Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C1291077 (bloating)
 1,674 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Irritable bowel syndrome (IBS) continues to provide a major therapeutic challenge to clinicians and those involved in drug development. It seems unlikely from the data before us that this multisymptom syndrome with peripheral and central components is likely to respond reliably in all patients to the same single agent. There is still a lack of well designed, appropriately powered, randomised clinical trials and the problems of dealing with the high placebo response rate in this group of patients remains a dilemma for trial designers. There are, however, some new ideas, particularly those relating to the role of hyperalgesia in IBS. For many patients, abdominal pain and bloating are the most distressing symptoms of this disease and the new drugs targeted at pain control, such as kappa agonists and serotonin antagonists (5-HT3) and possibly 5-HT4), may eventually find a place in the clinical management of this syndrome. Other candidates include somatostatin analogues and antidepressants, the latter predominantly for their effects on increasing pain threshold. More speculative new drugs for IBS include cholecystokinin antagonists such as loxiglumide and the gonadotrophin-releasing hormone analogue, leuprorelin (leuprolide). The results of on-going randomised clinical trials are still awaited for some of these newer agents. The irritable bowel syndrome (IBS) is the most common gastrointestinal condition encountered by general practitioners and is reported to account for up to 50% of the work of gastroenterologists in secondary care. However, most people with the symptoms of IBS (60 to 75%) do not consult a doctor. Its cause is unknown, its development is poorly understand and, perhaps not surprisingly, no universally agreed approach to treatment exists.
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PMID:New drugs in the management of the irritable bowel syndrome. 966 95

Tegaserod is a serotonin (5-hydroxytryptamine; 5-HT) receptor partial agonist which has been investigated for the treatment of irritable bowel syndrome (IBS). Specifically, it binds with high affinity to human 5-HT4 receptors, thereby stimulating the release of neurotransmitters and the peristaltic reflex in vitro. Small bowel transit (increased colonic filling over 6 hours) was accelerated in patients with constipation-predominant irritable bowel syndrome (IBS) receiving oral tegaserod 2mg twice daily for 1 week compared with those receiving placebo. In addition, there was a mean 20% increase of proximal colonic emptying in these patients. Oral tegaserod 2 (p < 0.05) or 6mg twice daily improved symptoms of abdominal discomfort, bloating and constipation (assessed using a Subjects' Global Assessment Scale) compared with placebo in patients with constipation-predominant IBS in a double-blind, dose-ranging study. The most frequent adverse events in patients with constipation-predominant IBS receiving oral tegaserod were transient diarrhoea and flatulence. No clinically relevant changes in blood pressure, pulse rate, QRS or QTc interval were reported with tegaserod doses of 25 to 100mg.
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PMID:Tegaserod. 1049 76

Existing pharmacotherapeutic options for the treatment of patients with irritable bowel syndrome (IBS) are limited in treating the multiple symptoms associated with the disorder. There is much interest in the use of serotonin agents as new therapeutics. Acting primarily through 5-HT3 and 5-HT4 receptors, serotonin elicits changes in motor function and possibly visceral sensation. Two serotonin agents were developed specifically for IBS: tegaserod, a 5-HT4 receptor partial agonist, and alosetron, a 5-HT3 receptor antagonist (which is no longer available). Phase III clinical trial data show that during a 12-week treatment period with tegaserod, IBS patients with abdominal pain and discomfort, bloating, and constipation experienced significant global relief (i.e., improvement in overall well-being, abdominal pain, and bowel habit) compared with placebo. Improvement in bowel movement frequency and consistency was achieved and pain was relieved by 1 week. During 12 weeks of treatment, alosetron was shown to elicit significant relief of abdominal pain and discomfort compared with placebo or mebeverine in female IBS patients with diarrhea. Alosetron slowed colonic transit and treatment efficacy was apparent after a week of treatment. Another 5-HT4 receptor agonist, prucalopride, which is being developed for chronic constipation, accelerates colonic transit and increases stool frequency. Therefore, this agent may be of benefit in IBS patients with constipation.
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PMID:Drug therapy options for patients with irritable bowel syndrome. 1147 11

Irritable bowel syndrome (IBS) is a common functional bowel disorder of unknown aetiology. It is defined by the presence of gastrointestinal (GI) symptoms including abdominal pain/discomfort, bloating and bowel motor dysfunction. No available therapy is yet effective against all the symptoms of the disorder. Current treatments therefore target individual symptoms but may be accompanied by unpleasant side-effects. Tegaserod is a novel selective serotonin receptor type-4 (5-HT4) partial agonist with structural similarity to 5-HT Tegaserod stimulates small bowel and colonic motility and helps to normalise GI function. Clinical trials using a patient's assessment of efficacy demonstrate that tegaserod significantly improves key symptoms of IBS: abdominal pain/discomfort, bloating and constipation. Tegaserod is well tolerated with an excellent safety profile and represents a significant treatment advance in this difficult-to-treat disorder.
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PMID:Tegaserod: a novel, selective 5-HT4 receptor partial agonist for irritable bowel syndrome. 1183 35

Tegaserod, a potent, partial serotonin 4 receptor (5-HT4) agonist, is an effective agent for the treatment of females with constipation-predominant irritable bowel syndrome. Tegaserod enhances gastric motility, stimulates peristaltic reflux and intestinal secretion, inhibits visceral sensitivity, and/or shortens colonic transit time. This agent may help women who have failed to respond to diet and exercise, laxatives, and other forms of therapy. The optimal dose of tegaserod is 6 mg twice daily and results in decreased number of days per month with pain, bloating, and days without bowel movements. Tegaserod is less effective in males than females in the treatment of constipation-predominant irritable bowel syndrome. Tegaserod is well tolerated. Diarrhea is the most frequent adverse effect. The diarrhea tends to occur most frequently during the first few months of therapy and decreases with continued administration.
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PMID:Tegaserod for the treatment of constipation-predominant irritable bowel syndrome. 1212 Jan 85

Anticholinergics and prokinetics are mainstays of therapy for Irritable Bowel Syndrome (IBS) patients despite their limited efficacy and troublesome side-effect profile. The clinical limitations of these drugs are a result of their relative broad and nonspecific pharmacologic interaction with various receptors. Recent advances in gut physiology have led to the identification of various receptor targets that may play a pivotal role in the pathogenesis of IBS. Medicinal chemists searching for safe and effective IBS therapies are now developing compounds targeting many of these specific receptors. The latest generation of anticholinergics, such as zamifenacin, darifenacin, and YM-905, provide selective antagonism of the muscarinic type-3 receptor. Tegaserod, a selective 5-HT4 partial agonist, tested in multiple clinical trials, is effective in reducing the symptoms of abdominal pain, bloating, and constipation. Ezlopitant and nepadudant, selective antagonists for neurokinin receptors type 1 and type 2, respectively, show promise in reducing gut motility and pain. Loperamide, a mu (mu) opioid receptor agonist, is safe and effective for IBS patients with diarrhea (IBS-D) as the predominant bowel syndrome. Fedotozine, a kappa (kappa) opioid receptor agonist, has been tried as a visccral analgesic in various clinical trials with conflicting results. Alosetron, a 5-HT3 receptor antagonist, has demonstrated efficacy in IBS-D patients but incidents of ischemic colitis seen in post-marketing follow-up resulted its removal from the market. Compounds that target cholecystokinin. A, N-methyl-D-aspartate, alpha 2-adrenergic, and corticotropin-releasing factor receptors are also examined in this review.
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PMID:Irritable bowel syndrome neuropharmacology. A review of approved and investigational compounds. 1218 41

Tegaserod is a new partial agonist of serotonin 5-HT4 receptors specifically developed for the treatment of nondiarrhoeal forms of irritable bowel syndrome (IBS). Among its various effects is the stimulation of the peristaltic reflex with its promotility action appearing to affect the whole length of the gastrointestinal tract. Tegaserod has been assessed in a number of international multicentre trials and its use leads to an improvement in abdominal pain and bowel dysfunction as well as global well-being, at the expense of remarkably few adverse effects. It is noteworthy that it also appears to improve bloating, a benefit that has not been previously reported for a medication used in IBS. The optimal dose is 6 mg twice daily and the advantage of tegaserod over placebo in different trials varies from 5-20% with the number needed to treat ranging from 5-15 depending on the time at which this effect is calculated during the course of a trial. Recent experience with other drugs acting on 5-HT receptors has focused attention on possible safety issues such as prolongation of the QTc interval on the electrocardiogram and ischaemic colitis. However, data from efficacy trials and studies specifically designed to address the safety of tegaserod have not revealed any evidence of cardiotoxicity or the potential for causing ischaemic colitis. Furthermore, investigation of possible interactions with other drugs such as warfarin or the oral contraceptive have not resulted in any prescribing restrictions. Inappropriate prescription of tegaserod to a subgroup of IBS patients for which the drug was not designed, does not appear to have any serious consequences. Most of the efficacy data on tegaserod has been accumulated in females, simply as a result of the failure to recruit adequate numbers of males or restriction of trials to females. There is therefore insufficient information to assess whether there might be any potential gender differences in responsiveness. For this reason, the drug is currently only licensed for use in females.
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PMID:Benefit-risk assessment of tegaserod in irritable bowel syndrome. 1500 35

The symptomatic management of irritable bowel syndrome (IBS) and functional dyspepsia, which often overlap, can be frustrating and difficult. Education and reassurance remain central for management although controlled trials are lacking. Psychological interventions may be useful in select patients but methodological inadequacies in clinical trials limit their interpretability. For symptom exacerbations, drug treatment is reasonable but no current treatment successfully targets the full symptom complex. Bulking agents are not of proven efficacy in IBS; they may improve constipation but worsen bloating and pain. Anticholinergics are of uncertain value in IBS. A meta-analysis of trials of smooth muscle relaxants for IBS has been reported to be positive but the quality of the trials included was poor. Antidepressants for IBS and functional dyspepsia appear to be efficacious based on the limited published evidence; both global symptoms and abdominal pain improve. Selective serotonin reuptake inhibitors (SSRIs) are of uncertain efficacy but anecdotally appear to be useful. Laxatives are not of proven efficacy in IBS. Loperamide improves diarrhea, but not abdominal pain in IBS. No drug is of proven efficacy for bloating. Acid suppression remains the mainstay of therapy for functional dyspepsia but the majority of patients do not have an adequate response. Promising drugs include new prokinetics for constipation-predominant IBS (e.g., tegaserod, a partial 5-HT4 agonist, prucalopride, a full 5-HT4 agonist, and dexloxiglumide, a cholecystokinin1 antagonist), agents for diarrhea-predominant IBS (e.g., 5-HT3 antagonists, alpha2 receptor agonists and corticotrophin receptor-1 antagonists), other visceral analgesics (e.g. tachykinin antagonists, opioid agonists) and in dyspepsia fundus relaxing agents (e.g., 5-HT1 agonists, tegaserod).
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PMID:New and emerging treatments for irritable bowel syndrome and functional dyspepsia. 1598 38

Chronic constipation is a multisymptom gastrointestinal motility disorder that negatively impacts the lives of those affected. New recommendations on diagnosing and treating this condition have recently been published. This review aims to assist clinicians in applying these recommendations in clinical practice. Although lifestyle interventions and bulking agents help some patients with constipation, data are lacking to support their efficacy in those with chronic constipation. If empirical treatment of patients with chronic constipation fails, osmotic laxatives (e.g. lactulose and polyethylene glycol), a serotonin (5-HT4) receptor agonist (e.g. tegaserod) or a chloride channel activator (e.g. lubiprostone) can be considered. Osmotic laxatives, though effective at increasing stool frequency, are often associated with adverse effects such as bloating and diarrhoea and typically do not effectively relieve the multiple symptoms of chronic constipation. Use of tegaserod and the recently approved lubiprostone is supported by high-quality evidence, and these agents have acceptable safety profiles in patients with chronic constipation. Recent advances in the definition of chronic constipation and in its pharmacological management have led to refinements in identifying the appropriate treatment needs of patients with this condition. It is hoped that these advancements will help clinicians select effective medical regimens for patients with chronic constipation.
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PMID:Treating chronic constipation : How should we interpret the recommendations? 1716 88

In the gut, 5-HT acts as a paracrine signalling molecule released by enterochromaffin cells and as a transmitter released by some descending serotonergic interneurons. It has a prominent role in the regulation of motility, vascular tone, secretion and perception both in normal and under certain pathophysiological conditions, such as the carcinoid syndrome and the irritable bowel syndrome (IBS). Serotonin is known to markedly influence bowel function by activating at least five receptor types (5-HT(1,2,3,4,7)). Among all 5-HT receptors, those belonging to the 5-HT3 (a ionotropic receptor) and 5-HT4 (a metabotropic receptor) type are the most extensively studied in gastroenterology, resulting in commercially available (although not worldwide) serotonergic agents for the treatment of IBS and functional dyspepsia. Recently, 5-HT7 receptors have been found to participate in the accommodation process of the circular muscle during the preparatory phase of ileal peristalsis. Since an exaggerated accommodation of the gut wall may contribute to abdominal distension and bloating, 5-HT7 receptor ligands may offer innovative opportunities for the pharmacological treatment of functional bowel disorders.
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PMID:[Recent insights into the pathogenesis of abdominal symptoms in functional bowel disorders]. 1743 64


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