Aspirin (ASA) Mechanism acetylates and irreversibly inhibits cyclooxygenase in platelets both COX-1 (more important) and COX-2 prevents conversion of arachidonic acid to thromboxane A2 (normally secreted by active platelets) decreases platelet activation ↑ bleeding time PT and PTT unchanged Clinical use prevent MI prophylaxis against clotting in atrial arrhythmias and stroke analgesic antipyretic anti-inflammatory low dose reduces the incidence of colon cancer Toxicity GI bleeding Reye's syndrome hyperventilation tinnitus affects CN VIII ADP receptor antagonists (thienopyridines) Drugs clopidogrel ticlopidine Mechanism blocks ADP-mediated platelet aggregation which decreases Gp IIb/IIIa expression via the P2y12 receptor via irreversible block of ADP receptors activated platelets secrete ADP prevents expression of glycoprotein IIb/IIIa by platelets inhibits binding of fibrinogen and clot formation Clinical use alternative to ASA reduce risk of thrombotic stroke post-stent surgery post-MI acute coronary syndrome unstable angina Toxicity neutropenia (ticlopidine) thrombotic thrombocytopenic purpura (ticlopidine) IIb/IIIa inhibitors Drugs abciximab eptifibatide tirofiban Mechanism monoclonal antibody antagonizes IIb/IIIa glycoprotein receptor on activated platelets prevents platelet aggregation Clinical use acute coronary syndromes percutaneous transluminal coronary angioplasty Toxicity bleeding thrombocytopenia PDE III inhibitors Drugs cilostazol dipyridamole Mechanism phosphodiesterase III inhibitor ↑ cAMP in platelets inhibits aggregation direct arterial vasodilation Clinical use intermittent claudication prevention of stroke and TIA with aspirin angina Toxicity nausea headache GI upset palpitations facial flushing hypotension