Glycoprotein IIbIIIa Receptor Antagonists

Activation of platelets by several agonists results in the expression of specific functional receptors for fibrinogen on the platelet surface, referred to as GP IIb/IIIa receptors. The GP IIb/IIIa receptor is a member of the integrin family of receptors.76 When platelets are activated by a variety of stimuli including thrombin, collagen, ADP, and epinephrine, the GP IIb/IIIa receptor changes its conformation to be receptive to one end of a fibrinogen dimer. Occupancy of a GP IIb/IIIa receptor by the other end of the dimer provides the basis for platelet aggregation. Thus, the GP IIb/IIIa receptor is considered the final common pathway of platelet aggregation.77

Abciximab (c7E3) is a chimeric mouse — human monoclonal antibody directed against the GP IIb/IIIa receptor. Its mechanism of action appears to be steric hindrance of the receptor as opposed to direct binding to the RGD binding site of the receptor. Abciximab also inhibits the vitronectin (av b3)receptor, which mediates both platelet coagulation in addition to endothelial and vascular smooth muscle cell proliferation. The significance of vitronectin-receptor blockade is unknown. It produces a direct antithrombotic effect by inhibiting the binding of fibrinogen to the receptor and consequently inhibiting platelet aggregation.78 Because abciximab is a more potent inhibitor of platelet function than aspirin, it potentially produces a greater degree of thrombolysis and prevents rethrombosis in short-term management of patients with STEMI.78,79

Eptifibatide (Figure 4) is another GP IIb/IIIa antagonist. It dose-dependently inhibits platelet aggregation and in a baboon model refractory to aspirin and heparin, inhibited aggregation, preventing acute thrombosis with only a modest prolongation (two- to threefold) of the bleeding time.

Tirofiban (Figure 4) is a nonpeptide inhibitor of the GP IIb/IIIa receptor. It reduces ischemic events at 48 h following infusion when compared to standard heparin therapy and is extensively used in percutaneous transluminal coronary angioplasty (PTCA) and acute coronary syndromes (ACS).

Platelet GP IIb/IIIa receptor antagonists have been shown to be effective and safe in reducing death and cardiac ischemic events among patients presenting with acute coronary syndromes without ST-segment elevation.80

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Aspirin

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Dipyridamole

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Blood Pressure Health

Blood Pressure Health

Your heart pumps blood throughout your body using a network of tubing called arteries and capillaries which return the blood back to your heart via your veins. Blood pressure is the force of the blood pushing against the walls of your arteries as your heart beats.Learn more...

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