Why do cyclo-oxygenase-2 inhibitors cause cardiovascular events?
This report confirms evidence that selective nonsteroidal anti-inflammatory drugs (NSAIDs), such as celecoxib, can lead to thrombotic cardiovascular events. Aspirin, a nonselective COX-1 (cyclo-oxygenase) and COX-2 inhibitor may result in gastric toxicity. For this reason, selective COX-2 inhibitors have been developed to reduce erosion of the gastric mucosa. Both selective and nonselective NSAIDs reduce prostacyclin formation in the infarcted heart; they accomplish this by tipping the balance of prostacyclin/thromboxane in favor of thromboxane, a prothrombotic eicosanoid. The relative increase in thromboxane, coupled with a diminution in prostacyclin in infarcted heart muscle, can lead to the development of thrombotic cardiovascular events. This may be prevented by the addition of a nitric oxide donor to NSAIDs.
Bing
Richard J
RJ
Huntington Medical Research Institutes, Department of Experimental Cardiology, Pasadena, California 91101, USA. cardio@hmri.org
Lomnicka
Magdalena
M
D000818:Animals; D002318:Cardiovascular Diseases / Q000139:chemically induced* / Q000503:physiopathology; D002986:Clinical Trials as Topic; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000009:adverse effects* / Q000378:metabolism*; D011464:Epoprostenol / Q000502:physiology; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors*; D008565:Membrane Proteins; D009569:Nitric Oxide / Q000502:physiology; D011451:Prostaglandin-Endoperoxide Synthases; D013927:Thrombosis / Q000139:chemically induced
D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D008565:Membrane Proteins; D009569:Nitric Oxide; D011464:Epoprostenol; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases