V2 vasopressin receptor antagonist ('aquaretic') that blocks ADH-mediated water reabsorption in collecting duct principal cells without causing electrolyte loss ✓

Explanation

Tolvaptan (and other vaptans — conivaptan, lixivaptan) are selective V2 receptor antagonists that competitively block ADH (vasopressin) binding at the basolateral membrane of collecting duct principal cells. Without V2 activation, adenylyl cyclase is not stimulated, cAMP does not rise, PKA does not phosphorylate aquaporin-2 vesicles, and AQP2 is not inserted into the apical membrane. The result is free water excretion (aquaresis) without urinary loss of sodium or potassium, making vaptans specifically useful for euvolemic and hypervolemic hyponatremia (SIADH, heart failure, cirrhosis).

Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.