Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022104 (irritable bowel syndrome)
 8,033 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Inflammatory bowel disease therapy can be considered in several subcategories, and this review is designed to provide selective updates for some of the most important therapeutic entities currently marketed or soon to be available for the medical management of IBD. Although conventional corticosteroids have been a major component of acute inflammatory bowel disease management, steroids have many serious disadvantages; and toxicity is heightened with chronic steroid therapy. Newer corticosteroids, particularly budesonide, may be less toxic than older agents such as prednisone. Budesonide may be used as an enema in active distal ulcerative colitis (UC) or as delayed release tablets in Crohn's disease (CD). However, budesonide is not completely free from steroid side effects, and may share in some of the toxicity of older corticosteroids, particularly when high dose budesonide is administered. Topical and oral aminosalicylates are widely utilized for the treatment of mild to moderate active UC and mild active CD, and they also are efficacious for maintenance of IBD remission. Recent data continue to support the concept that higher doses and prolonged use of mesalamine-based drugs are therapeutically superior to lower doses and short term treatment. In addition, the combination of oral and rectal aminosalicylate formulations often succeeds in patients refractory to either used alone. The immunomodulatory drugs azathioprine and 6-mercaptopurine are particularly effective in treating both CD and UC, and methotrexate has also shown some promise in CD therapy. Immunosuppressive therapy for inflammatory bowel disease initially met with strong physician resistance. However, views have shifted in response to positive data on the utility of immunosuppressive agents in many cases of IBD. Although cyclosporine may be used as a 'rescue' medication in some severe IBD cases, it has been associated with severe toxic reactions. Possible candidates for cyclosporine treatment should be offered such therapy only in academic centers highly experienced with the nuances of this modality. Clinical trials of the newer entities IL-10, IL-11, tacrolimus, and anti-TNFalpha, have demonstrated variable efficacy in refractory IBD patients. Anti-TNFalpha has been very impressive, particularly in the presence of fistulizing Crohn's disease. Many physicians have utilized various antibiotics empirically as part of their 'general' management of IBD. Only metronidazole has been adequately studied in controlled CD trials, but other antibiotic studies are pending. Further exploration of antimicrobial treatment for IBD is clearly warranted. Many other investigational agents in disparate pharmaceutical categories have been employed in IBD therapy; and some of these also show varying degrees of promise, including the aloe vera derivative acemannan, several formulations of heparin, and both transdermal and intra-rectal nicotine. Despite the growing list of medications and formulations promoted for the treatment of IBD, no single drug or recognized combination has yet been confirmed as dependably clinically effective. Many additional investigations of IBD medical therapy are needed, including permutations of conventional medications, along with newer agents that may be more precisely targeted to specific aspects of IBD pathophysiology. All physicians who care for UC and CD patients enthusiastically await more optimal regimens for these challenging disorders.
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PMID:Medical therapy of inflammatory bowel disease for the 21st century. 1002 72

Irritable bowel syndrome (IBS) is one of several functional gastrointestinal disorders commonly encountered in both the clinical setting and the general population. The biopsychosocial model is currently believed to be a more complete explanatory mechanism of IBS symptom genesis and propagation. Gut inflammation and immune activation is one of the biological mechanisms for which evidence is emerging. Experimental parasitic infection of mice bowel resulted in elevated substance P levels and increased expression of cyclooxygenase 2 (COX 2) enzyme, prostaglandin E2, IL-4, IL-5, and IL-13. In IBS patients, increased cellularity and proximity of the inflammatory or immune cells to the nerve trunks of the bowel, elevated interleukin-1beta mRNA expression in mucosal biopsies, and increased inducible nitric oxide synthase and nitrotyrosine elaboration (indicative of lymphocyte activation) were observed. Corticosteroids given after the elimination of an experimentally applied parasite from the bowel of mice resulted in the reversal of persistent gut muscle dysfunction. Selective COX-2 inhibitors attenuated the increased bowel smooth muscle contractility resulting from parasite infection of mice gut. In humans, it has been observed that the relative risk of developing IBS in asthma patients was reduced by 60% by the use of oral steroids. Despite such preclinical and human evidence for the role of inflammation and immune activation in IBS, the efficacy of anti-inflammatory and immunomodulatory agents has not been adequately investigated. Budesonide, a corticosteroid with a high mucosal activity and a low bioavailability, is an anti-inflammatory agent that may be worth investigating for its utility in diarrhea-predominant IBS.
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PMID:Will corticosteroids and other anti-inflammatory agents be effective for diarrhea-predominant irritable bowel syndrome? 1589 25

Pseudopolyps are a frequent finding in the course of inflammatory bowel disease. They are non-neoplastic lesions resulting from a regenerative and healing process that leaves inflamed colonic mucosa in polypoid configuration. Data about their management is lacking. "Giant" pseudopolyps can be mistaken for adenocarcinomas and, as they rarely regress with medical management alone, a surgical resection is often required. A case ofgiantpseudopolyposis treated non-surgically, in a patient with concomitant ulcerative colitis and chronic hepatitis B, is reported, representing a co-morbidity complicating an eventual conservative treatment. The clinical implementation of topical budesonide was originally tested, resulting in clinical, endoscopic and histological remission. Budesonide seems a promising therapy for IBD, particularly when a comorbidity with viral hepatitis exist.
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PMID:Topical budesonide for treating giant rectal pseudopolyposis. 1608 May 51

The ideal chemopreventative agent, in addition to being efficacious in the prevention of cancer, must be easily administered, affordable, safe, and well tolerated, with minimal side effects. In the past decade, a growing body of literature has emerged on the prevention of CRC in patients with long-standing CD and UC. The data are not definitive and consist almost exclusively of retrospective case-control and cohort studies rather than the more rigorous prospective RCTs. 5-ASA compounds have been most thoroughly studied, and most of the existing data support the use of 5-ASA in the prevention of CRC. Although the precise dose and duration are unclear, studies suggest that chronic systemic administration of 5-ASA at a dose of at least 1.2 g/d is most likely to be effective. A beneficial effect of folate, albeit not statistically significant, has been consistently shown in every study performed for this purpose. Folate supplementation, which is safe and affordable, should also be recommended for all patients with IBD, especially those taking sulfasalazine. UDCA has been shown to exert a protective effect in most studies on patients with UC and concomitant PSC. Because this patient population is at particularly high risk for CRC, it is advisable to consider UDCA in all patients with colitis complicated by PSC. For patients without PSC, sufficient data do not exist to recommend it for the purpose of cancer prevention. Five of the six corticosteroid studies have found a beneficial effect of systemic steroids, although most did not reach statistical significance. Regardless, given the frequent and serious adverse effects associated with chronic steroid use, systemic corticosteroids should not be prescribed for this indication. Budesonide, an oral corticosteroid with minimal systemic absorption, is a potential alternative, although it has not yet been studied as a chemopreventative agent. Similarly, until the long-term safety of chronic NSAID use can be demonstrated in patients with IBD, the role of NSAIDs in chemoprevention remains undefined. Although the data are conflicting, immune-modulating medications, such as AZA, do not seem to confer any reduction in the risk of dysplasia or CRC. The data on calcium supplementation and statin use are still too limited to endorse their use for the prevention of colitis-related CRC. Chemoprevention is an area that holds great promise in the reduction of morbidity and mortality associated with IBD. Further studies, including prospective trials when possible and cost-effectiveness analyses, need to be performed to develop an optimal strategy for the reduction of cancer risk in patients with IBD.
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PMID:Chemoprevention: risk reduction with medical therapy of inflammatory bowel disease. 1695 46

Chronic diarrhea is usually associated with a number of non-infectious causes. When definitive treatment is unavailable, symptomatic drug therapy is indicated. Pharmacologic agents for chronic diarrhea include loperamide, 5-hydroxytryptamine type 3 (5-HT3) receptor antagonists, diosmectite, cholestyramine, probiotics, antispasmodics, rifaximin, and anti-inflammatory agents. Loperamide, a synthetic opiate agonist, decreases peristaltic activity and inhibits secretion, resulting in the reduction of fluid and electrolyte loss and an increase in stool consistency. Cholestyramine is a bile acid sequestrant that is generally considered as the first-line treatment for bile acid diarrhea. 5-HT3 receptor antagonists have significant benefits in patients with irritable bowel syndrome (IBS) with diarrhea. Ramosetron improves stool consistency as well as global IBS symptoms. Probiotics may have a role in the prevention of antibiotic-associated diarrhea. However, data on the role of probiotics in the treatment of chronic diarrhea are lacking. Diosmectite, an absorbent, can be used for the treatment of chronic functional diarrhea, radiation-induced diarrhea, and chemotherapy-induced diarrhea. Antispasmodics including alverine citrate, mebeverine, otilonium bromide, and pinaverium bromide are used for relieving diarrheal symptoms and abdominal pain. Rifaximin can be effective for chronic diarrhea associated with IBS and small intestinal bacterial overgrowth. Budesonide is effective in both lymphocytic colitis and collagenous colitis. The efficacy of mesalazine in microscopic colitis is weak or remains uncertain. Considering their mechanisms of action, these agents should be prescribed properly.
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PMID:Pharmacologic Agents for Chronic Diarrhea. 2657 35

Budesonide is a recommended first-line therapy in non-cirrhotic patients with autoimmune hepatitis (AIH) (1). In women with AIH, maintaining remission pre- and peri-pregnancy is imperative in reducing adverse events and improving outcomes (2). Whilst pregnancy outcomes in AIH have been reported, there are currently no data on budesonide safety and efficacy in AIH pregnancies. Limited data of use during pregnancy exist in the IBD literature (3). We report the outcomes of 8 pregnancies in 5 women with AIH managed with budesonide.
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PMID:Safety and efficacy of budesonide during pregnancy in women with autoimmune hepatitis. 3318 8