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)

Octreotide, the long-acting somatostatin analogue, has been reported to modulate gastrointestinal motility in both animals and humans. A role in colonic peristalsis and a possible clinical application in common disorders, such as chronic constipation and irritable bowel syndrome, have not been evaluated. It has been previously suggested that octreotide promotes the descending relaxation of the peristaltic reflex arc. We hypothesized that this effect may involve inhibition of the motility index (MI) of the distal colon. To test this proposal, we studied peristalsis in isolated rabbit colons and also in the intact distal colons of anesthetized rabbits undergoing octreotide administration. Left colons of New Zealand white rabbits were harvested, placed in an isolated organ chamber and perfused with Krebs-Ringer bicarbonate solution via the inferior mesenteric artery. In a separate preparation, the colons were left in situ. Motility was quantified with a 6-port continuous infusion manometry catheter. The MI (mm Hg/min) was calculated by integration of the area of the digitalized signal (8/s), which reflected high-pressure peaks of different magnitudes. High-pressure waves were defined as > 20 mm Hg. Octreotide was infused via the inferior mesenteric artery in the isolated specimen or the lateral ear vein in the anesthetized animals in concentrations of 10(-12) to 10(-6) M. Octreotide inhibited high-pressure waves in a dose-dependent manner. These effects resulted in a decreased MI, with the maximum inhibition of 24.6% at 10(-11) M (p < 0.05 by ANOVA). At that concentration, the number of peaks > 20 mm Hg were reduced by 62.2%. The data indicate that octreotide decreases the MI by inhibition of high-pressure waves in the distal rabbit colon. These findings are consistent with the proposal that somatostatin may augment descending relaxation of the peristaltic reflex arc. This effect is independent of neural modulation.
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PMID:Octreotide acetate inhibits motility in the rabbit distal colon. 925 4

There are described the studies performed in Italy-especially at Montecatini-about activity of certain mineral waters, administered by mouth, in functional troubles of the digestive apparatus. The illnesses especially considered have been: idiopathic chronic constipation, irritable colon syndrome, biliary dyskinesias, correlated pathological conditions. The mineral waters analyzed had been: salso-sulphate-alkaline, bicarbonate, sulphate, bicarbonate-sulphate-alkaline, sulphate-bicarbonate waters and others. There are reported: research methods employed, the obtained results, the possible mechanisms of effect. The hydrological favourable influences about pathophysiology of digestive motor activity and in therapeutics of correlated diseases are demonstrated. The clinical results, and particularly their duration in time, are affermatif about therapeutic usefulness of thermal treatment by mouth. It's possible to suggest and to stress their better knowledge in Medicine and their increased employment in the treatment of functional dyskinesias of the alimentary tract.
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PMID:Thermal therapy of functional dyskinesias of the alimentary tract. 934 26

Constipation, diarrhea, and irritable bowel syndrome are commonly encountered in the primary care practice. Most episodes of constipation and diarrhea are benign and self-limited. Patients with chronic constipation should undergo a screening evaluation to exclude organic disease, after which most can be managed successfully with dietary modification and fiber supplementation. The cause of chronic diarrhea usually can be discerned clinically, with irritable bowel syndrome, inflammatory bowel disease, and lactose intolerance being diagnosed most frequently. Irritable bowel syndrome is a functional gastrointestinal disorder characterized by abdominal pain and disordered defecation, which is successfully managed with a strong physician-patient relationship and periodic pharmacologic intervention.
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PMID:Constipation, diarrhea, and irritable bowel syndrome. 992 98

Although it is unclear to what extent irritable bowel syndrome (IBS) symptoms represent a normal perception of abnormal function or an abnormal perception of normal function, many believe that IBS constitutes the clinical expression of an underlying motility disorder, affecting primarily the mid- and lower gut. Indeed, transit and contractile abnormalities have been demonstrated with sophisticated techniques in a subset of patients with IBS. As a consequence, drugs affecting gastrointestinal (GI) motility have been widely employed with the aim of correcting the major IBS manifestations, ie, pain and altered bowel function. Unfortunately, no single drug has proven to be effective in treating IBS symptom complex. In addition, the use of some medications has often been associated with unpleasant side effects. Therefore, the search for a truly effective and safe drug to control motility disturbances in IBS continues. Several classes of drugs look promising and are under evaluation. Among the motor-inhibiting drugs, gut selective muscarinic antagonists (such as zamifenacin and darifenacin), neurokinin2 antagonists (such as MEN-10627 and MEN-11420), beta3-adrenoreceptor agonists (eg, SR-58611A) and GI-selective calcium channel blockers (eg, pinaverium bromide and octylonium) are able to decrease painful contractile activity in the gut (antispasmodic effect), without significantly affecting other body functions. Novel mechanisms to stimulate GI motility and transit include blockade of cholecystokinin (CCK)A receptors and stimulation of motilin receptors. Loxiglumide (and its dextroisomer, dexloxiglumide) is the only CCKA receptor antagonist that is being evaluated clinically. This drug accelerates gastric emptying and colonic transit, thereby increasing the number of bowel movements in patients with chronic constipation. It is also able to reduce visceral perception. Erythromycin and related 14-member macrolide compounds inhibit the binding of motilin to its receptors on GI smooth muscle and, therefore, act as motilin agonists. This antibiotic accelerates gastric emptying and shortens orocecal transit time. In the large bowel a significant decrease in transit is observed only in the right colon, which suggests a shift in fecal distribution. Several 'motilinomimetics' have been synthesized. Their development depends on the lack of antimicrobial activity and the absence of fading of the prokinetic effect during prolonged administration. 5-hydroxytryptamine (5-HT)4 agonists with significant pharmacological effects on the mid- and distal gut (such as prucalopride and tegaserod) are available for human use. These 'enterokinetic' compounds are useful for treating constipation-predominant IBS patients. 5-HT3 receptor antagonists also possess a number of interesting pharmacological properties that may make them suitable for treatment of IBS. Besides decreasing colonic sensitivity to distension, these drugs prolong intestinal transit and may be particularly useful in diarrhea-predominant IBS. Finally, when administered in small pulsed doses, octreotide, besides reducing the perception of rectal distension, accelerates intestinal transit, although other evidence disputes such an effect.
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PMID:Management of irritable bowel syndrome: novel approaches to the pharmacology of gut motility. 1020 10

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

Treatment of idiopathic constipation requires precise definition of the physiological and pathophysiological changes. A colorectal work-up including colonoscopy, colorectal passage, colonic transit study, anorectal manometry, cinedefecography and electromyography help to distinguish between four different forms of idiopathic constipation: slow transit constipation, outlet obstruction, a combination of both problems and irritable bowel syndrome. 70% of patients with chronic constipation suffer from irritable bowel syndrome. In these cases there is no indication for surgery. Patients with pelvic outlet obstruction due to paradoxical puborectalis contraction can be successfully treated with biofeedback. Outlet obstruction due to rectal prolapse, rectocele and intussusception require surgery. Total colectomy with ileorectal anastomosis is the surgical option for selected patients with slow transit constipation. Where there is a mixed disorder, biofeedback for the outlet obstruction must be applied prior to colectomy for the inert colon. Thorough preoperative physiologic testing is mandatory for a successful outcome. When cases are carefully diagnosed and selected, the operative results are excellent.
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PMID:[Surgery for idiopathic constipation. The modest role of successful surgery]. 1112 56

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 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

Severe chronic constipation is defined as less than two bowel movements per week, hard stools, non productive urgency and the need of digital maneuvers in more than 25% of bowel evacuations. The best studied causes of chronic severe constipation are slow bowel transit constipation and pelvic floor dysfunction. However, there are mixed forms that cross link with irritable colon syndrome. The main diagnostic tests are anorrectal manometry, bowel evacuation, X-ray studies and anorrectal sphincteromyomectomy, that can be therapeutic. Five percent of patients are surgical candidates. In cases of slow bowel movement, total colectomy with ileorectal anastomosis has satisfactory results in 80 to 90% of patients. Some patients with pelvic floor dysfunction have an occult rectal prolapse, rectocele or sigmoidocele and obtain benefits with the correction of these conditions. The remaining patients require a training of bowel evacuation, known as biofeedback. We have performed a total colectomy in 10 patients with slow bowel movements with good functional results in 80%. After 56 months of follow-up, a mean 2.6 bowel movements per day is reported by the patients. Four patients were also operated due to a solitary rectal ulcer and two patients due to a sigmoidocele, with satisfactory results.
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PMID:[Severe chronic constipation. Is it a problem of surgery?]. 1223 7

Constipation is a common disorder and many patients fail to respond to the simple constipation remedies of increased fiber and fluid intake. When secondary to other conditions, medications, or disease processes, the focus of constipation management is correction of causative factors. However, primary constipation - ie, constipation with no identifiable causative factor - is very common. Patients generally present with one of three patterns: constipation-predominant irritable bowel syndrome, slow transit constipation, or pelvic floor dysfunction resulting in dyssynergic defecation. Baseline evaluation for patients with chronic constipation includes a careful history, focused physical examination, and limited laboratory studies. Patients with dyssynergic defecation usually respond best to biofeedback therapy and pelvic muscle re-education. Constipation-predominant irritable bowel syndrome is best managed with dietary monitoring and modifications, fiber therapy, and education regarding self-monitoring and self-care. Patients with slow transit constipation may benefit from fiber therapy and increased activity, but most also will require laxative therapy. Current guidelines for prescribing laxatives suggest bulk agents as first line and osmotic agents as second line therapy. Stimulant laxatives should generally be reserved for PRN use. Current understanding about the etiology, pathology, and classification of different types of constipation are summarized and a stepwise approach to evaluation and management is presented.
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PMID:When fiber is not enough: current thinking on constipation management. 1249 Jul 51


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