Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0012833 (dizziness)
 9,689 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

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