Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0184567 (acute pain)
 3,962 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Rofecoxib (Vioxx, Merck & Co., Inc.) is a new orally-effective non-steroidal anti-inflammatory drug (NSAID) approved for treatment of acute pain, fever, primary dysmenorrhea and pain and inflammation in osteoarthritis (OA). It is also being evaluated for treatment of rheumatoid arthritis and adenomatous polyps of the colon. Rofecoxib is a specific inhibitor of cyclooxygenase-2 (COX-2), thereby inhibiting prostanoid synthesis in cells that express COX-2, including inflammatory cells. As cells in the gastrointestinal (GI) tract principally express COX-1, a different isoform of cyclooxygenase, it is predicted that rofecoxib will have less GI toxicity than other less selective NSAIDs. In clinical trials, rofecoxib was found to be as effective as other NSAIDs for management of pain and inflammation. In trials that compare rofecoxib with ibuprofen, diclofenac and indomethacin, less GI toxicity has been observed, as assayed by a decrease in lesions visible on endoscopy, by GI blood loss and, in a meta-analysis, by frequency of serious adverse GI events. The presence of COX-2 in cells other than inflammatory cells results in side effects common among NSAIDs, including peripheral oedema and hypertension. These side effects are dose-dependent. Rofecoxib, together with other branded NSAIDs, are relatively expensive, which has led to concern regarding costs versus benefits. There is also concern regarding potential risks associated with the use of rofecoxib by populations that would otherwise not tolerate NSAIDs.
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PMID:Rofecoxib. 1124 95

The introduction of celecoxib (Celebrex, Figure 1; GD Searle and Co) as the first cyclooxygenase (COX)2 selective inhibitor in the US and the expected introduction of rofecoxib (Vioxx; Merck and Co Inc) as the first COX2 inhibitor with an acute pain indication, has prompted interest in this class of drugs as a possible therapeutic improvement on dual COX1/COX2 inhibitor NSAIDs, currently on the market. Recognition that the COX-2 enzyme may have a broader role than pain and inflammation has led to studies investigating the efficacy of COX-2 inhibitors for Alzheimer's disease (AD), stroke, cardiovascular disease and colon cancer. Speakers at the second annual conference sponsored by IBC, addressed issues ranging from the basic concepts of COX2 specificity versus selectivity, pathways and regulatory factors related to COX2 expression, the principles underlying the possible broad implications of the COX2 mechanisms, as well as summaries of recently completed clinical trials supporting the clinical efficacy and safety of COX2 inhibitors in humans. The timeliness of this meeting is emphasized by the recent approval of rofecoxib by the FDA Arthritis Advisory panel and the initial reports in the media of toxicity attributed to celecoxib. Preclinical and limited clinical data presented suggest possible therapeutic roles for selective COX2 inhibitors in neurodegeneration due to both AD and stroke, the prevention and treatment of colon cancer, prevention of premature labor, as well as pain and inflammation.
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PMID:COX-2 inhibitors--IBC conference. 12-13 April 1999, Coronado, CA, USA. 1612 36

London's first-in-man drug trial with the monoclonal anti-CD28 antibody TGN1412 used for the treatment of oncological and autoimmune diseases resulted in a disaster with life-threatening adverse events in the volunteers triggered by an unexpected cytokine storm. Potential mistakes and consequences from this trial are highlighted in the general context of drug development and its risks. Risks in drug testing are not only found for high risk substances, such as TGN1412, or in the critical first-in-man phase, but can sometimes be detected only in later phases of the clinical testing, such as the phase 3 submission studies, or even after market authorization, as for example was the case in the cyclooxygenase-2-inhibitor rofecoxib (Vioxx) used for the treatment of rheumatic diseases and acute pain. Regulatory requirements to minimize risks in drug trials, however, have improved substantially over the last decades. Moreover, in light of the London incident these are being continuously modified with great diligence.
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PMID:[Drug trials in humans. Risks in the light of the London catastrophe]. 1730 13