Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030193 (pain)
 261,466 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nimesulide, a non-steroidal anti-inflammatory drug (NSAID), is administered orally or rectally twice daily for a variety of inflammation and pain states. This is a unique NSAID, not only because of its chemical structure but also because of its specific affinity to inhibit cyclooxygenase-2 (COX-2), thus exerting milder effects on the gastrointestinal mucosa. Current data on selective COX-2 inhibitors suggest that they may have an efficacy similar to that of standard NSAIDs. Initial general clinical experience with selective COX-2 inhibitors appears to show that they are particularly promising in individuals at risk because of renal diseases, hypertension or congestive heart failure. Various experimental models and clinical studies have demonstrated the anti-inflammatory efficacy of nimesulide. Nimesulide is superior, or at least comparable in efficacy, to other NSAIDs, but is better tolerated and has less potential for adverse reactions. Thus, selective COX-2 inhibitors should have anti-inflammatory effects devoid of side effects on the kidney and stomach. They may also demonstrate new important therapeutic benefits as anticancer agents as well as help prevention of premature labour and even retard the progression of Alzheimer's disease. No clinically significant drug interactions have been reported for nimesulide. Not much has been reported about the pharmaceutical aspects of nimesulide. Its poor aqueous solubility poses bioavailability problems in-vivo. This could be overcome by the formation of inclusion complexes with beta-cyclodextrin, as has been reported by various researchers. However, absence of any in-vivo data regarding the relative absorption of nimesulide from beta-cyclodextrin complex compared with that from conventional formulations of the drug makes the use of such fast-releasing complexes rather questionable. Only a limited number of assay procedures (HPLC, spectrophotometric, spectrofluorimetric) for the determination of nimesulide and its metabolite in plasma/urine samples or in dosage forms have been reported in the literature. The purpose of this review is to provide a concise overview of the pharmacological and pharmaceutical profile of nimesulide. Various investigations carried out recently are reported, although older references to research performed on nimesulide have also been included, where appropriate.
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PMID:Nimesulide: some pharmaceutical and pharmacological aspects--an update. 1086 34

Nonsteroidal anti-inflammatory drugs (NSAIDs) play a major role in the management of inflammation and pain caused by arthritis. A new class of NSAIDs that selectively inhibit the cyclooxygenase-2 (COX-2) enzyme has been developed. The first COX-2 inhibitors, celecoxib and rofecoxib, are said to provide therapeutic benefit with less toxicity than traditional NSAIDs. A third COX-2-selective inhibitor, meloxicam, has recently been introduced. COX-2 inhibitors and traditional NSAIDs do not appear to differ significantly in their effectiveness in alleviating pain or inflammation. They have similar gastrointestinal side effects, including abdominal pain, dyspepsia and diarrhea. However, short-term studies show fewer gastrointestinal ulcers in patients treated with COX-2 inhibitors compared with traditional NSAIDs.
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PMID:Cyclooxygenase-2 enzyme inhibitors: place in therapy. 1123 80

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.
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PMID:COX-2 specific inhibitors offer improved advantages over traditional NSAIDs. 1091 95

Arthritis is a major burden on society and the individual. Arthritis affects all age groups and races, and is more prevalent in women than men by approximately 1.65:1. Nearly one half of people aged > or = 65 years report the presence of arthritic symptoms; however, by no means is arthritis a disease of only the elderly. The burden of arthritis will continue to increase due to expected future increases in the size and age of the general population. Currently, the total costs of medical care and lost wages due to arthritis are in excess of 64 billion dollars per year in the United States. For the individual, arthritis may cause substantial pain, impair mobility, curtail physical activity, and have a negative impact on mental health. The two most common forms of arthritis, osteoarthritis and rheumatoid arthritis, have major health complications. From the perspective of the orthopedic surgeon, the aim of treatment of arthritic conditions includes early, accurate diagnosis and appropriate treatment to minimize pain and maximize function. Nonsteroidal anti-inflammatory drugs (NSAIDs) are frequently used as part of the medical management of patients with arthritis. These medications are effective in mitigating pain and inflammation associated with arthritis. However, side effects (most notably of the gastrointestinal tract) have limited the more widespread use of NSAIDs. The newer cyclooxygenase-2 (COX-2) inhibitors have proven to be efficacious and have demonstrated fewer gastrointestinal adverse effects. Furthermore, COX-2 inhibitors do not appear to adversely affect platelet function. For these reasons, consideration may be given to using COX-2 perioperatively, however, drug interactions must be closely monitored.
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PMID:Use of COX-2 specific inhibitors in operative and nonoperative management of patients with arthritis. 1091 96

Arthritis does not escape the athlete. From the recreational athlete to the professional athlete, arthritis can be a common and perplexing problem. In the typical orthopedic sports medicine practice, it is no longer uncommon to see relatively young patients suffering from arthritis. It can affect the major joints such as the knee, hip, ankle, shoulder, and elbow. One of the most common problems is shoulder arthritis secondary to injury in recreational athletes. Athletes at risk for shoulder arthritis typically include overhead athletes and weight lifters. The clinical presentation is usually specific for pain, decreased range of motion, and sometimes mechanical symptoms. Physical examination reveals a loss of motion, crepitus, catching, and locking; often, there is associated underlying instability. Radiographs can confirm the diagnosis of glenohumeral degenerative arthritis. Pain control is a primary objective when treating these athletes with arthritis at any level. Cyclooxygenase-2 (COX-2) specific inhibitors are emerging as primary treatment because of their anti-inflammatory and analgesic effect. Although a nonsteroidal anti-inflammatory drugs, COX-2 inhibitors block the enzymes that trigger pain and inflammation, while sparing a related enzyme that helps maintain the normal stomach lining (cyclooxygenase-1). In contrast, traditional nonsteroidal anti-inflammatory drugs block both enzymes and may cause damage to the stomach lining, potentially leading to ulcers. Minimally invasive surgery can be performed as a palliative procedure for treating early arthritis in athletes. These procedures include removal of loose bodies, debridement, capsular release, and other associated procedures such as rotator cuff repair and decompression. Rehabilitation plays an important role in nonoperative treatment and also an important role in postoperative treatment particularly to restore motion. Modification of activities continues to be an important adjunct in managing these types of arthritic problems in relatively young athletes.
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PMID:Current concepts in sports medicine: the use of COX-2 specific inhibitors and the emerging trends in arthroscopic surgery. 1091 97

It is well recognized that nonsteroidal antiinflammatory drugs (NSAIDs) induce gastrointestinal (GI) ulcerations, perforation and bleeding, which clearly limit their therapeutic value. The recent introduction of NSAIDs with selective cyclooxygenase-2 (COX-2) inhibitory effect is a major pharmacologic milestone in therapeutics. Selective COX-2 inhibitors exhibit considerable dissociation between their antiinflammatory/analgesic action and their GI toxicity. However, from a therapeutic consideration, there are still several unresolved and confusing issues with these drugs such as: the pharmacologic classification of the COX-2 selectivity; therapeutic value as antirheumatic/analgesic drugs; potential toxicity in patients at risk for the development of ulcer-related complications or patients with inflammatory bowel disease and potential renal toxicity. Although existing clinical efficacy studies with celecoxib and rofecoxib, two selective COX-2 inhibitors, were associated with considerably lower ulcerogenic rates when compared with nonselective NSAIDs, there are no long term outcome studies with these drugs similar to the MUCOSA trial performed with misoprostol. Furthermore, the selectivity of COX-2 inhibitors appears to be specific to the stomach and duodenum but not the kidney. While awaiting additional long term studies with selective COX-2 inhibitors, we recommend instituting prophylactic therapy with misoprostol in patients at risk for the development of ulcer related complications. In conclusion, we believe that the introduction of selective COX-2 inhibitors will revolutionize the treatment of pain and inflammation. However, additional basic and clinical studies are required to address the pharmacologic and therapeutic uncertainties for this class of drugs.
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PMID:Selective COX-2 inhibitors and gastrointestinal mucosal injury: pharmacological and therapeutic considerations. 1095 41

Pain is the most important symptom of osteoarthritis (OA) and the reason why individuals seek medical treatment. The anatomic cause is unclear and is likely to vary between individuals. Recent work confirms the heterogeneity of pain in OA with differences in severity, location, precipitating and relieving factors, and response to intra-articular anesthetic. Nonpharmacologic treatment of OA is important and evidence is now accumulating for interventions such as aerobic exercise, quadriceps exercises, footwear modification, education, and social support. Analgesia remains the first choice drug therapy: compounds more potent than acetaminophen are now available and effective. New cyclooxygenase-2 (COX-2) inhibitors may have a role in subjects for whom simple analgesia is inadequate. Glucosamine is a simple, safe product that appears to have a weak pain-relieving effect, and intra-articular hyaluronate injections may also have a limited role. Recent community studies confirm the benefit of joint replacement in OA, though a number of questions remain about the timing, indications, and alternatives to surgery.
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PMID:Osteoarthritis pain and its treatment. 1099 Jan 86

Research strongly indicates that increased expression of the isoenzyme cyclooxygenase-2 (COX-2) is responsible for elevated production of prostaglandins in inflamed joint tissues and is involved in the mediation of pain. In contrast, COX-1 is a constitutively produced isoenzyme that is involved in the synthesis of eicosanoids that have important homeostatic functions, for example, in the gastric mucosa and platelets. This new knowledge led to the development of drugs that are highly specific inhibitors of COX-2 while not inhibiting COX-1 at maximally efficacious dosages. The first COX-2 specific agent approved for clinical use in the United States was celecoxib. Large multicenter trials have shown that celecoxib at dosages of 100 mg BID and 200 mg BID is as effective as naproxen 500 mg BID in patients with osteoarthritis of the knee or hip. Another large multicenter trial also demonstrated that celecoxib 200 mg BTD and 400 mg BID is as effective as naproxen 500 mg BID in patients with rheumatoid arthritis (RA). A comparative trial showed that celecoxib 200 mg BID is as effective as diclofenac SR 75 mg BID in patients with RA. The potential of COX-2 specific inhibitors to provide antiinflammatory and analgesic efficacy equivalent to that of conventional nonsteroidal antiinflammatory drugs without the adverse gastrointestinal mucosal and platelet effects associated with nonspecific COX inhibitors promises to revolutionize the clinical care of arthritis patients.
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PMID:Antiinflammatory and analgesic efficacy of COX-2 specific inhibition: from investigational trials to clinical experience. 1103 98

The prostaglandin series of bioactive compounds is formed by the interaction of two distinct but related enzymes, cyclo-oxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2). COX-1 is a constitutive form which is present mainly in the gastric mucosa, kidney and platelets. COX-2 is mainly an inducible form, although also to some extent present constitutively in the CNS, the juxtaglomerular apparatus of the kidney and in the placenta during late gestation. Both isoforms contribute to the inflammatory process, but COX-2 is of considerable therapeutic interest as it is induced, resulting in an enhanced formation of prostaglandins, during acute as well as chronic inflammation. Conventional NSAIDs inhibit both isoforms to a similar extent and in an approximately equal dose and concentration range. The two recently developed and clinically available selective COX-2 inhibitors, celecoxib and rofecoxib, are about 100-1000 times more selective on the COX-2 than on the COX-1 isoform. In Europe rofecoxib is today indicated for the symptoms and signs of osteoarthritis, whereas celecoxib is indicated for both osteoarthritis and rheumatoid arthritis. The major clinical interest of these drugs has been related to the lower incidence of gastrointestinal bleeding which, with the conventional COX-1/COX-2 agents has been a source of hospitalisation, disablement and death, especially in the elderly. Clinical trials have convincingly demonstrated that celecoxib and rofecoxib in clinical use induce very few gastrointestinal complications compared to conventional and non-selective NSAIDs. However, the well known contraindications for NSAIDs, such as late pregnancy, aspirin-induced asthma, congestive heart failure and renal dysfunction, will so far apply also to the COX-2 inhibitors. Compared to the traditional and non-selective NSAIDs, COX-2 inhibitors may provide an insight into additional therapeutic areas, such as gastrointestinal cancer and dementia, where the potential relevance to COX-2 mechanisms are currently being explored and clinical trials being performed. With the rapid clinical acceptance of celecoxib and rofecoxib, knowledge about their clinical usefulness in various inflammatory disease states and pain disorders is increasing. For the many patients suffering from such conditions, the selective COX-2 inhibitors are likely to become a significant addition to the therapeutic arsenal of analgesic and anti-inflammatory drugs.
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PMID:COX-2-Specific inhibitors--the emergence of a new class of analgesic and anti-inflammatory drugs. 1105 20

Cyclooxygenase-2 (COX-2) inhibitors constitute a new group of non-steroidal anti-inflammatory drugs (NSAIDs) which, at recommended doses, block prostaglandin production by cyclooxygenase-2, but not by cyclooxygenase-1. Two COX-2 inhibitors are currently available in Australia--celecoxib, which is taken twice daily, and rofecoxib, which is taken once daily. Both drugs act rapidly in providing pain relief and their anti-inflammatory analgesic effect in osteoarthritis and rheumatoid arthritis is equivalent to standard doses of non-selective NSAIDs. Celecoxib and rofecoxib show significantly lower incidences of gastrotoxicity (as measured by endoscopic studies and gastrointestinal ulcers and bleeds) than non-selective NSAIDs. There is Level 2 evidence that COX-2 inhibitors: reduce pain in classic pain models--third-molar extraction, dysmenorrhoea and after orthopaedic surgery; reduce pain and disability in osteoarthritis of the hip and knee; and reduce pain and disability in rheumatoid arthritis. Other adverse effects, such as interference with antihypertensive agents and the potential to produce renal dysfunction in patients with compromised renal function by COX-2 inhibitors, seem similar to those of non-selective NSAIDs.
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PMID:COX-2 inhibitors. 1134 18


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