A patient on furosemide for heart failure has been given regular NSAIDs post-surgery for pain. His urine output drops markedly. The mechanism of NSAID-furosemide interaction reducing diuretic efficacy is:

• A NSAIDs inhibit CYP2C9 reducing furosemide metabolism and paradoxically increasing its plasma half-life
• B NSAIDs directly block the NKCC2 cotransporter in the thick ascending limb independently of furosemide
• C NSAIDs cause sodium retention via aldosterone-independent mechanisms overwhelming furosemide's natriuresis
• D NSAIDs inhibit prostaglandin-mediated renal vasodilation and reduce furosemide's renal tubular secretion by competing for OAT transporters ✓

Explanation

NSAIDs blunt furosemide's diuretic response through two synergistic mechanisms: first, furosemide reaches its site of action (NKCC2 on the luminal side of thick ascending limb) via tubular secretion by OAT1/OAT3 transporters, and NSAIDs compete for these transporters reducing furosemide delivery to its site of action; second, furosemide's diuretic efficacy partly depends on prostaglandin-mediated renal vasodilation (PGE2 maintains glomerular perfusion) — NSAIDs abolishing prostaglandin synthesis reduce GFR and attenuate the natriuretic response. Both mechanisms together produce clinically significant diuretic resistance.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.