A 65-year-old woman on low-dose aspirin for secondary prevention of MI is started on a selective COX-2 inhibitor (celecoxib) for osteoarthritis. The combination is potentially harmful because:
- A Celecoxib displaces aspirin from COX-1 binding, blocking aspirin's irreversible platelet inhibition and increasing thrombotic risk
- B The combination increases gastric acid secretion by additive inhibition of COX-2 in parietal cells
- C Celecoxib reduces renal prostaglandin synthesis, causing sodium retention and worsening heart failure ✓
- D Celecoxib inhibits aspirin's hepatic metabolism, increasing aspirin toxicity to hepatocytes
Explanation
All NSAIDs (including selective COX-2 inhibitors) inhibit renal prostaglandin (PGE2, PGI2) synthesis. These prostaglandins normally maintain afferent arteriolar tone in the kidney, particularly under low-flow states. Their inhibition reduces GFR, promotes sodium and water retention, increases blood pressure, and can precipitate or worsen heart failure—counteracting the benefits of aspirin's cardiovascular protection. COX-2 inhibitors also reduce vascular PGI2 without reducing platelet TXA2 (which is COX-1-mediated), creating a prothrombotic imbalance. COX-2 inhibitors do not competitively displace aspirin from platelet COX-1 because aspirin irreversibly acetylates COX-1.
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
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Written and medically reviewed by the StethoPrep medical team.