[Coxibs: cyclooxygenase-2 inhibitors]

The oxygenating enzyme cyclooxygenase (COX) catalysis the conversion of arachidonic acid to proinflammatory prostaglandins. For many years it was thought that COX is a single enzyme that is present constitutively in most tissues. But in the late 80ies COX activity was found to be increased in inflammatory states with cytokines and bacterial lipopolysaccharides as inducing agents. The expression of the induced COX is inhibited by glucocorticoids which is not the case with the COX known up to then. According to these findings COX exists in two forms, the aminoacid sequences of which are known. The expression of COX-1 is not or only poorly regulated, the prostaglandins produced by it are responsible for the protection of the gastric mucosa, maintenance of normal kidney function and platelet aggregation. COX-2, in contrast, is highly regulated, the prostaglandins produced by this isoenzyme are involved in inflammation, fever and pain but also in the regulation of kidney function. Conventional non-steroidal antiinflammatory drugs (NSAIDs) inhibit both COX-1 and COX-2. The analgesic, antipyretic and antiinflammatory effects of these agents are accounted for by COX-2 inhibition, whereas the toxic effects on the stomach as well as the inhibition of platelet aggregation are attributed to COX-1 inhibition. In search for selective blockers of COX-2, celecoxib and rofecoxib were developed which have an analgetic and antirheumatic potency similar to that of conventional NSAIDs but are associated with significantly fewer adverse gastroduodenal events. The renal toxicity of the selective COX-2 inhibitors is not better than that of the non-selective NSAIDs.