Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0042963 (vomiting)
 31,883 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Delayed gastric emptying, gastroparesis, is one of the sequelae of diabetes mellitus. Symptoms may include postprandial nausea, epigastric pain, bloating, vomiting, early satiety and unpredictable blood sugar fluctuations. Nowadays diagnosis is made by the measurement of gastric emptying with a radionuclide test meal. Using this technique some 50% of diabetic patients show signs of disordered gastric emptying. Relief is best delivered by agents promoting gastric emptying. In phase II single-dose studies metoclopramide, domperidone, cisapride, erythromycin and renzapride were all able to enhance gastric evacuation of solid and liquid meals in patients with diabetic gastroparesis. A few short term studies support the efficacy of domperidone and renzapride, but long term trials are lacking. Erythromycin, mimicking the potent gastrokinetic effect of motilin, may hold considerable promise for the future. Experience with erythromycin in diabetic gastroparesis is nonetheless very limited. To some extent the therapeutic effectiveness of metoclopramide and cisapride has been established in placebo-controlled trials. In trials with a placebo-controlled crossover design, however, only metoclopramide showed a sustained positive effect. Metoclopramide, which combines gastrokinetic and antiemetic properties seems, so far, the best therapeutic option in diabetic gastroparesis. Cisapride may be considered as a good alternative in cases where limited efficacy or side effects preclude the use of metoclopramide.
 ...
PMID:Diabetic gastroparesis. A critical reappraisal of new treatment strategies. 128 Oct 70

Gastric and gallbladder emptying after a standard liquid meal were studied in 65 patients with early satiety, bloating, pain at the right hypochondrium or the epigastrium, nausea, and occasionally vomiting. Fifty normal subjects were studied as a control group. Gastric and gallbladder emptying were evaluated by means of real-time ultrasonography (RUS). Serial RUS scans were made after a 12-hr fast and every 15 min after a standard meal for 2 hr. Patients were considered to have delayed gastric emptying or hypokinetic gallbladder when gastric diameters and gallbladder volume evaluated 45 min after meal were 2 SD above the corresponding mean values of the normal subject group. Fifteen patients (23%) were found with delayed gastric emptying and 20 (30.7%) a reduced gallbladder emptying. None of our patients showed delayed gastric emptying and hypokinetic gallbladder simultaneously. The 20 patients with reduced gallbladder emptying were included in a double-blind randomized, placebo controlled, change-over study with cisapride (10 mg three times a day) for 30 days. Cisapride treatment reversed the gallbladder hypomotility within the normal range while placebo did not change the response to meal. Symptom score improved significantly after cisapride and placebo. It is concluded that in dyspeptic patients with reduced gallbladder response to a meal cisapride may be of help in improving the kinetic abnormality. Dyspeptic symptoms, however, do not seem to be corrected with the described gallbladder motor abnormality.
 ...
PMID:Gallbladder hypokinesia and normal gastric emptying of liquids in patients with dyspeptic symptoms. A double-blind placebo-controlled clinical trial with cisapride. 834 18

The pathophysiology, diagnosis, and treatment of diabetic gastroparesis are reviewed, and the mechanisms of action, pharmacokinetics, clinical efficacy, adverse effects, and dosage of metoclopramide, domperidone, and cisapride are described. Diabetic gastroparesis is a state of delayed gastric emptying that reportedly affects 20-30% of diabetic patients. Symptoms include nausea, early satiety, postprandial bloating and fullness, and vomiting. Diabetic gastroparesis has been managed most successfully with drugs that stimulate gastric emptying. Of the three agents studied--metoclopramide, domperidone, and cisapride--only metoclopramide is commercially available in the United States. The clinical efficacy of metoclopramide, domperidone, and cisapride has been well documented in several placebo-controlled trials. Metoclopramide effectively decreases mean gastric emptying time, although tolerance to this stimulation of gastric emptying may develop with long-term therapy. However, symptomatic relief persists with long-term therapy because of metoclopramide's antiemetic properties. Domperidone, which has also been shown to stimulate gastric motility and to possess antiemetic properties, improves symptoms in patients suffering from diabetic gastroparesis. Cisapride appears to have continued beneficial effects on gastric motility with long-term therapy. All three agents have favorable adverse-effect profiles. Although metoclopramide is currently the first-line agent for the management of gastroparesis, domperidone and cisapride both possess properties that may make them useful alternatives in patients who are unresponsive to or cannot tolerate metoclopramide therapy.
 ...
PMID:Use of metoclopramide, domperidone, and cisapride in the management of diabetic gastroparesis. 219 Jul 45

In a double-blind, placebo-controlled, crossover trial, we investigated the effects of the prokinetic drug cisapride in patients with cystic fibrosis and chronic recurrent distal intestinal obstruction syndrome (DIOS). After a baseline period, 17 patients (12.9 to 34.9 years; 12 boys) received, in random order, cisapride (7.5 to 10 mg) and placebo three times daily by mouth, each for 6 months. Gastrointestinal symptoms (flatulence, abdominal pain, fullness, abdominal distension, nausea, anorexia, heartburn, diarrhea, vomiting and regurgitation) were scored three times monthly and physical examinations assessed. At baseline and at each 6-month period, assessment included food intake for 7 days, 3-day stool collection, pulmonary function tests, and abdominal radiographs. During cisapride therapy compared with placebo, there were significant reductions in flatulence (p less than 0.005), fullness, and nausea (p less than 0.05). Patients with the worst symptom scores benefited most from cisapride. With cisapride, 12 patients felt better and three worse (p less than 0.05); physicians judged 11 patients improved and two worse (p less than 0.05). No side effects were noted. There were no significant differences between cisapride and placebo periods in nutritional status, x-ray scores, pulmonary function, food intake (fat, protein, calories), stool size and consistency, and fecal losses of fat, bile acids, chymotrypsin, and calories. For acute episodes of DIOS, intestinal lavage was needed 6 times in 4 patients during treatment with cisapride, and 11 times in 6 patients receiving placebo. In comparison with unselected patients with cystic fibrosis and pancreatic insufficiency who were receiving enzyme supplements and who had no distal intestinal obstruction, fecal fat losses (percentage of intake) were almost twice as high in the study group with DIOS (31.2 +/- 20.6% vs 16.2 +/- 17.6%; p less than 0.01). We conclude that in the dosage used, long-term treatment with cisapride appears to improve chronic abdominal symptoms in patients with cystic fibrosis and DIOS, but fails to abolish the need for intestinal lavage. Cisapride treatment had no effect on digestion and nutritional status of cystic fibrosis patients with pancreatic insufficiency.
 ...
PMID:Effects of cisapride in patients with cystic fibrosis and distal intestinal obstruction syndrome. 223 Dec 17

Twelve patients with chronic constipation refractory to the vigorous use of emollients, enemas, and/or laxatives were chosen for study of the investigational prokinetic agent, Cisapride. The patients included 8 boys and 4 girls with diagnoses of functional constipation. Ages ranged from 2 to 13 years; duration of symptoms before Cisapride use ranged from 1.5 to 9.75 years; duration of previous treatment ranged from 0.75 to 6 years. The mean number of doses of anticonstipation agents employed per week was 14. Of the 12 patients, 10 had persistent encopresis, while 11 required hospitalization for disimpaction an average of 1.6 times in the year prior to Cisapride use. Three had chronic urinary tract complaints. Anal manometry suggested a sensory deficit in 8 of 10 patients tested. Ganglion cells were identified by rectal biopsy in all 12 patients. Cisapride treatment (0.14-0.3 mg/kg/dose) spanned 26-72 weeks (61 +/- 12). Stool frequency per week was not significantly changed, but five of seven patients who had reported hard stools had softer stools on the drug (p less than 0.05). Encopresis ceased in 8 of 10 cases, while the number of episodes decreased substantially in the other 2 cases (p less than 0.05). All alternate forms of anticonstipation therapy were withdrawn in 8 of 12 cases (p less than 0.001). Urinary problems improved in two of the three patients reporting symptoms. One patient showed no improvement in any parameter while on the agent, despite 26 weeks of administration. Side effects were infrequent, generally occurred early, and were limited to cramping, nausea, mild vomiting, anorexia, and headaches. One patient ceased use of the drug for persistent headaches.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Cisapride for intractable constipation in children: observations from an open trial. 226 39

We have investigated the effect of oral cisapride (10 mg t.i.d.) in a double-blind, placebo-controlled trial in 26 patients with upper gut dysmotility: 11 with gastroparesis (8 diabetic, 3 idiopathic) and 15 with chronic idiopathic intestinal pseudoobstruction. Patients were evaluated at entry and at the end of the 6-wk study by upper gastrointestinal manometry, scintigraphic evaluation of gastric emptying of solids and liquids, measurement of body weight, and scoring of the following symptoms: abdominal pain, nausea, vomiting, early satiety, bloating, and distention. Cisapride and placebo groups were strictly comparable for all parameters assessed. Cisapride resulted in a significant increase in the gastric emptying of solids (p less than 0.05) compared with placebo; cisapride also tended to increase the postcibal antral motility and normalize the abnormal manometric features in the patients with intestinal dysmotility, particularly the characteristics of fasting interdigestive motor complexes and the fed motor pattern. Both cisapride and placebo groups showed an improvement in total symptom scores and there was no significant difference in overall symptom response between the two groups. However, the change in abdominal pain was greater with cisapride (p = 0.07). Cisapride facilitates gastric emptying in patients with upper gut dysmotility. The overall symptomatic benefit during a 6-wk trial of cisapride, 10 mg t.i.d., was not greater than that of placebo, and dose-response as well as longer term trials are necessary to determine the clinical efficacy of this medication.
 ...
PMID:Effect of six weeks of treatment with cisapride in gastroparesis and intestinal pseudoobstruction. 264 50

A newborn presented with a picture of intestinal obstruction. Multiple biopsies of the small and large bowel showed an unusual neurogenic innervation. The myenteric plexus of Auerbach was severely depleted of ganglion cells and nerve fibers, while the submucous plexus of Meissner was normally innervated. An ileostomy failed to function and extended trial with experimental smooth muscle stimulant (Cisapride) was equally ineffective. The patient was finally treated by a myectomy from the duodenum to the descending colon with a sigmoid colostomy. This procedure, coupled with a Nissen fundoplication, stopped the vomiting and allowed normal defecation through the colostomy. The patient is presently taking increasing increments of oral fluids with a concomitant decrease in the volume of parenteral nutrition. The myectomy initiated marked hypertrophy of the muscularis mucosa. Could this muscular hypertrophy account for the improvement in bowel function? Possible etiology will be discussed. We caution that rectal submucosal suction biopsy alone may be misleading if normal ganglion cells and nerve fibers are found, yet the patient's clinical symptoms fail to improve. A full thickness bowel wall biopsy is then recommended.
 ...
PMID:Deficient neurogenic innervation of the myenteric plexus with normal submucous plexus involving the entire small and large bowel. 272

In a double blind crossover comparison with placebo, the effects of cisapride (10 mg tid for two weeks), a non-antidopaminergic gastrointestinal prokinetic drug, on gastric emptying times and on symptoms were evaluated in 12 patients with chronic idiopathic dyspepsia and gastroparesis. Gastric emptying was studied by a radioisotopic gamma camera technique. The test meal was labelled in the solid component (99mTc-sulphur colloid infiltrated chicken liver). Nine symptoms (nausea, belching, regurgitations, vomiting, postprandial drowsiness, early satiety, epigastric pain or burning, heartburn) were graded weekly on a questionnaire. Cisapride was significantly more effective than placebo in shortening the t1/2 of gastric emptying (p2 = 0.04), but no significant difference was observed between the two treatments with regard to the improvement of total symptom score (p2 = 0.09). No side effects were reported during the study.
 ...
PMID:Effect of chronic administration of cisapride on gastric emptying of a solid meal and on dyspeptic symptoms in patients with idiopathic gastroparesis. 355 6

A greater understanding of the various serotonin receptor subtypes has led to a clearer appreciation of the role of serotonin in gastrointestinal motility, sensation and secretion. Serotonin is definitely involved in the aetiopathogenesis of cisplatin-induced emesis and carcinoid diarrhoea. The application of serotonergic drugs in clinical therapeutics for gut disturbances is presently dominated by the use of 5-HT3 antagonists for acute chemotherapy-induced nausea and vomiting, and the use of substituted benzamides which are 5-HT4 agonists stimulating gut motor function through 5-HT4 neuronal receptors. The best-studied 5-HT4 agonist is cisapride, which has been shown to stimulate motility at several levels of the gut. Cisapride is approved for healing and maintenance treatment of reflux oesophagitis and is used in several countries for the alleviation of symptoms consistent with regional stasis, from dyspepsia to constipation. Carcinoid diarrhoea is a prototypic disease associated with deranged serotonin metabolism, and a rationale for using 5-HT3 or 5-HT4 antagonists is based on the recent appreciation of the important role of impaired gut motor function in carcinoid diarrhoea. In the future, greater understanding of the serotonin receptor subtypes and their role in gut disorders may lead to novel approaches to alleviate increased visceral perception of functional gastrointestinal disorders, to correct changes in colonic capacitance, or to alter gastrointestinal motility that contributes to diarrhoea or constipation. However, at the present time, it must be stressed that these uses are still at an experimental stage and that careful validation and proper controlled studies are still required.
 ...
PMID:Drugs affecting serotonin receptors. 794 60

Cisapride induces acetylcholine release in cells of the myenteric plexus, thus promoting gastrointestinal motility. We studied the effects of cisapride on 11 patients with idiopathic gastroparesis. All had negative gastrointestinal endoscopy, normal glucose, and took no drugs capable of influencing motility. Most (9/11) were prior metoclopramide treatment failures. Patients' symptoms were scored (0-60) for pain, satiety, bloating, nausea, vomiting, and heartburn. All underwent a solid gastric emptying study using a Technetium-99-labeled egg meal and received placebo prior to cisapride. There were 10 females and one male with a mean (+/- SE) age of 37.8 +/- 2.6 years. Disease duration was 7.9 +/- 2.8 years. The dose of cisapride was 30-60 mg/day and the duration of therapy was 12.6 +/- 2.6 months (range 2.5-25 months). The symptom score improved on cisapride from 30.9 +/- 3.6 to 14.4 +/- 2.7 (P < 0.002 signed rank test). Emptying half-time improved from 113 +/- 4 min to 94 +/- 6 min, and 46.9 +/- 2.4% food remaining at 120 min decreased to 35.5 +/- 3.6% (both P < 0.05). Emptying half-time in normals was 68 +/- 5 min with 16.9 +/- 2.9% remaining at 120 min. Nine of 11 patients gained weight, with a mean increase of 6.7 +/- 1.6 lb (range 2-12 lb). We conclude that cisapride significantly reduces gastrointestinal symptoms and promotes weight gain in patients with idiopathic gastroparesis and is associated with improvement in solid gastric emptying. The drug is useful in patients who previously failed metoclopramide.
 ...
PMID:Open label study of long-term effectiveness of cisapride in patients with idiopathic gastroparesis. 802 48


1 2 Next >>