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Query: UMLS:C0003864 (arthritis)
 69,039 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Arthritis is a major source of disability for the American population. It results in significant morbidity for the millions of patients affected and costs billions of dollars yearly for diagnosis and management. Nonsteroidal antiinflammatory drugs (NSAIDs) are the principal therapy for the majority of arthritis patients. It has been estimated that more than 15 million people with arthritis take these drugs daily. This use is predicted to increase greatly not only as a result of an aging population, with the consequent increase in the prevalence of arthritis, but also because NSAIDs may prove to have a role in decreasing colonic neoplasia and in reducing the likelihood of conditions such as Alzheimer's disease. It is therefore increasingly important to understand the nature of the side effects associated with these agents as well as ways of decreasing or preventing their occurrence. NSAIDs inhibit the enzymes cyclooxygenase-1 and cyclooxygenase-2. This reduces the synthesis of prostaglandins and therefore decreases joint inflammation, but it may also lead to the development of gastric and duodenal ulcers. For this reason, exogenous prostaglandins have been studied for their potential role in preventing NSAID-associated ulcers and ulcer complications. This paper reviews the development of the prostaglandin E1 analog misoprostol, the theory behind its use as a mucosal protective agent, and the results of studies in animals as well as in normal volunteers and patients with arthritis. Ultimately, a study was performed to evaluate whether misoprostol reduces the incidence of serious ulcer complications in patients taking NSAIDs. It is an interesting story, which promises to be of increasing importance as NSAID use expands to new indications while concern remains about their associated complications, especially those related to the gastrointestinal tract.
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PMID:Improving the gastrointestinal safety of NSAIDs: the development of misoprostol--from hypothesis to clinical practice. 953 36

The pharmacological profile of a novel and newly discovered non-steroidal anti-inflammatory and analgesic compound, 3-(difluoromethyl)-1-(4-methoxyphenyl)-5-[4-(methylsulfinyl)phenyl]pyraz ole (FR140423), was investigated. In recombinant human cyclooxygenase enzyme assays, the inhibition of prostaglandin E2 formation by FR140423 was 150 times more selective for cyclooxygenase-2 than cyclooxygenase-1. Oral administration of FR140423 dose dependently reduced carrageenin-induced paw edema and adjuvant arthritis. These effects were two- to three-fold more potent than those of indomethacin. Unlike indomethacin, FR140423 did not induce mucosal lesions in the stomach. FR140423 showed dose-dependent anti-hyperalgesic effects in the yeast-induced hyperalgesic model. This effect was five-fold more potent than that of indomethacin. Furthermore, FR140423 increased the pain threshold in non-inflamed paws and, unlike indomethacin, it produced an analgesic effect in the tail-flick test. These analgesic effects were blocked by the mu-opioid antagonist naloxone. These results suggest that FR140423, a selective cyclooxygenase-2 inhibitor, is a potent non-steroidal anti-inflammatory drug (NSAID) without gastrointestinal side effects and is a unique compound having morphine-like analgesic effects.
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PMID:Anti-inflammatory and analgesic effects of a novel pyrazole derivative, FR140423. 998 10

Approximately half of Americans 70 years of age or older suffer from arthritis. Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most effective nonsurgical therapies for arthritis, but usage often causes harmful side effects, especially in the gastrointestinal tract. Such effects require supplemental therapy that adds an economic burden and may even cause death. The benefits derived from NSAIDs are believed to be due to suppression of cyclooxygenase-2 (COX-2), while the harmful side effects are believed to be due to suppression of cyclooxygenase-1 (COX-1). COX-2-specific inhibitors that do not inhibit COX-1 may meet arthritis sufferers' needs for therapies that are safe, convenient, and as effective as conventional NSAIDs.
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PMID:The unmet anti-inflammatory needs in orthopedics. 1019 96

Celecoxib offers the unique therapeutic prospect of alleviating pain and inflammation without the untoward gastrointestinal, renal, and platelet effects associated with conventional nonsteroidal anti-inflammatory drugs. This is possible because celecoxib is a cyclooxygenase-2 (COX-2)-specific inhibiting agent that inhibits the conversion of arachidonic acid to the prostaglandins that mediate pain and inflammation while having no effect on the formation of the prostaglandins that mediate normal homeostasis in the gastrointestinal tract, kidneys, and platelets and that are formed under the control of cyclooxygenase-1 (COX-1). Double-blind clinical trials have demonstrated that celecoxib is as effective in ameliorating the signs and symptoms of osteoarthritis and rheumatoid arthritis as naproxen and as effective as aspirin in reducing pain following dental extraction. Controlled trials have also shown that the incidence of gastroduodenal ulcers and the combined incidence of gastroduodenal ulcers and erosions are significantly lower with celecoxib therapy than with naproxen therapy and are similar to those associated with placebo administration. In a study of platelet function, it was found that a single 650-mg dose of aspirin profoundly diminished platelet function, while therapeutic doses of celecoxib exhibited no such effect. Celecoxib has been shown to be well tolerated, with incidences of adverse events similar to placebo in most instances. In summary, evidence to date indicates that celecoxib is a safe and effective therapeutic modality for the management of arthritis and pain.
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PMID:Celecoxib, a COX-2--specific inhibitor: the clinical data. 1019 98

Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely prescribed for the treatment of many conditions including rheumatoid arthritis, osteoarthritis, gouty arthritis, the joint and muscle discomfort associated with systemic lupus erythematosus, and other musculoskeletal disorders. Yet, their benefits, which are believed to be a result of their ability to inhibit cyclooxygenase-2 (COX-2), are accompanied by considerable toxicity. NSAIDs' untoward effects are attributed to their inhibition of the constitutively expressed enzyme cyclooxygenase-1 (COX-1), with attendant suppression of the synthesis of prostanoids, substances that mediate key homeostatic functions. Side effects include suppression of hemostasis through inhibition of platelet aggregation, adverse effects in patients with heart failure and cirrhosis, and those with certain renal diseases, as well as complicating antihypertensive therapies involving diuretics or beta-adrenoceptor blockade. Perhaps most importantly, NSAIDs disrupt the gastrointestinal mucosal-protective and acid-limiting properties of prostaglandins, frequently leading to upper gastrointestinal erosions and ulceration, with possible subsequent hemorrhage and perforation. These complications can be reduced through identification of patients at risk, with circumspect use of NSAIDs, careful functional monitoring, and, in the case of gastrointestinal toxicity, co-administration of such agents as misoprostol or omeprazole. However, these strategies introduce complexity into the treatment paradigm. Moreover, side effects and adverse events may be significantly reduced through the use of COX-2-specific inhibitors, new agents that alleviate pain and inflammation without the liability for adverse events caused by COX-1 inhibition.
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PMID:Gastrointestinal effects of nonsteroidal anti-inflammatory therapy. 1039 Jan 23

Inflammation and pain, the principal signs and symptoms of arthritis along with swelling and stiffness, are routinely controlled by treatment with a nonsteroidal anti-inflammatory drug (NSAID). Celecoxib, an anti-inflammatory and analgesic agent indicated for the treatment of osteoarthritis and rheumatoid arthritis, is the first cyclooxygenase (COX) inhibitor with well-defined cyclooxygenase-2 (COX-2) specificity. Preclinical studies of celecoxib in vitro and in vivo support the COX-2 hypothesis that the therapeutic effects of NSAIDs are due to the inhibition of COX-2, and the adverse events associated with NSAID therapy are due to the inhibition of cyclooxygenase-1 (COX-1), the constitutively expressed isoform of COX. Clinical trials in patients with osteoarthritis or rheumatoid arthritis found that the efficacy of celecoxib is superior to that of placebo and comparable to that of naproxen, a conventional NSAID. Clinical studies also found celecoxib to be safe and well tolerated, with no evidence of alteration in platelet aggregation or gastrointestinal ulceration.
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PMID:Celecoxib for the treatment of pain and inflammation: the preclinical and clinical results. 1064 76

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

Arthritis and related musculoskeletal conditions occur with great frequency in the population world wide, causing significant morbidity and, in some instances, increased mortality. Affecting both the young and the old, 15% of the population in the US was estimated in 1995 to have some form of arthritis with an increase to 18% projected by the year 2020 [1]. The economic impact of arthritis and related disorders in the US alone was estimated to be 194.4 billion US dollars in 1992 and future costs are virtually certain to increase given the chronic nature of these diseases, their expanding prevalence and the considerable expense associated with newer therapies [2]. With no cure presently available, the aim of current treatment is to reduce inflammation, ameliorate symptoms and improve functional capacity. Non-steroidal anti-inflammatory drugs (NSAIDs), which suppress the formation of pro-inflammatory prostaglandins by antagonising the action of cyclooxygenase (COX), have been the mainstay of arthritis treatment for hundreds, if not, thousands of years. The clinical use of NSAIDs, however, has long been associated with significant toxicity. The recognition of two COX isoforms, cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2), both suppressed by traditional NSAIDs, has led to an expanded hypothesis of NSAID action which consists of two postulates, namely, the efficacy of NSAIDs in the treatment of arthritis is due to the suppression of COX-2, while much of the toxicity associated with non-selective NSAIDs is the consequence of COX-1 suppression. The emergence of agents which selectively inhibit COX-2 has made it possible to clinically evaluate the validity of each of these postulates. In this report, the published experience with selective COX-2 inhibitors in the treatment of mechanical and inflammatory arthropathies is reviewed to examine the premise that isolated COX-2 suppression is comparable in efficacy to the dual COX-1/COX-2 suppression produced by non-selective NSAIDs.
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PMID:Therapeutic potential of COX-2 inhibitors in arthritis. 1177 54

The anti-arthritic effect of NM-3, a new isocoumarin, was examined using a type II collagen-induced arthritis model for human rheumatoid arthritis in DBA/1J mice. NM-3 by oral administration suppressed dose-dependently (2-20 mg/kg/day) not only macroscopic changes such as erythema and swelling of limbs but also histopathologic changes and radiographic changes such as bone lesions. The efficacy of NM-3 was greater than those of disease-modifying anti-rheumatoid drugs (DMARDs), auranofin (40 mg/kg/day) and bucillamine (10 mg/kg/day). NM-3 failed to suppress carageenan-induced edema and to inhibit the activities of inflammation-related enzymes including cyclooxygenase-1 and -2, 5-lipoxygenase and phospholipase A2, suggesting that the mode of anti-arthritic action of NM-3 may be different from those of non-steroidal anti-inflammatory agents (NSAIDs). Since NM-3 inhibits angiogenesis in a mouse dorsal air-sac model, the observed anti-arthritic effect of NM-3 might be partly attributed to the antiangiogenic activity. Thus, NM-3 is a potential orally active therapeutic agent for the treatment of human rheumatoid arthritis.
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PMID:Suppression of type II collagen-induced arthritis by a new isocoumarin, NM-3. 1195 83

Nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit cyclooxygenase-1 (COX-1), thereby inhibiting platelet function via blockade of thromboxane A2 (TxA2) formation, and COX-2, the enzyme that mediates inflammatory responses. Meloxicam is a relatively COX-2-selective anti-arthritis drug that shows significant TxA2 inhibition, albeit less than traditional NSAIDs. A randomized, double-blind, placebo-controlled trial was conducted in 79 healthy adults to compare the effects of once-daily therapeutic (7.5 mg, 15 mg) and supratherapeutic (30 mg) doses of meloxicam with extended-release indomethacin (Indo-ER 75 mg once daily) on bleeding time, TxA2 formation, and platelet aggregation. The authors measured platelet aggregation to COX-1-dependent (ADP arachidonate) and COX-1-independent (high-dose collagen) agonists, bleeding time, serum TxB2, and clotting times (aPTT and PT) after 8 days' administration and at 3 and 6 hours after steady-state dosing. Meloxicam significantly decreased TxB2 production compared with placebo in a dose-dependent fashion, reaching a peak of 77% inhibition 6 hours after 30 mg meloxicam; Indo-ER blocked TxB2 formation by 96% at the same time point. However, neither acute nor 8 days' administration of meloxicam at any dose caused a significant increase in bleeding time or inhibition of platelet aggregation to any agonist when compared with placebo. By contrast, Indo-ER significantly increased the bleeding time and inhibited platelet aggregation to COX-1-dependent agonists 6 hours after dosing. Clotting times were unaffected by any drug. It was concluded that unlike nonselective NSAIDs, meloxicam's blockade of TxA2 formation (even at supratherapeutic doses) does not reach levels that result in decreased in vivo platelet function, as measured by bleeding time and aggregometry. In this study of healthy subjects, meloxicam did not interfere with platelet-mediated hemostasis.
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PMID:Effects of meloxicam on platelet function in healthy adults: a randomized, double-blind, placebo-controlled trial. 1216 70


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