A patient with heart failure and moderate hyponatremia (Na+ = 128 mEq/L) related to inappropriate ADH secretion is started on tolvaptan. Unlike loop diuretics, tolvaptan corrects hyponatremia without worsening hypokalemia because it:

• A Inhibits the NKCC2 cotransporter in the thick ascending limb, diluting the medullary gradient selectively
• B Selectively blocks V2 receptors in the collecting duct, causing excretion of free water (aquaresis) without electrolyte loss ✓
• C Activates V1a receptors in the proximal tubule, promoting sodium reabsorption while losing water
• D Blocks aquaporin-2 (AQP2) channels directly rather than through receptor antagonism

Explanation

Tolvaptan is a selective oral V2-receptor antagonist (vaptans). ADH/vasopressin acts on V2 receptors in collecting duct principal cells to insert aquaporin-2 channels, enabling water reabsorption. By blocking V2 receptors, tolvaptan prevents aquaporin-2 insertion, causing excretion of large volumes of electrolyte-poor free water (aquaresis). This corrects dilutional hyponatremia without removing electrolytes like sodium or potassium (unlike loop diuretics which cause natriuresis, kaliuresis).

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

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Written and medically reviewed by the StethoPrep medical team.