Tolvaptan is used in hyponatraemia associated with SIADH and in autosomal dominant polycystic kidney disease (ADPKD). Its mechanism is:

• A Selective antagonism of vasopressin V2 receptors in the collecting duct, blocking aquaporin-2 insertion and causing aquaresis (electrolyte-free water excretion) ✓
• B Inhibition of Na+/K+/2Cl- cotransporter (NKCC2) in the thick ascending limb, producing free water loss
• C Inhibition of the epithelial sodium channel (ENaC) in the collecting duct, reducing Na+ reabsorption and indirectly reducing water reabsorption
• D Competitive inhibition of vasopressin synthesis in the posterior pituitary

Explanation

Tolvaptan is an oral V2 receptor antagonist (vaptans class). Vasopressin normally binds V2 receptors in principal cells of the collecting duct, triggering cAMP-mediated aquaporin-2 (AQP2) insertion into the apical membrane and water reabsorption. By blocking V2 receptors, tolvaptan prevents AQP2 insertion, causing excretion of electrolyte-free water (aquaresis) — raising plasma sodium in SIADH. In ADPKD, cyst growth is partly driven by cAMP-mediated tubular cell proliferation; V2 blockade reduces cAMP and slows cyst progression.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.