NSAIDs, acetaminophen & non-opioid analgesics

Mechanism (COX-1 vs COX-2), GI/renal/cardiac risks, aspirin dosing tiers, APAP toxicity, adjuvant analgesics.

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◆NSAID classes

•Non-selective (ibuprofen, naproxen, indomethacin, diclofenac, ketorolac) — block COX-1 + COX-2
•COX-2 selective (celecoxib) — less GI but ↑ cardiovascular risk (rofecoxib pulled from market)
•Aspirin: irreversible COX inhibitor (rest of NSAIDs reversible)

•81 mg/day — antiplatelet (cardio-protective in secondary prevention; primary controversial)
•325–650 mg PRN — analgesic / antipyretic
•650 mg q4h or higher — anti-inflammatory (rheum diseases historically)
•Acute MI: 325 mg CHEWED at presentation
•TIA / stroke: 81–325 mg/day (after exclude hemorrhage)

•GI: ulcer, bleeding, perforation — ↑↑ with steroid co-use, anticoagulation, age >60, prior PUD
•PPI prophylaxis if ≥2 GI risk factors
•Renal: AKI (vasoconstriction of afferent arteriole), interstitial nephritis, papillary necrosis
•↓ ACE-I/ARB/diuretic efficacy + ↑ BP
•Cardiovascular: ↑ MI/stroke risk (except aspirin) — esp diclofenac, COX-2 selective
•Bronchospasm in aspirin-sensitive asthma (Samter triad: asthma + nasal polyps + ASA sensitivity)
•Reye syndrome — AVOID aspirin in viral illness in children
•Bleeding (irreversible with aspirin × 7–10 days; reversible with others)
•Premature closure of ductus arteriosus in pregnancy after 30 wks (avoid in 3rd trimester)

•Mechanism: weak central COX inhibitor + other actions
•GOOD: no GI/renal toxicity, no antiplatelet effect, safe in pregnancy
•BAD: hepatotoxic in overdose (>4 g/day in healthy adults; less in alcoholic/malnourished)
•Antidote: N-acetylcysteine (NAC); follow Rumack-Matthew nomogram
•Phases: 1 (0–24 hr) asymptomatic, 2 (24–72) RUQ pain + ↑ AST/ALT, 3 (72–96) fulminant hepatic failure
•Combined products (Percocet, Vicodin) — watch APAP totals to avoid hepatotoxicity

•Gabapentin, pregabalin — diabetic neuropathy, postherpetic neuralgia; weight gain, sedation
•TCAs (amitriptyline, nortriptyline) — neuropathic pain, migraine prophylaxis; anticholinergic
•SNRIs (duloxetine, venlafaxine) — fibromyalgia, diabetic neuropathy, depression with pain
•Topical lidocaine — postherpetic neuralgia, focal neuropathy
•Topical capsaicin — burning sensation initially, then desensitization
•Carbamazepine — trigeminal neuralgia (first-line)

◆Aspirin + viral illness in kids = Reye syndrome → use ibuprofen or APAP instead
◆NSAID + ACE-I + diuretic = 'triple whammy' AKI risk
◆Ketorolac max 5 days (renal + GI risk with longer use)
◆Aspirin-exacerbated respiratory disease (Samter triad): aspirin + asthma + nasal polyps → use leukotriene modifiers or biologics
◆APAP overdose: NAC before phase 3 (72 hr) prevents most hepatotoxicity
◆Carbamazepine for trigeminal neuralgia (NOT NSAIDs)
◆Pregnancy + NSAIDs after 30 weeks = premature PDA closure + oligohydramnios — use APAP

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