## Adverse Effects and Drug Interactions of NSAIDs **Key Point:** NSAIDs carry significant cardiovascular, renal, gastrointestinal, and haematological risks. Concurrent use with anticoagulants is a major safety concern. ### Renal Adverse Effects **High-Yield:** NSAIDs reduce renal blood flow by inhibiting prostaglandin E₂ and prostacyclin, which normally cause afferent arteriolar vasodilation. - Decreased glomerular filtration rate (GFR) - Acute kidney injury, especially in volume-depleted or elderly patients - Hyperkalemia (reduced renal K⁺ excretion) - Sodium and water retention → hypertension, oedema, heart failure exacerbation - **Contraindicated in severe renal impairment (eGFR < 30 mL/min/1.73m²)** ✓ (Statement 1 is correct) ### Cardiovascular Adverse Effects **Clinical Pearl:** NSAIDs increase thrombotic cardiovascular events via two mechanisms: 1. **COX-2 selective inhibitors** → unopposed thromboxane A₂ (TXA₂) production in platelets → prothrombotic state 2. **Non-selective NSAIDs** → inhibit protective prostacyclin in endothelium → increased atherothrombotic risk - Increased risk of MI, stroke, and stent thrombosis - Risk rises with prolonged duration and higher doses - ~~Aspirin is protective~~ — NSAIDs actually antagonise aspirin's antiplatelet effect - **Statement 2 is correct** ✓ ### Haematological Effects and Drug Interactions | NSAID Effect | Clinical Consequence | |--------------|---------------------| | Inhibits platelet aggregation (COX-1 effect) | Increased bleeding tendency | | Displaces warfarin from protein binding | Increased anticoagulant effect | | Inhibits platelet function + anticoagulant synergy | **HIGH BLEEDING RISK** | **Warning:** NSAIDs + anticoagulants (warfarin, DOACs) = **CONTRAINDICATED combination** due to synergistic bleeding risk. This is NOT a safe pairing. - Increased risk of GI bleeding, intracranial haemorrhage, and other major bleeds - If NSAID is essential, use lowest dose for shortest duration + gastroprotection (PPI) - **Statement 3 is FALSE** — NSAIDs are NOT safe with anticoagulants ✗ ### Heart Failure Exacerbation **Key Point:** NSAIDs promote sodium and water retention by inhibiting renal prostaglandins, worsening fluid overload in heart failure patients. - Contraindicated in symptomatic heart failure (NYHA Class II–IV) - **Statement 4 is correct** ✓ **Mnemonic:** **NSAID Renal Risks = SHARK** → **S**odium retention, **H**yperkalemia, **A**cute kidney injury, **R**enal blood flow ↓, **K**idney contraindicated in severe disease [cite:Harrison 21e Ch 297]
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