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)

Lubiprostone [RU 0211, SPI 0211] is a bicyclic fatty acid that acts as a chloride channel opener, increasing intestinal water secretion. Lubiprostone, an orally-administered formulation, is one of a series of functional fatty acid compounds discovered by Dr Ryuji Ueno, and is currently undergoing development for the treatment of constipation, constipation-predominant irritable bowel syndrome (IBS-C) and postoperative ileus with Sucampo Pharmaceutical's. Lubiprostone activates a specific chloride channel (CLC2) on cells lining the gut, thereby naturally increasing intestinal fluid secretion. The increased fluid level softens the stool, promotes spontaneous bowel movements, and reduces abdominal discomfort/pain and bloating. The chloride channel is a protein that controls cell membrane transport of chloride ion. Lubiprostone acts on the ClC-2 chloride channel, which is located in the apical intestinal membrane. In November 2004, Takeda Pharmaceuticals entered into a collaboration and licensing agreement for Lubiprostone with Sucampo Pharmaceuticals for the treatment of chronic constipation and constipation-predominant Irritable Bowel Syndrome (c-IBS). Under the terms of the agreement, Takeda received the right to market the product in the US and Canada, while Sucampo reserved the co-promotion rights for these countries. Takeda's wholly-owned US subsidiary, Takeda Pharmaceuticals North America Inc., will sell lubiprostone once the product is approved by the US FDA. Takeda will also receive an option for marketing rights in other territories, including Japan and Europe. Takeda and Sucampo agreed on the exclusive manufacturing and supply of Lubiprostone by R-Tech Ueno, Ltd, a member of the Sucampo Group. Sucampo has the potential to receive up to dollar US 210 million in initial and milestone payments, some of which are contingent upon the successful achievement of several milestones. Takeda will fund a major part of development costs not only for chronic constipation and c-IBS, but also for other indications in the gastroenterology field. Takeda will make royalty payments to Sucampo after the product is launched. In May 2005, Sucampo received dollar US 20 million from Takeda Pharmaceutical as payment for achieving a development milestone of initiating a phase III clinical trial of lubiprostone to treat patients with constipation-predominant irritable bowel syndrome. Sucampo Pharmaceuticals submitted a new drug application (NDA) for lubiprostone to the FDA on 31 March 2005 for approval in the treatment of chronic idiopathic constipation (CIC) and associated symptoms in adults. Sucampo completed three long-term, open-label safety studies, which will support the NDA for lubiprostone, in treating constipation. Results from its second open-label safety study with lubiprostone were announced in February 2004, with the first two studies demonstrating long-term safety and sustained effectiveness in constipated subjects. In the US, the final phase III study for chronic constipation was completed in the fourth quarter of 2004. In November 2004, Sucampo announced completing a phase II safety and efficacy study of lubiprostone for the treatment of IBS-C. This study, which was initiated in April 2003, randomised 195 patients with documented IBS into four treatment groups (three doses of SPI 0211 and placebo) from 19 locations throughout the US.
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PMID:Lubiprostone: RU 0211, SPI 0211. 1599 86

Irritable bowel syndrome (IBS) is one of several highly prevalent, multi-symptom gastrointestinal motility disorders that have a wide clinical spectrum and are associated with symptoms of gastrointestinal dysmotility and visceral hypersensitivity. Symptom overlap and comorbidity between IBS and other gastrointestinal motility disorders (eg, chronic constipation, functional dyspepsia, gastroesophageal reflux disease), with gastrointestinal disorders that are not related to motility (eg, celiac disease, lactose intolerance), and with somatic conditions (eg, fibromyalgia, chronic fatigue syndrome), are frequent. The clinical associations and pathophysiologic links between IBS and these disorders continue to be explored. This review discusses overlapping symptoms and comorbidity of IBS with select gastrointestinal and non-gastrointestinal disorders and attempts to identify commonalities among these conditions.
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PMID:Symptom overlap and comorbidity of irritable bowel syndrome with other conditions. 1604 9

Irritable bowel syndrome with constipation (IBS-C) and chronic constipation are 2 common gastrointestinal motility disorders that place a substantial burden on patients and society. Symptoms of both disorders are chronic, sometimes severe, and often respond poorly to treatment with traditional approaches, resulting in reduced quality of life, polypharmacy, and frequent healthcare utilization. Because structural, physical, or biochemical markers cannot be used to identify either disorder, diagnosis is symptom-based. In the absence of alarm features suggestive of organic disease or secondary causes of symptoms, these disorders can be positively and confidently diagnosed. In general, traditional agents used to treat patients with constipation target only a single symptom, and do not provide adequate relief of symptoms in the majority of IBS-C patients. Although patients with mild constipation symptoms may respond to treatment with fiber and laxatives, others with moderate-to-severe symptoms may require additional therapies and/or referral to a specialist for further evaluation. The advent of novel serotonergic agents has rejuvenated the therapeutic approach to patients with IBS-C and chronic constipation.
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PMID:Diagnosis, treatment, and management of irritable bowel syndrome with constipation and chronic constipation. 1636 97

Tegaserod is a 5-HT(4) receptor partial agonist approved for the treatment of irritable bowel syndrome in women with constipation and in both men and women with chronic constipation. The efficacy of tegaserod is based on the importance of 5-HT(4) receptors regulating intestinal peristalsis and secretion, and possibly visceral sensory pathways. Our aim was to investigate the effect of tegaserod on colorectal sensitivity using models of normal and exaggerated responsiveness to colorectal distension (CRD). The visceromotor responses (VMR) to CRD at graded pressures (0-60 mmHg) were measured by the number of reflex abdominal contractions. Acute colorectal hypersensitivity was induced by intracolonic infusion of dilute acetic acid. Chronic hypersensitivity was observed in rats following spontaneous resolution of trinitrobenzenesulfonic acid-induced colitis. Rats with normosensitive colons served as controls. Tegaserod (0.1-10 mg kg(-1)) caused dose-dependent reduction of the VMR to CRD in control rats and in those with colonic hypersensitivity. 5-HT(4) antagonists reversed the effects of tegaserod in rats with normosensitive colons, and partially inhibited effects in rats with colonic hypersensitivity. Central administration of tegaserod had no inhibitory effect. These results support the assumption that colonic hypersensitivity could be normalized by tegaserod acting, at least in part, through peripheral 5-HT(4) receptors.
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PMID:Activation of peripheral 5-HT receptors attenuates colonic sensitivity to intraluminal distension. 1637 Oct 86

The management and treatment of gastrointestinal ailments in pregnant women requires special attention and expertise, since the safety of the mother, fetus and neonate remains the primary focus. Nausea and vomiting during pregnancy is common, as is symptomatic gastroesophageal reflux disease. Peptic ulcer disease occurs less frequently and with fewer complications. Gastroenterologists and obstetricians should be familiar with safe treatment options for these conditions, because they can profoundly impair the quality of life of pregnant women. During pregnancy, constipation can develop de novo, or chronic constipation can increase in severity. Given the array of therapies for constipation, physicians must apprise themselves of drugs that are safe for both mother and fetus. Management of acute, self-limited diarrhea should focus on supportive therapy, dietary changes and maintenance of hydration. Treatment of chronic diarrhea should be considered in the context of therapy for the underlying disorder. Inflammatory bowel disease and irritable bowel syndrome present a unique therapeutic challenge--to control the disease while minimizing toxicity to the fetus and mother. Initiation and alteration of medical therapy for gastrointestinal disorders during pregnancy must be undertaken after discussion with the patient's obstetrician.
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PMID:Therapy insight: drugs for gastrointestinal disorders in pregnant women. 1667 5

Chronic constipation is defined as a symptom-based disorder based on the presence for at least 3 months in the last year of unsatisfactory defecation characterized by infrequent stools, difficult stool passage, or both. On the other hand, the presence of clinically important abdominal discomfort or pain associated with constipation defines irritable bowel syndrome (IBS) with constipation. Intake of dietary fibre and bulking agents (psyllium) may be effective in alleviating chronic constipation in patients without slow colonic transit or disordered constipation. On the other hand, fibre may improve stool consistency in patients with IBS with constipation, but it is considered to be not effective in improving abdominal pain, distension or bloating. Probiotics may be effective in relieving constipation; however, the effect of lactic acid bacteria ingestion may be dependent on the bacterial strain used and the population being studied. Lactulose, which is a substrate for lactic acid bacteria (prebiotic), is effective to treat patients with chronic constipation.
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PMID:Nutritional care of the patient with constipation. 1678 30

Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder that can present with a wide array of symptoms that make treatment difficult. Current therapies are directed at relieving symptoms of abdominal pain or discomfort, bloating, constipation, and diarrhea. Pharmacologic agents used to treat IBS-associated pain include myorelaxants, peppermint oil, and peripherally acting opiates. Dicyclomine and hyoscyamine, the two myorelaxants available in the United States, have not been proven effective in reducing abdominal pain in patients with IBS. The efficacy of peppermint oil is debated, but methodological problems with existing studies preclude definitive judgment. Loperamide is ineffective for relief of abdominal pain. For IBS patients with excessive abdominal bloating, a small number of studies suggest that bacterial eradication with gut-directed antibiotics and bacterial reconstitution with nonpathogenic probiotics may reduce flatulence. For constipation-predominant (C-IBS) symptoms, current treatment options include fiber supplementation, polyethylene glycol, and tegaserod. Soluble fibers (ispaghula, calcium polycarbophil, psyllium) are more effective than insoluble fibers (wheat bran, corn fiber) in alleviating global symptoms and relieving constipation, although fiber in general has marginal benefit in treatment of overall IBS symptoms. Polyethylene glycol increases bowel frequency in chronic constipation, but its overall efficacy against IBS is unclear. Tegaserod, a 5-HT(4) agonist, demonstrates superiority over placebo in improving bowel frequency and stool consistency and alleviating abdominal pain and bloating in women with C-IBS. Overall global symptoms are modestly improved with tegaserod when compared with placebo. Additional agents under investigation for C-IBS include the ClC(2) chloride channel opener lubiprostone, mu-opioid receptor antagonist alvimopan, and 5-HT(4) agonist renzapride. For diarrhea-predominant (D-IBS) symptoms, available therapies include loperamide, alosetron, and clonidine. Alosetron, a 5-HT(3) antagonist, is superior to placebo for reducing bowel frequency, improving stool consistency, and relieving abdominal pain in women with D-IBS. However, alosetron is available under a restricted license because of concerns for ischemic colitis and severe constipation necessitating colectomy. Clonidine may be helpful in alleviating global symptoms for D-IBS patients.
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PMID:Current gut-directed therapies for irritable bowel syndrome. 1683 50

Gastrointestinal motility disorders encompass a wide array of signs and symptoms that can occur anywhere throughout the luminal gastrointestinal tract. Motility disorders are often chronic in nature and dramatically affect patients' quality of life. These prevalent disorders cause a tremendous impact both to the individual patient and to society as a whole. Significant progress has been made over the last 5 years in understanding the etiology and pathophysiology of gastrointestinal motility disorders. This clinical update will focus on seven of the most common gastrointestinal motility disorders (achalasia, non-achalasia esophageal motility disorders, dyspepsia, gastroparesis, chronic intestinal pseudo-obstruction, irritable bowel syndrome, and chronic constipation) with an emphasis on current treatment options and new therapeutic modalities.
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PMID:Gastrointestinal motility disorders: an update. 1684 50

Irritable bowel syndrome (IBS) and chronic constipation (CC) are two of the most common functional disorders of the gut. CC and IBS are estimated to affect up to 20% and 27% of the North American population respectively. Although not life-threatening, CC and IBS can profoundly and negatively affect quality of life and are associated with a significant economic burden related to direct and indirect annual health-care costs. Possible etiologies for IBS and CC include alterations in visceral sensation and gastrointestinal motility. IBS may be caused by disturbances in brain-gut interactions affecting gastrointestinal motility and visceral sensitivity. Research efforts in CC have begun to identify abnormalities in myenteric neurons, alterations in neurotransmitters and their receptors, and incoordination of the muscles of the pelvic floor or anorectum. Both disorders may be influenced by genetic predisposition, environmental factors, and stress. In this article, the safety and efficacy of traditional and emerging therapies for CC and IBS are examined. In addition, their pathophysiology and symptoms are briefly reviewed.
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PMID:Irritable bowel syndrome and chronic constipation: emerging drugs, devices, and surgical treatments. 1688 69

Constipation is a common gastrointestinal symptom and affects about 20% of the general population. This symptom can reflect a vast array of problems, from inadequate fiber intake to colonic dismotility function. Identifying chronic constipation subtypes on underlying physiology guides the therapeutic choices. Chronic constipation subtypes includes: slow-transit constipation, functional constipation, irritable bowel syndrome with constipation predominance and pelvic floor dysfunction. The most useful tests for the evaluation of those patients are the colonic transit time with radiopaque markers and anorrectal manometry with balloon expulsion test. Patients with both normal tests have either functional constipation or irritable bowel syndrome with constipation. Subjects with a delayed colonic transit and normal anorectal manometry maybe classified as colonic inertia. Pelvic floor dysfunction maybe suspected if the patient had an abnormal manometry with failure to expulse de balloon. Initial treatments of chronic constipation are dietary fiber and medicinal bulk. Subsequent treatments if fiber is not successful or tolerated would include saline osmotic laxatives such as lactulose and polyethylene glycol, or stimulants like senna or bisacodyl. For patients with pelvic floor dyssynergia biofeedback therapy is the first therapeutic option. In this article we present an overview of current diagnostic tools for patients with chronic constipation.
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PMID:[Constipation: Initial evaluation and diagnostic approach]. 1706 88


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