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)

Eleven patients with so-called collagenous colitis are described and the literature reviewed. The disease presents with persisting watery diarrhoea in middle-aged subjects, predominantly women. The fairly uniform clinical features of abdominal discomfort are suggestive of the irritable bowel syndrome. The morphological changes in colorectal biopsy specimens are diagnostic, showing an excessive intercryptal subepithelial collagen deposition throughout the large bowel. Associated hyperplasia, degeneration, and desquamation are seen in the intercryptal epithelial cells and a mild inflammatory response in the lamina propria. A comparable collagenization has not been demonstrated in other disorders, but otherwise the changes demonstrated histologically and ultrastructurally are of a quantitative nature. Collagenous colitis is unrelated to other diseases and the cause unknown. It has either a benign, continuous course or exacerbations and remissions. Loperamide relieved diarrhoea in five of six patients. The collagen deposition seems to be slowly progressive, but clinical and histopathological resolution may occasionally be seen.
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PMID:Collagenous colitis. A clinical, histological, and ultrastructural study. 385 40

Symptom scores, stool data, and the transit of a standard, solid meal were measured in 28 patients with irritable bowel syndrome (IBS) during baseline conditions and after five weeks of treatment with placebo and loperamide, given as a flexible dosage regime in the form of a double-blind, cross-over trial. All patients had undergone a comprehensive series of diagnostic investigations and had failed to respond to dietary supplementation with coarse wheat bran (10-30 g daily). Loperamide treatment accelerated gastric emptying, compared with placebo (1.2 +/- 0.1 vs 1.5 +/- 0.1 hr; P less than 0.001) and delayed both small bowel (6.2 +/- 0.3 vs 4.3 +/- 0.3 hr; P less than 0.001) and whole gut transit (56 +/- 5 vs 42 +/- 4 hr; P less than 0.01). Eighteen patients said they felt better taking loperamide compared with placebo and, at follow up, 15 of these patients remained satisfied with the effects of the drug. Most symptoms improved significantly on placebo compared with the baseline period, but three of these [diarrhea (P less than 0.01), urgency (P less than 0.01) and borborygmi (P less than 0.05)] showed a further significant improvement on loperamide. Improvement in diarrhea was not associated with any change in stool weight but was associated with reductions in stool frequency (P less than 0.001), passage of unformed stools (P less than 0.01), and incidence of urgency (P less than 0.001). Urgency was the only symptom that was significantly more common in the success group, compared with the group who did not feel better on loperamide.
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PMID:Role of loperamide and placebo in management of irritable bowel syndrome (IBS). 636 90

A method is described for the measurement of hydrogen in expired air, using an electrochemical detector. The apparatus is simple to use and sensitive. Its application is illustrated by studies of small bowel transit time made by measuring the time between oral ingestion of the unabsorbable carbohydrate lactulose and a rise in the concentration of hydrogen in expired air. In 20 control subjects transit time was 93.0 +/- 6.6 minutes, while in 16 patients with diarrhoea due to the irritable bowel syndrome it was 54.1 +/- 6.3 minutes (P less than 0.001), suggesting an abnormality in small intestinal motility in these patients. Loperamide, a potent antidiarrhoeal agent, increased transit time in 12 of these patients from 56.3 +/- 6.7 to 100.0 +/- 10.2 minutes (P less than 0.001).
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PMID:Electrochemical detector for breath hydrogen determination: measurement of small bowel transit time in normal subjects and patients with the irritable bowel syndrome. 729 14

This review summarizes the clinical evidence to support current therapies in irritable bowel syndrome (IBS). Fibre is indicated at a dose of at least 12 g per day in patients with constipation-predominant IBS. Loperamide (and probably other opioid agonists) are of proven benefit in diarrhoea-predominant IBS; loperamide may also aid continence by enhancing resting anal tone. In general, smooth muscle relaxants are best used sparingly, on an 'as needed' basis, as their overall efficacy is unclear. Psychotropic agents are important in relieving depression and of proven benefit for pain and diarrhoea in patients with depression associated with IBS. Further trials with selective serotonin reuptake inhibitors (SSRIs) are awaited. Psychological treatments including hypnotherapy are less widely available, but may play an important role in relief of pain. In summary, current therapies targeted on the predominant symptoms in IBS are moderately successful. New therapies are needed to more effectively relieve this syndrome, not just symptoms.
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PMID:Review article: clinical evidence to support current therapies of irritable bowel syndrome. 1042 40

This article reviews briefly the evidence to support current therapies in irritable bowel syndrome (IBS) and the novel therapeutic approaches on the threshold of clinical application. Fiber is indicated at a dose of at least 12 grams per day in patients with constipation-predominant IBS. Loperamide (and probably other opioid agonists) are of proven benefit in diarrhea-predominant IBS; loperamide may also aid continence by enhancing resting anal tone, but there is no evidence that it results in pain relief. In general, smooth muscle relaxants are best used sparingly, on an as-needed basis, because their overall efficacy is unclear. The 5-HT3 antagonist, alosetron, results in adequate relief of pain and improvements in bowel function in female nonconstipated patients with IBS. Psychotropic agents are important in relieving depression and are of proven benefit for pain and diarrhea in patients with depression associated with IBS. Further trials with selective serotonin reuptake inhibitors are awaited. Psychological treatments including hypnotherapy are less widely available but may play an important role in the relief of pain. In summary, current therapies targeted on the predominant symptoms in IBS are moderately successful. As the bowel sensorimotor and limbic system disturbances of IBS are more clearly understood, we should anticipate other pharmacologic approaches in the near future, including alpha-adrenergic agonists and 5-HT4 agonists. New therapies directed at treatment of the syndrome, rather than relief of symptoms, are needed.
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PMID:Therapeutic approach to the patient with irritable bowel syndrome. 1058 70

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

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

A small but significant subgroup of patients with irritable bowel syndrome (IBS) report a sudden onset of their IBS symptoms after a bout of gastroenteritis. Population-based surveys show that although a history of neurotic and psychologic disorders, pain-related diseases, and gastroenteritis are all risk factors for developing IBS, gastroenteritis is the most potent. More toxigenic organisms increase the risk 11-fold, as does an initial illness lasting more than 3 weeks. Hypochondriasis and adverse life events double the risk for postinfective (PI)-IBS and may account for the increased proportion of women who develop this syndrome. PI-IBS is associated with modest increases in mucosal T lymphocytes and serotonin-containing enteroendocrine cells. Animal models and some preliminary human data suggest this leads to excessive serotonin release from the mucosa. Both the histologic changes and symptoms in humans may last for many years with only 40% recovering over a 6-year follow-up. Celiac disease, microscopic colitis, lactose intolerance, early stage Crohn's disease, and bile salt malabsorption should be excluded, as should colon cancer in those over the age of 45 years or in those with a positive family history. Treatment with Loperamide, low-fiber diets, and bile salt- binding therapy may help some patients. Serotonin antagonists are logical treatments but have yet to be evaluated.
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PMID:Postinfectious irritable bowel syndrome. 1276 24

Irritable bowel syndrome (IBS) is an extremely common cause of consultation, and at present is diagnosed on the basis of symptoms and a few simple exclusion tests. Exclusion diets can be successful, but many patients have already attempted and failed such treatments before consulting. Anxiety and somatization may be an important driver of consultation. Patients' concerns should be understood and addressed. Those with prominent psychiatric disease may benefit from psychotherapy. Hypnotherapy benefits symptoms in those without psychologic disturbance, but its availability is limited. Antidepressants are effective in improving both mood and IBS symptoms globally, and the evidence is particularly good for tricyclic antidepressants. Although antispasmodics are currently the most commonly prescribed drugs, most responses (75%) are due to the placebo effect and not specific to the drug. Bulk laxatives such as ispaghula can increase stool frequency and help pain, but bloating may be aggravated. Loperamide is effective treatment for urgency and loose stools, but less effective for bloating and pain. 5-HT(3) antagonists such as alosetron improve urgency, stool consistency, and pain in diarrhea-predominant-IBS. The 5-HT(4) agonist tegaserod shows modest benefit in constipation-predominant IBS, improving stool frequency, consistency, and bloating as well as global improvement. There are many new drugs, such as cholecystokinin, neurokinin, and corticotropin receptor antagonists, in development.
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PMID:Treatment of Irritable Bowel Syndrome. 1284 42

The irritable bowel syndrome (IBS) remains a therapeutic challenge in part because of the limited understanding of the pathophysiology. The placebo response rate varies in randomized controlled trials from 20 to 70%, and can persist for up to at least 1 year. It is contentious whether dietary fibre and bulking agents relieve the symptoms of IBS; constipation probably improves. Anticholinergic and antispasmodic agents are of questionable benefit in IBS despite positive meta-analyses of poor quality trials. A meta-analysis concluded that the tricyclic antidepressants were superior to placebo in IBS, although the individual trial results were variable. Selective serotonin reuptake inhibitors are of uncertain benefit. Laxatives are used for constipation but probably poorly control the IBS symptom complex. Loperamide is superior to placebo in improvement of diarrhoea but not abdominal pain in IBS. Tegaserod is a well- tolerated aminoguanidine indole derivative of serotonin that is a partial 5HT4-receptor agonist with prokinetic properties; a therapeutic gain over placebo of 5% to 15% has been observed in constipation-predominant IBS in females. Alosetron is a 5HT3-receptor antagonist that is efficacious in females with diarrhoea-predominant IBS, with a 12% to 17% therapeutic gain; the risk of ischaemic colitis is 1 in 350, with very severe constipation occurring in about 1 in 1000. Optimizing study design remains a challenge in IBS. New visceral analgesic and motility modifying agents, as well as anti-inflammatory agents are in trials, and hopefully additional efficacious therapeutic options for patients with IBS will soon emerge.
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PMID:Evaluation of drug treatment in irritable bowel syndrome. 1296 80


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