Chest
Platelet-Active Drugs: The Relationships Among Dose, Effectiveness, and Side Effects: The Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy
Section snippets
1.0 Aspirin and Other COX Inhibitors
Aspirin has been thoroughly evaluated as an antiplatelet drug, and it has been found to prevent vascular death by approximately 15% and to prevent nonfatal vascular events by about 30% in a meta-analysis19 of > 100 randomized trials in high-risk patients.
2.0 Reversible COX Inhibitors
A variety of NSAIDs can inhibit TXA2-dependent platelet function through competitive, reversible inhibition of platelet COX-1.159 In general, these drugs, when used at a conventional analgesic dosage, inhibit reversibly platelet COX activity by 70 to 90%. This level of inhibition may be insufficient to block adequately platelet aggregation in vivo, because of the very substantial biosynthetic capacity of human platelets to produce TXA2.160161 Population-based observational studies162163164 have
3.0 Dipyridamole
Dipyridamole is a pyrimidopyrimidine derivative with vasodilator and antiplatelet properties. The mechanism of action of dipyridamole as an antiplatelet agent has been a subject of controversy.182 Both the inhibition of cyclic nucleotide phosphodiesterase (the enzyme that degrades cyclic adenosine monophosphate [AMP] to 5′-AMP, resulting in the intraplatelet accumulation of cyclic AMP, a platelet inhibitor) and blockade of the uptake of adenosine (which acts at A2 receptors for adenosine to
4.0 Thienopyridines
Ticlopidine and clopidogrel are structurally related thienopyridines with platelet-inhibitory properties. Both drugs selectively inhibit ADP-induced platelet aggregation with no direct effects on arachidonic acid metabolism.185 Although ticlopidine and clopidogrel also can inhibit platelet aggregation induced by collagen and thrombin, these inhibitory effects are abolished by increasing the agonist concentration and, therefore, are likely to reflect the blockade of ADP-mediated amplification of
5.0 Integrin αIIbβ3 (GPIIb/IIIa) Receptor Antagonists
Given the redundance of discrete pathways leading to platelet aggregation, it is not surprising that the clinical efficacy of aspirin, ticlopidine, and clopidogrel is only partial. These drugs, while inhibiting TXA2-mediated or ADP-mediated platelet aggregation, leave the activity of other platelet agonists such as thrombin largely unaffected. Following recognition that the expression of functionally active integrin αIIbβ3 (GPIIb/IIIa) on the platelet surface is the final common pathway of
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