Non-steroidal anti-inflammatory drugs or NSAIDs are a class of drugs that include the drugs, ibuprofen, naproxen, and indomethacin. They work by inhibiting COX or cyclooxygenase enzymes, reducing the production of prostaglandins and thromboxanes from arachidonic acid. They are widely used clinically for their anti-inflammatory and analgesic effects. Notably, indomethacin is the treatment of choice to close a patent ductus arteriosus or PDA in neonates.

Despite these clinical uses, NSAIDs have their own share of side effects. The most important side effect of NSAIDs is an increased risk for GI ulcers and bleeding. Long-term NSAID use can also increase the risk of thrombotic events like MI and stroke. Lastly, NSAID use  can also damage the kidney, leading to various presentations, including interstitial nephritis, renal papillary necrosis, and reductions in glomerular filtration.

Key Points

  • (Non-selective) NSAIDs
    • Drug Names:
      • Ibuprofen
      • Naproxen
      • Indomethacin
      • Ketorolac
      • Diclofenac
      • Fenoprofen
      • Piroxicam
      • Meloxicam
    • Mechanism
      • Reversible inhibition of COX-1 and COX-2
        • Block synthesis of prostaglandin, leukotriene, thromboxane, and other arachidonic acid derivatives
        • Contrast vs. aspirin (irreversible inhibition)
    • Clinical Indications
      • Analgesia
        • Often used in osteoarthritis and other arthritic conditions
      • Anti-inflammatory (and antipyretic)
        • May be used to reduce fever and inflammation
      • Indomethacin used to close patent ductus arteriosus
        • PGE1 maintaining the PDA is reduced by inhibiting the COX enzymes which synthesize it
    • Adverse Effects
      • Gastric ulcers and bleeding
        • Second most common cause of gastric ulcers (after H. pylori)
        • PGE2 and PGE1 produced by COX-1 are important in GI mucosal protection, which is impaired by NSAIDs
        • Use selective COX-2 inhibitor (e.g. celecoxib) or prostaglandin agonists (e.g. misoprostol) to avoid these side effects
        • May cause pill-induced esophagitis via similar mechanisms
      • Increased risk of adverse cardiovascular events (e.g. MI, stroke)
      • Acute kidney injury
        • Usually by interstitial nephritis or renal vasoconstriction
        • ↓ prostaglandin (PG) E2 and PGI2 results in vasoconstriction of afferent arteriole
        • May induce renal papillary necrosis
      • Aplastic anemia
        • Documented in rare cases with use of indomethacin
      • Allergic reactions/asthma