Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018099 (gout)
 5,192 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

One hundred male patients who presented with acute gouty arthritis were alternately assigned to 2 treatment groups. Seventy-six patients completed the study protocol, in which each gout attack during a 1-year period was treated. For each gout episode, 36 patients received a single intramuscular injection of 40 IU of adrenocorticotropic hormone (ACTH), and 40 patients received oral indomethacin, 50 mg 4 times daily with meals, until the pain abated. The time interval until the pain was relieved, as well as any untoward effects, were recorded for each gout attack treated. Both groups were of similar age, and had similar values for intercritical serum uric acid, 24-hour urinary uric acid, and creatinine clearance (1 month after entry into the study). The mean interval (+/- SD) to relief of pain was significantly shorter for the ACTH group (3 +/- 1 hours) than for the indomethacin group (24 +/- 10 hours). No side effects were noted in the ACTH group. However, of the 40 patients receiving indomethacin, 22 had abdominal discomfort of dyspepsia, 15 had headaches, and 12 had difficulty with mentation. Single-dose parenteral ACTH appeared to be effective more rapidly and was associated with fewer side effects than oral indomethacin in the treatment of acute gout.
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PMID:Comparison of parenteral adrenocorticotropic hormone with oral indomethacin in the treatment of acute gout. 245 35

The adrenal cortical hormone, cortisone, and the pituitary adrenocorticotropic hormone (ACTH) possess potent antirheumatic properties. Their administration produces strikingly beneficial effects on a number of rheumatic diseases including rheumatoid arthritis, rheumatoid (ankylosing) spondylitis, acute rheumatic fever, disseminated lupus erythematosus, periarteritis nodosa, psoriatic arthritis, dermatomyositis, and gout. In general the effects of these substances are temporary and they cause suppression rather than cure of the disease processes. Improvement is maintained usually only by continuing administration, and on hormonal withdrawal prompt or fairly prompt relapse of the disease manifestations ensues. In addition to their antirheumatic effects cortisone and ACTH influence a wide variety of physiologic functions. Administration of them therefore may produce a number of metabolic and clinical changes, some of which are not advantageous from a therapeutic standpoint. Adverse side-reactions are more liable to occur when large doses of the hormones are given for prolonged periods; such reactions appear to be reversible and disappear when administration of the hormones is stopped. With cortisone, comparatively few untoward signs develop when smaller amounts are administered continuously even for periods of months. Greater clinical experience is needed before optimal doses and schedules of administration are finally determined. It appears that some severe cases, many moderately severe cases, and most moderate and mild cases of rheumatoid arthritis may be adequately controlled with smaller "maintenance" doses of cortisone ranging from 32 to 65 mg. a day, providing larger doses to suppress the disease manifestations are employed initially. Neither cortisone nor ACTH should be considered as a therapeutic agent for general use until more information regarding their physiologic activities and the consequences of prolonged or repeated administration of them are available. Until the potential dangers of these hormones can be determined precisely, the use of them should be considered as an investigative procedure.
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PMID:The effects of cortisone and adrenocorticotropic hormone (ACTH) on certain rheumatic diseases. 1541 40

Gouty arthritis is a characteristically intense acute inflammatory reaction that erupts in response to articular deposits of monosodium urate (MSU) crystals. Important recent molecular biologic advances in this field have given us a clear picture of the mechanistic basis of gouty inflammation. The innate immune inflammatory response is critically involved in the pathology of gout. Specifically, MSU crystals promote inflammation directly by stimulating cells via Toll-like receptor signaling and by providing a surface for cleavage of C5 and formation of complement membrane attack complex (C5b-9), culminating in secretion of cytokines, chemokines, and other inflammatory mediators with a dramatic influx of neutrophils into the joint. Despite the detailed mechanistic picture for gouty inflammation, there are no placebo-controlled, randomized clinical studies for any of the therapies commonly used, although comparative studies have demonstrated that many nonsteroidal anti-inflammatory drugs are equivalent to indomethacin with respect to controlling acute gouty attacks. In general, the first line of anti-inflammatory therapy for acute gout is nonsteroidal anti-inflammatory drugs, and the selective cyclo-oxygenase-2 inhibitor celecoxib can be used where appropriate. The second line of treatment is glucocorticosteroids, given systemically (oral, intravenous, or intramuscular) or intra-articularly. Alternatively, synthetic adrenocorticotropic hormone is effective, partly via induction of adrenal glucocorticosteroids and partly via rapid peripheral suppression of leukocyte activation by melatonin receptor 3 signaling. The third line of treatment is oral colchicine, which is highly effective when given early in an acute gouty attack, but it is poorly tolerated because of predictable gastrointestinal side effects.
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PMID:The inflammatory process of gout and its treatment. 1700 28

Gout, a common inflammatory arthritis, can be diagnosed with absolute certainty. Gout results from the body's reaction to urate crystals deposited in tissues, and this pathophysiology is well understood. If used appropriately, available therapies can be entirely effective in not only treating the symptoms of gout, but also in eliminating the excess urate from the body, thereby eradicating the disease. Because of these facts, management of patients with gout should be successful. However, management of gout is particularly challenging in the elderly, even though the principles of management are the same for all age groups. The purpose of this article is to review these principles and discuss them as they pertain to the elderly. The classic gout attack is acute in onset, extremely painful and associated with marked swelling, warmth, erythema and tenderness of a single joint. However, the diagnosis of gout may be challenging in the elderly because atypical presentations are more common in this group. Treatment of acute gout involves the use of NSAIDs, colchicine, corticosteroids or corticotropin (adrenocorticotropic hormone). Unfortunately, co-morbid conditions such as chronic kidney disease, peptic ulcer disease and congestive heart failure may make the use of these agents dangerous or contraindicated. Thus, it is important to try to treat an acute flare of gout at the earliest sign, because the sooner treatment is initiated, the faster the inflammation will resolve. Urate-lowering agents include allopurinol and uricosuric agents. These also must be used judiciously in the elderly. However, if used at the lowest dose that maintains the serum urate level below 5.0-6.0 mg/dL, the excess urate in the body will be eliminated, acute flares will no longer occur and tophi will resolve. Gout is often seen in association with hypertension, excessive alcohol consumption, obesity and hypertriglyceridaemia. These conditions and the medications used to treat them may contribute to the hyperuricaemia. Treating these conditions and using medications that do not promote hyperuricaemia will aid in the management of gout. Despite the challenges that often complicate the management of gout in the elderly, an understanding of the pathophysiology of the disease and both the indications and limitations of the medications used should allow successful treatment.
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PMID:Management of gout in older adults: barriers to optimal control. 1723 45

It is important to distinguish between therapy used to reduce acute inflammation in gout and therapy used to manage hyperuricaemia in patients with chronic gouty arthritis. This article discusses treatments for acute gout, emphasizing the use of corticotrophin (adrenocorticotropic hormone; ACTH) and the evidence on which we base our treatment of acute gout. There are no formal guidelines for the treatment of acute gout and only a few randomized controlled trials have been conducted to evaluate the efficacy of the various treatments for acute gout. The options available for the treatment of acute attacks of gout are NSAIDs, colchicine, corticosteroids, corticotropin and intra-articular corticosteroids. Most rheumatologists practicing in the US use combination therapy to treat acute gout, a practice that merits study. In a patient without complications, NSAIDs are the preferred therapy. The most important determinant of therapeutic success is not which NSAID is chosen, but rather how soon NSAID therapy is initiated. Exciting new research shows that corticotropin acts peripherally by activation of the melanocortin type 3 receptor, and this could be responsible, at least in part, for its efficacy in acute gout. Hopefully, this will lead to renewed interest in corticotropin as a treatment for acute gout.
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PMID:Overview of the management of acute gout and the role of adrenocorticotropic hormone. 1831 60

Gouty arthritis is a form of acute joint inflammation provoked by joint deposition of urate crystals. Although this acute pathology resolves after a few days, the marked degree of inflammation in the joint and--possibly more important to the patient--the excruciating pain it causes require proper therapeutic management. Often deemed a "poor sibling" of chronic joint pathologies such as rheumatoid arthritis and psoriatic arthritis, the increasing incidence of gout makes it a more palatable disease for novel drug discovery programs. This fact, associated with novel insights into the molecular mechanisms activated by the urate crystal deposition, is at the basis of new therapeutics under clinical development for gout, a valid example being the effective targeting of the proinflammatory cytokine interleukin-1. Here we briefly review the current status of antigout drug development and propose another target; our focus is on melanocortin receptor agonists as novel therapeutics for gout and inflammatory arthritides, a prototype of which, the adrenocorticotropic hormone, is already used in clinical settings.
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PMID:Role of melanocortin receptors in the regulation of gouty inflammation. 2124 57

Treatment of acute gout consists of non-steroidal anti-inflammatory drugs (NSAIDs), colchicine and steroids. However, the typical patient with gout has multiple comorbidities such as cardiovascular disease, hypertension, renal dysfunction or diabetes/metabolic syndrome that represent contraindications to these therapeutic options. The aim of this study is to review the available evidence regarding the use of ACTH as an alternative therapeutic option for acute gout and explore potential mechanisms of action. We performed an electronic search (MEDLINE, Scopus and Web of Science) using the keywords ACTH or adrenocorticotropic hormone combined with gout or crystal-induced arthritis. ACTH appears suitable for patients with many comorbidities due to its good safety profile. Clinical evidence shows that ACTH is at least as effective as classic agents. The mechanism of action of ACTH in gout is not entirely known. Robust experimental evidence points to the direction that ACTH does not act solely by triggering the release of endogenous steroids but also appears to downregulate inflammatory responses by activating melanocortin receptors on innate immune cells, such as macrophages. Moreover, indirect evidence indicates that ACTH may have an IL-1 antagonistic effect. We propose that ACTH may be an alternative therapeutic option for gout in patients with multiple comorbidities. Large-scale studies assessing the efficacy and safety of ACTH compared to classic therapeutic options are needed.
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PMID:Adrenocorticotropic hormone: an effective "natural" biologic therapy for acute gout? 3271 40