Generic Name

Aspirin

Mechanism

• Aspirin (acetyl‑salicylic acid) irreversibly acetylates serine residues in the active sites of cyclo‑oxygenase enzymes COX‑1 and COX‑2.
• Inhibition of COX‑1 in platelets ↓ thromboxane A₂ → potent, long‑lasting antiplatelet effect.
• Inflammatory tissues: COX‑2 inhibition reduces prostaglandin‑mediated pain, fever, and swelling.
• Low‑dose aspirin (≤100 mg/day) primarily targets platelets; higher doses (≥300 mg) provide additional anti‑inflammatory effects.

Pharmacokinetics

• Absorption: Rapid from the GI tract; peak plasma levels 30–60 min after oral dose.
• Metabolism: Hydrolysis to salicylic acid (active metabolite); conjugation via glucuronidation and sulfation.
• Bioavailability: ~80 % after a single oral dose; reduced by gastric acid production and food.
• Elimination: Renal excretion of salicylate conjugates; half‑life 2–3 h for salicylate, 1–2 days for aspirin itself.
• Drug interactions: NSAIDs, anticoagulants, lithium, methotrexate, warfarin, and CYP inhibitors can alter efficacy and toxicity.

Indications

• Cardiovascular: Primary & secondary prevention of myocardial infarction, ischemic stroke, and peripheral arterial disease.
• Antithrombotic: As adjunct to antiplatelet therapy in coronary stent placement or acute coronary syndrome.
• Anti‑inflammatory: Rheumatoid arthritis, osteoarthritis, gout, and other inflammatory disorders.
• Pain & fever: Mild to moderate pain, low‑grade fever, and dysmenorrhea.
• Miscellaneous: Prevention of pre‑eclampsia in high‑risk pregnancies, prophylaxis of venous thromboembolism in select surgical patients (low dose).

Contraindications

• Absolute contraindications:
• Active peptic ulcer disease or GI hemorrhage.
• Known hypersensitivity to salicylates or other NSAIDs.
• Bleeding disorders or platelet function defects.
• Co‑administration with anticoagulants unless monitored.
• Relative contraindications:
• Severe hepatic or renal impairment.
• Asthma (risk of aspirin‑induced bronchospasm).
• Pediatric or young adult (<18 y) with viral infections (Reye’s syndrome).
• Warnings:
• Aspirin‑related GI bleeding risk; consider gastroprotective agents (PPIs/PPIs) when needed.
• Salicylate toxicity: tinnitus, respiratory depression, metabolic acidosis.

Dosing

*Patients with renal impairment: start at 200 mg every 8 h.
Children <12 y: avoid unless under pediatric supervision.

Adverse Effects

• Common:
• Gastro‑intestinal upset (N/V, dyspepsia).
• Dental erosion.
• Pruritus and rash.
• Mild tinnitus (dose‑dependent).
• Serious:
• Upper GI bleeding (gastric ulceration, perforation).
• Hemorrhagic stroke or intracranial bleeding.
• Hypersensitivity reactions (angioedema, anaphylaxis).
• Reye’s syndrome (pediatric viral illness).
• Acute kidney injury (especially in volume‑depleted states).
• Acid–base disturbances: metabolic acidosis or alkalosis.

Monitoring

• Platelet function tests (if on anticoagulants or high‑risk bleeding).
• CBC for thrombocytopenia.
• Serum creatinine/CrCl for renal function.
• Liver enzymes (AST/ALT) in chronic users.
• GI surveillance: upper endoscopy for long‑term users or those with GI history.
• Blood pressure: monitor if combined with antihypertensives.

Clinical Pearls

• Irreversibility = long‑lasting effect: Aspirin’s platelet inhibition persists for ~7–10 days because platelets cannot synthesize new COX‑1.
• Low‑dose aspirin ≠ low‑risk: Even at 75 mg, gastric ulcer risk is ~0.5 / 100 PYA; concomitant PPI markedly reduces this.
• Timing matters: Take aspirin 30 min before meals for optimal absorption; avoid with alcohol.
• Salicylate toxicity: In overdose, look for tinnitus and a *fish‑y* metabolic acidosis; decontaminate with activated charcoal and consider dialysis if severe.
• Pregnancy: 1st trimester contraindicated; 3rd trimester low‑dose aspirin (81 mg) may prevent pre‑eclampsia in high‑risk women.
• Drug interactions: Aspirin competes with warfarin for platelet and plasma‑protein binding → higher INR; monitor closely.

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• Key take‑away: Low‑dose aspirin remains a cornerstone for antiplatelet therapy due to its irreversible COX‑1 inhibition, while higher doses confer anti‑inflammatory benefits. Proper dosing, patient selection, and vigilance for GI, renal, or bleeding complications are essential for safe and effective use.