Asprin
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Here is a comprehensive overview of Aspirin (Acetylsalicylic Acid).
Aspirin (Acetylsalicylic Acid) — Full Overview
Chemical Identity
Aspirin is acetylsalicylic acid (ASA), a salicylate derived from willow bark. It belongs to the NSAID class but has unique, irreversible activity that distinguishes it from other members.
Mechanism of Action
Aspirin is a weak organic acid that irreversibly acetylates the serine residue (Ser-530) of cyclooxygenase (COX) enzymes, permanently inactivating them. This blocks the conversion of arachidonic acid (from membrane phospholipids) → prostaglandin H₂ → thromboxane A₂ (TXA₂).
Figure: Aspirin blocks the COX-1 pathway — arachidonic acid → PGH₂ → TXA₂ — in platelets.
COX isoforms affected:
| Dose | COX-1 | COX-2 |
|---|---|---|
| Low (75–325 mg) | Irreversibly inhibited | Minimal effect |
| High (~1 g/day) | Inhibited | Also inhibited (including prostacyclin synthesis in endothelium) |
Because platelets lack nuclei, they cannot regenerate COX. The antiplatelet effect of a single aspirin dose therefore lasts 7–10 days (the platelet lifespan). This is the basis of its antiplatelet potency.
- Lippincott Pharmacology, p. 440; Harrison's 22E, p. [block 13]
Three Core Pharmacological Actions
| Action | Mechanism | Clinical Use |
|---|---|---|
| Anti-inflammatory | ↓ Prostaglandins (mediators of inflammation) | Arthritis, rheumatic fever |
| Analgesic | ↓ PGE₂ → less sensitization of pain receptors | Mild–moderate pain, headache, dysmenorrhea |
| Antipyretic | ↓ PGE₂ in hypothalamus → resets thermostat | Fever reduction |
NSAIDs do NOT affect normal body temperature — antipyretic effect is selective to febrile states.
Pharmacokinetics
| Parameter | Detail |
|---|---|
| Absorption | Oral; passive diffusion |
| Hydrolysis | Rapidly → salicylic acid (mainly in liver) |
| Half-life (aspirin) | 15–20 minutes |
| Half-life (salicylate) | 3–12 hours (dose-dependent) |
| Protein binding | High (salicylate) |
| Excretion | Renal (pH-dependent); alkaline urine promotes excretion |
Enteric-coated formulations delay absorption but do not eliminate GI side effects.
Clinical Indications
1. Antiplatelet / Cardiovascular
- Secondary prevention of MI, stroke, TIA, and peripheral artery disease: ~25% reduction in cardiovascular death, MI, or stroke
- ACS/STEMI: Load with ≥160 mg non-enteric-coated; maintain 75–100 mg/day
- Post-PCI / post-CABG: Dual antiplatelet therapy (with a P2Y₁₂ inhibitor)
- Primary prevention: No longer routine. Recommended only if 10-year cardiovascular risk ≥10% AND low bleeding risk — recent RCTs show GI/intracerebral hemorrhage risk outweighs benefit in lower-risk individuals
2. Anti-inflammatory / Analgesic
- Rheumatic fever: 4–8 g/day in divided doses
- Osteoarthritis, RA (older use, now largely replaced by other NSAIDs/DMARDs)
- Mild–moderate pain: headache, myalgia, dysmenorrhea
3. Antipyretic
- Fever management in adults (not children — see contraindications)
4. Colorectal Cancer Prevention
- Long-term low-dose aspirin may reduce colorectal cancer risk; also gastric cancer (but increases GI bleeding risk)
Dosing
| Indication | Dose |
|---|---|
| Antiplatelet (maintenance) | 75–100 mg/day |
| Antiplatelet (loading, rapid effect) | 160–325 mg (non-enteric-coated) |
| Analgesic / antipyretic | 325–1000 mg q4–6h |
| Anti-inflammatory (rheumatic fever) | 4–8 g/day in divided doses |
Higher antiplatelet doses are not more effective and carry greater bleeding risk. Some analyses suggest reduced antiplatelet efficacy at higher doses.
Side Effects
Gastrointestinal (most common, dose-related)
- Dyspepsia, nausea
- Erosive gastritis, peptic ulcer
- GI bleeding and perforation
- Major bleeding risk: 1–3% per year
- Enteric-coated/buffered aspirin does not eliminate this risk
- Risk mitigation: PPI co-administration; H. pylori eradication in peptic ulcer patients
Bleeding
- Prolonged bleeding time (irreversible platelet inhibition)
- Risk 2–3× higher with dual antiplatelet therapy (+ clopidogrel/ticagrelor) or anticoagulants (+ warfarin)
Respiratory / Hypersensitivity
- Aspirin-exacerbated respiratory disease (AERD): Bronchospasm in ~0.3% general population; more common in asthmatics, those with nasal polyps/chronic rhinitis
- Universal cross-reactivity with other NSAIDs
- COX-2 inhibitors are generally tolerated in AERD patients
Drug Interactions
- Ibuprofen: Competes at COX-1 catalytic site. If ibuprofen is taken within 2 hours before aspirin, it blocks acetylation → negates antiplatelet effect. Aspirin should be taken ≥60 min before or ≥8 hours after ibuprofen.
- Warfarin / anticoagulants: Significantly increased bleeding risk
- Methotrexate: Aspirin reduces renal clearance → toxicity risk
Contraindications & Cautions
| Contraindication | Reason |
|---|---|
| Children/teenagers with viral illness | Reye syndrome (hepatic encephalopathy) |
| Aspirin allergy / AERD | Bronchospasm risk |
| Active peptic ulcer / GI bleeding | Worsens hemorrhage |
| Severe hepatic or renal impairment | Toxicity risk |
| Pregnancy (≥20 weeks, high doses) | Premature closure of ductus arteriosus |
| Gout (low-dose) | Low-dose aspirin reduces uric acid excretion → can precipitate gout |
Aspirin Resistance
- True pharmacological resistance is rare
- Pseudo-resistance: delayed/reduced absorption (common with enteric-coated), non-compliance, drug interactions (ibuprofen), accelerated platelet turnover
- Clinical "resistance" = failure to prevent ischemic events despite therapy — multifactorial
Toxicity / Overdose (Salicylate Poisoning)
Acute ingestion >200 mg/kg is likely to produce intoxication.
Pathophysiology: Uncoupling of oxidative phosphorylation + medullary stimulation
Classic acid-base pattern:
- Respiratory alkalosis (early) — medullary stimulation → hyperventilation
- Metabolic acidosis (later) — lactate accumulation + bicarbonate excretion → increased anion gap
- ABG often shows a mixed respiratory alkalosis + metabolic acidosis
Other features: Tinnitus, fever (hyperthermia), vomiting, dehydration, seizures, coma, pulmonary edema, cardiovascular collapse in severe cases
Management:
| Severity | Treatment |
|---|---|
| All | Supportive care; IV fluids |
| Massive ingestion | Gastric lavage + activated charcoal + whole bowel irrigation |
| Moderate | IV sodium bicarbonate → alkalinize urine → trap ionized salicylate → promote excretion |
| Severe (coma, acidosis, salicylate >90–100 mg/dL) | Emergency hemodialysis |
Recent Evidence Update
Recent systematic reviews (2024–2025) are shifting practice on post-PCI antiplatelet therapy:
- A 2025 meta-analysis in The Lancet (PMID 40902613) found clopidogrel monotherapy may be superior to aspirin monotherapy for secondary prevention of coronary artery disease after initial dual antiplatelet therapy.
- A 2025 BMJ meta-analysis (PMID 40467090) confirmed that P2Y₁₂ inhibitor monotherapy (dropping aspirin after the initial DAPT period) after PCI is associated with lower bleeding without increasing ischemic events — challenging aspirin's traditional role as the default long-term agent post-stenting.
Sources: Harrison's Principles of Internal Medicine 22E · Braunwald's Heart Disease · Lippincott Illustrated Reviews Pharmacology · Katzung's Basic & Clinical Pharmacology · Goodman & Gilman's Pharmacological Basis of Therapeutics · Goldman-Cecil Medicine
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