Question
Aspirin.
Answer
Aspirin (acetylsalicylic acid) is the prototype NSAID, with a distinctive irreversible mechanism.
Mechanism: irreversibly acetylates and inhibits cyclooxygenase (COX-1 and COX-2), blocking prostaglandin and thromboxane A2 synthesis. At low doses, this predominantly and durably suppresses platelet thromboxane A2 (platelets cannot resynthesize COX, so the effect lasts the platelet’s ~10-day lifespan), giving a selective antiplatelet effect while relatively sparing endothelial prostacyclin. At higher (anti-inflammatory) doses, COX inhibition throughout the body gives analgesic, antipyretic, and anti-inflammatory effects.
Uses: mild-moderate pain and fever (analgesic-antipyretic dose), rheumatic fever/rheumatoid arthritis (high anti-inflammatory dose, now largely superseded by other agents), and — its most distinctive contemporary use — antiplatelet prophylaxis at low dose for secondary prevention of myocardial infarction and ischemic stroke, and immediately in acute coronary syndrome.
Adverse effects: GI irritation and peptic ulceration (loss of COX-1-mediated mucosal protection), increased bleeding risk, hypersensitivity/bronchospasm in aspirin-sensitive asthmatics (aspirin-exacerbated respiratory disease), Reye’s syndrome (avoided in children/adolescents with viral illness), salicylism (tinnitus, hyperventilation) and severe toxicity (metabolic acidosis, hyperthermia) in overdose.
Contraindications: peptic ulcer disease, bleeding disorders, children with viral infections, third-trimester pregnancy (premature ductus closure).