antiplatelets
Summary
Antiplatelet drugs inhibit platelet aggregation, reducing arterial thrombus formation. They are used for secondary prevention of cardiovascular events (MI, stroke) and in patients with coronary stents or peripheral arterial disease. Key agents include aspirin, P2Y12 inhibitors (clopidogrel, ticagrelor, prasugrel), and GPIIb/IIIa inhibitors (abciximab, eptifibatide, tirofiban).
Detail
Platelets play a central role in arterial (white) thrombus formation, which is distinct from venous (red) thrombus formation driven mainly by the coagulation cascade. Antiplatelet agents target different steps in platelet activation and aggregation:
1. Aspirin: Irreversibly inhibits COX-1, preventing thromboxane A2 (TXA2) synthesis, which normally promotes platelet aggregation and vasoconstriction. Effect lasts the lifetime of the platelet (~7-10 days) since platelets lack nuclei to resynthesize COX.
2. P2Y12 receptor inhibitors (clopidogrel, prasugrel, ticagrelor, ticlopidine): Block ADP-induced platelet activation by inhibiting the P2Y12 receptor, preventing GPIIb/IIIa receptor activation. Clopidogrel and prasugrel are irreversible prodrugs requiring hepatic activation (clopidogrel via CYP2C19, subject to genetic polymorphisms affecting efficacy); ticagrelor is reversible and does not require activation.
3. GPIIb/IIIa inhibitors (abciximab, eptifibatide, tirofiban): Block the final common pathway of platelet aggregation by preventing fibrinogen cross-linking between platelets. Used primarily in acute coronary syndromes and during PCI, given IV.
4. Dipyridamole: Inhibits phosphodiesterase, increasing cAMP, which inhibits platelet activation; often combined with aspirin for stroke prevention.
5. Cilostazol: PDE3 inhibitor with antiplatelet and vasodilatory effects, used in peripheral arterial disease (claudication).
Clinical significance: Dual antiplatelet therapy (DAPT, e.g., aspirin + clopidogrel) is standard after ACS or coronary stent placement to prevent stent thrombosis. Antiplatelets increase bleeding risk, particularly GI bleeding and bruising, and must be used cautiously with anticoagulants. Unlike anticoagulants (which target the coagulation cascade and are more effective for venous thromboembolism), antiplatelets are preferred for arterial thrombosis prevention.
Board relevance: Know mechanisms, indications (ACS, stroke prevention, stent thrombosis prevention), and the distinction between antiplatelet and anticoagulant use based on thrombus type.
Sources
- First Aid for the USMLE Step 1
- Katzung's Basic and Clinical Pharmacology
- Goodman & Gilman's The Pharmacological Basis of Therapeutics
Reviewed by AnkiBoss editorial — medical student review. Information here is for study reference only and is not medical advice. Spotted an error? Let us know.