Tolvaptan is a vaptane used for hyponatraemia in SIADH. Its mechanism of action is:

• A Inhibition of the epithelial sodium channel (ENaC) in the collecting duct, reducing sodium reabsorption
• B Inhibition of Na+/K+/ATPase in the collecting duct principal cells
• C Activation of renal prostaglandin synthesis, reducing collecting duct water permeability
• D Selective V2 vasopressin receptor antagonism in the collecting duct, blocking ADH-mediated aquaporin-2 insertion and producing electrolyte-free water diuresis (aquaresis) ✓

Explanation

Tolvaptan is an oral, selective V2 receptor antagonist. Vasopressin (ADH) normally binds V2 receptors in the collecting duct, activating adenylyl cyclase → cAMP → PKA, which phosphorylates and inserts aquaporin-2 water channels in the apical membrane, enabling water reabsorption. Tolvaptan blocks V2 receptors, preventing aquaporin-2 insertion and producing 'aquaresis' (electrolyte-free water excretion), which raises serum sodium in dilutional hyponatraemia (SIADH, heart failure, cirrhosis). It is rate-limited in correction speed to avoid osmotic demyelination syndrome. ENaC inhibition is the mechanism of amiloride. Na+/K+/ATPase is the target of ouabain/cardiac glycosides.

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

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Written and medically reviewed by the StethoPrep medical team.