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)

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 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 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

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

Carmint contains total extracts of Melissa officinalis, Mentha spicata, and Coriandrum sativum, which have antispasmodic, carminative, and sedative effects. As abdominal pain/discomfort and bloating are commonly observed in patients with irritable bowel syndrome, we decided to evaluate the effectiveness of Carmint in relieving these symptoms in irritable bowel syndrome patients. We randomly assigned 32 irritable bowel syndrome patients to receive either Carmint or placebo, plus Loperamide or psyllium (based on their predominant bowel function), for 8 weeks. T-test analysis of the results showed that the severity and frequency of abdominal pain/discomfort were significantly lower in the Carmint group than the placebo group at the end of the treatment (P=0.016 and P=0.001, respectively), as were the severity and frequency of bloating (P=0.02 and P=0.002, respectively). This pilot study suggests that Carmint plus loperamide or Carmint plus psyllium (depending on the irritable bowel syndrome subtype) might be effective in these patients.
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PMID:The efficacy of an herbal medicine, Carmint, on the relief of abdominal pain and bloating in patients with irritable bowel syndrome: a pilot study. 1686 24

Loperamide is an effective therapy for a variety of diarrheal syndromes, including acute, nonspecific (infectious) diarrhea; traveler's diarrhea; and chemotherapy-related and protease inhibitor?associated diarrhea. Loperamide is effective for the "gut-directed" symptom of diarrhea in patients with painless diarrhea or diarrhea-predominant irritable bowel syndrome. Loperamide and diphenoxylate are commonly used to treat diarrhea in numerous settings of inflammatory bowel disease. Loperamide has also been observed to increase anal sphincter tone, which may lead to improvement of fecal continence in patients with and without diarrhea. Loperamide is generally well tolerated at recommended nonprescription doses, with the most common side effects related to the impact on bowel motility (abdominal pain, distention, bloating, nausea, vomiting, and constipation).
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PMID:The role of loperamide in gastrointestinal disorders. 1847 66

Functional bowel disorders (i.e., constipation and diarrhea) are characterized by abdominal pain, bloating, distention, and/or bowel habit abnormalities in the absence of obvious anatomic or physiologic abnormalities on routine diagnostic tests. These symptoms are attributable to gastrointestinal sensorimotor dysfunctions resulting from peripheral and/or central mechanisms. Available drugs target the underlying bowel disturbance (i.e., constipation, diarrhea, or both), supplemented when necessary by management of pain. Osmotic and stimulant laxatives, secretagogues, and serotonin 5-HT4 receptor agonists are approved for treating constipation. Loperamide, anticholinergic agents, rifaximin, bile-acid binding agents, eluxadoline, and clonidine are used to treat diarrhea. Several exciting new compounds, some of which have been evaluated in humans, are currently under development.
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PMID:Existing and emerging therapies for managing constipation and diarrhea. 2917 23