Tolvaptan is a selective vasopressin V2 receptor antagonist (vaptан) used for hyponatraemia in SIADH. Why is it CONTRAINDICATED in hypovolaemic hyponatraemia?

• A Tolvaptan reduces sodium reabsorption at the thick ascending limb, worsening sodium loss
• B Blocking V2 receptors in already volume-depleted patients promotes free water excretion (aquaresis), worsening volume depletion without correcting the underlying cause ✓
• C Tolvaptan cross-reacts with V1a receptors causing vasoconstriction and reducing renal perfusion
• D In hypovolaemia, tolvaptan inhibits aldosterone secretion, worsening hyponatraemia further

Explanation

Tolvaptan promotes excretion of electrolyte-free water (aquaresis) by blocking V2 receptors in the collecting duct, preventing water reabsorption. In hypovolaemic hyponatraemia (e.g., from vomiting, diarrhoea, diuretics), the elevated ADH is an appropriate compensatory response to maintain perfusion — blocking it would cause further free water loss, worsening volume depletion and potentially leading to haemodynamic compromise without addressing the true sodium deficit. Tolvaptan is appropriate for euvolaemic (SIADH) or hypervolaemic (heart failure, cirrhosis) hyponatraemia.

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

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