piperidines and Gastroparesis

Pharmacological interventions of diabetic gastroparesis (DG) constitute an essential element of a patient's management. This article aimed to systematically review the available pharmacological approaches of DG, including their efficacy and safety. A total of 24 randomised clinical trials (RCTs) that investigated the efficacy and/or safety of medications targeting DG symptoms were identified using several online databases. Their results revealed that metoclopramide was the only approved drug for accelerating gastric emptying and improving disease symptoms. However, this medication may have several adverse effects on the cardiovascular and nervous systems, which might be resolved with a new intranasal preparation. Acceptable alternatives are oral domperidone for patients without cardiovascular risk factors or intravenous erythromycin for hospitalised patients. Preliminary data indicated that relamorelin and prucalopride are novel candidates that have proven to be effective and safe. Future RCTs should be conducted based on unified guidelines using universal diagnostic modalities to reveal reliable and comprehensive outcomes.

Topics: Antiemetics; Cisapride; Diabetes Complications; Domperidone; Gastric Emptying; Gastrointestinal Agents; Gastroparesis; Humans; Metoclopramide; Piperidines; Practice Guidelines as Topic; Randomized Controlled Trials as Topic; Treatment Outcome

Topics: Adult; Animals; Child; Cisapride; Constipation; Esophageal Motility Disorders; Gastrointestinal Diseases; Gastrointestinal Motility; Gastroparesis; Humans; Infant; Intestinal Pseudo-Obstruction; Piperidines

The use of prokinetic agents by pediatric patients, geriatric patients, and patients taking other drugs that may affect or be affected by the prokinetic agent is reviewed. The use of such agents to treat motility disorders has expanded over the past few years. These agents may be administered to patients who have special physiologic considerations, have other diseases, or require concomitant drug therapy. The appropriate use of prokinetic agents in these groups requires an understanding of the unique dosage considerations that may be necessary to ensure safe, effective therapy.

Topics: Age Factors; Cisapride; Drug Interactions; Gastroesophageal Reflux; Gastrointestinal Agents; Gastrointestinal Motility; Gastroparesis; Humans; Metoclopramide; Piperidines; Serotonin Antagonists

Administration of cisapride, 3 x 5 mg in a suspension one day before surgery and 30 mg 3 and 8 hours after abdominal surgery with subsequent administration of 2 x 30 mg in suppositories up to the time when oral ingestion is possible, hastens significantly the restoration of GIT motility as compared with placebo. It can be therefore recommended as effective medication in the prevention of complications caused by impaired motility of the digestive tract.

Topics: Cisapride; Female; Gastrointestinal Agents; Gastrointestinal Motility; Gastroparesis; Humans; Male; Middle Aged; Piperidines; Postoperative Complications

Abnormal gastric slow-wave frequencies have been observed in diabetic gastroparesis. To evaluate the effect of cisapride on gastric dysrhythmia and emptying of indigestible solids, 20 type-II diabetic patients with symptoms suggestive of gastroparesis were enrolled in this study.. Cutaneous electrogastrography, gastric emptying of radiopaque markers, and evaluation of upper gastrointestinal symptoms were performed before and after administration of an 8-week course of cisapride.. The fasting-state percentages of dominant frequency in normal and tachygastric ranges improved significantly after an 8-week course of cisapride treatment (P < 0.01 and P < 0.05, respectively). The post-meal percentages of dominant frequency in the tachygastric range also improved significantly after cisapride treatment (P < 0.05). The upper gastrointestinal symptoms score decreased significantly, and gastric emptying of radiopaque markers also increased significantly after 8 weeks of cisapride treatment (P < 0.01).. In conclusion, this study showed that cisapride can improve gastric dysrhythmia during both fasting and post-meal phases in patients with diabetic gastroparesis. In addition, upper GI symptoms and gastric emptying of indigestible solids may also show significant improvement after 8 weeks of cisapride treatment.

Topics: Blood Glucose; Cisapride; Diabetes Mellitus, Type 2; Female; Gastric Emptying; Gastrointestinal Agents; Gastrointestinal Motility; Gastroparesis; Humans; Male; Middle Aged; Piperidines

The C57BLKS/J db/db mouse develops hyperglycemia and has delayed gastric emptying that is improved with tegaserod, a partial 5-HT4 agonist. Our aims here were to determine regional gastric contractility alterations in C57BLKS/J db/db mice and to determine the effects of serotonin and tegaserod. The contractile effects of bethanechol, serotonin, and tegaserod in fundic, antral, and pyloric circular muscle were compared in C57BLKS/J db/db mice and normal littermates. The effects of tetrodotoxin, atropine, and 5-HT receptor antagonists were studied. Contractions in response to bethanechol were decreased in the fundus, similar in the antrum, but increased in the pylorus in diabetic mice compared with controls. Serotonin and, to a lesser extent, tegaserod caused contractions that were more pronounced in the fundus than in the antrum and pylorus in both diabetic and normal mice. Serotonin-induced contractions were partially inhibited by atropine, the 5-HT4 antagonist GR113808, and the 5-HT2 antagonist cinanseron but not tetrodotoxin. Regional gastric contractility alterations are present in this diabetic gastroparesis mouse model. Fundic contractility was decreased, but pyloric contractility was increased in the pylorus to cholinergic stimulation in diabetic mice. Serotonin's contractile effect is mediated, in part, through muscarinic, 5-HT2, and 5-HT4 receptors. This study suggests that fundic hypomotility and pyloric hypercontractility, rather than antral hypomotility, play important roles for the gastric dysmotility that occurs in diabetes.

Topics: Animals; Bethanechol; Cholinergic Agonists; Diabetes Mellitus, Experimental; Dose-Response Relationship, Drug; Electric Stimulation; Enteric Nervous System; Female; Gastroparesis; In Vitro Techniques; Indoles; Mice; Mice, Inbred C57BL; Muscarinic Agonists; Muscle Contraction; Muscle, Smooth; Piperidines; Potassium; Receptors, Muscarinic; Serotonin; Serotonin Receptor Agonists; Stomach

Topics: Cisapride; Drug Administration Routes; Gastrointestinal Agents; Gastroparesis; Humans; Piperidines

Erythromycin, a macrolide antibiotic, has been shown to have gastric prokinetic effects and has been proposed as an alternative therapeutic option for diabetic gastroparesis. However, its efficacy has not yet been compared with that of other prokinetic drugs.. The purpose of the present study was to compare the effects of erythromycin (250 mg 60 min before meals) and cisapride (10 mg 30 min before meals) on gastric emptying of healthy subjects and insulin-dependent diabetics.. Six type 1 diabetic patients with a previous scintigraphic demonstration of gastroparesis and five healthy subjects were recruited for the study. Gastric emptying was scintigraphically studied by labelling the solid component of a standard test meal. Three scintigraphic studies, spaced at least 3 days apart, were carried out on each subject, basally and after erythromycin or cisapride.. Cisapride significantly accelerated gastric emptying in both the healthy subjects and the diabetic patients without any significant effect on the lag-time, whereas erythromycin in addition to a significant improvement of the overall gastric emptying also showed a pronounced effect on the lag-time in both groups (controls 25 +/- 5 vs. 37 +/- 8 min, P < or = 0.04; diabetics 65 +/- 11 vs. 112 +/- 16 min, P < 0.03).. Erythromycin may represent an effective therapeutic alternative to more established forms of treatment in patients with diabetic gastroparesis, especially when other drugs have failed.

Topics: Adult; Cisapride; Diabetes Mellitus, Type 1; Erythromycin; Female; Gastric Emptying; Gastroparesis; Humans; Male; Middle Aged; Piperidines; Serotonin Antagonists

The influence of diabetic hyperglycemia on solid gastric emptying in rats was examined. Diabetes was produced by streptozotocin (STZ, 40 mg/kg i.v.), and diabetic hyperglycemia was observed from 1 day after the STZ injection. The gastric emptying of glass beads in the diabetic rats was significantly delayed compared with that in age-matched control rats at 1, 3 and 7 days after diabetes induction. A slight decrease in gastric emptying was observed in the diabetic rats from 2 to 52 weeks after the diabetes induction. We also investigated the influence of gastroprokinetic agents on STZ-induced diabetic gastroparesis and subdiaphragmatic vagotomy-induced gastroparesis in rats. The selective 5-HT3 receptor antagonists ramosetron (YM060), YM114 (KAE-393), granisetron and ondansetron, and the substituted benzamides (5-HT4 receptor agonist/5-HT3 receptor antagonists) cisapride mosapride and SC-53116 dose-dependently enhanced gastric emptying in normal rats. These compounds also reversed the impairment of diabetic gastroparesis rats at 7 days after the STZ injection, but higher doses were required. The solid gastric emptying in subdiaphragmatic vagotomized rats was also delayed. Ramosetron and the substituted benzamides cisapride and zacopride partially reversed the gastroparesis in the vagotomized rats. These results suggest that acute hyperglycemia is important mechanism for the delay of solid gastric emptying in diabetic rats. It is also suggested that selective 5-HT3 receptor antagonists and substituted benzamides enhance gastric emptying not only in normal rats but also in diabetic and vagotomized rats.

Topics: Animals; Benzamides; Benzimidazoles; Blood Glucose; Cisapride; Diabetes Mellitus, Experimental; Gastric Emptying; Gastrointestinal Motility; Gastroparesis; Granisetron; Male; Morpholines; Ondansetron; Piperidines; Pyrroles; Rats; Rats, Wistar; Serotonin Antagonists; Serotonin Receptor Agonists; Vagotomy

We describe the clinical features and long-term outcome of 11 children who had persistent gastroparesis after an acute viral illness, eight of whom tested positive for rotavirus. Gastric emptying was delayed in the 10 children evaluated with scintigraphy. Antroduodenal manometry confirmed postprandial antral hypomotility in 10 subjects. All children recovered within 6 to 24 months.

Topics: Acute Disease; Adolescent; Child; Child, Preschool; Cisapride; Female; Gastrointestinal Agents; Gastrointestinal Motility; Gastroparesis; Humans; Infant; Male; Manometry; Piperidines; Postprandial Period; Rotavirus Infections

Gastroparesis is a well-documented finding among patients with severe traumatic brain injuries. The treatment of choice has been metoclopramide, but it is less than ideal given its central dopaminergic blocking activity. Cisapride is a newer prokinetic agent without side effects on the central nervous system and might be a superior treatment. The case of a healthy 22-year-old man who suffered a severe traumatic brain injury and multiple trauma in a motor vehicle accident is reported. The patient required gastrostomy tube placement but developed recurrent aspiration pneumonia once feedings were initiated. Despite receiving metoclopramide, barium studies revealed gastroparesis, a significant decrease in gastric peristalsis, and reflux. A jejunostomy tube was placed to prevent further aspiration. The administration of cisapride was begun, and 2 days later the patient was changed back to G-tube feedings with no evidence of residual aspirates. Repeat barium study showed definite improvement in peristalsis. This case demonstrates the potential usefulness of cisapride in patients with traumatic brain injury. Although further research is necessary, efficacy without central dopamine blockage may make cisapride the treatment of choice for gastroparesis and reflux in traumatic brain injury.

Topics: Adult; Brain Injuries; Cisapride; Enteral Nutrition; Gastric Emptying; Gastroparesis; Humans; Male; Parasympathomimetics; Piperidines; Sympathomimetics

Assessment of gastric emptying time by ultrasonography is increasingly used to evaluate gastroparesis. At first normal values have to be defined. In 20 healthy volunteers the upper value of half emptying time after a semisolid meal was 50 min. A good correlation of gastric emptying time evaluated by scintigraphy was found. Diabetics with autonomous neuropathy had a remarkable delay in gastric emptying, not seen in patients with functional dyspepsia. In dyspeptic patients pathologic width of the antrum (measured by planimetry after overnight fasting) decreased during therapy with cisapride in correlation to the improvement of symptoms.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Cisapride; Diabetic Neuropathies; Dyspepsia; Female; Gastric Emptying; Gastroparesis; Humans; Male; Middle Aged; Piperidines; Reference Values; Sympathomimetics; Ultrasonography

To investigate the effect on glycemic control of improving diabetic gastroparesis, we evaluated symptoms (scored), gastric motor functions (solid and liquid gastric emptying studies and electrogastrography), and glycemic control in 11 patients with diabetic gastroparesis (5 men, 6 women, 50.4 +/- 4.5 years old) before and after treatment with cisapride (15 mg/day p.o., 12 weeks). None of the patients had organic abnormalities on gastrointestinal endoscopy. The dysmotility symptom score (maximum: 18) on cisapride significantly improved from 13.1 to 4.0 (p < 0.01). Retention rates at 15 and 80 minutes after ingestion improved in a solid-food gastric emptying study using a test meal of instant noodles labeled with 37 MBq (1 mCi) technetium-99m (both p < 0.05). Liquid gastric emptying, evaluated using a sulfamethizole technique, also improved but not significantly. Electrogastrography revealed no significant changes after treatment, but the postprandial rate of normal frequency waves tended to increase. Glycemic control was assessed based on HbA1C, fructosamine and M value. There were no significant changes in glycemic control after treatment with cisapride. We conclude that long-term administration of cisapride reduced dysmotility symptoms and improved solid and liquid gastric emptying without adversely affecting glycemic control.

Topics: Adult; Aged; Blood Glucose; Cisapride; Diabetes Complications; Diabetes Mellitus; Female; Gastric Emptying; Gastroparesis; Humans; Male; Middle Aged; Piperidines; Sympathomimetics

Topics: Cisapride; Female; Gastric Emptying; Gastroparesis; Humans; Middle Aged; Multiple Sclerosis; Parasympathomimetics; Piperidines

Topics: Cisapride; Domperidone; Dyspepsia; Gastroesophageal Reflux; Gastroparesis; Humans; Metoclopramide; Piperidines; Serotonin Antagonists