COX-2 specific inhibitors offer improved advantages over traditional NSAIDs.
Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most widely prescribed medications worldwide and are often the first choice of treatment for acute myalgias, orthopedic injuries, postoperative pain, chronic rheumatoid arthritis, and osteoarthritis. The mechanism through which NSAIDs provide analgesia and suppress inflammation is the inhibition of the enzyme cyclooxygenase, resulting in decreased prostaglandin synthesis. The suppression of prostaglandin synthesis can also produce gastric and renal toxicity, as well as impair normal platelet function. Thus, NSAIDs are associated with potentially harmful side effects. Cyclooxygenase exists in two isoenzymatic forms, cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2). Cyclooxygenase-1 appears to be constitutively expressed in many tissues and produces prostaglandins, which regulate normal cellular functions. However, COX-2 activity is induced by proinflammatory cytokines and produces prostaglandins that mediate the inflammatory response and pain signaling transmission. Traditional nonspecific NSAIDs inhibit both COX-1 and COX-2, and in doing so, not only decrease inflammation and pain, but also promote gastrointestinal tract damage and bleeding. The potential clinical benefit of COX-2 inhibitors is significant due to the number of patients chronically treated with NSAIDs and the three- to ten-fold higher risk of gastrointestinal injury and death associated with traditional NSAIDs. Recently, a class of anti-inflammatory medications has been developed that primarily inhibits COX-2 while sparing the enzymatic activity of COX-1 at therapeutic dosages. Two medications that predominantly inhibit only COX-2, rofecoxib and celecoxib, are currently available by prescription in the United States.
Hospital for Special Surgery, New York, NY 10021, USA.
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Urban
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects* / Q000627:therapeutic use; D001168:Arthritis / Q000188:drug therapy*; D000068579:Celecoxib; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000627:therapeutic use*; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D007783:Lactones / Q000627:therapeutic use; D008565:Membrane Proteins; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D011453:Prostaglandins / Q000378:metabolism; D011720:Pyrazoles; D011788:Quality of Life; D013449:Sulfonamides / Q000627:therapeutic use; D013450:Sulfones
D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D016207:Cytokines; D007527:Isoenzymes; D007783:Lactones; D008565:Membrane Proteins; D011453:Prostaglandins; D011720:Pyrazoles; D013449:Sulfonamides; D013450:Sulfones; C116926:rofecoxib; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D000068579:Celecoxib