piperidines and Intestinal-Obstruction

Ileus is a common postoperative complication after major abdominal surgery. Surgical manipulation of the bowel and stimulation of opiod receptor are the main causes of ileus. An investigational drug (ADL 8-2698, Alvinopam) a selective opioid antagonist with a very low oral absorption was recently introduced to clinical medicine. Unlike other opioid antagonist its activity is restricted to GI tract, it is potent, has a long duration of action, is orally effective, does not readily cross the blood-brain barrier even after intravenous administration in animals. Two randomized controlled clinical studies tested its effects in humans. Liu et al.'s study confirmed peripheral restriction of ADL 8-2698 by its lack of central effect on morphine analgesia and pupil miosis. They also showed that ADL 8-2698 prevents increases in gastrointestinal transit time. Taguchi et al. concluded that high dose (6 mg) of ADL 8-2698 archived fast recovery of gastrointestinal function, without antagonising analgesic efficacy of systemic opioid. In summary, selective inhibition of gastrointestinal opioid receptor by a peripherally restricted oral antagonist speeds recovery of bowel function, shortens times of hospitalization and preserves the analgesic effects of opiods.

Topics: Adolescent; Adult; Aged; Humans; Intestinal Obstruction; Middle Aged; Narcotic Antagonists; Piperidines; Postoperative Complications; Postoperative Nausea and Vomiting; Randomized Controlled Trials as Topic

All horses undergoing coeliotomy for an acute abdominal crisis are at risk of developing ileus and should receive therapy aimed at promoting gastrointestinal function by restoring fluid and electrolyte balance. Adequate analgesia and prevention against peritonitis, bacteraemia and endotoxaemia should be provided. Horses that at the time of surgery have a strangulating or non-strangulating small intestinal obstruction should be considered to be at greater risk of developing a persistent ileus that is refractory to treatment than those horses with lesions involving the large intestine. In horses considered to be at greater risk of developing a persistent ileus, the use of prokinetic agents should be considered. Agents that may be used to improve gastrointestinal motility include adrenergic receptor antagonists, cholinergic agonists, benzamides, dopamine antagonists, macrolide antimicrobials, opiate receptor agonists and antagonists, somatostatin analogues and local anaesthetics. There are limited studies into the use of these agents in the horse. Until further research provides more information on motility disorders following intestinal surgery and the efficacy of prokinetic agents in this species, only selective use of some of these drugs can be recommended.

Topics: Adrenergic Antagonists; Anesthetics, Local; Animals; Anti-Bacterial Agents; Cholinergic Agonists; Cisapride; Dopamine Antagonists; Electric Stimulation; Gastrointestinal Agents; Gastrointestinal Motility; Horse Diseases; Horses; Intestinal Obstruction; Macrolides; Metoclopramide; Narcotic Antagonists; Narcotics; Octreotide; Piperidines; Postoperative Complications

Topics: Abdomen; Cisapride; Dopamine Antagonists; Erythromycin; Gastric Emptying; Gastrointestinal Agents; Humans; Intestinal Obstruction; Intubation, Gastrointestinal; Metoclopramide; Parasympathomimetics; Piperidines; Postoperative Complications; Protein Synthesis Inhibitors

Postoperative recovery of gastrointestinal function and resumption of oral intake are critical determinants of the length of hospital stay. Although opioids are effective treatments for postoperative pain, they contribute to the delayed recovery of gastrointestinal function.. We studied the effects of ADL 8-2698, an investigational opioid antagonist with limited oral absorption that does not readily cross the blood-brain barrier, on postoperative gastrointestinal function and the length of hospitalization. We randomly assigned 79 patients--including 1 whose surgery was canceled--to receive one capsule containing 1 mg or 6 mg of ADL 8-2698 or an identical-appearing placebo capsule two hours before major abdominal surgery and then twice daily until the first bowel movement or until discharge from the hospital. Data were analyzed for 26 patients in each of the three groups; all received opioids for postoperative pain relief. Observers who were unaware of the group assignments evaluated the outcomes.. Fifteen patients underwent partial colectomy and 63 underwent total abdominal hysterectomy. Patients given 6 mg of ADL 8-2698 had significantly faster recovery of gastrointestinal function than those given placebo. The median time to the first passage of flatus decreased from 70 to 49 hours (P=0.03), the median time to the first bowel movement decreased from 111 to 70 hours (P=0.01), and the median time until patients were ready for discharge decreased from 91 to 68 hours (P=0.03). Effects in the group that received 1 mg of ADL 8-2698 were less pronounced.. Selective inhibition of gastrointestinal opioid receptors by an antagonist with limited oral absorption that does not readily cross the blood-brain barrier speeds recovery of bowel function and shortens the duration of hospitalization.

Topics: Adolescent; Adult; Aged; Analgesics, Opioid; Colectomy; Defecation; Digestive System; Female; Flatulence; Humans; Hysterectomy; Intestinal Obstruction; Length of Stay; Male; Meperidine; Middle Aged; Morphine; Narcotic Antagonists; Pain, Postoperative; Piperidines; Postoperative Complications; Receptors, Opioid; Time Factors

The effect of cisapride pretreatment on gastric emptying in horses was determined by measuring serum concentrations of acetaminophen, a drug known to be readily absorbed in the small intestine but not in the stomach. The time to reach maximum serum acetaminophen concentrations (Tmax), the maximum serum concentrations (Cmax) and the area under the serum acetaminophen concentration vs. time curves (AUC) were compared among treatment groups. In the first part of the study, the effect of orally administered cisapride (0.1, 0.2 and 0.4 mg/kg bwt) on gastric emptying was examined in 6 normal fasted horses. In the second part of the study, gastric emptying in horses given endotoxin i.v. (n = 6) was compared to those that received cisapride per os prior to administration of endotoxin (n = 6) and those that received neither compound (n = 6). Cisapride did not alter gastric emptying in normal horses. Endotoxin caused a profound delay in gastric emptying and pretreatment with cisapride significantly attenuated this effect. It is concluded that cisapride may be useful as a prophylactic measure when administered prior to the development of endotoxaemia.

Topics: Acetaminophen; Administration, Oral; Analgesics, Non-Narcotic; Animals; Area Under Curve; Cisapride; Endotoxins; Female; Gastric Emptying; Gastrointestinal Agents; Horse Diseases; Horses; Intestinal Obstruction; Piperidines; Postoperative Complications

To assess the efficacy of cisapride in reducing ileus persisting to the tenth postoperative day after neonatal abdominal surgery.. A prospective, randomised, double blind trial comparing rectal cisapride (1.4-2.3 mg/kg/day) with placebo over seven days was undertaken in 33 neonates.. Seven of 12 (58%) patients receiving placebo and eight of 11 (73%) receiving cisapride achieved a first sustained feed during treatment. Of those receiving cisapride, the first sustained feed occurred at 2.3 days (SEM 0.6) compared with 4.7 days (SEM 0.8) with placebo. By the seventh day the mean daily net enteral balance was 69 (SEM 18) ml/kg in the cisapride subgroup and 17 (SEM 8) ml/kg for those receiving placebo. Stool was passed on 6.3 (SEM 0.4) treatment days in the cisapride subgroup compared with 4.1 (SEM 1.0) treatment days in the placebo subgroup.. Cisapride is effective in neonates with a prolonged ileus after abdominal surgery.

Topics: Administration, Rectal; Cisapride; Double-Blind Method; Gastrointestinal Agents; Gastrointestinal Motility; Humans; Infant, Newborn; Intestinal Obstruction; Piperidines; Postoperative Complications; Prospective Studies

This study was designed to investigate the modulatory effect of cisapride on colonic motility in the postoperative period.. A prospective, double-blind, randomized, placebo-controlled trial of 14 patients undergoing left colonic anastomosis was carried out. Manometric probes were positioned with transducers on either side of the anastomosis, and colonic activity was recorded continuously for a median of 98 (range, 72-144) hours using an ambulatory system. Quantitative indices of motility were calculated with an automated analysis program.. Isolated waveform activity returned at a median of 1.8 (interquartile range, 1-3) hours and motor complex activity at 24 (interquartile range, 19-30) hours in the placebo group and at similar times in the cisapride group. All motility variables except mean amplitude increased significantly with time in both groups. In the cisapride group the motility index was significantly increased compared with the placebo group (P = 0.03), resulting from an increase in percentage duration of activity (P = 0.002). Activity index, mean amplitude of waveforms, and number of waves greater than 50 cm H2O did not differ between groups. In contrast to placebo, cisapride significantly increased the median number of waves greater than 13 cm H2O and percentage duration of activity distal to the anastomosis compared with proximally. The return of bowel sounds (median, 43, interquartile range, 24-48 hours vs. 67, 29-69 hours; P = 0.2) or first passage of flatus (78, 54-94 hours vs. 94, 81-105 hours; P = 0.1) did not differ between groups.. Although cisapride may have a differential effect on the colon proximal and distal to an anastomosis and significantly increases some indices of motility in the early postoperative period, these are unlikely to be of any clinical relevance.

Topics: Aged; Aged, 80 and over; Anastomosis, Surgical; Cisapride; Colon; Double-Blind Method; Drug Administration Schedule; Gastrointestinal Motility; Humans; Intestinal Obstruction; Manometry; Middle Aged; Piperidines; Postoperative Complications; Prospective Studies; Reoperation; Serotonin Antagonists

The effect of cisapride on duration of post-operative ileus after surgery was investigated in a randomized, double-blind, placebo-controlled study. Patients undergoing elective upper gastrointestinal (n = 47) or colonic (n = 22) surgery were pre-operatively randomly allocated to treatment with either cisapride 30 mg t.d.s., by rectal administration, or placebo. Treatment started exactly 48 h after surgery if the patient at this time had not passed stool. Time to passage of first stool after surgery was estimated. Mean time to passage of stool was 85 (32) h (s.d.) for cisapride-treated and 91 (43) h for placebo-treated patients. No difference between the treatment groups was noted. Treatment with cisapride did not shorten the duration of postoperative ileus after either upper gastrointestinal or colonic surgery.

Topics: Aged; Aged, 80 and over; Cisapride; Defecation; Double-Blind Method; Humans; Intestinal Obstruction; Middle Aged; Piperidines; Postoperative Complications; Time Factors

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.

Topics: Adolescent; Adult; Chronic Disease; Cisapride; Cystic Fibrosis; Double-Blind Method; Female; Humans; Intestinal Obstruction; Male; Piperidines; Recurrence; Serotonin Antagonists; Syndrome

Cisapride and domperidone were both effective in restoring electrical and mechanical activity, coordination between gastric and small intestinal activity cycles and the stomach to anus transit time in three ponies in which post operative ileus was induced experimentally. Cisapride (0.1 mg/kg bodyweight intramuscularly) for three to eight doses prevented idiopathic post operative ileus in 22 clinical cases requiring colic surgery. The only side effects after cisapride were increased bowel sounds and slight, transient sounds of discomfort. No adverse side effects were seen in 16 cases following anastomosis or enterotomy. Cisapride appears safe and effective in the prophylaxis of equine post operative ileus.

Topics: Animals; Antiemetics; Cholinergic Agents; Cisapride; Domperidone; Dose-Response Relationship, Drug; Female; Gastrointestinal Motility; Horse Diseases; Horses; Intestinal Obstruction; Intestine, Small; Male; Piperidines; Postoperative Complications

The effect of 4 mg of the gastrointestinal motility enhancing agent cisapride on postoperative ileus was compared with that of a placebo in 53 patients who had undergone various types of surgery. They received one i.v. injection of the double-blind medication, or two if no distinct flatus occurred within an hour after the first injection. The placebo response was very limited; borborygmi or flatus did not occur in more than 12% of the patients not even after the second injection. Cisapride was significantly effective: bowel sounds were present in 43% and 50% within 1 hour after the first and second injection of 4 mg, respectively, and flatus in 36% and 43%. The recognition that colon inactivity probably is the major determinant of the ileus, may be indicative of a substantial relative impact of cisapride's stimulating effects on colon motility.

Topics: Adult; Cisapride; Clinical Trials as Topic; Double-Blind Method; Female; Gastrointestinal Diseases; Gastrointestinal Motility; Humans; Intestinal Obstruction; Male; Piperidines; Postoperative Complications

Topics: Anesthesia, General; Anesthesia, Intravenous; Anesthetics, Intravenous; Female; Humans; Ileal Neoplasms; Intestinal Obstruction; Malignant Carcinoid Syndrome; Middle Aged; Piperidines; Propofol; Remifentanil; Treatment Outcome

Topics: Abdomen; Humans; Intestinal Obstruction; Narcotic Antagonists; Piperidines; Postoperative Complications

Topics: Digestive System; Humans; Hysterectomy; Intestinal Obstruction; Narcotic Antagonists; Piperidines; Postoperative Complications

The relationship between intestinal motor activity and the influence of prostaglandin F2alpha (PGF) and cisapride were investigated during the early postoperative period in 26 patients who underwent abdominal surgery. Records of intestinal motility were made using an infusion catheter. PGF, 0.4 microg/kg per minute, given intravenously over 60 min, and cisapride, 5 mg, given intraintestinally, were administered to 13 patients each, first immediately after the operation, and then after the migrating motor complexes (MMCs) had reappeared following a period of intestinal quiescence. The MMCs were reestablished within the first postoperative day. Both PGF and cisapride stimulated irregular, high-amplitude contractions; however, the MMCs reappeared following these induced contractions only if the drugs were administered just after the postoperative MMCs became evident. These prokinetic drugs did not affect gastrointestinal hormone concentrations, but induced contractile activity even in the early postoperative period. Although the findings of this study demonstrate that these drugs may be useful as prokinetic agents to promote recovery from postoperative ileus just after the reappearance of MMCs in the early postoperative period, their precise mode of action has not been established.

Topics: Abdomen; Cisapride; Dinoprost; Female; Gastrointestinal Agents; Gastrointestinal Motility; Humans; Infusions, Intravenous; Intestinal Obstruction; Male; Middle Aged; Piperidines; Postoperative Complications; Surgical Procedures, Operative

We report a case of oesophageal disease as the first manifestation in a patient with CREST syndrome. A 46-year-old man with achalasia-like syndrome developed CREST syndrome 4 years later. A pneumatic dilatation of the cardia was performed. After pneumatic dilatation the dysphagia and regurgitation disappeared but the patient developed reflux oesophagitis. Four years after diagnosis of oesophageal disease he presented with a clinical picture of CREST syndrome. An acute ileus and constipation developed later. After receiving medical therapy with omeprazole and cisapride the patient is free of oesophageal symptoms and bowel movements are normal. Oesophageal disease is common in patients with limited and diffuse scleroderma, but to our knowledge achalasia-like syndrome has not been previously described as the first manifestation of the systemic disease.

Topics: Anti-Ulcer Agents; Cardia; Cisapride; Constipation; CREST Syndrome; Dilatation; Esophageal Achalasia; Esophagitis, Peptic; Humans; Intestinal Obstruction; Male; Middle Aged; Omeprazole; Piperidines

Topics: Alginates; Aluminum Hydroxide; Amylases; Antacids; Anti-Ulcer Agents; Bromelains; Cisapride; Colon; Colonic Diseases; Constriction, Pathologic; Cystic Fibrosis; Drug Combinations; Humans; Infant; Intestinal Mucosa; Intestinal Obstruction; Lipase; Male; Piperidines; Silicic Acid; Sodium Bicarbonate; Trypsin

Topics: Animals; Cisapride; Colonic Diseases; Fecal Impaction; Gastrointestinal Motility; Horse Diseases; Horses; Intestinal Obstruction; Male; Parasympathomimetics; Piperidines

Topics: Child, Preschool; Developing Countries; Female; Humans; Infant; Intestinal Obstruction; Loperamide; Male; Pakistan; Piperidines; Product Surveillance, Postmarketing

Attempts have previously been made to reduce adhesion formation by promoting early intestinal motility. The prokinetic agent Cisapride was used in an animal model of end-to-end large bowel anastomoses. Twenty Wistar rats receiving Cisapride 1 mg/kg subcutaneously (sc) twice daily for two days post-operatively were compared with 20 controls receiving saline 0.2 mL in a similar regimen. The points of adhesion of the anastomosis to the following structures were enumerated: tubal fat; mesentery; omentum; caecum; small bowel; and abdominal wall. The treatment group had significantly fewer adhesions: 2.8 +/- 0.9 v 4.3 +/- 1.0. This was mainly in the number of small bowel attachments, 3.8% compared with 37.8%. The study was repeated using small bowel anastomoses. Cisapride again reduced the number of adhesions compared with controls: 2.1 +/- 0.4 v 4.2 +/- 1.4. Cisapride therapy resulted in greater post-operative stool weights and food consumption: control, 3.87 +/- 1.1 stool, 17.04 +/- 4.3 g food; Cisapride 4.43 +/- 0.9 g stool, 19.8 +/- 4.7 g food. The enhanced motility did not affect the anastomotic strength of the small bowel; bursting pressures at a constant inflation rate of 1.1 mL/min were: control 212.8 +/- 56.0 mmHg; Cisapride, 215.8 +/- 58.9 mmHg (NS).

Topics: Administration, Cutaneous; Anastomosis, Surgical; Animals; Cisapride; Disease Models, Animal; Female; Intestinal Diseases; Intestinal Obstruction; Piperidines; Postoperative Complications; Random Allocation; Rats; Rats, Inbred Strains; Tissue Adhesions

One hundred and eighteen patients in whom postoperative gastrointestinal atony had lasted for 48-72 hours, were given one or two intravenous injections of different doses of cisapride (2, 4 or 8 mg), or vehicle. The first occurrence of flatus was taken to mark the cessation of ileus. There was no significant difference in remission of ileus between the groups in the first hour following injection. All patients not responding to treatment in the first hour were given a repeat dosage and observed for the following 3 hours. Among this group, there was a significant remission of ileus in patients who had received 2 X 8 mg, which was particularly marked in those who had undergone intraperitoneal surgery. This study suggests that cisapride in repeated dosage may be of value in inducing remission in prolonged surgical ileus, particularly in patients who have undergone intraperitoneal operations.

Topics: Cisapride; Digestive System; Dose-Response Relationship, Drug; Female; Gastrointestinal Diseases; Gastrointestinal Motility; Humans; Intestinal Obstruction; Male; Piperidines; Postoperative Complications

Chronic intestinal pseudoobstruction is a clinical syndrome whose pathophysiology, objective diagnosis, and treatment are poorly understood. We investigated 8 patients with this syndrome in whom intestinal dysmotility was established manometrically by two or more of the following criteria: abnormal configuration or propagation of interdigestive motor complexes, sustained incoordinate pressure activity, non-propagated bursts of phasic pressure activity, and failure of a solid-liquid meal to induce a fed pattern. To establish the functional impairment and region of the gut primarily affected by the disease, we quantified radio-scintigraphically the gastrointestinal transit of the solid (131I-fiber) and liquid (99 mTc-DTPA) components of a meal. Our techniques allowed us to quantify separately gastric emptying and pylorus-to-cecum transit. Furthermore, we evaluated the effects of a new prokinetic agent, cisapride. Gastric emptying times in pseudoobstruction were not significantly delayed; however, transit times through the small bowel (t1/2) were markedly prolonged [solids, 235 +/- 43 min (mean +/- SEM) vs. 138 +/- 25 controls, p less than 0.05; liquids, 310 +/- 67 vs. 181 +/- 28 controls, p = 0.07]. Cisapride was effective in reducing the delayed intestinal transit time to within the normal range (delta solids = -115 +/- 25 min; delta liquids = -146 +/- 71 min; p less than 0.05 for both). These studies suggest that intestinal dysmotility in this group of patients with pseudoobstruction was associated with delayed small bowel transit of radiolabeled solid and liquid components of chyme. Cisapride can restore to normal the delayed transit, indicating that it may potentially correct the impaired propulsive activity in the small bowel of these patients.

Topics: Adult; Cisapride; Eating; Female; Gastric Emptying; Gastrointestinal Motility; Humans; Intestinal Obstruction; Intestinal Pseudo-Obstruction; Iodine Radioisotopes; Male; Middle Aged; Pentetic Acid; Piperidines; Technetium; Technetium Tc 99m Pentetate

Topics: Antidiarrheals; Humans; Intestinal Obstruction; Loperamide; Male; Middle Aged; Piperidines

Topics: Aged; Antidiarrheals; Humans; Intestinal Obstruction; Intestinal Pseudo-Obstruction; Loperamide; Male; Middle Aged; Piperidines

Topics: Antidiarrheals; Humans; Intestinal Obstruction; Intestinal Pseudo-Obstruction; Loperamide; Male; Piperidines

Topics: Child, Preschool; Humans; Infant; Intestinal Obstruction; Intestinal Pseudo-Obstruction; Loperamide; Piperidines

Topics: Diarrhea, Infantile; Humans; Infant; Intestinal Obstruction; Intestinal Pseudo-Obstruction; Loperamide; Piperidines

Topics: Adult; Analgesics; Cholecystitis; Gastrointestinal Hemorrhage; Haloperidol; Humans; Intestinal Obstruction; Male; Neuroleptanalgesia; Nitrous Oxide; Peritonitis; Piperidines; Wounds and Injuries

Topics: Digestive System Abnormalities; Duodenum; Esophagus; Female; Gastrointestinal Motility; Humans; Infant; Infant, Newborn; Infant, Newborn, Diseases; Intestinal Absorption; Intestinal Obstruction; Malabsorption Syndromes; Male; Megacolon; Piperidines; Postoperative Complications

Topics: Antidiarrheals; Child; Diagnosis, Differential; Diarrhea; Iatrogenic Disease; Intestinal Obstruction; Piperidines; Radiography; Toxicology

Topics: Acetazolamide; Chlorothiazide; Intestinal Obstruction; Intestinal Pseudo-Obstruction; Piperidines