Tolvaptan is used in autosomal dominant polycystic kidney disease (ADPKD). Its mechanism to slow cyst growth involves:
- A Antagonism of V2 vasopressin receptors in the collecting duct, reducing cAMP and blocking cyst fluid accumulation ✓
- B Blockade of aldosterone receptors in principal cells reducing potassium-wasting
- C Inhibition of carbonic anhydrase in cyst epithelium reducing bicarbonate-driven fluid secretion
- D mTOR inhibition in tubular epithelial cells reducing cellular proliferation in cysts
Explanation
Tolvaptan is a selective, oral V2 receptor antagonist (vaptans). In ADPKD, dysregulated cAMP signalling (downstream of vasopressin V2-receptor activation) drives both tubular epithelial cell proliferation and transepithelial fluid secretion into cysts. Blocking V2 receptors reduces renal cAMP, slowing cyst cell proliferation and fluid accumulation. Tolvaptan is the only FDA-approved disease-modifying agent for ADPKD. It causes aquaresis (free water loss without significant electrolyte loss). Option D describes rapamycin/sirolimus, which did not show benefit in ADPKD trials.
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.