Published online by Cambridge University Press: 15 October 2009
INTRODUCTION
Antiplatelet therapies are the mainstay in the treatment of acute coronary syndromes (ACSs) as well as in the chronic primary and secondary prevention of acute coronary events. This chapter describes the established antiplatelet agents in cardiology and introduces the novel drugs currently in advanced development.
ASPIRIN
Acetylsalicylic acid, known as aspirin, is an inhibitor of the production of prostaglandins and thromboxanes.
Mechanism of action
The prostaglandin (PG) endoperoxide H synthases-1 and -2, or cyclooxygenase (COX)-1 and -2, catalyze the conversion of arachidonic acid to PGH2, the first reaction of prostanoids synthesis. PGH2 is the immediate precursor of PGD2, PGE2, PGF2α, PGI2, and thromboxane (Tx) A2. Aspirin permanently inactivates COX-1 and COX-2. COX-1 is a constitutive enzyme of platelets and is 50- to 100-fold more sensitive to aspirin than COX-2 (which is predominantly expressed in response to inflammatory stimuli by monocytes/macrophages). Aspirin inhibits the synthesis of TxA2, a potent platelet-aggregating agonist and vasoconstrictor agent that is primarily produced by platelets from PGH2 and of PGI2 (prostacyclin), a platelet inhibitor and vasodilator agent that is produced by vascular endothelial cells. TxA2 is mainly produced by the COX-1 of platelets and therefore is most sensitive to the effect of aspirin, whereas PGI2 can be produced by both COX-1 and COX-2.
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