Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver
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The introduction of selective inhibitors of cyclo-oxygenase-2 to the marketplace has been much anticipated for several years. It would appear that these compounds have lived up to the expectations of having reduced gastrointestinal toxicity and, at least for some indications, of efficacy similar to that of conventional non-steroidal anti-inflammatory drugs. However, there is a growing body of evidence suggesting that cyclo-oxygenase-2 plays a very important role in gastrointestinal mucosal defence, particularly in situations in which the mucosa is damaged or inflamed. ⋯ Indeed, there is recent evidence of increased rates of myocardial infarction in arthritis patients taking a selective cyclo-oxygenase-2 inhibitor. Use of low-dose aspirin concurrently with use of a selective cyclo-oxygenase-2 inhibitor may provide some degree of protection against the potential cardiovascular toxicity of the latter but both laboratory and clinical studies suggest that the concomitant use of these two types of drugs results in gastrointestinal ulceration comparable to what is seen with conventional non-steroidal anti-inflammatory drugs. These recent results suggest that care must be exercised in the use of selective cyclo-oxygenase-2 inhibitors by individuals who are at increased risk of myocardial infarction and stroke, and the use of low-dose aspirin by these patients may place them at increased risk of gastrointestinal complications.
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Non-steroidal anti-inflammatory drugs are among the most commonly used medications and they are a mainstay in the treatment of inflammatory diseases. Non-steroidal anti-inflammatory drugs are widely used to reduce pain associated with acute or chronic inflammation. Recently, a new class of inhibitors of the inducible enzyme cyclo-oxygenase-2 have become available. ⋯ While a role of cyclo-oxygenase-2 in the development of chronic inflammation has been well established, its role in pain perception is still unclear. Recent experimental data led to the hypothesis that cyclo-oxygenase-1 plays an important role in pain perception. This short review addresses some recent preclinical data as well as some clinical evidence showing that cyclo-oxygenase-1 is an important component of inflammatory pain.
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Cyclo-oxygenase (prostaglandin endoperoxide synthase) is the enzyme which metabolizes the conversion of arachidonic acid to prostaglandin. It exists in at least two isoforms: the constitutive (cyclo-oxygenase-1) and the inducible (cyclo-oxygenase-2) which is controlled by a number of factors, including cytokines and intracellular messengers. These enzymes are the therapeutic targets of non-steroidal anti-inflammatory drugs such as aspirin and ibuprofen. ⋯ Although cyclo-oxygenase-1 seems to be expressed in physiological conditions and cyclo-oxygenase-2 in inflammatory conditions, it is not yet possible to identify all their different roles. Cyclo-oxygenase-2 may be expressed constitutively, whereas the generation of prostaglandin by cyclo-oxygenase-2 may replace that by cyclo-oxygenase-1 in some situations (or vice-versa). Both cyclo-oxygenase isoenzymes contribute to mucosal defence and the inhibition of the two isoforms contributes to the pathogenesis of non-steroidal anti-inflammatory drug-induced gastric damage.