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)

Gastric motor dysfunction and concomitant gastric stasis have been implicated in the pathogenesis of nonulcer dyspepsia, but a cause-and-effect relationship is not established. Essential dyspepsia refers to a subgroup of nonulcer dyspepsia patients who have no evidence of irritable bowel syndrome, gastroesophageal reflux, or pancreaticobiliary disease. In 32 patients with essential dyspepsia, and 32 randomly selected dyspepsia-free community controls of similar age and sex, we measured gastric emptying of solids using Tc99m-Sulphur Colloid in a fried egg sandwich. Subjects with neuromuscular or other diseases that may alter gastric emptying were excluded. Symptoms were assessed by a standard questionnaire. Data processing was carried out "blinded" to the subjects' clinical status. Female patients took significantly longer to empty half the initial stomach activity (mean 90 min) than female controls (mean, 73 min; p = 0.02). The rate of emptying at 25 min was also significantly less in female patients than in controls. Female and male controls, and male patients, had similar emptying times. Delayed emptying was not associated with the occurrence of postprandial pain, belching, or nausea; there was a trend for the half-time rate of emptying to be greater in patients with abdominal distention. While gastric emptying of solids is slightly delayed in females with essential dyspepsia as a group, this may not explain their symptoms.
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PMID:Lack of association between gastric emptying of solids and symptoms in nonulcer dyspepsia. 258 62

This study was undertaken to evaluate (1) the colonic response to eating for a prolonged time in healthy subjects and patients with the irritable bowel syndrome (IBS); (2) the effect of octylonium bromide, a new smooth muscle relaxant acting by interfering with calcium ion mobilization, on the postprandial colonic motility; and (3) whether chronic gastric stasis could be responsible for both the dyspeptic symptoms often complained of by IBS patients and the faulty colonic response to eating. The colonic response to a 1000-kcal mixed meal in ten healthy subjects was characterized by two transient (from 0 to 60 and from 120 to 150 min postprandially, respectively) increases in colonic motor activity; ten IBS patients showed a continuous postprandial increase in colonic motor activity that was not terminated 180 min after eating. Treatment of IBS patients with octylonium bromide (80 mg, qid, per os) for 5-7 days reduced their colonic response to eating to a very short increase in colonic motor activity limited to the first 30 min. Finally, gastric emptying was not different in the two groups.
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PMID:Colonic motility and gastric emptying in patients with irritable bowel syndrome. Effect of pretreatment with octylonium bromide. 394 28

During a 2 year period, 83 patients with gastric motility problems were evaluated using radionuclide imaging. The patients presented with epigastric distress, postprandial fullness, pain, nausea, vomiting, and diarrhea; signs and symptoms suggestive of either gastroparesis or gastric outlet obstruction. Upper gastrointestinal series or endoscopy, or both, demonstrated no mechanical obstruction. After oral administration of a 300 g meal labeled with 600 muCi of technetium-99m sulfur colloid, a gastric emptying study consisting of serial images and data acquisition was performed. Of the patients studied, 52 had had peptic ulcer surgery, 17 were suspected of having gastroesophageal reflux, 8 were diabetic and suspected of having visceral enteropathy, and 6 had a history of irritable bowel syndrome. The normal mean gastric half emptying time was 77 +/- 16 minutes. Of the patients who had had gastric surgery, 90.4 percent had abnormal emptying: 69.2 percent had delayed gastric emptying and 21.2 percent had rapid gastric emptying time; 9.6 percent had normal emptying time. Of the gastroesophageal reflux group, all but two had normal gastric emptying time; 65 percent demonstrated gastroesophageal reflux within 15 minutes. Two of the patients with irritable bowel syndrome had prolonged emptying; the rest had normal emptying. All diabetic patients with gastroparesis had prolonged gastric emptying time, and all responded favorably to metoclopramide. Of the patients who previously had peptic ulcer surgery and had prolonged emptying time, 72 percent also responded favorably to metoclopramide. We conclude that radionuclide gastric imaging is a useful diagnostic test for the measurement of gastric emptying in patients with a variety of gastrointestinal motility disorders and may be helpful in assessing medical therapy and selecting those who may be candidates for surgery.
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PMID:Assessment of gastric motility using meal labeled with technetium-99m sulfur colloid. 665 Jul 70

Cisapride is an orally administered prokinetic agent which facilitates or restores motility throughout the length of the gastrointestinal tract. It is a substituted piperidinyl benzamide, chemically related to metoclopramide, but unlike metoclopramide, cisapride is largely devoid of central depressant or antidopaminergic effects. In placebo-controlled trials, cisapride improved healing rates and symptoms in both adults and children with reflux oesophagitis. Maintenance therapy with cisapride at half the healing dose is effective in reducing the incidence of relapse. Symptoms are also alleviated in patients with functional dyspepsia, and gastric emptying and symptoms are improved in most patients with gastroparesis, an effect which is sustained during long term administration. However, the efficacy of cisapride in end-stage gastroparesis remains less clear. Cisapride increases stool frequency in patients with chronic constipation, and limited data suggest that the drug may also be beneficial in treating chronic intestinal pseudo-obstruction and irritable bowel syndrome. Cisapride demonstrated efficacy comparable with or superior to that of metoclopramide, and was at least as effective as cimetidine and ranitidine in patients with reflux disease. In patients with functional dyspepsia, cisapride has shown at least equal efficacy to domperidone, metoclopramide and ranitidine, and superior efficacy to cimetidine in the small comparative trials conducted to date. Adverse effects in patients receiving cisapride are generally transient and mild, with abdominal cramping, borborygmi, diarrhoea or loose stools most frequently reported. Central nervous system adverse effects are rare. Thus, with its favourable tolerability profile and demonstrated efficacy in a variety of gastrointestinal motility disorders, the position of cisapride as a valuable agent in the management of patients with gastrointestinal motility disorders is strengthening. However, larger well-controlled comparative trials of the drug with other agents are necessary before the relative position of cisapride in therapy can be categorically defined.
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PMID:Cisapride. An updated review of its pharmacology and therapeutic efficacy as a prokinetic agent in gastrointestinal motility disorders. 751 Jun 17

Forty three subjects with DU confirmed at endoscopy and healed after eight weeks of sucralfate therapy were subjected to a randomized double-blind controlled trial for six months. Twenty one subjects received sucralfate (1 g one hour before breakfast and dinner). Twenty two subjects received placebo. Symptoms were evaluated every month. The subjects were endoscoped at the end of the trial or earlier in case symptoms recurred. Sucralfate was found to be significantly more effective than placebo (6/21 vs. 17/22, p < 0.005) in preventing DU relapse. Age at presentation, age at onset, duration of illness, sex, periodicity, smoking, gastric stasis like symptoms, associated irritable bowel syndrome, degree of deformity of the bulb and initial presence of duodenitis were the factors examined for their effect upon the relapse. In the placebo group relapsers had significantly shorter mean duration of illness indicating that DU may relapse more frequently in earlier part of its natural course. Other factors did not influence the relapse rate. In the sucralfate group, higher ages at onset and at presentation were associated with significantly higher relapse rate. Sucralfate may be less effective in preventing relapse in elderly and late onset DU patients.
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PMID:Sucralfate in the prevention of duodenal ulcer relapse and factors influencing the relapse rate. 774 45

Major advances have been made in the understanding of the pathophysiology of stress-related alteration of gut function. A wealth of information indicates that CRF is involved in the central mechanisms by which stress inhibits gastric emptying while stimulating colonic motor function. CRF acts in the PVN to trigger both the inhibition of gastric emptying and the stimulation of colonic motor function in response to stress, in addition to previously established endocrine and behavioral responses. Preliminary evidence exists that CRF acts in the locus coeruleus to induce a selective stimulation of colonic transit without influencing gastric emptying. The central actions of CRF to alter gastric and colonic motor function are conveyed by autonomic pathways and are unrelated to the associated stimulation of pituitary hormone secretion. The demonstration that central CRF plays a role in mediating gastric stasis resulting from surgery, peritonitis or high levels of central interleukin-1 provides new insight into the mechanisms involved in gastric ileus induced postoperatively or by infectious disease. Likewise, the demonstration that CRF in the PVN and locus coeruleus induce the anxiogenic and colonic motor responses to stress and that colonic distention activates neurons in the locus coeruleus opens new avenues for the understanding of the pathogenesis of a subset of IBS patients with colonic hypersensitivity associated with psychopathological disturbance and diarrhea-predominant symptoms.
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PMID:Role of CRF in stress-related alterations of gastric and colonic motor function. 825 13

Prokinetic agents are currently being investigated as potential therapies for motility disorders of the lower gastrointestinal tract. Cholinergic agonists such as bethanechol are known to improve postoperative ileus but are limited because of side effects. Dopamine antagonists such as domperidone appear to have maximal prokinetic effect in the proximal gastrointestinal tract and are effective for such conditions as gastroparesis and gastroesophageal reflux, but they appear to have little physiologic effect in the colon or in colonic motility disorders. Naloxone, an opioid antagonist, appears to hold promise in patients with irritable bowel syndrome, small intestinal pseudo-obstruction, and constipation. Erythromycin exerts its prokinetic effect by acting as a motilin agonist; it has been used in the treatment of diabetic gastroparesis and appears to improve symptoms of colonic pseudo-obstruction and postoperative ileus. Metoclopramide, a combined cholinergic agonist and dopamine antagonist, is currently used exclusively for proximal motility dysfunction. Cisapride appears to hold the most promise for patients with colonic motility disorders. In patients with postoperative ileus, cisapride is associated with an increased return of bowel function compared with placebo. In patients with chronic constipation, cisapride increases stool frequency and decreases laxative abuse in both adults and children. Hopefully, as an understanding of gastrointestinal motility increases, effective prokinetic agents will be developed that will improve symptoms of patients with large bowel motility disorders and may also help to predict those patients who benefit from surgical management for constipation.
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PMID:Prokinetic agents for lower gastrointestinal motility disorders. 813 79

Cisapride is a substituted benzamide compound that stimulates motor activity in all segments of the gastrointestinal tract by enhancing the release of acetylcholine from the enteric nervous system. Cisapride is administered orally in the treatment of gastro-oesophageal reflux disease, functional dyspepsia, gastroparesis, chronic intestinal pseudo-obstruction syndromes and chronic constipation. In gastro-oesophageal reflux disease in both adults and children, cisapride provides symptomatic improvement and mucosal healing. Long term treatment with cisapride is effective in the prevention of relapse of oesophagitis. Cisapride improves gastric emptying rates and improves symptoms in patients with gastroparesis of various origins. Unlike domperidone and metoclopramide, long term administration of cisapride seems to result in persistently enhanced gastric emptying. Cisapride is also effective in improving symptoms in patients with functional dyspepsia. In comparative studies in patients with functional dyspepsia, cisapride was at least as effective as metoclopramide, domperidone, clebopride, ranitidine and cimetidine. Cisapride increases stool frequency and reduces laxative consumption in patients with idiopathic constipation. Severe cases of slow transit constipation seem refractory to cisapride. Clinical studies also indicate that cisapride might be effective in the treatment of chronic intestinal pseudo-obstruction, postoperative ileus, peptic ulcer and irritable bowel syndrome. Further clinical studies are warranted to define the role of cisapride in these conditions. The dosage of cisapride ranges from 5mg 3 times daily to 20mg twice daily. Cisapride is generally well tolerated, both during short and long term treatment. In children, cisapride is also well tolerated in doses of 0.2 to 0.3 mg/kg, 3 to 4 times daily.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:A risk-benefit assessment of cisapride in the treatment of gastrointestinal disorders. 852 13

The 5-HT4 receptor is a member of the seven transmembrane spanning G-protein-coupled family of receptors. The receptor is positively coupled to adenylate cyclase and exists in two isoforms (5-HT4S and 5-HT4L) that differ in the length and sequence of their carboxy termini. The 5-HT4 receptor is pharmacologically defined by selective agonists such as SC 53116 and RS 67506, and selective antagonists such as GR 113808, SB 204070, and RS 39604. The receptor is widely distributed in the central nervous system and peripheral tissues. In the periphery, the receptor plays an important role in the function of several organ responses including the alimentary tract, urinary bladder, heart and adrenal gland. In the alimentary tract, stimulation of 5-HT4 receptors has a pronounced effect on smooth muscle tone, mucosal electrolyte secretion, and the peristaltic reflex. In the urinary bladder, activation of 5-HT4 receptors modulates cholinergic/purinergic transmission. In the heart, stimulation of atrial 5-HT4 receptors produces positive inotropy and tachycardia that can precipitate arrhythmias. In the adrenal gland, agonism of 5-HT4 receptors stimulates release of cortisol, corticosterone, and aldosterone. Since its discovery in 1988, significant advances have been made in our understanding of the physiology and pharmacology of the 5-HT4 receptor. These advances have led to the development of several selective 5-HT4 receptor agonists and antagonists that may have therapeutic utility in the treatment of peripheral disorders such as irritable bowel syndrome, gastroparesis, urinary incontinence and cardiac arrhythmias.
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PMID:Peripheral 5-HT4 receptors. 890 10

The objective of the study was to assess the efficacy of sucralfate in promoting duodenal ulcer healing and to assess the value of some variables in predicting outcome of such therapy. Following variables were tested for predicting the outcome: age at onset, age at presentation, duration of symptoms, sex, periodicity, smoking, nocturnal pain, relief by food, relief by antacid, gastric stasis like symptoms, associated irritable bowel syndrome, site, size and number of ulcers and degree of deformity of bulb. Sixty patients with uncomplicated DU confirmed at endoscopy were treated with sucralfate one gram before three major meals and 1 g at bedtime for two months. Endoscopy was repeated at the end of the trial. There were four drop-outs. Complete, partial and no healing occurred in 45 (80.36)%, 3 (5.36%) and 8 (14.28%) subjects. Ulcer healing rate was higher in those without gross bulbar deformity (41/46) than in those with gross deformity (4/10), (Odd's ratio 12.3, 95% ci 1.98 to 78.44). Other variables were not found to be associated with ulcer healing.
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PMID:Predictors of duodenal ulcer healing in sucralfate treated patients. 910 58


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