25.3.1.1 Platelet Aggregation Inhibitors

The anti-platelet drugs (or platelet aggregation inhibitors) work by decreasing the synthesis, release or action of the chemical molecules that promote platelet aggregation preventing clot formation. Aspirin inhibits cyclooxygenase-1 (COX-1), the enzyme responsible for the production of thromboxane A2 from arachidonic acid, thus blocking the synthesis of the aggregating agent. The main adverse effects of aspirin administration are gastrointestinal ulcers, stomach bleeding and tinnitus.

Another drug which targets thromboxane A2 synthesis is dipyridamole which is a cyclic nucleotide phosphodiesterase inhibitor. Dipyridamole increases intracellular cyclic AMP levels which results in decreased thromboxane A2 synthesis. This agent is usually given in combination with aspirin or warfarin.

Clopidogrel is approved for the prevention of atherosclerotic events following recent myocardial infarction, stroke or established peripheral vascular disease. Clopidogrel selectively inhibits the binding of ADP to its platelet receptor, an event that leads to inhibition of platelet aggregation by blocking activation of the GpIIb/IIIa pathway.

Working in a similar way, abciximab is a monoclonal antibody that is indicated for percutaneous coronary intervention (angioplasty). It binds to the platelet GpIIb/IIIa receptor, preventing binding of von Willebrand factor, fibrinogen, and other adhesion molecules inhibiting receptor-mediated platelet activation and subsequent thrombus formation. The major adverse effect is potential for bleeding.

Eptifibatide and tirofiban have similar indications, adverse reactions and mechanisms of action to abciximab except that they are not antibodies but chemical antagonists of the GpIIb/IIIa receptor.