Antiplatelet Drugs

Aspirin (ASA)

Antiplatelet Drugs

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