NSAIDs

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.

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.

Key Distinctions

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.

Adverse Effects & Contraindications

NSAIDs block cyclooxygenase (COX), reducing protective prostaglandins throughout the body — not just at the pain site. GI effects are the most common: prostaglandin depletion thins the gastric mucosal barrier, causing epigastric pain, ulceration, and GI bleeding. The patient should take NSAIDs with food and report dark, tarry stools immediately. Renal effects matter next: prostaglandins maintain renal blood flow, so NSAIDs can precipitate acute kidney injury, especially in patients who are dehydrated, elderly, or already on ACE inhibitors or diuretics. Monitor BUN, creatinine, and urine output. Cardiovascular risk increases with prolonged use — COX-2 selective agents (celecoxib) carry a black-box warning for MI and stroke. NSAIDs also inhibit platelet aggregation (except celecoxib), increasing bleeding risk; they must be held before surgery (7–10 days for aspirin due to irreversible platelet inhibition; shorter holds for other NSAIDs based on half-life). Key contraindications: active peptic ulcer disease, third trimester of pregnancy (risk of premature ductus arteriosus closure), severe renal impairment, aspirin-sensitive asthma (cross-reactivity can trigger bronchospasm), and patients on anticoagulants without careful risk-benefit evaluation. Ketorolac (Toradol) deserves special attention — limited to 5 days maximum due to high GI and renal toxicity risk.

Key Distinctions

Don't confuse NSAID-related GI bleeding (prostaglandin loss → mucosal erosion) with acetaminophen hepatotoxicity — completely different organ targets. Students assume celecoxib is 'safer' across the board, but it spares the stomach and platelets while carrying higher cardiovascular risk. Aspirin-sensitive asthma is a contraindication to ALL NSAIDs, not just aspirin — cross-reactivity through the COX pathway triggers bronchospasm with any agent in the class.

Clinical Pearl

Black stool, rising creatinine, or wheezing in an NSAID patient — stop, assess, and call. GI, renal, respiratory: those are your three alarm systems.