Antiplatelet Drugs

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