Most of the current available antiplatelet drugs, such as aspirin, dipyridamole, ticlopidine, and
sulfinpyrazone, exert their actions by affecting only the secondary platelet aggregation pathways
(87). For example, aspirin and sulfinpyrazone work by inhibiting the biosynthesis of TXA2 in the
platelets. Aspirin works by irreversibly and permanently inactivating cyclooxygenase
(COX) through covalent acetylation of a serine residue in close proximity to the active site of the
enzyme. A cumulative inactivation effect occurs on platelets with long-term therapy, because
platelets do not synthesize new COX (i.e., platelets are unable to synthesize, via de novo pathway,
COX-1, because they are anucleated cells). Therefore, the effects of aspirin last for the lifetime of
the platelet (7–10 days). Sulfinpyrazone also is a potent but reversible COX inhibitor that does not
affect PGI2 synthesis in endothelial cells. Like nonsteroidal anti-inflammatory agents (NSAIDs), such
as aspirin, this action inhibits the aggregation of platelets into thrombi. Dipyridamole interrupts
platelet function through its effect of increasing cellular concentration of cAMP by inhibiting
phosphodiesterase, an enzyme needed for degradation of cAMP. Dipyridamole also may stimulate
PGI2 release and inhibits TXA2 formation. Ticlopidine and clopidogrel selectively inhibit
ADP-induced platelet aggregation with no direct action on prostaglandin production. New and more
selective antiplatelet drugs, such as integrin αIIbβ3 receptor antagonists (GPIIa/IIIb blockers),
thromboxane synthase inhibitor, and TXA2 receptor antagonists, are currently being developed.
