Cyclooxygenase inhibition and thrombogenicity.
Cyclooxygenase (COX)-1 and COX-2 catalyze the formation of prothrombotic and antithrombotic eicosanoids, respectively. Aspirin, conventional nonsteroidal anti-inflammatory drugs (NSAIDs), and COX-2-specific inhibitors exhibit different patterns of inhibition of COX-1-mediated thromboxane biosynthesis and COX-2-mediated prostacyclin biosynthesis. The relationship between the pharmacologic inhibition of these vasoactive eicosanoids and the thromboprophylaxis or thrombogenicity exhibited by different therapeutic agents is currently unclear. Future studies are needed to assess the antithrombotic properties of commonly used NSAIDs, the hypothetical thrombogenicity of COX-2-specific inhibitors in high-risk patients, the need for concomitant aspirin with selective versus nonselective COX inhibitors, and the antiplatelet and gastric toxicity of the aspirin/COX-2-specific inhibitor combination in comparison with the aspirin/conventional NSAID combination.
Catella-Lawson
F
F
Division of Experimental Therapeutics, University of Pennsylvania, Philadelphia, Pennsylvania 19014, USA.
Crofford
L J
LJ
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology / Q000627:therapeutic use*; D002318:Cardiovascular Diseases / Q000209:etiology / Q000517:prevention & control; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D004347:Drug Interactions; D011464:Epoprostenol / Q000037:antagonists & inhibitors* / Q000096:biosynthesis*; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors* / Q000502:physiology*; D008565:Membrane Proteins; D011451:Prostaglandin-Endoperoxide Synthases / Q000502:physiology*; D012307:Risk Factors; D013927:Thrombosis / Q000209:etiology / Q000517:prevention & control*; D013928:Thromboxane A2 / Q000037:antagonists & inhibitors* / Q000096:biosynthesis*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D008565:Membrane Proteins; D013928:Thromboxane A2; D011464:Epoprostenol; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases