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)

Subjects deficient in lactase may experience bloating, cramps and diarrhoea after ingesting milk, due to the unhydrolysed and poorly-absorbed lactose. The diarrhoea may result from an osmotic effect of the lactose itself or its poorly-absorbed acidic products of fermentation (Weijers, van de Kamer & others, 1961; Christopher & Bayless, 1971), possibly together with an alteration of sodium and water absorption due to the lowered colonic pH (Rousseau & Sladen, 1971). Laxation by lactulose (1-4-beta-galactosidofructose) may operate through an analogous mechanism. The drug is a synthetic dissaccharide which, in oral doses of 10-20 g, relieves chronic constipation (Wesselius-de Casparis, Braadbaart & others, 1968). It is neither hydrolysed by intestinal dissaccharidase (Dahlqvist & Gryboski, 1965) nor absorbed in the gut, but it is converted in the colon mainly to lactic and acetic acids by various bacteria including Lactobacillus acidophilus. Apart from the increased osmotic effect, the pH in the proximal colon falls markedly (Bown, Gibson & others, 1974), and larger doses may reduce stool pH. Weijers & others (1961) inferred that the acidic products formed from lactose in the colon stimulate propulsion, and K.S. Liem (Philips-Duphar) suggested to us that lactulose may relieve constipation partly by stimulation of propulsion due to the lowered pH. The experiments described below support this view.
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PMID:Intestinal pH and propulsion: an explanation of diarrhoea in lactase deficiency and laxation by lactulose. 0 91

This study investigated the hypothesis that some features of functional gastrointestinal disorders may be associated with abnormalities of ileocaecal transit by measuring ileocaecal transit using a scintigraphic technique in 43 patients with chronic constipation, 20 patients with irritable bowel syndrome (IBS), and 18 control subjects. Subjects ingested enteric coated capsules, which delivered 111-indium radionuclide to the distal ileum. Gammacamera images were acquired at hourly intervals until caecal filling was complete. Ileocaecal transit was defined as the time between peak scintigraphic activity in the terminal ileum and peak activity in the caecum. The mean (SD) ileocaecal transit of 103 (50) minutes in patients with IBS was significantly faster than that in control subjects (mean (SD) ileocaecal transit 174 (78) minutes, p < 0.002). There were no significant differences in ileocaecal transit between patients with chronic idiopathic constipation and the control subjects, or between patients with constipation predominant and diarrhoea predominant IBS. This study developed a practical scintigraphic method of measuring ileocaecal transit. The rapid ileocaecal transit in both the constipation and diarrhoea predominant forms of IBS suggests that bloating may not after all result from delayed ileal emptying.
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PMID:Scintigraphic measurement of ileocaecal transit in irritable bowel syndrome and chronic idiopathic constipation. 773 69

Chronic constipation is a common clinical condition that frequently does not respond to routine therapeutic measures. We hypothesized that colchicine would be effective in this condition because we reported that it stimulates intestinal motility in rats and commonly causes diarrhea in patients taking the drug for either gouty arthritis or Familial Mediterranean fever. We prospectively studied seven patients with chronic constipation who were refractory to medical therapy and treated them with oral colchicine 0.6 mg per os three times a day for eight weeks in an open-label pilot study. During the study, the mean number of spontaneous bowel movements significantly increased (P < 0.05) from 1.7 +/- 0.5 noted during routine therapy of constipation with laxatives and enemas to 6.4 +/- 0.7 per week; mean colonic transit time significantly (P < 0.05) decreased from 58.1 +/- 2.5 to 47.1 +/- 5.0 hr; and symptoms of abdominal pain, nausea, and bloating significantly (P < 0.05) improved during therapy with colchicine. Oral colchicine (0.6 mg three times a day) therapy appears to be an a promising treatment for chronic constipation and a placebo-controlled trial is indicated to confirm these findings.
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PMID:Colchicine is an effective treatment for patients with chronic constipation: an open-label trial. 933 Nov 62

Personality changes have been reported in chronic constipation. Hostility is an important personality factor involved in psychosomatic disorders. The aim of this study was to investigate hostility in patients with chronic constipation. Sixty subjects with chronic constipation (24 males, 36 females, mean age 44.5 years) were investigated with the hostility scale of the Minnesota Multiphasic Inventory. The patients were divided in four groups according to their symptoms: functional chronic constipation (Group I, n = 18), irritable bowel syndrome expressed as chronic constipation and abdominal pain (Group II, n = 21), irritable bowel syndrome expressed as chronic constipation, abdominal pain and bloating (Group III, n = 13) and irritable bowel syndrome expressed as chronic constipation alternating with episodes of diarrhoea (Group IV, n = 8). Twenty-five clinically healthy subjects were investigated as controls. Hostility was as follows (mean +/- SD): 68 +/- 9 in group I, 62 +/- 12 in group II, 70 +/- 14 in group III, 56 +/- 12 in group IV and 40 +/- 12 in controls. The scores were significantly higher in all groups of patients with constipation versus controls (p < 0.01; < 0.001; < 0.001; < 0.02, respectively). These data suggest that hostility is increased in patients with chronic constipation. It is rather a feature of the functional bowel disorders than of constipation, as symptom, only.
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PMID:Hostility in patients with chronic constipation. 1082 20

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

Laxatives are among the most commonly used drugs or additives. Most are quite safe when used judiciously, intermittently when possible, and in the absence of contraindications. Bulking agents and nonabsorbable compounds such as lactulose can cause bloating but have very few serious adverse effects except for the allergic reaction to psyllium preparations. Osmotic laxatives containing poorly absorbable ions such as magnesium or phosphate can cause metabolic disturbances, particularly in the presence of renal impairment. However, if taken intermittently, in the absence of conditions such as ileus or bowel obstruction, they have few adverse effects. Polyethylene glycol solutions are emerging as an effective and safe mode of treatment for chronic constipation. Of stimulant laxatives, senna compounds and bisacodyl are the most commonly used. Although there are data to support the neoplastic potential of this class of drugs in in vitro studies, epidemiologic data in humans so far has not established a clear link between these laxatives and colonic neoplasia. The link between stimulant laxatives and structural changes, such as the "cathartic colon" or enteric nerve damage, is not well established either. Danthron compounds should be avoided because of hepatotoxicity.
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PMID:Adverse effects of laxatives. 1153 63

Irritable bowel syndrome (IBS) is common and can be disabling. Several drugs that modulate serotonin (5HT) and other neurotransmitters in the gut (neuroenteric modulators) have either become available or are in development, but progress has been slowed by toxicity. Blockade of 5HT(3) receptors slows colonic transit, increases fluid absorption and increases left colon compliance. Alosetron, a potent 5HT(3) receptor antagonist, has, in women but not in men, a clinically significant but modest therapeutic gain over placebo in the relief of abdominal pain and discomfort and bowel-habit disturbance (but not bloating) in diarrhoea-predominant IBS. However, the drug unexpectedly was associated with ischaemic colitis and, very rarely, severe constipation-induced complications, and alosetron has been withdrawn. Cilansetron may have similar efficacy in men and women. 5HT(4) receptor stimulation results in accelerated colonic transit, and tegaserod, a partial 5HT(4) receptor agonist, has modest but clinically significant advantage over placebo in constipation-predominant IBS; the benefit seems to be confined to females. Long-term published data are lacking and safety concerns have been raised. Prucalopride, a full 5HT(4) agonist that has been promising in idiopathic chronic constipation, may also be limited by toxicity. Other 5HT receptor antagonists and agonists are under development for IBS. However, for modulators of single receptors to achieve a substantial therapeutic gain, and to do so safely, drug targets based on the pathophysiology of IBS need to be better defined.
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PMID:Serotoninergic neuroenteric modulators. 1175 32

It is estimated that one third of the population in Western industrial countries suffers from constipation at least from time to time. Constipation may have somatopathic or functional causes. Furthermore, a great number of substances are known to cause medication-induced constipation, i.e. opioid-induced constipation is caused by linkage of the opioid to opioid receptors in the bowel and the central nerve system. Whenever possible, causal therapy should be undertaken. Patients in palliative care mostly suffer from chronic functional constipation. The treatment consists of basic measures and the application of laxatives. According to their mode of action, they are divided into bulk-forming laxatives, osmotic laxatives, stimulant laxatives, lubricating agents and others. Bulk-forming laxatives are not recommended for use in palliative care patients, for such patients are normally not able to take in the required amount of fluids. Osmotic laxatives are divided into (magnesium) salts, saccharine, alcohols and macrogols. Lactulose is the most popular saccharine laxative. Because of its side effects (flatulence, bloating and abdominal cramping), lactulose is not a laxative of our choice; instead, we prefer to give macrogol. Orally administered, macrogol is not metabolised and pH value and bowel flora remain unchanged. Macrogol hydrates hardened stools, increases stool volume, decreases the duration of colon passage and dilates the bowel wall that then triggers the defecation reflex. Even when given for some time, the effectiveness of macrogol will not decrease. Because of its high effectiveness and commonly good tolerance, macrogol has become the laxative of first choice in palliative care patients with all kinds of chronic constipation, if these patients are able to take in the necessary amount of fluids. From the general medical point of view, lubricating agents have become obsolete. In palliative care patients, however, they are still important laxatives for prophylactic treatment or therapy of constipation. Due to clinical experience, in palliative care a laxative ladder has proven successful.
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PMID:Constipation--modern laxative therapy. 1450 58

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

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


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