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Query: UMLS:C0000737 (abdominal pain)
 31,184 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

The irritable bowel syndrome (IBS) is a consortium of symptoms including abdominal pain and alterations in the pattern of defaecation. There is no single pathophysiological marker of IBS although it is generally accepted that some patients do have abnormalities of intestinal motility and/or enhanced visceral sensitivity. There is also an increasing acceptance that the central nervous system, an important component of the brain-gut axis, also plays an important role in symptom production both in the response to stress and when there is an underlying affective disorder. During the past decade new therapeutic targets have been identified that have permitted the development of new drugs with therapeutic potential for IBS. Identification and characterization of 5-hydroxytryptamine (5-HT) receptors in the gastrointestinal tract particularly 5-HT3 and 5-HT4 receptors, which are involved not only in modulating gut motility but in visceral sensory pathways, has led to a number of studies of 5-HT3 (Alosetron, Granisetron and Ondansetron) and 5-HT4 (SB-207266A) antagonists. Both classes of drug appear to reduce visceral sensitivity and have inhibitory effects on motor activity in the distal intestine. Early clinical studies suggest that these agents may have a role in painful, diarrhoea-predominant IBS. 5-HT4 agonists (HTF919, Zelmac) may improve constipation-predominant IBS by normalizing bowel habit and thereby reducing abdominal pain. Alternative approaches to reducing visceral sensation include the use of the opioid kappa agonists, which have no central opioid effects although clinical trials have suggested that these agents are not highly effective in relieving IBS pain. There are in addition, new approaches to modify intestinal motility including the development of gut selective muscarinic M3 receptor antagonists such as zamifenacin and the 5-HT4 partial agonist, HTF919. Preliminary studies suggest that these agents may have therapeutic potential in IBS. Anti-depressants are increasingly used to treat affective disorder in IBS but in addition appear to have added value because of their ability to reduce visceral hypersensitivity and alter gut transit. Therapeutic effects are often obtained at doses below those normally used to treat depression. IBS continues to be a therapeutic challenge because of its diverse symptomatology and lack of a single pathophysiological target for drug intervention.
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PMID:Irritable bowel syndrome: new pharmaceutical approaches to treatment. 1058 Sep 22

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

Because treatment of irritable bowel syndrome (IBS) patients can be frustrating to the clinician and patient as well, the physician should strive to gain the patient's confidence with a concise, appropriate work-up and by offering reassurance and education that IBS is a functional disorder without significant long-term health risks. First-line treatment should be aimed at treating the most bothersome symptom. Tricyclic antidepressants are superior to placebo in reducing abdominal pain scores, as well as improving global symptom severity. Loperamide is superior to placebo in managing IBS-associated diarrhea. Whereas fiber has a role in treating constipation, its value for IBS or, specifically, in the relief of abdominal pain or diarrhea associated with IBS is controversial. Although certain antispasmodics have demonstrated superiority over placebo in managing abdominal pain, none of these agents are available in the United States. Probiotic therapy using Lactobacillus plantarum has demonstrated superiority to placebo in improving pain, regulating bowel habits, and decreasing flatulence. As studied in a recent placebo-controlled prospective study, Chinese herbal medicines significantly improved bowel symptom scores and global symptom profile, and reduced IBS-related quality of life impairment. Some of the most promising emerging therapies in IBS revolve around targeted pharmacotherapeutic modulation of serotonin receptors (ie, 5-HT3 and 5-HT4 subtypes), which are involved in sensory and motor functions of the gut. Other investigational agents that are also being explored include cholecystokinin antagonists, alpha2-adrenergic agonists (eg, clonidine), serotonin reuptake inhibitors (eg, citalopram), and neurokinin antagonists. IBS is best understood through the biopsychosocial paradigm, and therefore, its effective management requires a comprehensive multidisciplinary approach based on patient education and reassurance, enhanced by diet recommendations and lifestyle modifications, and complemented by pharmacotherapy and psychosocial intervention in more severe cases.
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PMID:Irritable Bowel Syndrome. 1209 74

Irritable bowel syndrome (IBS) comprises a major proportion of gastrointestinal and primary care practice worldwide. The past several years have seen the rapid evolution of a new and comprehensive model of IBS based on alterations in brain-gut interactions. Alterations in the bidirectional communication between the enteric nervous system and the central nervous system are implicated in the pathogenesis of IBS. 5-Hydroxytryptamine (5-HT; serotonin), a major neurotransmitter in the gastrointestinal tract, and its receptors 5-HT3 and 5-HT4 are involved in the control of gastrointestinal function. A number of abnormal motor and sensory patterns have been reported in patients with IBS. However, it is not known whether these abnormalities are related to symptoms or have a role in establishing a diagnosis of functional gastrointestinal disorders. Visceral hyperalgesia in IBS patients can be secondary to altered receptor sensitivity at the viscus itself and altered central modulation of sensation involving psychological influences in the interpretation of these sensations. The development of diagnostic criteria for IBS helps to avoid unnecessary and costly investigations. A detailed history allows us to diagnose IBS and search for another cause if warning symptoms are present. The Rome criteria are presently used to define IBS and are currently the most widely applied criteria used in clinical diagnosis and research purposes. Abdominal pain or discomfort associated with chronic altered bowel habits are the mainstay in diagnosis, while the supportive criteria may be used to further classify IBS patients into diarrhea-predominant or constipation-predominant subgroups. Minimal diagnostic tests have been advocated in the initial diagnostic approach to patients with suspected IBS, depending on the predominant symptom. The therapeutic goals in IBS must focus on the overall well-being of the patient, including abdominal symptoms and the accompanying nonbowel symptoms and affective disorders. It is important to establish an effective physician-patient relationship and to reassure the patient once the diagnosis of IBS is made. Dietary modification may be of value in some patients with IBS. Dietary fiber is frequently recommended for patients with constipation-predominant IBS. Two novel serotonin agonists are currently under development for constipated IBS patients, tegaserod and prucalopride. Antidiarrheal agents, including loperamide and diphenoxylate, may help patients with diarrhea-predominant IBS. 5-HT3 receptor antagonists may play a role in the management of such patients in the future. Psychological treatment and antidepressants should be considered when IBS symptoms are severe or refractory or associated with psychological distress and impaired quality of life.
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PMID:Irritable bowel syndrome: update on pathogenesis and management. 1211 90

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

Irritable bowel syndrome (IBS) is a common functional bowel disorder characterized by abdominal pain and change in defecation pattern. This review addresses the topic of possible sex (genetic, biological) and gender (experiential, perceptual) differences in individuals with and without IBS. Several observations make the topic important. First, there is a predominance of women as compared to men who seek health care services for IBS in the United States and other industrialized societies. Second, menstrual cycle-linked differences are observed in IBS symptom reports. Third, women with IBS tend to report greater problems with constipation and nongastrointestinal complaints associated with IBS. Fourth, serotonin (5-HT3) receptor antagonist and 5-HT4 partial agonist drugs appear to more effectively diminish reports of bowel pattern disruption in women with IBS as compared to men. This review examines sex and gender modulation of gastrointestinal motility and transit, visceral pain sensitivity, autonomic nervous system function, serotonin biochemistry, and differences in health care-seeking behavior for IBS.
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PMID:Impact of sex and gender on irritable bowel syndrome. 1288 71

Irritable bowel syndrome (IBS) is a common gastrointestinal disorder characterised by recurrent abdominal pain and altered bowel habits in the absence of any discernible structural, biochemical and physiological abnormalities. Although there is no specific biological marker for the diagnosis of this disorder, recently developed symptom-based criteria provide the tools necessary to make a diagnosis. The precise underlying pathophysiology of IBS remains unknown. However, disturbances in the brain-gut axis involving the central nervous system and the enteric nervous system have emerged as an underlying concept for IBS. In this regard, conventional treatment has been recognised as unsatisfactory for many patients with IBS and novel, neuroenteric modulatory compounds have been introduced for use by clinicians. Specifically, compounds interacting with the 5-hydroxytryptamine (5-HT, serotonin) receptors of the 5-HT3 and 5-HT4 subtype have been demonstrated of benefit in some patients for the treatment of IBS. In this leading article, we present the current data on the pharmacology, clinical trials, indications and adverse effects of alosetron, a potent and selective 5-HT3 antagonist. As a result of the recognition of serious adverse effects, the indication for alosetron has been restricted and it is now indicated only for women with severe diarrhoea-predominant IBS who have symptoms for at least 6 months and who have failed to respond to conventional therapy. Prescribing restrictions and the risk-management programme implemented as required by the US FDA is reviewed along with a summary of the studies to be performed after reintroduction of alosetron to monitor safety.
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PMID:Alosetron in irritable bowel syndrome: strategies for its use in a common gastrointestinal disorder. 1293 Jan 62

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


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