Analgesics / Anti-inflammatory · Medicine Class
Inhibition of cyclooxygenase (COX-1 and COX-2) enzymes
NSAIDs inhibit cyclooxygenase (COX) enzymes — COX-1 (constitutively expressed, protective prostaglandins in gastric mucosa and platelets) and COX-2 (inducible by inflammation, mediates pain and fever prostaglandins). By blocking prostaglandin synthesis, NSAIDs reduce inflammation, pain, and fever. COX-1 inhibition also blocks thromboxane A2 production — the basis of aspirin's antiplatelet effect. Selective COX-2 inhibitors (celecoxib) spare GI prostaglandins, reducing GI toxicity, but without antiplatelet effect.
Ibuprofen (Advil, Motrin)
Most widely used NSAID. OTC 200-400mg; prescription up to 800mg TID. Short half-life.
Naproxen (Aleve, Naprosyn)
Longer half-life (12h) — twice daily dosing. OTC available. May have lower cardiovascular risk than ibuprofen.
Celecoxib (Celebrex)
Selective COX-2 inhibitor. Significantly less GI toxicity; no antiplatelet effect. CV risk similar to non-selective NSAIDs.
Indomethacin (Indocin)
Most potent NSAID; high GI/CNS toxicity. Gold standard for acute gout and pericarditis.
Ketorolac (Toradol)
IV/IM/oral; potent analgesic. Maximum 5 days use (renal/GI toxicity).
Aspirin (Bayer, Bufferin)
Irreversible COX-1/2 inhibitor. Low-dose (81mg): antiplatelet for CV prevention. Higher doses: analgesic/anti-inflammatory.
Anticoagulants (warfarin, DOACs) → markedly increased bleeding risk
Antihypertensives (ACE inhibitors, ARBs, diuretics) → reduced efficacy; worsened renal function
Lithium → NSAIDs reduce lithium renal excretion → lithium toxicity
Methotrexate (low and high dose) → increased toxicity
SSRIs → additive GI bleeding risk (reduced platelet serotonin)
Aspirin + other NSAIDs → aspirin's antiplatelet effect may be blocked (take aspirin 30 min before ibuprofen)
For inflammation-related pain (arthritis, sports injury, dental pain), NSAIDs like ibuprofen are more effective. For general pain and fever without significant inflammation, acetaminophen is equally effective with fewer GI and cardiovascular risks. Patients with kidney disease, heart failure, or GI ulcers should prefer acetaminophen. Combining acetaminophen and NSAIDs provides better pain relief than either alone for some conditions.
Yes — non-aspirin NSAIDs increase cardiovascular risk, including heart attack and stroke, with chronic use. This is a class effect related to COX-2 inhibition reducing prostacyclin (a vasodilatory, antithrombotic prostaglandin). Naproxen may have a lower CV risk than other NSAIDs. Risk increases with dose and duration. NSAIDs should be used at the lowest effective dose for the shortest time.