## Mechanism of Aspirin **Key Point:** Aspirin is the only antiplatelet agent that irreversibly acetylates and inactivates platelet COX-1, preventing thromboxane A₂ (TXA₂) synthesis for the entire lifespan of the platelet (~7–10 days). ## Comparison of Antiplatelet Agents | Agent | Mechanism | Reversibility | Target | | --- | --- | --- | --- | | **Aspirin** | COX-1 inhibition → ↓ TXA₂ | **Irreversible** (acetylation) | Platelet COX-1 | | **Clopidogrel** | P2Y₁₂ ADP receptor antagonist | Reversible | ADP pathway | | **Ticagrelor** | P2Y₁₂ ADP receptor antagonist | Reversible | ADP pathway | | **Dipyridamole** | Phosphodiesterase inhibitor → ↑ cAMP | Reversible | Platelet cAMP | **High-Yield:** The irreversibility of aspirin's action is why: - A single dose produces antiplatelet effects for 7–10 days - Platelet function recovers only when new platelets are synthesized - It is the gold standard for primary prevention of cardiovascular events [cite:KD Tripathi 8e Ch 12] **Clinical Pearl:** Because aspirin's effect is irreversible, it should be discontinued 5–7 days before elective surgery (time for ~50% platelet turnover), whereas reversible P2Y₁₂ inhibitors need only 3–5 days washout. ## Why Aspirin Is Unique 1. **Acetylation of serine 529** in platelet COX-1 permanently blocks the enzyme 2. **No new COX-1 synthesis** in mature platelets (anucleate cells) 3. **Duration of effect** = platelet lifespan, not drug half-life All other antiplatelet agents produce reversible inhibition and have shorter durations of action.
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