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.
 ...
PMID:Rofecoxib. 1124 95

Rofecoxib is a selective cyclo-oxygenase (COX)-2 inhibitor which has little or no effect on the COX-1 isoenzyme at doses up to 1000 mg/day. Rofecoxib has greater selectivity for COX-2 than celecoxib, meloxicam, diclofenac and indomethacin. In well-controlled clinical trials, rofecoxib 12.5 to 500 mg/day has been evaluated for its efficacy in the treatment of osteoarthritis, acute pain and rheumatoid arthritis [lower dosages (5 to 125 mg/day) were generally used in the chronic pain indications]. In the treatment of patients with osteoarthritis, rofecoxib was more effective in providing symptomatic relief than placebo, paracetamol (acetaminophen) and celecoxib and was similar in efficacy to ibuprofen, diclofenac, naproxen and nabumetone. Overall, both the physician's assessment of disease status and the patient's assessment of response to therapy tended to favour rofecoxib. In patients with postsurgical dental pain, pain after spinal fusion or orthopaedic surgery, or primary dysmenorrhoea, rofecoxib provided more rapid and more sustained pain relief and reduced requirements for supplemental morphine use after surgery than placebo. Rofecoxib was more efficacious than celecoxib in patients with acute dental pain and pain after spinal fusion surgery, although celecoxib may have been used at a subtherapeutic dose. In comparison with traditional nonsteroidal anti-inflammatory drugs (NSAIDs) ibuprofen, diclofenac and naproxen sodium, rofecoxib was similar in efficacy in the treatment of acute pain. Although naproxen sodium provided more rapid pain relief than rofecoxib in patients with primary dysmenorrhoea, the reverse was true after orthopaedic surgery: rofecoxib provided more rapid pain relief and less supplemental morphine was needed. Rofecoxib was as effective as naproxen in providing symptomatic relief for over 8700 patients with rheumatoid arthritis. Compared with traditional NSAID therapy, rofecoxib had a significantly lower incidence of endoscopically confirmed gastroduodenal ulceration and, in approximately 13,000 patients with osteoarthritis and rheumatoid arthritis, a lower incidence of gastrointestinal (GI) adverse events. Rofecoxib was generally well tolerated in all indications with an overall tolerability profile similar to traditional NSAIDs. The most common adverse events in rofecoxib recipients were nausea, dizziness and headache. In conclusion, rofecoxib is at least as effective as traditional NSAID therapy in providing pain relief for both chronic and acute pain conditions. Rofecoxib provides an alternative treatment option to traditional NSAID therapy in the management of symptomatic pain relief in patients with osteoarthritis. Initial data from patients with primary dysmenorrhoea and postoperative pain are promising and further trials may confirm its place in the treatment of these indications. Rofecoxib has also shown promising results in patients with rheumatoid arthritis and is likely to become a valuable addition to current drug therapy for this patient population. Importantly, rofecoxib is associated with a lower incidence of GI adverse events than traditional NSAIDs making it a primary treatment option in patients at risk of developing GI complications or patients with chronic conditions requiring long term treatment.
 ...
PMID:Rofecoxib: a review of its use in the management of osteoarthritis, acute pain and rheumatoid arthritis. 1139 14

Rofecoxib is a selective cyclooxygenase (COX)-2 inhibitor that is approved for the treatment of acute pain and osteoarthritis in adults. A sensitive and rapid high-performance liquid chromatographic (HPLC) method of determining rofecoxib in human serum is described. Alkalinized plasma samples are extracted into an organic solvent containing an internal standard and evaporated under nitrogen. The dried sample residues are reconstituted with mobile phase and analyzed by HPLC. The method uses 100 microL of the sample and is linear from 20 to 2000 ng/mL of rofecoxib. Precision and accuracy studies are performed. Stability of the drug in serum over four weeks is documented. This new method is simple, sensitive, precise, and accurate. Its use will translate into faster laboratory turnaround time, and the small sample volume required (100 microL) makes this assay suitable for pediatric patients. This assay will expedite pharmacokinetic studies and the therapeutic drug monitoring of rofecoxib and possibly other COX-2 inhibitors.
 ...
PMID:A rapid and sensitive high-performance liquid chromatography assay for rofecoxib in human serum. 1186 83

A series of 4-(4-cycloalkyl/aryl-oxazol-5-yl)benzenesulfonamide derivatives were synthesized and evaluated for their abilities to inhibit cyclooxygenase-2 (COX-2) and cyclooxygenase-1 (COX-1) enzymes. In this series, substituent effects at the ortho position to the sulfonamide group on the phenyl ring were examined. Most substituents reduced or lost both COX-2 and COX-1 activities. In contrast, introduction of a fluorine atom preserved COX-2 potency and notably increased COX1/COX-2 selectivity. This work led to the identification of a potent, highly selective, and orally active COX-2 inhibitor JTE-522 [9d, 4-(4-cyclohexyl-2-methyloxazol-5-yl)-2-fluorobenzenesulfonamide], which is currently in phase II clinical trials for the treatment of rheumatoid arthritis, osteoarthritis, and acute pain.
 ...
PMID:4-(4-cycloalkyl/aryl-oxazol-5-yl)benzenesulfonamides as selective cyclooxygenase-2 inhibitors: enhancement of the selectivity by introduction of a fluorine atom and identification of a potent, highly selective, and orally active COX-2 inhibitor JTE-522(1). 1190 92

Pharmacia (formerly Searle), in collaboration with Pfizer and Yamanouchi, has developed valdecoxib, a second-generation cyclooxygenase (COX)-2 inhibitor as a follow-up to celecoxib, for the treatment of arthritis. Pharmacia filed an NDA with the FDA in March 2001 for the treatment of acute pain, dysmenorrhea, osteoarthritis (OA) and rheumatoid arthritis (RA). At this time, Pharmacia anticipated a 12-month review [402883]. In June 2001, launch was anticipated in 2002 [412616], and in November 2001, valdecoxib was granted FDA approval [429715]. The company claims that valdecoxib has improved potency and broader therapeutic range than other COX-2 inhibitors including celecoxib, and has the potential for once-daily dosing [287279], [313957]. By 1999, due to the poor water solubility of valdecoxib, Searle was also developing the prodrug parecoxib [324667]. Valdecoxib has been described by Searle as almost superimposable at the site critical for COX-2 inhibition, a structural side pocket in the enzyme which coincides with the sulfonamide group of the drug [324667]. In April 2000, Morgan Stanley Dean Witter estimated sales would be US $400 million in 2003, rising to US $750 million in 2004 [375906]. In April 2001, Merrill Lynch predicted world sales of US $460 million in 2002, rising to $1,065 million in 2005 [420574]. In September 2000, Merrill Lynch reported that additional pain data were being accumulated for this drug, the possible inclusion of which could push filing back to later in the first half of 2001 [382577]. In May 2001, Merrill Lynch expected launch in 2002 [411811]. In August 2001, Lehman Brothers predicted that launch would take place in thefirst half of 2002 and the product would make peak sales of US $1,500 million [420809]. Credit Suisse predicted in this month that total sales would reach US $330 million in 2002, rising to US $1832 million in 2004 [422318]. In September 2001, Morgan Stanley expected launch in the first half of 2002 [427113]. By October 2001, Credit Suisse had revised its sales predictions to US $180 million in 2002, US $790 million in 2003 and US $1,430 in 2004 [427185].
 ...
PMID:Valdecoxib (Pharmacia). 1202 53

The economic evaluation of health care programs is undertaken to assess health care costs and benefits. Part of the goal of cost-effectiveness analysis is to maximize health benefits given the constraint of limited health care resources. The identification of costs is critical in a cost-effectiveness analysis of clinical interventions. The recent introduction of the cyclooxygenase (COX)-2-selective inhibitors, coxibs, for treatment of rheumatoid arthritis, osteoarthritis, and acute pain gives rise to cost-effectiveness issues. These new agents provide similar efficacy with fewer gastrointestinal events compared with nonselective nonsteroidal anti-inflammatory drugs (NSAIDs), but are more expensive on a per-dose basis. However, several modeled cost analyses have suggested that COX-2 inhibitors are cost effective in subsets of patients because they are associated with fewer downstream costs, particularly medical and surgical treatment of gastrointestinal adverse effects. Three cost-effectiveness models of interventions for rheumatoid arthritis and osteoarthritis, including COX-2 inhibitors, are reviewed. Prospective clinical investigation of the potential costs and benefits of these new agents is necessary to further support these findings.
 ...
PMID:Pharmacoeconomics of coxib therapy. 1220 85

The aim of this study was to evaluate the utility of the American Pain Society (APS) questionnaire in the assessment of osteoarthritis (OA) pain and to determine the onset of action of celecoxib in the treatment of acute flare pain in patients with OA of the knee or hip. Pooled data from three pivotal, randomized, double-blind, placebo-controlled, 12-week trials of patients with OA who exhibited a flare of disease activity after withdrawal of nonsteroidal anti-inflammatory drug or analgesic therapy were evaluated. Patients completed the APS Pain Measure Questionnaire, which evaluates pain intensity and quality of life, at baseline and daily for the first 7 days of therapy. In addition, patients underwent a range of standard OA assessments to evaluate the analgesic efficacy of celecoxib up to 12 weeks. Three thousand two hundred fifty-eight patients were enrolled in the three studies, of whom 2041 completed the APS questionnaire (1010 received celecoxib, 513 received naproxen, and 518 received placebo). Within the first 24 hours, celecoxib at a dose of 200 or 400 mg/d significantly reduced the amount of acute pain experienced compared with placebo for four of the five measures, and statistical significance for the remaining parameter, "pain in the last 24 hours," was achieved on day 2. Celecoxib at a dose of 200 to 400 mg/d provided similar efficacy to naproxen at a dose of 1000 mg/d. The pain relief observed with celecoxib was maintained for the APS evaluation period. Long-term efficacy assessments showed the efficacy of 200 mg/d of celecoxib to be continuous and maintained for at least the 12 weeks of the study and that it was equivalent to 400 mg/d of celecoxib and 1000 mg/d of naproxen. This study demonstrates that the APS questionnaire is a useful measure of pain and therapeutic response in OA. Celecoxib furthermore seems to be an effective acute and chronic analgesic in OA.
 ...
PMID:American pain society pain questionnaire and other pain measures in the assessment of osteoarthritis pain: a pooled analysis of three celecoxib pivotal studies. 1252 15

The development of COX2 inhibitors with improved biochemical selectivity (such as etoricoxib and valdecoxib) over that of commercially available coxibs has been driven by the potential advantage of safety using higher coxib doses for increased efficacy. Etoricoxib has been approved in the UK as a once-daily medicine for symptomatic relief in the treatment of osteoarthritis (OA), rheumatoid arthritis (RA) and acute gouty arthritis. It is currently approved with additional indications (i.e., for relief of acute pain associated with dental surgery, for primary dysmenorrhoea and for chronic musculo-skeletal pain, including chronic lower-back pain) in Mexico, Brazil and Peru. Etoricoxib has an in vitro COX1/COX2 IC(50) ratio of 344, the highest of any coxib. The administration of therapeutic doses of etoricoxib to healthy subjects does not affect COX1 activity in circulating platelets and gastric biopsies. The profound inhibition of monocyte COX2 activity at 24 h after dosing, as predicted by a pharmacological half-life of approximately 22 h, supports a once-daily dosing regimen of etoricoxib. In randomised, well-controlled clinical trials, etoricoxib has been shown to have a comparable clinical efficacy with traditional NSAIDs. Combined analysis of efficacy trials with etoricoxib versus non-selective NSAIDs has shown that the drug halves both investigator-reported upper gastrointestinal perforation, ulcers and bleeds (PUBs) and confirmed PUBs, and reduces the need for gastroprotective agents and gastrointestinal comedications by approximately 40%. The risk of lower extremity oedema and hypertension adverse experiences with etoricoxib was low and generally similar to comparator NSAIDs in a combined analysis of eight Phase III studies in OA, RA, chronic low-back pain and surveillance endoscopy. Large, randomised clinical trials have been planned to confirm the renal, gastrointestinal and cardiovascular safety of etoricoxib.
 ...
PMID:Clinical pharmacology of etoricoxib: a novel selective COX2 inhibitor. 1256 17

Coxibs are a new group of non-steroidal anti-inflammatory drugs (NSAIDs), which inhibit cyclooxygenase-2 selectively. They can be prescribed for treatment of osteoarthritis, rheumatoid arthritis, primary dysmenorrhea, and acute pain. Their main advantage is a reduction in the frequency of serious gastrointestinal complications compared to NSAIDs, but they have the same tendency to induce oedema and renal side effects. The coxibs do not influence platelet function. Meta-analysis of studies with coxibs suggests that they increase the risk of heart attack, but according to recent information this may have been exaggerated. Coxibs should be used for patients at risk for gastrointestinal complications and bleeding, but perhaps not for patients at risk for arterial thrombotic diseases.
 ...
PMID:[Coxiber and risk of myocardial infarction--the apprehension might have been exaggerated]. 1257

The role of the coxibs in the management of osteoarthritis and rheumatoid arthritis has been widely discussed, but there are other potential applications for the coxibs that have received less attention. Here we consider the use of the coxibs in acute pain syndromes such as primary dysmenorrhea and the pain associated with dental extraction, as well as considering their application in chronic low back pain and cancer pain. Another area where the coxibs may prove particularly beneficial is in the management of post-surgical pain. Traditional post-surgical analgesia has involved the use of non-selective NSAIDs and opioids, but these agents can be associated with side effects such as post-operative bleeding, gastrointestinal problems, nausea, and constipation. Because the coxibs do not inhibit COX-1 dependent platelet aggregation like traditional NSAIDs, the risk of post-surgical bleeding is reduced. The careful application of coxibs as part of a multi-modal approach to pain management in the perioperative period can reduce the requirement for opioid medications and thus reduce the risk of post-operative complications such as ileus. In the future, coxibs are likely to play an important role in multi-modal perioperative analgesic regimens with the aim of reducing post-operative periods of convalescence.
 ...
PMID:Strategies in pain management: new and potential indications for COX-2 specific inhibitors. 1260 54


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>