Cox-2 inhibitors: today and tomorrow.
The elucidation of inducible cyclooxygenase (Cox-2) dependent inflammatory pathways led to the development of specific Cox-2 inhibitors, the coxibs. These agents include the currently available celecoxib and rofecoxib and such second-generation agents as parecoxib, valdecoxib, and etoricoxib. The therapeutic advantage of coxibs is founded primarily in their lack of significant gastrointestinal (GI) side effects. Clinical trials have demonstrated the efficacy of coxibs to be completely comparable with traditional nonsteroidal anti-inflammatory drugs (NSAIDs), and pharmacoeconomics suggest favorable cost/benefit ratios with these agents compared with traditional NSAIDs, related to their reduced GI complication profiles and lower indirect costs associated with disability. Although several clinical questions remain (eg, use with low-dose aspirin, risk of thrombosis, myocardial infarction, edema, and hypertension), the emergence and clinical utility of coxibs is likely to continue on the basis of their efficacy and relative GI safety advantage. Although newer, more specific Cox-2 inhibitors may alter the choice, it is likely that this class of anti-inflammatories will become (if they have not already) the drugs of first choice in the treatment of acute pain, chronic pain, and most rheumatic conditions in the 21st century. In addition to the treatment of rheumatic conditions, it is possible that coxibs will also be of clinical utility in protection against malignant transformation and Alzheimer disease.
McMurray
Robert W
RW
Department of Internal Medicine, University of Mississippi Medical Center, Jackson 39216, USA. robert.mcmurray@med.va.gov
Hardy
Kenneth J
KJ
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D000068579:Celecoxib; D002986:Clinical Trials as Topic; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000627:therapeutic use*; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D000077613:Etoricoxib; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors*; D007555:Isoxazoles / Q000627:therapeutic use; D007783:Lactones / Q000627:therapeutic use; D008565:Membrane Proteins; D011451:Prostaglandin-Endoperoxide Synthases; D011720:Pyrazoles; D011725:Pyridines / Q000627:therapeutic use; D012106:Research / Q000639:trends; D013449:Sulfonamides / Q000627:therapeutic use; D013450:Sulfones / Q000627:therapeutic use; D000096926:Benzenesulfonamides
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000068579:Celecoxib; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D000077613:Etoricoxib; D007527:Isoenzymes; D007555:Isoxazoles; D007783:Lactones; D008565:Membrane Proteins; D011451:Prostaglandin-Endoperoxide Synthases; D011720:Pyrazoles; D011725:Pyridines; D013449:Sulfonamides; D013450:Sulfones; C116926:rofecoxib; C406224:valdecoxib; D000096926:Benzenesulfonamides; C409945:parecoxib; C496540:PTGS2 protein, human