A patient with cirrhosis and resistant ascites is started on tolvaptan. Its mechanism of action and the specific FDA black box warning are:
- A Tolvaptan is a V1a receptor antagonist reducing splanchnic vasoconstriction, improving portal hypertension; black box warning is for rapid sodium correction causing osmotic demyelination syndrome
- B Tolvaptan is an aldosterone receptor antagonist reducing sodium reabsorption; FDA warning is for hyperkalaemia in CKD patients
- C Tolvaptan is a selective V2 receptor antagonist (vaptans) that blocks vasopressin-mediated aquaporin-2 insertion into collecting duct principal cells, causing free water excretion (aquaresis) without electrolyte loss; FDA warning: risk of acute liver failure in cirrhotic patients — use for ≤30 days only for hyponatraemia of cirrhosis ✓
- D Tolvaptan blocks ENaC channels in the collecting duct, causing potassium-sparing natriuresis; black box warning is for prolonged QT interval
Explanation
Tolvaptan selectively antagonises the vasopressin V2 receptor (renal collecting duct), preventing AVP-stimulated cAMP production and subsequent PKA-mediated aquaporin-2 (AQP2) phosphorylation, insertion into the apical membrane, and water reabsorption. The result is 'aquaresis' — excretion of electrolyte-free water — which corrects dilutional hyponatraemia without worsening electrolyte losses. The FDA issued a black box warning specifically for hepatotoxic liver injury in cirrhotic patients (TEMPO trial in ADPKD showed hepatotoxicity risk); tolvaptan is restricted to ≤30 days for hyponatraemia of cirrhosis. Over-rapid correction of sodium (>12 mEq/L in 24h) with any agent risks osmotic demyelination syndrome, requiring careful monitoring.
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
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Written and medically reviewed by the StethoPrep medical team.