NSAIDs — MOA & Use
NSAIDs don't just mask pain — they block the enzyme that drives inflammation at its source. Knowing which COX pathway they target explains both their power and their limits.
Core Concept
NSAIDs (ibuprofen, naproxen, ketorolac, celecoxib) work by inhibiting cyclooxygenase (COX) enzymes, which convert arachidonic acid into prostaglandins. Prostaglandins mediate inflammation, pain sensitization, and fever — so blocking their production delivers three therapeutic effects: anti-inflammatory, analgesic, and antipyretic. Two COX isoforms matter. COX-1 is constitutive — it maintains gastric mucosal protection, platelet aggregation, and renal blood flow. COX-2 is inducible — it ramps up at sites of tissue injury and inflammation. Most traditional NSAIDs (ibuprofen, naproxen) are nonselective, blocking both COX-1 and COX-2. Celecoxib is COX-2 selective, targeting inflammation while relatively sparing COX-1 protective functions. Clinical indications include mild-to-moderate pain, osteoarthritis, rheumatoid arthritis, dysmenorrhea, fever reduction, and acute musculoskeletal injury. Ketorolac (Toradol) is the strongest analgesic NSAID, used short-term (≤5 days) for moderate-to-severe pain — often as an opioid-sparing strategy postoperatively. NSAIDs are first-line for inflammatory pain because they reduce the source of nociceptor activation, unlike opioids which modulate pain perception centrally.
Watch Out For
Don't confuse NSAIDs with acetaminophen — acetaminophen is analgesic and antipyretic but has no clinically significant anti-inflammatory effect because it acts primarily through central rather than peripheral COX inhibition. Students often assume all NSAIDs are equal in potency; ketorolac approaches opioid-level analgesia but is limited to 5 days. COX-2 selective (celecoxib) does NOT mean side-effect-free — it still carries cardiovascular risk; it simply spares the gastric lining relative to nonselective agents.
Clinical Pearl
Think of COX-1 as the 'housekeeping' enzyme (stomach, kidneys, platelets) and COX-2 as the 'alarm' enzyme (inflammation). NSAIDs that silence both hit the alarm but also shut down housekeeping.
Test Your Knowledge
3 quick questions — see how well you understood NSAIDs — MOA & Use