Cardiovascular pharmacology of nonselective nonsteroidal anti-inflammatory drugs and coxibs: clinical considerations

The American Journal of Cardiology
Garret A FitzGerald

Abstract

Cyclooxygenase (COX)-2 inhibitors have been developed with the goal of providing similar efficacy and greater safety compared with traditional nonsteroidal anti-inflammatory drugs. Development was based on the hypothesis that COX-1 is the housekeeping enzyme necessary for production of prostaglandins (PGs) with homeostatic functions, whereas COX-2 is a mediator of pathophysiologic processes. However, later research has demonstrated a role of COX-2 in production of PGs that have functions under normal physiologic conditions. In the vasculature, COX-2 seems to be the main enzyme responsible for the production of prostacyclin. Increased synthesis of this vasodilatory and antithrombotic PG represents a homeostatic response during periods of accelerated platelet-vessel wall interactions and counteracts increased synthesis of COX-1-derived prothrombotic prostanoid thromboxane A(2) (TXA(2)). The clinical sequelae of inhibiting prostacyclin activity in the absence of concomitant inhibition of TXA(2) are not currently clear. Animal studies show that inhibition of prostacyclin activity does not lead to spontaneous thrombosis but may increase response to thrombotic stimuli. Therefore, prostacyclin synthesis may be important for limiting t...Continue Reading

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