Clinical implications of selective cyclooxygenase-2 inhibition.
Inducible cyclooxygenase-2 (COX-2), but not constitutive COX-1, can be upregulated in rheumatoid synovial tissue by interleukin-1 beta and phorbol esters and is inhibited by dexamethasone. This supports the role of COX-2 in acute inflammation in arthritis. Selective inhibition of COX-2 by non-steroidal anti-inflammatory drugs (NSAIDs) has been proposed as an approach to reduce their associated side effects while maintaining efficacy. The improved safety profile of selective COX-2 inhibitors will allow more widespread and sustained use than is currently possible with standard NSAIDs. In rheumatoid arthritis they may be used as effective symptomatic relief, in combination with disease modifying therapy at an early stage of disease. In osteoarthritis, and, more particularly, soft tissue rheumatism, pain contributes to the development of chronic disease, therefore the main benefit of selective COX-2 inhibition will be to provide safe, effective pain relief to maintain mobility and reduce disability.
Emery
P
P
Department of Rheumatology and Rehabilitation, Leeds University, UK.
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D018501:Antirheumatic Agents / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000627:therapeutic use*; D006801:Humans; D007527:Isoenzymes / Q000502:physiology*; D008565:Membrane Proteins; D010003:Osteoarthritis / Q000188:drug therapy*; D011451:Prostaglandin-Endoperoxide Synthases / Q000502:physiology*; D013583:Synovial Membrane / Q000201:enzymology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D018501:Antirheumatic Agents; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D008565:Membrane Proteins; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases