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(Circulation. 2000;101:1206.)
© 2000 American Heart Association, Inc.
Cardiovascular Drugs |
Aspirin
From the Cardiology Section, Evans Department of Medicine, Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, Mass.
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Introduction |
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Salicylates, in the form of willow bark, were used as an analgesic during the time of Hippocrates, and their antipyretic effects have been recognized for more than 200 years.1 Acetylsalicylic acid, or aspirin, was introduced in the late 1890s2 and has been used to treat a variety of inflammatory conditions; however, the antiplatelet activity of this agent was not recognized until almost 70 years later.3 Recent advances in our understanding of the central role of platelets in the pathophysiology of cardiovascular disease have spurred in-depth investigations into the mechanisms of action of aspirin and the clinical utility of this agent in the treatment of common cardiovascular disorders.
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Mechanism of Action |
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Aspirin exerts its effect primarily by interfering with the biosynthesis of cyclic prostanoids, ie, thromboxane A2 (TXA2), prostacyclin, and other prostaglandins. These prostanoids are generated by the enzymatically catalyzed oxidation of arachidonic acid, which is itself derived from membrane phospholipids4 (Figure
). Arachidonic
acid is metabolized by the enzyme prostaglandin (PG)
H-synthase, which, through its cyclooxygenase (COX)
and peroxidase activities, results in the production of
PGG2 and PGH2,
respectively. PGH2 is then modified by specific
synthases, thus producing prostaglandins
D2, E2,
F2
, I2 (prostacyclin),
and TXA2, all of which mediate specific cellular
functions.
|
PGH-synthase, also referred to as COX, exists in 2 isoforms that have
significant homology of their amino acid sequences.5 A
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