Pain, Rheumatology & Pulmonary

Generally 4 g/day (≤3 g/day or lower is often advised with hepatic risk, chronic use, or alcohol use). Toxicity is dose-related hepatotoxicity from the reactive metabolite NAPQI.

N-acetylcysteine (NAC) — replenishes glutathione to detoxify NAPQI. Most effective within ~8 hours of ingestion; dosing guided by the Rumack-Matthew nomogram against acetaminophen level.

It is essentially devoid of antiplatelet, GI-ulcer, and renal effects, and lacks significant anti-inflammatory action. It is first-line for mild pain/fever in patients with GI bleed risk, anticoagulation, or CKD.

Reversible inhibition of cyclooxygenase (COX-1 and COX-2), reducing prostaglandin synthesis → analgesic, antipyretic, anti-inflammatory effects. (Aspirin is the exception: irreversible acetylation.)

GI (dyspepsia, ulcer/bleed), renal (decreased GFR, AKI, fluid retention/hyperkalemia), cardiovascular (increased MI/stroke risk, BP elevation), and antiplatelet effects. COX-1 inhibition drives GI/antiplatelet harm.

Sparing COX-1 preserves protective gastric prostaglandins (less ulcer/bleed) but suppressing endothelial prostacyclin without inhibiting platelet thromboxane creates a prothrombotic imbalance → increased CV events.