highly selective COX-2 inhibitors may increase the incidence of edema and hypertension.As of August 2006,celecoxib is the only COX-2 inhibitor marketed in the USA.Rofecoxib and valdecoxib,two previously marketed,highly selective COX-2 inhibitors,have been withdrawn from the market due to their association with increased cardiovascular thrombotic events.In early 2005 a joint meeting of the Arthritis Advisory Committee and the Drug Safety and Risk Management Advisory Committee conducted by the FDA convened to assess the risk and give recommendations concerning the COX-2 inhibitors and other NSAIDs.It was concluded that there was not sufficient evidence to withdraw the COX-2 inhibitors but "black box"warnings concerning the cardiovascular risks were added to the product label.Additionally,it was recommended that all other NSAID product labels be revised to include cardiovascular risks.Presently,the future of the COX-2 inhibitors is unclear. The NSAIDs decrease the sensitivity of vessels to bradykinin and histamine,affect lymphokine production from T lymphocytes,and reverse the vasodilation of inflammation.To varying degrees,all newer NSAIDs are analgesic, anti-inflammatory,and antipyretic,and all(except the COX-2-selective agents and the nonacetylated salicylates)inhibit platelet aggregation.NSAIDs are all gastric irritants as well,although as a group the newer agents tend to cause less gastric irritation than aspirin.Nephrotoxicity has been observed for all of the drugs for which extensive experience has been reported,and hepatotoxicity can also occur with any NSAID Nephrotoxicity is due,in part,to interference with the autoregulation of renal blood flow,which is modulated by prostaglandins. Although these drugs effectively inhibit inflammation,there is no evidence that%in contrast to drugs such as methotrexate and goldthey alter the course of an arthritic disorder. Several NSAIDs (including aspirin)appear to reduce the incidence of colon cancer when taken chronically.Several large epidemiologic studies have shown a 50% reduction in relative risk when the drugs are taken for 5 years or longer.The mechanism for this protective effect is unclear. ASPIRIN Introduction Aspirin's long use and availability without prescription diminishes its glamour compared with that of the newer NSAIDs.Aspirin is now rarely used as an anti-inflammatory medication;it has been replaced by ibuprofen and naproxen,since they are effective,are also available over the counter,and have good to excellent safety records.highly selective COX-2 inhibitors may increase the incidence of edema and hypertension. As of August 2006, celecoxib is the only COX-2 inhibitor marketed in the USA. Rofecoxib and valdecoxib, two previously marketed, highly selective COX-2 inhibitors, have been withdrawn from the market due to their association with increased cardiovascular thrombotic events. In early 2005 a joint meeting of the Arthritis Advisory Committee and the Drug Safety and Risk Management Advisory Committee conducted by the FDA convened to assess the risk and give recommendations concerning the COX-2 inhibitors and other NSAIDs. It was concluded that there was not sufficient evidence to withdraw the COX-2 inhibitors but "black box" warnings concerning the cardiovascular risks were added to the product label. Additionally, it was recommended that all other NSAID product labels be revised to include cardiovascular risks. Presently, the future of the COX-2 inhibitors is unclear. The NSAIDs decrease the sensitivity of vessels to bradykinin and histamine, affect lymphokine production from T lymphocytes, and reverse the vasodilation of inflammation. To varying degrees, all newer NSAIDs are analgesic, anti-inflammatory, and antipyretic, and all (except the COX-2-selective agents and the nonacetylated salicylates) inhibit platelet aggregation. NSAIDs are all gastric irritants as well, although as a group the newer agents tend to cause less gastric irritation than aspirin. Nephrotoxicity has been observed for all of the drugs for which extensive experience has been reported, and hepatotoxicity can also occur with any NSAID. Nephrotoxicity is due, in part, to interference with the autoregulation of renal blood flow, which is modulated by prostaglandins. Although these drugs effectively inhibit inflammation, there is no evidence that¾in contrast to drugs such as methotrexate and gold¾they alter the course of an arthritic disorder. Several NSAIDs (including aspirin) appear to reduce the incidence of colon cancer when taken chronically. Several large epidemiologic studies have shown a 50% reduction in relative risk when the drugs are taken for 5 years or longer. The mechanism for this protective effect is unclear. ASPIRIN Introduction Aspirin's long use and availability without prescription diminishes its glamour compared with that of the newer NSAIDs. Aspirin is now rarely used as an anti-inflammatory medication; it has been replaced by ibuprofen and naproxen, since they are effective, are also available over the counter, and have good to excellent safety records