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Query: UMLS:C0018681 (headache)
 56,091 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The purpose of this paper is to review the rationale for a new class of nonsteroidal anti-inflammatory drugs (NSAIDs) known as selective cyclooxygenase (COX)-2 inhibitors and to present preliminary clinical data on 2 COX-2 inhibitors that are approved for use in the United States. The primary mechanism of NSAIDs in the treatment of inflammation is the inhibition of COX, which exists in 2 forms. COX-I appears to regulate many normal physiologic functions, and COX-2 mediates the inflammatory response. Theoretically, an NSAID that inhibits COX-2 selectively should decrease inflammation but not influence normal physiologic functions and thus should cause fewer gastrointestinal side effects. Preliminary data suggest that celecoxib, a highly selective COX-2 inhibitor, is superior to placebo and similar to traditional NSAIDs in the short-term treatment of pain due to osteoarthritis, although it has been associated with adverse effects such as headache, change in bowel habits, abdominal discomfort, and dizziness. Celecoxib also has been shown to be as effective as traditional NSAIDs in the treatment of rheumatoid arthritis, but it may cause fewer adverse effects, including endoscopically documented ulcers. Celecoxib is metabolized in the liver by the cytochrome P-450 isozyme CYP2C9, and thus serious drug interactions are possible. In the treatment of osteoarthritis, rofecoxib has been shown to be as effective as traditional NSAIDs and may cause fewer endoscopically documented ulcers, but its complete adverse-effect profile is not known. Until the selective COX-2 inhibitors are widely used and more clinical as well as pharmacoeconomic studies are published, the exact role of COX-2 therapy cannot be determined. words: cyclooxygenase, celecoxib, rofecoxib, rheumatoid arthritis, osteoarthritis.
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PMID:Selective cyclooxygenase-2 inhibitors for the treatment of arthritis. 1046 13

Rofecoxib selectively inhibits cyclo-oxygenase-2 in a dose-dependent manner in humans. No significant inhibition of cyclo-oxygenase-1 is observed with rofecoxib up to doses of 1000 mg. In 4 large double-blind randomised trials performed in patients with osteoarthritis, rofecoxib 12.5 and 25 mg/day significantly improved physical functioning, assessed using the Western Ontario and McMasters Universities Osteoarthritis Index and patient or investigator global assessment, compared with placebo. In addition, rofecoxib showed similar clinical efficacy to that observed with diclofenac 50 mg 3 times daily, ibuprofen 800 mg 3 times daily and nabumetone 1500 mg once daily. Rofecoxib is also an effective analgesic in patients with primary dysmenorrhoea or postoperative dental pain and demonstrates similar analgesic efficacy to that of naproxen sodium and ibuprofen. Rofecoxib is generally well tolerated. The most common adverse events associated with rofecoxib are diarrhoea, headache, nausea and upper respiratory tract infection. There was a significantly lower incidence of upper-gastrointestinal adverse events (perforations, ulcers and bleeds) in patients with osteoarthritis receiving rofecoxib 12.5, 25 or 50 mg/day than in those receiving ibuprofen, diclofenac or nabumetone.
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PMID:Rofecoxib. 1049 77

Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most frequently prescribed drugs, despite their well-established association with gastroduodenal injury. Recent discovery of the cyclooxygenase (COX) isoenzymes COX-1 and COX-2 has improved our knowledge of the action of NSAIDs. COX-1 is continuously expressed in almost all tissues, where it converts arachidonate to the prostaglandins (PGs) important in homeostatic function; COX-2 is present in immune cells, blood vessel endothelial cells, and synovial fibroblasts. Classic NSAIDs inhibit both COX isoenzymes by occupying the cyclooxygenase-active site, preventing access by arachidonic acid. In theory, a drug such as celecoxib that selectively inhibited COX-2 might block inflammation, pain, and fever while reducing the side effects (gastric erosions and ulcers) associated with inhibition of COX-1. In animal models of inflammation and pain, celecoxib has shown marked suppression of PG production and inflammation compared with indomethacin, the standard COX-1/COX-2 inhibitor. In clinical trials, celecoxib dosed at 100, 200, and 400 mg BID was found to significantly reduce the signs and symptoms of rheumatoid arthritis (RA) and osteoarthritis. In one RA study, celecoxib was found to be as clinically effective as diclofenac after 24 weeks of treatment; at the end of the study, gastroduodenal ulcers occurred significantly more frequently in the diclofenac group (15%) than in the celecoxib group (4%). In a 1-week endoscopy study comparing celecoxib with naproxen and placebo, the incidence of gastric erosions/ulcers was significantly greater in the naproxen group than in the celecoxib or placebo group. The most common adverse effects of celecoxib in clinical studies were headache, diarrhea, abdominal discomfort, and dizziness. Celecoxib has shown significant equivalent anti-inflammatory and analgesic efficacy and has produced less endoscopically apparent gastrointestinal (GI) ulceration or erosion than have 3 classic NSAIDs. Whether it will have long-term GI adverse effects or interact with other medications to cause serious adverse responses (eg, increased GI bleeding or rash in conjunction with other sulfonamide-like drugs) is unknown and remains to be established.
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PMID:Celecoxib, a selective cyclooxygenase-2 inhibitor for the treatment of rheumatoid arthritis and osteoarthritis. 1050 45

The efficacy and tolerability of amtolmetin guacyl (AMG), a new non-steroidal anti-inflammatory drug, were compared with piroxicam, in patients with osteoarthritis. In a randomized double-blind study patients with arthritis (n = 99) received either 600 mg AMG on an empty stomach or 20 mg of piroxicam on a full stomach, once daily for 30 days. All clinical parameters improved significantly with both drugs; there were no significant differences between the two treatments. Tolerability, assessed by the patients, was significantly better in the AMG group. In the piroxicam group nine of 50 patients withdrew because of side-effects (gastrointestinal) compared with two of 49 (nausea and headache) in the AMG group. There were three cases of perforation, ulcer and bleeding in the piroxicam group but no serious side-effects with AMG. Total numbers of side-effects were similar in the two groups, but epigastric and abdominal pain were more frequent and more intense with piroxicam. AMG was as effective as piroxicam in controlling the symptoms of osteoarthritis, but showed better gastrointestinal tolerability.
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PMID:Amtolmetin guacyl versus piroxicam in patients with osteoarthritis. 1089 21

Following a fortuitous observation that migraine headaches ceased in a patient receiving glucosamine therapy for osteoarthritis, a further ten patients with migraine or migraine-like vascular headaches, refractory to established preventive or abortive therapies, have been treated with daily oral glucosamine. After a lag of 4-6 weeks, a substantial reduction in headache frequency and/or intensity has been noted; in some cases, the benefit appears to be dose-dependent. Since glucosamine can be a rate-limiting precursor for mucopolysaccharide synthesis, it is germane to note previous reports that heparin and pentosan polysulfate may have migraine-preventive activity. There is reason to suspect that mast cells are central mediators of the neurogenic inflammation associated with migraine and cluster headaches. The heparin produced by mast cells may function to provide feedback down-regulation of mast cell activation, and exerts a range of other anti-inflammatory effects. We postulate that supplemental glucosamine can boost mast cell heparin synthesis - perhaps correcting a functional heparin deficiency - thereby preventing or ameliorating the neurogenic inflammation that mediates pain in vascular headache. Whether or not this idea has validity, a controlled study of glucosamine for migraine prophylaxis appears to be warranted.
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PMID:Glucosamine for migraine prophylaxis? 1098 8

The pharmacokinetic interactions between BAY 12-9566 and two nonsteroidal anti-inflammatory drugs (NSAIDs), naproxen and ibuprofen, were investigated in osteoarthritis (OA) patients. The study comprised six groups: two NSAID groups with three levels of treatment (BAY 12-9566 400 mg, BAY 12-9566 100 mg, and placebo). Plasma pharmacokinetic parameters (AUC(0-tau), Cmax, and tmax) were determined for each treatment group following 5 days of NSAID administration, 14 days of BAY 12-9566 administration, and 14 days of concurrent NSAID and BAY 12-9566 administration. For most conditions, the total plasma drug concentrations of both NSAID and BAY 12-9566 were diminished by coadministration; total plasma BAY 12-9566 was not affected by ibuprofen treatment. Importantly, the free drug concentrations were largely unaffected by coadministration. Most side effects were mild or moderate in intensity, and all events, with the exception of headache, were reported in both NSAID groups and in both placebo and BAY 12-9566 groups.
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PMID:Pharmacokinetics, safety, and tolerability of BAY 12-9566 and nonsteroidal anti-inflammatory agents (naproxen, ibuprofen) during coadministration in patients with osteoarthritis. 1126 74

Paracetamol (acetaminophen) is one of the most widely used of all drugs, with a wealth of experience clearly establishing it as the standard antipyretic and analgesic for mild to moderate pain states. First used clinically by von Mering in 1893, paracetamol did not appear commercially until 1950 in the United States and 1956 in Australia. During the 1960s and 1970s, increasing concern was raised about the toxicity of nonprescription analgesics, but in normal use paracetamol exhibited a consistent safety profile. Its exemplary safety record was marred by the discovery in 1966 that a major overdose could be complicated by severe and sometimes fatal liver damage. Fortunately, early treatment with N-acetylcysteine prevents liver toxicity. A turning point in the choice of pediatric analgesic came in the 1980s when aspirin was linked to Reye's syndrome. As a consequence, paracetamol became the mainstay analgesic and antipyretic for children with a subsequent reduction in the incidence of Reye's syndrome. Currently, paracetamol is a first-line choice for pain management and antipyresis in a variety of patients, including children, pregnant women, the elderly, those with osteoarthritis, simple headaches, and those with noninflammatory musculoskeletal conditions. With proper use, paracetamol seldom causes adverse events and reports of serious side effects are rare. It has a broad tolerability and is of particular value in the treatment of patients in whom nonsteroidal anti-inflammatory drugs are contraindicated such as aspirin-sensitive asthmatics and people at risk of gastrointestinal complications. In the future, a better insight into the mechanism of action of paracetamol may be gained from a fuller understanding of the cyclooxygenase enzymes. In the meantime, paracetamol may find applications in other therapeutic areas, such as the prevention of atherosclerosis via a potential antioxidant activity. In summary, although it is more than a century since the first clinical use of paracetamol, it continues to be a first-line therapy of choice in adults and children with fever and pain. In addition, current research suggests that paracetamol may have a much broader clinical utility in years to come.
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PMID:Paracetamol: past, present, and future. 1131 82

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.
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PMID:Rofecoxib: a review of its use in the management of osteoarthritis, acute pain and rheumatoid arthritis. 1139 14

Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used in the elderly for the treatment of fever, pain, pain associated with inflammation in rheumatoid arthritis and osteoarthritis, neuromuscular disorders, headache, and musculoskeletal conditions. Each year in the United States, people spend 5 to 10 billion dollars to purchase prescription and over-the-counter NSAIDs. Gastrointestinal side effects such as ulcers and bleeding are the most prevalent and life-threatening problems associated with NSAIDs. Specifically in the elderly, NSAIDs have become a leading cause of hospitalization and may increase the risk of death from ulceration more than 4-fold. NSAIDs and the new class of cyclo-oxygenase-2 selective NSAIDs continue as drugs of choice for analgesia and anti-inflammatory effects. Physiological changes of aging worsen the side-effect profile of NSAIDs in the elderly. These side effects, when added to the increased potential for drug interactions, lead to a much greater risk for adverse outcomes when NSAIDs are used in the elderly patient. The similarities and differences in the NSAID agents warrant review in light of the newer drugs--celecoxib and rofecoxib--with their expected improvement in gastrointestinal side effects. This article reviews current information about using NSAIDs in elderly persons.
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PMID:Nonsteroidal anti-inflammatory drugs in the elderly. 1170 58

A prospective, open trial to evaluate the safety and efficacy of oral meloxicam 7.5 mg once daily over a period of 28 days in Thai patients with osteoarthritis was conducted in 3 major hospitals in Bangkok, Thailand. A total of 137 patients were enrolled and completed the study protocol. The mean age of the patients was 57.6 years and 88 per cent were female. Pain on movement and pain at rest evaluated after treatment by visual analog scale (VAS) were significantly improved with respect to the baseline status (p<0.001). The final efficacy was reported as satisfactory or good in 97 per cent and 94 per cent as determined by patients and physicians respectively. Patient status evaluated at the end of the study reported improvement of their arthritic condition in 84 per cent. Drug tolerability assessed by patients and physicians and was good or satisfactory in 99 per cent and 98 per cent. GI adverse event was reported in 8.8 per cent. Other adverse events were itching/rash in 2.0 per cent and headache/insomnia in 1.5 per cent of patients. No patients withdrew from the study due to adverse events. No GI bleeding or perforation were observed. No hospitalization was observed during the study. There was no significant change of blood chemistry and hematological profile between pre and post treatment examination. Results from this study suggest that oral meloxicam 7.5 mg for 28 days is a safe and effective treatment regimen with high GI tolerability profile for the treatment of osteoarthritis in Thai patients.
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PMID:Safety and efficacy of meloxicam 7.5 mg in the treatment of osteoarthritis in Thai patients. 1185 78


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