piperidines and Gastroesophageal-Reflux

The place of acid pump inhibitors at the top of the efficacy table in the league of reflux therapies, and their eager patient acceptance, has aroused debate on their role.. To understand the role of gastric acid and its inhibition in the pathogenesis and treatment of gastroesophageal reflux disease.. Gastroesophageal reflux disease results from excessive exposure of the oesophagus to acidic contents. Acid pump inhibitors provide the most effective medical control of gastric acid throughout day and night, returning oesophageal pH to normal levels. They provide fast symptom relief and rapidly restore quality of life in all reflux patients more effectively than H2 receptor antagonists or prokinetic drugs. APIs heal oesophagitis of all grades of severity and provide safe, effective maintenance of healing with prevention of complications in longer term use.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Anti-Ulcer Agents; Benzimidazoles; Cisapride; Gastroesophageal Reflux; Histamine H2 Antagonists; Humans; Lansoprazole; Omeprazole; Pantoprazole; Piperidines; Ranitidine; Sulfoxides

Identify and critically review the peer-reviewed, English-language studies of the effects of medical antireflux therapy in asthmatics with gastroesophageal reflux (GER).. Using the 1966 to 1996 MEDLINE database, asthma was combined with GER to identify all studies of the effects of medical antireflux therapy on asthma control. The articles' bibliographies were also reviewed. Studies were graded according to Sackett's criteria and grouped by levels of evidence.. A total of 242 citations were found; 171 were published in English. Twelve studies of the effects of medical antireflux therapy on asthma control, with a total of 326 treated patients, were identified. Eight studies were placebo-controlled, three were open studies, and one used an untreated control. Eight studies treated 20 or fewer patients. Reflux symptoms either did not improve or the effects of antireflux therapy on them were not reported in four studies. The combined data from the controlled medical antireflux studies showed that: (1) asthma symptoms improved in 69% of the subjects; (2) asthma medication use was reduced in 62% of the subjects; (3) evening peak expiratory flow (PEF), but not PEF at other times, improved in 26% of the subjects; and (4) spirometry did not improve in any of the placebo-controlled antireflux studies.. Analysis of the combined data suggests that medical antireflux therapy improves asthma symptoms, may reduce asthma medication use, but has minimal or no effect on lung function.

Topics: Antacids; Anti-Asthmatic Agents; Anti-Ulcer Agents; Asthma; Cimetidine; Circadian Rhythm; Cisapride; Gastroesophageal Reflux; Humans; Lung; Omeprazole; Peak Expiratory Flow Rate; Piperidines; Placebos; Randomized Controlled Trials as Topic; Ranitidine; Spirometry

There is a growing body of pathophysiological evidence that gastroesophageal reflux disease (GERD) is caused by disordered motility and not acid hypersecretion. The key factor in the pathogenesis of GERD is disordered function of the lower esophageal sphincter. Other factors include delayed gastric emptying and decreased peristalsis in the body of the esophagus. The principal symptoms of GERD are heartburn and regurgitation. Studies have demonstrated that up to 50% of patients may have other symptoms of dysmotility including epigastric discomfort or fullness, nausea and early satiety. The use of a prokinetic agent in such patients seems logical. Given its proven superior efficacy over domperidone and metaclopramide in treating GERD, cisapride has become the prokinetic drug of choice for the acute management and maintenance therapy of GERD. In the acute management of GERD, cisapride is superior to placebo and has the same efficacy as H2 receptor antagonists (H2RAs) in several clinical trials. It is also effective in maintenance therapy for GERD. These studies are reviewed. Cisapride (10 mg qid or 20 mg bid) is effective in the acute treatment of mild to moderate GERD, particularly in patients with heartburn associated with other symptoms of dysmotility, and particularly in patients with heartburn associated with gastroparesis. Combination therapy with an H2RA may be considered if symptoms (particularly dysmotility symptoms) persist with H2RA alone. In severe GERD that is not responsive to conventional doses of a proton pump inhibitor, cotherapy with cisapride or increasing the dose of the proton pump inhibitor are the two therapeutic options to consider. Cisapride 20 mg at bedtime is effective maintenance therapy for patients with mild to moderate GERD.

Topics: Cisapride; Domperidone; Esophagus; Gastroesophageal Reflux; Gastrointestinal Agents; Histamine H2 Antagonists; Humans; Metoclopramide; Piperidines

Topics: Cisapride; Gastroesophageal Reflux; Gastrointestinal Agents; Humans; Piperidines

Topics: Alginates; Aluminum Hydroxide; Antacids; Child; Cisapride; Drug Combinations; Gastroesophageal Reflux; Humans; Piperidines; Serotonin Antagonists; Silicic Acid; Sodium Bicarbonate

Dyspepsia affects one in four Australians; of those who present in general practice, the majority will have functional or non-ulcer dyspepsia, with no structural explanation for their symptoms. Older patients who present for the first time with dyspepsia, and those with 'alarm features' deserve immediate investigation (preferably by upper endoscopy), to exclude cancer, peptic ulcer or oesophagitis. Other patients may be given empiric therapy (for example, a prokinetic or H2 blocker) initially, but require investigation if this fails. The role of Helicobacter pylori infection in functional dyspepsia is uncertain.

Topics: Adult; Aged; Antacids; Anti-Inflammatory Agents, Non-Steroidal; Anti-Ulcer Agents; Bismuth; Child; Cholelithiasis; Chronic Disease; Cisapride; Diagnosis, Differential; Domperidone; Dopamine Antagonists; Dyspepsia; Gastroesophageal Reflux; Helicobacter Infections; Helicobacter pylori; Histamine H2 Antagonists; Humans; Metoclopramide; Peptic Ulcer; Piperidines; Stomach Neoplasms

Regurgitation in infants is a common problem. Recent issues, such as the increased risk of sudden infant death in the prone sleeping position, the finding of persisting occult gastro-oesophageal reflux with feed thickeners, and the increasing awareness of the cost-benefit ratio of medications may challenge the currently recommended management approach. A round table was organized to elaborate on the impact of (i) the pro supine sleeping campaigns in relation to sudden infant death and (ii) advancement in medical treatment on therapeutic strategies in regurgitating infants. The participants were opinion leaders from Europe and North America (Belgium, Canada, France, UK, Italy, Switzerland and The Netherlands). The importance of parental reassurance is stressed. As a consequence of the supine sleeping campaigns aiming to decrease the incidence of sudden infant death syndrome, the "prone elevated sleeping position" is no longer advised as a first-line therapeutic approach, although it is still recommended in "complicated reflux". It is emphasized that milk thickeners are an adequate therapeutic tool for regurgitation, but not in reflux disease. According to the literature, the efficacy of (alginate )antacids, although very popular in some countries, is questionable. These recommendations will be of interest to first-line paediatricians, since about 40% of their patients, according to the literature, present because of regurgitation.

Topics: Anti-Ulcer Agents; Antiemetics; Cisapride; Gastroesophageal Reflux; Humans; Infant; Infant Food; Metoclopramide; Piperidines; Practice Guidelines as Topic; Prone Position

This article summarizes the pathophysiology of gastroesophageal reflux disease (GERD) and the wide spectrum in disease and symptom severity as they influence the selection of cost-effective treatment strategies. The vast majority of patients with GERD have mild symptoms, no gross endoscopic evidence of esophagitis, and little risk of developing complications. More than 85% of patients with GERD symptoms have uncomplicated disease. Diffuse ulcerations or complications (grade III or IV esophagitis) occur in only 3.5% of patients < 65 years of age. However, some patients with GERD can develop severe complications, including esophageal obstruction, significant blood loss, and, in rare circumstances, perforation. Furthermore, adenocarcinoma of the esophagus, which is increasing in incidence faster than any other cancer, is caused by GERD. Although severe ulcerations are uncommon in young patients, they occur in 20-30% of patients over age 65. Patients with ulcerative esophagitis are not only more prone to develop complications, they are also more resistant to treatment. Cost-effective medical management of GERD must take into account the wide spectrum of symptom and disease severity. Therapy consists of both nonpharmacologic treatment and the appropriate use of medications from several classes of drugs, either alone or in combination. Traditionally, prokinetic agents or histamine receptor antagonists have been used as primary therapy; proton-pump inhibitors are reserved for more resistant cases. The rationale for this and for alternative approaches is discussed.

Topics: Aged; Anti-Ulcer Agents; Cisapride; Drug Interactions; Drug Therapy, Combination; Esophagitis, Peptic; Gastroesophageal Reflux; Histamine H2 Antagonists; Humans; Metoclopramide; Omeprazole; Piperidines; Serotonin Antagonists; Ulcer

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

In the treatment of gastrointestinal motility disorders 3 prokinetic agents are principally available. They are differentiated from their pharmacological mode of action, their clinical efficacy and tolerability. Metroclopramide is an antidopaminergic benzamide with mainly antiemetic effects and minor prokinetic efficacy in the GI-Tract. Domperidon is a pure dopaminantagonist. It accelerates gastric emptying but has less effect on bowel motility. Cisapride stimulates indirect the secretion of acetylcholine and acts via 5 HT-receptors selective at the plexus myentericus. These pharmacological differences have clinical relevance: metoclopramide and domperidon could not consistently prove efficacy in functional dyspepsia and GORD. In addition the data in other indications are rare. Only cisapride has shown significant responder rates in controlled studies in the treatment of gastrointestinal motility disorders particularly in long term treatment. As concerns tolerability cisapride presents a progress by its selective mode of action in contrast to the agents crossing the blood-brain-barrier.

Topics: Adult; Antiemetics; Child; Cisapride; Clinical Trials as Topic; Domperidone; Dopamine Antagonists; Dyspepsia; Gastric Emptying; Gastroesophageal Reflux; Gastrointestinal Motility; Humans; Metoclopramide; Piperidines; Postoperative Complications; Serotonin Receptor Agonists; Treatment Outcome

Hospital malnutrition continues to be a serious problem. Although enteral feeding of hospitalized patients is safe and less expensive than parenteral feeding, it is associated with side effects involving the gastrointestinal tract and respiratory systems.

Topics: Bethanechol; Cisapride; Enteral Nutrition; Gastroesophageal Reflux; Humans; Nutrition Disorders; Parasympathomimetics; Piperidines; Pneumonia, Aspiration

Gastro-oesophageal reflux disease (GORD) is a very common disorder of upper gastro-intestinal motility, differing widely in severity and prognosis. Medical therapy of GORD has involved antacids, alginates, prokinetic agents and antisecretory compounds, primarily H2 receptor antagonists and proton pump inhibitors. Knowledge of the pharmacokinetics of these compounds is important, to optimise the therapeutic benefit in each patient. GORD patients are often elderly and pharmacokinetics are move variable in this group. Furthermore, they often suffer from other diseases needing medical therapy and may need a combination of drugs to heal reflux oesophagitis and relieve reflux symptoms. The ideal therapy for GORD will have linear pharmacokinetics, a relatively long plasma half-life (t1/2), a duration of action allowing once daily administration, and a stable effect independent of interactions with food, antacids and other drugs. Over-the-counter antacids and alginates are widely used, buy may affect absorption of H2 receptor antagonists like cimetidine and ranitidine. Aluminium-containing antacids may, over time, cause toxicity in patients with renal insufficiency. In the treatment of GORD, cisapride presents important advantages over earlier prokinetic compounds, with a longer plasma t1/2, low penetration of the blood-brain barrier and fewer adverse effects. The group of H2 receptor antagonists is still the most frequently use therapy for GORD. Linear pharmacokinetics make dose adjustments easy and safe. In individual patients, suppression of gastric secretion is related to the area under the plasma concentration-time curve (AUC), but there is wide interindividual variation in the effect of the same oral dose. Only with frequent administration and high doses will acid suppression approximate that of proton pump inhibitors. Tolerance, with loss of effect over time, however, is most pronounced in this situation. H2 receptor antagonists seem well suited for on-demand treatment of reflux symptoms, due to the rapid onset of effect and a decrease likelihood of the development of tolerance. Effervescent formulations provide more rapid absorption and almost immediate clinical effect. Cimetidine, however, causes interference with the metabolism of several other drugs in common use. In elderly patients elimination is delayed and in patients with renal insufficiency, dose reductions of all H2 receptor antagonists are recommended. The most effective medical therapy for any

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Antacids; Benzimidazoles; Cimetidine; Cisapride; Domperidone; Famotidine; Gastroesophageal Reflux; Histamine H2 Antagonists; Humans; Lansoprazole; Metoclopramide; Nizatidine; Omeprazole; Pantoprazole; Piperidines; Proton Pump Inhibitors; Ranitidine; Sucralfate; Sulfoxides

Topics: Animals; Cisapride; Esophagus; Gastric Emptying; Gastroesophageal Reflux; Gastrointestinal Motility; Humans; Parasympathomimetics; Piperidines; Vomiting

Prokinetic drugs theoretically have the ability to correct the pathophysiologic abnormalities of gastrointestinal motility that lead to gastroesophageal reflux disease. However, the prokinetic agents bethanechol and metoclopramide have been associated with central nervous system and other side effects, as well as uncertain efficacy. In addition, erythromycin seems unsuitable for use as an oral prokinetic agent. A recently introduced prokinetic agent, cisapride, has a minimum incidence of side effects and is effective in the treatment of reflux symptoms, but trials in the United States have not confirmed the symptomatic improvement or healing of erosive esophagitis that has been demonstrated in studies abroad. An expanded role may unfold for cisapride and additional new prokinetic drugs as primary therapy for reflux in some patients, as adjunctive treatment with an antisecretory agent, or as maintenance treatment for a subset of patients with gastroesophageal reflux. Therapy tailored to individual pathophysiology is appropriate and may offer cost savings and improved clinical outcome.

Topics: Bethanechol; Cisapride; Domperidone; Erythromycin; Gastroesophageal Reflux; Humans; Metoclopramide; Parasympathomimetics; Piperidines

Severe gastroesophageal reflux disease is usually a chronic problem with periods of relapse, but effective medical and surgical therapies are available. Two recently introduced agents, omeprazole (Prilosec) and cisapride (Propulsid), represent advances in medical therapy; the safety of long-term, continuous omeprazole therapy is under investigation. Used by surgeons with sufficient experience, the new laparoscopic approach offers potential advantages over conventional anti-reflux surgery in suitable candidates. The decision of whether to recommend long-term medical therapy or surgery must be individualized. Medical therapy may be the best choice in elderly patients and poor surgical candidates, in patients whose symptoms are well controlled with omeprazole and who accept its benefit-risk profile, and when a highly experienced anti-reflux surgeon is not available. Surgery may be appropriate (assuming a skilled surgeon is available) in patients who are young, have trouble taking medication, need multiple agents to control symptoms, and need continuous omeprazole therapy but are unwilling to accept the theoretical risk of gastric carcinoid tumors that accompanies it.

Topics: Antacids; Anti-Ulcer Agents; Cisapride; Drug Therapy, Combination; Esophageal Diseases; Esophagogastric Junction; Fundoplication; Gastroesophageal Reflux; Hernia, Hiatal; Histamine H2 Antagonists; Humans; Laparoscopy; Life Style; Long-Term Care; Omeprazole; Peristalsis; Piperidines; Risk-Taking; Severity of Illness Index

Although gastroesophageal reflux disease is among the most common disorders seen by gastroenterologists, the wide variation in both its symptoms and severity has led to a lack of consensus about the most appropriate practical approach to treatment of patients with acute symptoms. This review considers the efficacy of the most widely used pharmacologic agents in the acute treatment of gastroesophageal reflux disease: H2-receptor antagonists, proton-pump inhibitors, and prokinetic agents. Possible treatment strategies in which they may be used are discussed and it is proposed that individualized treatment strategies should be developed based on symptoms and severity of disease. Emphasis is placed on the fact that, given the wide variety of effective agents available, the use of the same agent in every patient, regardless of their symptoms, is a most inappropriate approach. A stepwise approach to therapy utilizing a number of drug classes is discussed and the rationale for and appropriate use of both a 'step-up' and 'step-down' approach is considered.

Topics: Anti-Ulcer Agents; Cisapride; Gastroesophageal Reflux; Gastrointestinal Agents; Histamine H2 Antagonists; Humans; Piperidines; Treatment Outcome

Topics: Anti-Ulcer Agents; Child, Preschool; Cisapride; Gastroesophageal Reflux; Humans; Infant; Infant, Newborn; Parasympathomimetics; Piperidines

To summarize the pharmacology, pharmacokinetics, efficacy, and safety of cisapride, and to evaluate its potential therapeutic role.. A computerized search of the MEDLINE database was used to identify English-language publications of cisapride data in humans. The MEDLINE search was supplemented by review article bibliographies. There was no attempt to limit the search to a specific gastrointestinal motility disorder.. The MEDLINE search alone identified 165 citations. Because of the volume of available human cisapride data, the focus of the efficacy section is on complete published reports of controlled clinical studies. Abstracts and uncontrolled data are discussed only when other information is unavailable to address important aspects.. Information regarding study design, study population, results, and safety was recorded from each publication. The placebo response to gastrointestinal complaints in patients with motility disorders is high. Therefore, objective evidence of improvement was emphasized when documentation was available.. Cisapride stimulates the motility of smooth muscle lining the esophagus, stomach, small intestine, and colon, and increases the tone of gut sphincters in vitro and in vivo. In controlled investigations, cisapride was superior to placebo in relieving symptoms associated with reflux esophagitis, nonulcer dyspepsia, and gastroparesis. Similar symptom and healing effects were observed with cisapride and histamine (H)2-antagonists in reflux esophagitis. Cisapride was either equal to or superior to metoclopramide in relieving reflux symptoms. However, metoclopramide was associated with significantly more central nervous system adverse effects. Cisapride was well tolerated, with adverse effects limited primarily to the gastrointestinal tract.. Cisapride represents an attractive alternative to metoclopramide for the treatment of a variety of motility disorders. Because it addresses a primary underlying cause of reflux esophagitis, cisapride may also prove to be an effective alternative to acid suppressants in the management of this disorder.

Topics: Adult; Anti-Ulcer Agents; Cisapride; Clinical Trials as Topic; Constipation; Double-Blind Method; Dyspepsia; Gastroesophageal Reflux; Gastrointestinal Motility; Humans; Infant; Infant, Newborn; Parasympathomimetics; Piperidines

Gastro-oesophageal reflux disease is a primary motility disorder of the upper gastro-intestinal tract, with varying degrees of disturbed lower oesophageal sphincter function, disturbed peristalsis of the oesophageal body and delayed gastric emptying. Traditional treatment has focused on "detoxifying" the refluxate by suppressing gastric acid secretion. With the advent of cisapride (Prepulsid), prokinetic drugs offer a possibility of influencing the underlying motility disturbances without causing the serious side effects of earlier prokinetic drugs. It seems to be well documented that cisapride is useful in both the short-term and the long-term treatment of grade 1 reflux oesophagitis, and also in more severe cases as part of combination regimens involving acid suppressive drugs.

Topics: Cisapride; Gastroesophageal Reflux; Gastrointestinal Motility; Humans; Piperidines; Serotonin Antagonists

Prokinetic agents are drugs that increase contractile force and accelerate intraluminal transit. They are often used in treating disorders of gastrointestinal motility including gastro-oesophageal reflux disease (GERD). The most widely studied agents include bethanechol, metoclopramide, domperidone and cisapride. These drugs act either by enhancing the effect of acetylcholine or by blocking the effect of an inhibitory neurotransmitter such as dopamine. With the exception of cisapride, the clinical efficacy of the various prokinetic agents in treating GERD has not been confirmed consistently. These agents have variable effects on oesophageal and gastric motor function and are fraught with side-effects. They are effective in relieving mild reflux symptoms but do not predictably heal oesophagitis. On the other hand, cisapride is thus far the most effective prokinetic agent studied for the treatment of GERD. It relieves reflux symptoms and promotes healing of grade I-II oesophagitis, with few side-effects or tachyphylaxis. Its most important role may be in the maintenance treatment of GERD either as a single agent or in combination therapy with an H2-antagonist after oesophagitis healing.

Topics: Adult; Benzamides; Bethanechol; Bethanechol Compounds; Child; Cisapride; Erythromycin; Gastroesophageal Reflux; Gastrointestinal Motility; Humans; Infant; Metoclopramide; Piperidines; Receptors, Cholecystokinin; Serotonin Antagonists

Gastro-oesophageal reflux is a common phenomenon in infants, and is an aspecific complaint. The balance between negligence and overconcern is therefore very difficult to make, and requires experienced physicians. The approach in infants with uncomplicated reflux consists of non-drug treatment and reassurance of the parents about the almost physiological nature of the regurgitations of the baby. If the parents persist in their complaints, the administration of prokinetics such as cisapride can be considered before performing investigations (oesophageal pH monitoring). The efficacy and the lack of side-effects of cisapride makes this the drug of choice. The frequency of side-effects of other drugs necessitates the diagnosis of reflux disease before their administration. Upper gastrointestinal tract endoscopy is the investigation of choice in children suspected of reflux oesophagitis. In the majority of cases, the efficacy of cisapride, H2-blockers and Na-K-ATP-ase-blockers should be given a chance. Unusual presentations, such as chronic respiratory disease, as a manifestation of reflux disease should be confirmed with oesophageal pH monitoring.

Topics: Anti-Ulcer Agents; Child, Preschool; Cisapride; Endoscopy, Gastrointestinal; Esophagitis, Peptic; Gastroesophageal Reflux; Humans; Infant; Piperidines; Serotonin Antagonists

In this paper, a Working Group on Gastro-Oesophageal Reflux discusses recommendations for the first line diagnostic and therapeutic approach of gastro-oesophageal reflux disease in infants and children. All members of the Working Group agreed that infants with uncomplicated gastro-oesophageal reflux can be safely treated before performing (expensive and often unnecessary) complementary investigations. However, the latter are mandatory if symptoms persist despite appropriate treatment. Oesophageal pH monitoring of long duration (18-24 h) is recommended as the investigation technique of choice in infants and children with atypical presentations of gastro-oesophageal reflux. Upper gastro-intestinal endoscopy in a specialised centre is the technique of choice in infants and children presenting with symptoms suggestive of peptic oesophagitis. Prokinetics, still a relatively new drug family, have already obtained a definitive place in the treatment of gastro-oesophageal reflux disease in infants and children, especially if "non-drug" treatment (positional therapy, dietary recommendations, etc.) was unsuccessful. It was the aim of the Working Group to help the paediatrician with this consensus statement and guide-lines to establish a standardised management of gastro-oesophageal reflux disease in infants and children.

Topics: Child; Child Nutritional Physiological Phenomena; Cisapride; Esophagitis; Esophagoscopy; Esophagus; Europe; Gastroenterology; Gastroesophageal Reflux; Gastrointestinal Motility; Gastroscopy; Humans; Hydrogen-Ion Concentration; Infant; Pediatrics; Piperidines; Posture; Societies, Medical

The pathologic potential of chronic esophagitis cannot be overemphasized. Persistent reflux causing cycles of mucosal damage followed by healing may eventually lead to end-stage disease, with development of peptic stricture. The most effective drugs available are those that inhibit acid production. Drugs that will enhance lower esophageal function are still in the future.

Topics: Alginates; Antacids; Barium; Bethanechol Compounds; Cisapride; Endoscopy, Gastrointestinal; Gastric Acidity Determination; Gastroesophageal Reflux; Glucuronic Acid; Hexuronic Acids; Histamine H2 Antagonists; Humans; Hydrochloric Acid; Life Style; Metoclopramide; Monitoring, Physiologic; Omeprazole; Piperidines; Serotonin Antagonists

Topics: Antacids; Cisapride; Esophagus; Gastroesophageal Reflux; Heartburn; Histamine H2 Antagonists; Humans; Hydrogen-Ion Concentration; Life Style; Monitoring, Physiologic; Piperidines; Posture; Serotonin Antagonists

Disorders of gastric emptying are observed in many clinical situations. Their symptoms are diverse and correlate poorly with the objective abnormalities of gastric emptying. The underlying mechanism consists of abnormalities of basal electrical rhythm, fundic compliance, post-prandial antral motricity and, above all, antro-pyloro-duodenal co-ordination, associated to varying degrees. Among possible causes 3 clinical situations predominate: diabetes mellitus, functional gastrointestinal disorders (idiopathic dyspepsia) and sequelae of gastric surgery where retention of solids and accelerated evacuation of liquids may coexist in the same patient. Treatment of gastric incontinence rests, almost exclusively, on dietary measures, but several drugs, such as metoclopramide, domperidone and cisapride, are available to treat gastric stasis. Other compounds, notably motilin agonists (erythromycin and its derivatives) are currently being evaluated and will reinforce this therapeutic armentarium in a not too distant future.

Topics: Cisapride; Diabetes Complications; Domperidone; Dyspepsia; Gastric Emptying; Gastroesophageal Reflux; Humans; Metoclopramide; Piperidines; Postoperative Complications; Serotonin Antagonists; Stomach Diseases; Stomach Ulcer

The author discusses the role of prokinetic agents, such as bethanechol, metoclopramide, domperidone, and cisipride in the management of gastroesophageal reflux disease. These agents address the upper gastrointestinal motility disturbances that contribute to this disease and therefore have an important role in the acute and long-term medical management of reflux esophagitis.

Topics: Bethanechol; Bethanechol Compounds; Cisapride; Domperidone; Esophagogastric Junction; Gastric Emptying; Gastroesophageal Reflux; Humans; Metoclopramide; Piperidines; Serotonin Antagonists

Topics: Cisapride; Dyspepsia; Gastroesophageal Reflux; Gastrointestinal Motility; Humans; Metoclopramide; Piperidines

Gastro-oesophageal reflux occurs when the pressure barrier of the lower oesophageal sphincter (LOS) fails due to a low basal pressure (less than or equal to 6 mm Hg), sphincteric relaxations or a noncompensated increase in intragastric pressure. This reflux becomes pathological when it leads to symptoms severe enough for the patient to seek medical help or results in reflux oesophagitis or its complications. Damage to the oesophageal mucosa develops when the balance between aggressive and defensive factors is no longer in equilibrium. The main aggressive factor is acid-pepsin or alkaline bile secretion. Defence against this aggression is based on rapid removal of the refluxate from the oesophagus (oesophageal clearance) and on poorly understood mucosal resistance. The length of time acid is in contact with the oesophageal mucosa is shortened by adoption of an upright position, by swallow-induced oesophageal peristalsis and saliva. Treatment of pathological reflux aims (1) to decrease acid aggression by means of H2-receptor antagonists or proton pump inhibitors; (2) to strengthen the anti-reflux barrier and improve oesophageal clearance by prokinetic drugs that increase the LOS pressure and enhance peristaltic contractions; and (3) to boost mucosal resistance by sucralfate or prostaglandin analogues. Initial treatment of gastro-oesophageal reflux disease may be symptomatic provided that there are no alarming symptoms, such as dysphagia, anaemia or weight loss. Usually either H2-receptor blockers or prokinetic drugs are used. Endoscopy is indicated whenever alarming symptoms are present and when there is insufficient symptomatic improvement after a 4-6-week therapeutic trial. Moderate oesophagitis may be treated in the same way.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Anti-Ulcer Agents; Cisapride; Clinical Trials as Topic; Esophagitis, Peptic; Esophagogastric Junction; Gastroesophageal Reflux; Histamine H2 Antagonists; Humans; Omeprazole; Piperidines; Serotonin Antagonists

Several studies have clearly demonstrated that omeprazole is highly efficacious in the management of patients with gastro-oesophageal reflux disease. In particular, wherever H2-receptor antagonists fail to produce results--in patients with severe disease--omeprazole has been shown to be of major value. However, new alternatives are forthcoming; a new generation of more potent H2-receptor antagonists will be available, while 24 pH studies with high-dose ranitidine have shown that acid reflux is suppressed more efficiently than with standard doses. The prokinetic drug cisapride appears to be of importance, not only in the management of patients with mild reflux disease, but also of cases with severe disease when cisapride is combined with a H2-receptor antagonist. Such a combination could also be of value as an alternative to omeprazole in long-term therapy, since it has not yet been shown that indefinite treatment with omeprazole of patients with reflux disease will be safe. In addition, the value of long-term sucralfate, effective in short-term therapy, needs to be evaluated in patients with chronic reflux disease who will not be operated. In forthcoming studies, it will be advisable to incorporate 24-hour pH measurements to detect periods of nonacid suppression more accurately. The future of medical management of gastro-oesophageal reflux disease appears to be promising.

Topics: Cisapride; Drug Administration Schedule; Gastroesophageal Reflux; Histamine H2 Antagonists; Humans; Omeprazole; Piperidines; Serotonin Antagonists; Therapeutic Equivalency

Topics: Cisapride; Constipation; Dyspepsia; Esophagitis; Esophagus; Forecasting; Gastric Emptying; Gastroesophageal Reflux; Gastrointestinal Motility; Humans; Hydrogen-Ion Concentration; Intestinal Pseudo-Obstruction; Intestines; Manometry; Piperidines; Serotonin Antagonists; Stomach

Prokinetic drugs enhance the motility of the luminal organs of the gastrointestinal tract. Few drugs developed in this decade are likely to have a greater impact on the treatment of disorders of the gastrointestinal tract. Bethanechol and metaclopramide have proven the potential utility of this class of drugs, whereas newer agents promise to have both a greater margin of safety and tolerability and a broader scope of utility. The efficacy of these agents is reviewed for the treatment of impaired motility from gastroesophageal reflux to severe chronic constipation.

Topics: Biomechanical Phenomena; Cisapride; Domperidone; Forecasting; Gastroenterology; Gastroesophageal Reflux; Gastrointestinal Motility; Humans; Intestinal Diseases; Metoclopramide; Paralysis; Parasympathomimetics; Piperidines; Stomach Diseases

Several promotility drugs have been used to correct disorders caused by disturbed gastrointestinal motility. However these drugs have various drawbacks. Their effects on smooth muscle activity may be restricted to part of the digestive system, or may not be very efficient. On the other hand, their use is somewhat limited by side effects: drugs may not be specific for the motor functions of the gastrointestinal tract or not even for the gastrointestinal tract itself. The desirability of improving the promotility effects and eliminating the secondary effects of existing drugs constituted the rationale for developing cisapride. This aim was achieved by influencing--in a physiological way--the release of acetylcholine, the main neurotransmitter in the 'gut brain', the myenteric plexus.

Topics: Cisapride; Gastric Emptying; Gastroesophageal Reflux; Humans; Myenteric Plexus; Piperidines; Serotonin Antagonists; Stomach

Cisapride is a new drug which stimulates gastrointestinal motility via facilitation of acetylcholine release from myenteric nerves. European studies have addressed its clinical efficacy in treating gastro-oesophageal reflux disease in three areas. 1) Symptom relief: Cisapride, usually at a dose of 10 mg t.i.d., was superior to placebo and metoclopramide in relief of daytime and night-time heartburn and regurgitation. 2) Healing oesophagitis: Six studies showed that cisapride 10 mg q.i.d effectively heals oesophagitis over 6-16 weeks. Cisapride was superior to placebo and as effective as H2-antagonists in healing grades I-III oesophagitis. Combination therapy with H2-antagonists may be superior to H2-blocker alone. 3) Paediatric efficacy: Cisapride 1 mg/kg/day was effective in the treatment of infants and children with oesophagitis and pulmonary symptoms related to acid reflux. In conclusion, cisapride offers a promising alternative for the treatment of gastrooesophageal reflux disease without the troubling side effects of existing promotility drugs.

Topics: Adult; Child; Cisapride; Clinical Trials as Topic; Dose-Response Relationship, Drug; Double-Blind Method; Esophagitis, Peptic; Gastroesophageal Reflux; Humans; Piperidines; Serotonin Antagonists; Wound Healing

Topics: Anemia, Pernicious; Anorexia Nervosa; Cisapride; Connective Tissue Diseases; Diabetes Complications; Domperidone; Drug-Related Side Effects and Adverse Reactions; Gastric Emptying; Gastroesophageal Reflux; Gastrointestinal Motility; Humans; Intestinal Pseudo-Obstruction; Metoclopramide; Piperidines; Postgastrectomy Syndromes; Stomach Diseases

Besides changes in behaviour and lifestyle we nowadays have the choice of specific drugs in the treatment of reflux oesophagitis. A distinction can be made in motility modulating drugs, which stimulate oesophageal peristalsis and LOS pressure, mucosa-protecting drugs, which form a protective layer on the oesophageal mucosa, acid neutralizing (antacids) and acid suppressing drugs (H2-receptor antagonists, omeprazole). So far the results of medical therapy of reflux oesophagitis are still suboptimal. Giving the H2-receptor antagonists with the evening meal would possibly be more appropriate. A valid alternative is the mucosa-protecting agent sucralfate. Monotherapy will probably be insufficient for full healing, which explains why trials of combination therapy (H2-receptor antagonists plus sucralfate or plus cisapride) are being conducted. If omeprazole becomes available, it will revolutionize the therapy of severe reflux oesophagitis. Many questions (dose, duration, maintenance, safety monitoring etc.) remain to be determined.

Topics: Antacids; Bethanechol; Bethanechol Compounds; Cimetidine; Cisapride; Domperidone; Esophagitis, Peptic; Gastroesophageal Reflux; Humans; Metoclopramide; Omeprazole; Piperidines; Ranitidine; Sucralfate

Vonoprazan, a novel potassium-competitive acid blocker, elicits potent acid inhibition and hypergastrinemia at a dose of 20 mg. Its recommended maintenance dose for gastro-esophageal reflux disease is 10 mg, which is sometimes insufficient for preventing nocturnal acid breakthrough (NAB). Concomitant use of a histamine 2 receptor antagonist (H. The aim of this study is to compare the levels of acid inhibition and serum gastrin attained by addition of lafutidine to vonoprazan 10 mg with levels after a dose increase of vonoprazan from 10 to 20 mg.. Thirteen healthy volunteers underwent 24-h intragastric pH monitoring and serum gastrin measurements on day 7 of three different regimens: vonoprazan 10 mg, vonoprazan 10 mg plus lafutidine 10 mg, and vonoprazan 20 mg.. Median pH 4 holding time ratios (range) by vonoprazan 10 mg, vonoprazan 10 mg plus lafutidine 10 mg, and vonoprazan 20 mg were 82% (47-88%), 88% (76-93%), and 99% (95-100%) while those at nighttime from 10 p.m. to 8 a.m. were 94% (29-100%), 100% (95-100%), and 100%, respectively. The incidences of NAB with vonoprazan 10 mg, vonoprazan plus lafutidine, and vonoprazan 20 mg were 38, 8, and 0%, respectively. Respective serum gastrin levels were 420 (173-508), 323 (196-521), and 504 (400-812) pg/ml.. Addition of lafutidine 10 mg to vonoprazan 10 mg achieved sufficient acid inhibition, especially at nighttime, without further increase of serum gastrin levels.

Topics: Acetamides; Adolescent; Adult; Cross-Over Studies; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Gastric Acid; Gastric Acidity Determination; Gastrins; Gastroesophageal Reflux; Healthy Volunteers; Histamine H2 Antagonists; Humans; Hydrogen-Ion Concentration; Male; Piperidines; Proton Pump Inhibitors; Pyridines; Pyrroles; Sulfonamides; Young Adult

To compare the clinical efficacy of the second-generation H2RA lafutidine with that of lansoprazole in Japanese patients with mild gastroesophageal reflux disease (GERD).. Patients with symptoms of GERD and a diagnosis of grade A reflux esophagitis (according to the Los Angeles classification) were randomized to receive lafutidine (10 mg, twice daily) or lansoprazole (30 mg, once daily) for an initial 8 wk, followed by maintenance treatment comprising half-doses of the assigned drug for 24 wk. The primary endpoint was the frequency and severity of heartburn during initial and maintenance treatment. The secondary endpoints were the sum score of questions 2 and 3 in the Gastrointestinal Symptom Rating Scale (GSRS), and the satisfaction score.. Between April 2012 and March 2013, a total of 53 patients were enrolled, of whom 24 and 29 received lafutidine and lansoprazole, respectively. After 8 wk, the frequency and severity of heartburn was significantly reduced in both groups. However, lafutidine was significantly inferior to lansoprazole with regard to the severity of heartburn during initial and maintenance treatment (P = 0.016). The sum score of questions 2 and 3 in the GSRS, and satisfaction scores were also significantly worse in the lafutidine group than the lansoprazole group (P = 0.0068 and P = 0.0048, respectively).. The clinical efficacy of lafutidine was inferior to that of lansoprazole, even in Japanese patients with mild GERD.

Topics: Acetamides; Adult; Aged; Aged, 80 and over; Esophagitis, Peptic; Female; Gastroesophageal Reflux; Heartburn; Histamine H2 Antagonists; Humans; Japan; Lansoprazole; Male; Middle Aged; Piperidines; Proton Pump Inhibitors; Pyridines; Severity of Illness Index; Treatment Outcome

Transient lower oesophageal sphincter relaxations (TLESRs) are the main mechanism underlying gastro-oesophageal reflux and are a potential pharmacological treatment target. We evaluated the effect of the CB(1)/CB(2) receptor agonist delta(9)-tetrahydrocannabinol (delta(9)-THC) on TLESRs in dogs. Based on these findings, the effect of delta(9)-THC was studied in healthy volunteers.. In dogs, manometry was used to evaluate the effect of delta(9)-THC in the presence and absence of the CB(1) receptor antagonist SR141716A on TLESRs induced by gastric distension. Secondly, the effect of 10 and 20 mg delta(9)-THC was studied in 18 healthy volunteers in a placebo-controlled study. Manometry was performed before and for 3 h after meal ingestion on three occasions.. In dogs, delta(9)-THC dose-dependently inhibited TLESRs and reduced acid reflux rate. SR141716A significantly reversed the effects of delta(9)-THC on TLESRs. Similarly, in healthy volunteers, delta(9)-THC significantly reduced the number of TLESRs and caused a non-significant reduction of acid reflux episodes in the first postprandial hour. In addition, lower oesophageal sphincter pressure and swallowing were significantly reduced by delta(9)-THC. After intake of 20 mg, half of the subjects experienced nausea and vomiting leading to premature termination of the study. Other side-effects were hypotension, tachycardia and central effects.. Delta(9)-THC significantly inhibited the increase in meal-induced TLESRs and reduced spontaneous swallowing in both dogs and humans. In humans, delta(9)-THC significantly reduced basal lower oesophageal sphincter pressure. These findings confirm previous observations in dogs and indicate that cannabinoid receptors are also involved in the triggering of TLESRs in humans.

Topics: Adult; Animals; Cannabinoid Receptor Agonists; Deglutition; Dogs; Dose-Response Relationship, Drug; Double-Blind Method; Dronabinol; Esophageal Sphincter, Lower; Female; Gastroesophageal Reflux; Humans; Hydrogen-Ion Concentration; Male; Middle Aged; Muscle Relaxation; Piperidines; Postprandial Period; Pyrazoles; Receptor, Cannabinoid, CB1; Rimonabant; Species Specificity; Young Adult

Aspiration of acid to the airway causes airway inflammation, and acid stress to the airway caused by gastroesophageal reflux disease (GERD) has been known as a potential mechanism of deteriorated asthma symptoms. However, the efficacy of the acid suppressive drugs, H(2)-receptor blockers (H(2) blocker) and proton pump inhibitors, on asthma symptoms and pulmonary functions remains controversial. We therefore designed the randomized prospective study to determine the efficacy of an H(2) blocker (roxatidine, 150 mg/day) and a proton pump inhibitor (lansoprazole, 30 mg/day) on asthma symptoms of 30 asthmatic patients with GERD. These patients were divided in the two groups (15 patients for each group) and treated with either roxatidine or lansoprazole. The diagnosis of GERD was established by the method of Los Angeles classification including mucosal minimum change of Grade M and questionnaire for the diagnosis of reflux disease (QUEST) score. The efficacy of acid suppressive drugs was evaluated by peak expiratory flow (PEF), asthma control questionnaire (ACQ) that evaluates the improvement of asthma symptoms, and forced expiratory volume in 1 second (FEV(1.0)). Lansoprazole, but not roxatidine, significantly improved PEF and ACQ scores (p < 0.05) with the improved QUEST scores. However, these acid suppressive drugs did not change the pulmonary function of FEV(1.0) in asthmatic patients. In conclusion, treatment with a proton pump inhibitor, lansoprazole, appears to be useful in improvement of asthma symptoms in asthmatic patients with GERD.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Administration, Oral; Adult; Aged; Asthma; Drug Evaluation; Female; Forced Expiratory Volume; Gastroesophageal Reflux; Humans; Lansoprazole; Male; Middle Aged; Omeprazole; Peak Expiratory Flow Rate; Piperidines; Prospective Studies; Proton Pump Inhibitors; Surveys and Questionnaires

We evaluated the efficacy and safety of a twice-daily dosage regimen of cisapride 20 mg in relieving the symptoms of mild-moderate gastroesophageal reflux disease (GERD) in patients with moderate intensity heartburn and no history of erosive esophagitis.. After a 2-wk, single-blind, placebo run-in period, 398 patients who continued to experience moderate intensity heartburn were randomized to either placebo (n = 196) or cisapride 20 mg (n = 202) twice daily for 4 wk.. Compared with placebo, cisapride significantly reduced scores for daytime and nighttime heartburn (p < 0.001), total regurgitation (p < 0.001), eructation (p = 0.04), and early satiety (p = 0.04). Cisapride 20 mg b.i.d. was also superior to placebo in reducing total use of rescue antacid medication (p < 0.001); reducing, in concordance analyses, daytime and nighttime heartburn with antacid usage (p < 0.001); increasing the percentage of heartburn-free days and antacid-free nights (p < 0.5); and increasing the percentage of patients self-rated as having minimal or better symptomatic improvement (p = 0.01). Cisapride 20 mg b.i.d. was well tolerated. The most common adverse event in the cisapride group was diarrhea, reported by 10% of patients, compared with an incidence of 4% in the placebo group.. Cisapride 20 mg b.i.d. was shown to be effective and safe for the short-term treatment of daytime and nighttime heartburn and for other symptoms associated with mild-moderate GERD.

Topics: Adolescent; Adult; Aged; Antacids; Cisapride; Eructation; Female; Gastroesophageal Reflux; Gastrointestinal Agents; Heartburn; Humans; Male; Middle Aged; Piperidines; Single-Blind Method

Cisapride is a prokinetic agent that facilitates gastrointestinal motility and is widely used for the treatment of gastroesophageal reflux disease (GERD) in adults and children. However, reports of ventricular proarrhythmia have been noted in patients taking cisapride, particularly in conjunction with other drugs that may inhibit hepatic metabolism of cisapride via the cytochrome P450 3A4 system.. We designed a prospective, blinded study to evaluate the effect of cisapride on ventricular repolarization in children with GERD.. We analyzed the electrocardiograms (ECGs) from 35 children (age 0.4 to 18 years, mean 5.2 years) including measurement of the resting QT interval (QTc), JT interval (JTc), as well as QT and JT interlead dispersion markers. Data from these patients were compared with ECGs from a control group of 1000 normal children.. Eleven (31%) of 35 patients receiving cisapride had a prolonged QTc (> or = 450 ms). The JTc was prolonged > or = 360 ms in 16 of 35 patients (46%). The mean QTc in the cisapride group was 428 +/- 35 ms and mean JTc was 336 +/- 35 ms. An increased QT or JT dispersion (> 70 ms) was seen in only 3 of 35 children. Of the 11 children with QTc prolongation, 2 had documented torsades de pointes ventricular tachycardia. Both patients were taking cisapride concomitantly with a macrolide antibiotic. All other patients were treated with either cisapride alone or in conjunction with other GERD agents, such as ranitidine or omeprazole.. Cisapride may cause prolongation of ventricular repolarization in children. There does not appear to be increased heterogeneity of repolarization or delayed depolarization in this small sample. The proarrhythmia may be exacerbated by medications that inhibit cytochrome P450 3A4 hepatic metabolism, overdosage, or mechanisms that result in decreased serum clearance. ECG intervals should be monitored in children maintained on cisapride, particularly when used in combination with other known QT-prolonging medications.

Topics: Adolescent; Child; Child, Preschool; Cisapride; Electrocardiography; Gastroesophageal Reflux; Gastrointestinal Agents; Humans; Infant; Long QT Syndrome; Piperidines; Prospective Studies; Single-Blind Method

To assess the efficacy and tolerance of sodium alginate compared to cisapride in patients suffering from reflux symptoms, without severe oesophagitis.. A total of 353 patients with symptoms of reflux oesophagitis (average age 40 years, 51% men, 33% smokers, 43% consumers of alcoholic drinks) were selected at random--180 treated with sodium alginate (4 sachets per day) and 173 treated with cisapride (5 mg four times a day) for 1 month, with a consultation every 2 weeks. Patients with severe oesophagitis or with predominant symptoms of motor dyspepsia were not included. The principal assessment criterion was the change in the severity of the reflux symptoms as evaluated using a visual analogue scale (VAS) at 4 weeks (extremes 0-100). The secondary criteria were the VAS score at 2 weeks, the number of patients considered as treatment failures, the number of episodes of pain, the impact of the reflux on daily activities and on sleep, and an estimate of costs. The statistical analyses were planned without any knowledge of the treatments allocated and on an intention-to-treat basis.. There was no difference between the groups at the time of randomization. There were differences in the VAS in favour of the alginate at 2 weeks (29 +/- 22 vs. 35 +/- 25, P = 0.01) at 4 weeks (13 +/- 17 vs. 20 +/- 23, P = 0.001), for the number of episodes at 4 weeks (2 +/- 2 vs. 3 +/- 4, P = 0.001), for pain interfering with daily activities (3% vs. 10%, P = 0.009), for pain disturbing sleep (2% vs. 9%, P = 0.004), and for the proportion of patients considered as treatment failures (11% vs. 24%, P < 0.001). Compliance was similar in the two groups. The average cost for 1 month was lower for alginate (130 fr.) than for cisapride (175 fr.).. Sodium alginate is more effective, and costs less, than cisapride for the treatment of symptoms presented by patients suffering from reflux without severe oesophagitis.

Topics: Adult; Alginates; Anti-Ulcer Agents; Cisapride; Female; France; Gastroesophageal Reflux; Glucuronic Acid; Hexuronic Acids; Humans; Male; Middle Aged; Piperidines

Partial posterior fundoplication improves esophageal peristalsis in patients with gastroesophageal reflux disease (GERD) associated with poor esophageal body function. The aim of this study was to investigate whether postoperative administration of cisapride enhances the effect of surgery on esophageal peristalsis. Laparoscopic partial posterior fundoplication was performed on 34 consecutive GERD patients with poor esophageal body motility. These patients were randomized in groups without and with postoperative treatment with cisapride 20 mg twice daily for six months. Esophageal manometry was performed preoperatively and six months following surgery. Esophageal body function improved significantly following partial posterior fundoplication without or with postoperative treatment with cisapride. However, this effect was more pronounced in the group of patients receiving cisapride. Partial posterior fundoplication combined with postoperative treatment with cisapride should be the therapy of choice in GERD patients with poor esophageal body motility.

Topics: Adult; Aged; Cisapride; Esophagus; Female; Fundoplication; Gastroesophageal Reflux; Gastrointestinal Agents; Humans; Male; Middle Aged; Muscle Contraction; Parasympathomimetics; Piperidines; Severity of Illness Index; Treatment Outcome

The HT4-agonist Cisapride (CIS) and the peripheral D2-antagonist Domperidone (DOMP) have distinct prokinetic actions. We compared their clinical efficacy in 127 dyspeptic patients. Patients with upper abdominal complaints of > 1 month duration, who had a normal UGE were allocated to the REFLUX-group (RG), (predominance of heartburn, acid regurgitation or retrosternal pain) or if devoid of this specific symptomatology to the DYSPEPSIA-group (DG) In a double-blind randomised fashion and allocated to 10 mg CIS or 20 mg DOMP qid (RG) or tid (DG) for 1 month and followed-up for further 2 months. In RG (N = 43, p < 0.05) the response rates were clearly in favour of CIS, but not in DG (N = 84). In RG DOMP was more effective against nausea. The benefit of both therapies was largely maintained in the follow-up period. Cisapride and domperidone were effective in the treatment of dyspepsia. Cisapride was more effective than domperidone in the REFLUX-Group.

Topics: Adult; Anti-Ulcer Agents; Cisapride; Domperidone; Double-Blind Method; Dyspepsia; Female; Follow-Up Studies; Gastroesophageal Reflux; Gastrointestinal Agents; Humans; Male; Middle Aged; Piperidines; Treatment Outcome

Few studies have specifically addressed the management of the symptoms of gastro-oesophageal reflux disease, and there are no comparative data in this respect for acid pump inhibitors and prokinetic agents.. Following endoscopy 424 patients presenting with heartburn as the predominant symptom of gastro-oesophageal reflux disease were randomized to treatment with omeprazole 20 or 10 mg once daily, or cisapride 10 mg four times daily, in a double-blind, double-dummy, parallel group, multicentre study. Symptoms and quality of life were assessed at 4 weeks. Patients still experiencing heartburn continued therapy for a further 4 weeks and the assessments were repeated.. At 4 weeks, heartburn was resolved in 65% (95% CI: 57-73%), 56% (48-64%) and 41% (32%-49%) of patients treated, respectively, with omeprazole 20 mg and 10 mg once daily, and cisapride. Both omeprazole doses were significantly more effective than cisapride (P < 0.01). The same order of efficacy was observed regardless of the presence of erosive oesophagitis. Regurgitation and epigastric pain also improved to a greater degree with omeprazole than with cisapride. Quality of life was improved in all treatment groups, and the improvement in the reflux dimension of the Gastrointestinal Symptom Rating Scale (GSRS) score was significantly different between groups (P = 0.002).. Omeprazole 20 or 10 mg once daily is significantly more effective than cisapride in the resolution of heartburn, regardless of the presence of erosive oesophagitis, and this is accompanied by an improvement in patient quality of life.

Topics: Adult; Anti-Ulcer Agents; Cisapride; Double-Blind Method; Enzyme Inhibitors; Esophagitis; Female; Gastroesophageal Reflux; Heartburn; Humans; Male; Middle Aged; Omeprazole; Piperidines; Proton Pump Inhibitors; Quality of Life

Gastroesophageal reflux is a common condition that in infants may lead to serious complication. This study assessed the efficacy and safety of oral cisapride suspension in the treatment of children 6 weeks to 2 years old with daily regurgitant reflux.. A randomized, prospective, double-blind, placebo-controlled clinical trial was conducted at three study sites. After a 1 week baseline assessment, 45 infants 6 weeks to 2 years old were randomized to a double-blind trial in which they received a 6 week course of cisapride (0.2 mg/kg q6h) or a placebo suspension. Efficacy was assessed with 24 hour esophageal pH monitoring, esophageal manometry, and esophageal biopsy before and after the treatment period. A diary of regurgitation frequency and severity was kept by the parents. Safety was assessed by adverse event monitoring and standard laboratory measurements.. Compared with placebo, cisapride significantly (p < 0.05) reduced the mean duration of upright and supine reflux episodes. Compared to baseline, cisapride significantly reduced the mean duration of the longest reflux episode, and placebo increased the mean number of reflux episodes longer than 5 minutes. Cisapride was not significantly different from placebo for the following mean measurements: percent of total time pH < 4, number of reflux episodes, lower esophageal sphincter pressure, swallow pressure, regurgitation frequency or global evaluation scores.. Cisapride is a safe, well tolerated prokinetic agent that improves the esophageal clearance of refluxed gastric acid in children under the age of 2 years.

Topics: Biopsy; Cisapride; Double-Blind Method; Esophagus; Gastroesophageal Reflux; Gastrointestinal Agents; Humans; Hydrogen-Ion Concentration; Infant; Manometry; Piperidines; Placebos; Pressure; Prospective Studies

Successful treatment of gastro-oesophageal reflux disease (GORD) has traditionally been assessed as healing of reflux oesophagitis, which may not be relevant in patients with moderate disease. In these patients symptom relief and patient satisfaction with therapy are of fundamental importance. Cisapride has well-documented prokinetic effects and may be well suited for long-term therapy of GORD, but its effectiveness in purely symptomatic treatment is unknown. We therefore compared two dosage regimens of cisapride with placebo over a period of 6 months in patients with evidence of gastrooesophageal reflux, initially treated with antisecretory medication, with regard to maintaining symptom relief and satisfaction with treatment.. Five hundred and thirty-five patients with reflux oesophagitis grade 1 (n = 293) or 2 (n = 124) or with no reflux oesophagitis but pathologic 24-h pH-metry (n = 118) achieved satisfactory symptom relief with an H2-receptor antagonist or proton pump inhibitor within 4-8 weeks. In a double-blind randomized, parallel-group study, they were then treated with cisapride, 20 mg at night or 20 mg twice daily, or placebo and followed up for a maximum period of 6 months. Relapse was defined as dissatisfaction with therapy or an average consumption of more than two antacid tablets a day.. Median time to relapse was 63 days for cisapride, 20 mg twice daily; 59 days for cisapride, 20 mg at night; and 49 days for placebo. Time to relapse was not significantly different (P = 0.09). Presence and grade of oesophagitis at base line, type of therapy before randomization, and pattern of non-reflux symptoms at base line did not influence these findings significantly.. The study indicates that cisapride is of limited value in maintenance therapy of GORD in patients in whom symptom relief has been accomplished with potent antisecretory medication. This 'step-down' approach to therapy seems disadvantageous in the long-term therapy of GORD.

Topics: Abdominal Pain; Cisapride; Constipation; Diarrhea; Drug Administration Schedule; Endoscopy; Esophagitis, Peptic; Female; Flatulence; Gastroesophageal Reflux; Gastrointestinal Agents; Heartburn; Humans; Male; Middle Aged; Piperidines; Recurrence; Remission Induction; Severity of Illness Index; Time Factors

Prospective survey of the effects of cisapride on QTc interval in neonates given cisapride.. QTc interval was determined just before and 2.9 (0.9) days after outset of the treatment in 49 neonates treated with cisapride between 1 August 1995 and 29 February 1996.. Cisapride significantly increased QTc interval (p = 0.0001), and this was higher when birthweight or gestational age were lower. The prolongation of QTc interval above the arbitrary value of 0.450 (n = 7) was clinically asymptomatic and was significantly more common in the infants born with a gestational age < or = 33 weeks (n = 6).. The findings indicate that cisapride accumulates in less mature neonates. Further pharmacokinetic studies are needed.

Topics: Cisapride; Electrocardiography; Gastroesophageal Reflux; Gestational Age; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Male; Piperidines; Prospective Studies; Serotonin Antagonists

Both gastric acid and duodenal juice have been implicated in Barrett's oesophagus. The aim of this study was to look at duodenal reflux in the oesophagus together with motility characteristics in a group of patients with Barrett's oesophagus and compare them with a mild oesophagitis group and to assess the effect of cisapride on any abnormalities.. A prospective study comparing the two groups of patients was carried out.. Twenty patients with histologically proven Barrett's oesophagus and 20 patients with Savary-Miller grade 2 oesophagitis were studied. Standard oesophageal manometric measurements were carried out and on a separate occasion duodenogastro-oesophageal reflux (DGOR) was measured over a 4-h period using a sodium ion selective electrode. Patients with more than 5% DGOR were given cisapride (10 mg four times daily) and the studies repeated after 7 days of treatment.. Barrett's patients showed more DGOR, 12.2% of the study time compared to 5.1% in the mild oesophagitis group, P = 0.012, but manometric findings were not significantly different. Sixteen patients were treated with cisapride. DGOR was reduced in 8 out of 12 Barrett's patients and 2 out of 4 oesophagitis patients, and proximal amplitude and distal oesophageal pressures were significantly elevated (P = 0.05 and P = 0.03, respectively).. Monitoring of sodium ions in the oesophagus shows that patients with Barrett's oesophagus have significantly more DGOR than patients with uncomplicated oesophagitis and cisapride may be effective in removal of this reflux.

Topics: Adult; Aged; Barrett Esophagus; Bile Acids and Salts; Cisapride; Duodenogastric Reflux; Electrodes; Esophagus; Female; Gastroesophageal Reflux; Gastrointestinal Agents; Humans; Intubation, Gastrointestinal; Male; Manometry; Middle Aged; Monitoring, Physiologic; Piperidines; Prospective Studies; Sodium

Medical treatment of duodenogastroesophageal reflux in postgastrectomy patients has been disappointing. Using ambulatory esophageal bilirubin monitoring, we evaluated the efficacy of cisapride in this disorder. Ten chronically symptomatic partial gastrectomy patients (5 Billroth I, 5 Billroth II; 8 men; average age 57) with duodenogastroesophageal reflux were randomized to four weeks of either placebo or cisapride (20 mg four times a day) in a double-blind crossover study. Significantly improved patients continued to take cisapride for an additional four months. Duodenogastroesophageal reflux was assessed at baseline and after four weeks on each therapy. Daily diary recorded symptoms and mean monthly scores were determined. Global symptom improvements were assessed at the end of each treatment period. Compared to placebo, cisapride significantly (P < 0.05) decreased duodenogastroesophageal reflux. Overall symptom improvements were assessed at the end of each treatment period. Compared to placebo, cisapride significantly (P < 0.05) decreased duodenogastroesophageal reflux. Overall symptoms improved in 70% of patients on cisapride compared to 10% on placebo (P < 0.01). Mean monthly scores significantly (P < 0.05) improved for abdominal pain, regurgitation, and belching. These symptoms remained improved after four months of chronic therapy. We conclude that cisapride significantly reduces duodenogastroesophageal reflux and results in short- and long-term symptom improvements in postgastrectomy patients and that cisapride offers the first successful medical therapy for duodenogastroesophageal reflux in postgastrectomy patients.

Topics: Anti-Ulcer Agents; Bilirubin; Cisapride; Cross-Over Studies; Double-Blind Method; Duodenogastric Reflux; Female; Gastroesophageal Reflux; Gastrointestinal Motility; Humans; Hydrogen-Ion Concentration; Male; Manometry; Middle Aged; Monitoring, Ambulatory; Piperidines; Postgastrectomy Syndromes; Time Factors; Treatment Outcome

In a randomized multicentric trial the effect of sleeping with the bed-head raised was studied in inpatients with reflux symptoms. All patients underwent an endoscopic and pH-metric examination. As a result from the diagnostic procedures three groups were formed: group 1 - refluxlike dyspepsia (endoscopic and pH-metric examination normal), group 2 - reflux disease without esophagitis (endoscopy normal, pH-metric examination abnormal), group 3 - refluxesophagitis (endoscopy abnormal). All patients were randomly assigned to either sleeping with horizontal bed-head or having the bed-head raised (15 cm). Furthermore, the patients in group 3 were put on treatment with omeprazole (20 mg twice a day) those in group 2 were treated with a procinetic drug (cisapride 30 mg). The patients in group 1 had no drug therapy. However, antacids were allowed in all patients. For a two-week-period reflux symptoms and use of antacids were registered. No difference was seen in the symptom-score or use of antacids. Also sub-group analysis (sex, age, body-mass-index, severity of esophagitis and nocturnal reflux) did not reveal any impact of sleeping with the bed-head raised on reflux symptoms or use of antacids.

Topics: Adult; Antacids; Anti-Ulcer Agents; Cisapride; Combined Modality Therapy; Esophagitis, Peptic; Female; Gastric Acidity Determination; Gastroesophageal Reflux; Humans; Male; Middle Aged; Omeprazole; Piperidines; Posture; Prospective Studies; Treatment Outcome

Salivary drooling is a common and debilitating problem in cerebral palsy (CP). We hypothesised that gastro-oesophageal reflux (GOR) may exacerbate drooling by stimulation of the oesophago-salivary reflex. The aim of our study was to assess the role of GOR in children with CP and severe drooling. Twenty-four children with CP and severe drooling underwent oesophageal pH monitoring (N = 23) or oesophagoscopy (N = 1). Nine had pathological GOR and were enrolled in a double blinded, placebo controlled cross-over trial of medical antireflux therapy (ranitidine plus cisapride) versus placebo. Drooling was measured by semi-quantitative observation (drooling quotient) and a questionnaire-based scoring system (rated by the child's caregivers). Mean drooling quotients and scores for drooling severity and frequency were not significantly different between active medication and placebo. In our study, treatment of pathological GOR did not improve salivary drooling in children with CP.

Topics: Adolescent; Cerebral Palsy; Child; Child, Preschool; Cisapride; Esophagus; Female; Gastroesophageal Reflux; Histamine H2 Antagonists; Humans; Hydrogen-Ion Concentration; Male; Parasympathomimetics; Piperidines; Ranitidine; Salivation; Severity of Illness Index; Sialorrhea

To compare the efficacy of the prokinetic drug cisapride and the antisecretory agent ranitidine in relieving symptoms of functional dyspepsia, as well as their effect on the recurrence of symptoms after the discontinuation of treatment.. A randomized double-blind parallel-group trial of cisapride 30 mg daily and ranitidine 300 mg daily given for 2, 4 or 8 weeks, followed by a 4-week drug-free follow-up of the patients with a good or excellent response. Rescue antacid tablets were allowed only if pain was unbearable.. A total of 203 patients (99 cisapride, 104 ranitidine) with symptoms of functional dyspepsia for more than 4 weeks, after the exclusion of organic disease by endoscopy and sonography or radiology.. Cisapride and ranitidine improved the symptoms of diffuse epigastric pain, postprandial epigastric fullness, epigastric distension, belching, heartburn, regurgitation, and nausea when compared with baseline. Pain at night and gastric discomfort also greatly improved. Cisapride produced a greater reduction in epigastric pain (P = 0.07) and epigastric distension (P = 0.03) scores than ranitidine. Both drugs were equally effective in reducing the concomitant reflux-like symptoms of heartburn and regurgitation. At week 8, 87% of cisapride patients versus 61% of ranitidine patients had an excellent or good result. The deterioration of symptoms during the follow-up phase was limited in both groups. However, after the withdrawal of medication there was a greater reduction in scores in the cisapride group than in the ranitidine group for diffuse epigastric pain (P = 0.05), epigastric distension (P = 0.002), the cluster of six symptoms of epigastric discomfort (P = 0.05), and the cluster of all nine upper gastrointestinal symptoms (P = 0.06). Adverse events occurred in 15 cisapride patients and 18 ranitidine patients, and two of the ranitidine patients were withdrawn from treatment.. Although cisapride and ranitidine both improved the symptoms of functional dyspepsia, cisapride was superior to ranitidine, particularly on the combined evaluation of the response to treatment and the recurrence of symptoms.

Topics: Adult; Antacids; Anti-Ulcer Agents; Cisapride; Double-Blind Method; Dyspepsia; Eructation; Female; Follow-Up Studies; Gastroesophageal Reflux; Gastroscopy; Heartburn; Humans; Male; Nausea; Piperidines; Ranitidine; Recurrence

To perform a further Cox proportional hazards logistic regression analysis of data from two large-scale placebo-controlled trials with cisapride as maintenance treatment in reflux disease.. Analysis of each of the two databases, allowing the model to operate freely, led to the identification of a number of unexpected putative predictors of outcome in the 6 to 12 months following initial healing of oesophagitis with an H2-receptor antagonist or omeprazole. This allowed us to delineate more accurately the patient population that is likely to respond to long-term continuous treatment with low or standard dose cisapride. The analysis revealed that symptom severity may be more useful than endoscopic severity in predicting relapse or in guiding therapy. Reflux oesophagitis outcome is particularly poor in the presence of treatment-recalcitrant symptoms or severe mucosal damage. Analysis showed cisapride to be effective in the maintenance treatment of patients with non-refractory symptoms, irrespective of the initial severity of oesophagitis, the healing agent used, or a history of previous endoscopic relapses.

Topics: Cisapride; Esophagitis, Peptic; Gastroesophageal Reflux; Humans; Piperidines; Prognosis; Prospective Studies

To evaluate the safety and efficacy of cisapride in patients with gastroesophageal reflux disease.. Patients (N = 177) were randomized to double-blind treatment with cisapride (10 or 20 mg q.i.d.) or placebo for 12 wk. Efficacy was determined by pre- and poststudy endoscopies, symptom assessments by patient and physician, and Maalox consumption. Safety evaluations included vital signs, electrocardiograms, clinical laboratory tests, and reports of adverse events.. Cisapride 10 mg significantly reduced daytime and nighttime heartburn at 4 wk compared with placebo. Cisapride 20 mg reduced both daytime and nighttime heartburn at 4, 8, and 12 wk, compared with placebo, and was also significantly superior to the 10-mg dose at 12 wk. The percent of patients with endoscopic healing was significantly higher with cisapride 20 mg than with placebo [healing: 51 vs 36% (p < or = 0.044)]. Maalox usage declined significantly with cisapride 20 mg compared with placebo. No clinically significant changes in safety variables occurred with cisapride. The most frequently reported adverse events in the cisapride group were diarrhea, headache, and sinusitis.. Cisapride 10 and 20 mg q.i.d. were safe and well tolerated in a population of patients with mild-to-moderate gastroesophageal reflux disease. Both symptoms and endoscopic grade improved after 12 wk of treatment with cisapride 20 mg q.i.d.

Topics: Aluminum Hydroxide; Antacids; Anti-Ulcer Agents; Cisapride; Double-Blind Method; Drug Administration Schedule; Drug Combinations; Esophagitis, Peptic; Esophagoscopy; Female; Gastroesophageal Reflux; Heartburn; Humans; Magnesium Hydroxide; Male; Middle Aged; Piperidines; Time Factors

The severity of gastro-oesophageal reflux disease is generally considered to be related to the extent of oesophageal acid exposure. Current therapies include antisecretory and prokinetic agents. We compared two of these, ranitidine and cisapride, in their ability to lower oesophageal acid exposure in patients with erosive oesophagitis.. Seven patients with Savary-Miller's grade II-IV oesophagitis and with oesophageal contact time > or = 8% were studied. Mean lower oesophageal sphincter pressure was 4.6 mmHg. Oesophageal acid contact time was 25.6 +/- 5.6%. Each patient received ranitidine 150 mg b.d., ranitidine 150 mg q.d.s., or cisapride 10 mg q.d.s. in a randomized 3-way cross-over design. Intra-oesophageal pH was monitored during 24 h for each of these treatments in a controlled hospital environment, while consuming a high fat, high calorie diet.. Cisapride and ranitidine at both doses decreased the acid contact time and the number of reflux episodes. However, a minority of patients treated with ranitidine, and none with cisapride, diminished their oesophageal acid contact time to a normal value of < 5%. No treatment significantly decreased nocturnal acid exposure.. In patients with severe gastro-oesophageal reflux disease both cisapride and ranitidine demonstrably lower oesophageal acid exposure, but neither therapy predictably normalizes it.

Topics: Adult; Anti-Ulcer Agents; Cisapride; Esophagitis, Peptic; Female; Gastric Acid; Gastric Acidity Determination; Gastroesophageal Reflux; Humans; Male; Middle Aged; Piperidines; Ranitidine

Several studies have shown the relationship between gastro-oesophageal reflux, bronchial asthma and chronic nocturnal cough and this should not be neglected, particularly in patients who present an unfavourable development in spite of conventional treatment. For diagnosis of gastroesophageal reflux, amongst other investigations, esophageal gammagraphy of swallowing, that detects alterations in the mobility of the oesophagus, secondary to a possible oesophagitis. The objective of this study was to evaluate the clinical progress and gammagraphy of a group of children with chronic predominantly nocturnal cough (with or without bronchial asthma) with initially pathological esophageal gammagraphy, after three months of treatment with gastrokinetic drugs (cisapride against domperidone) and postural dietetic limits, in comparison with a reference group who, although having followed the limits in question had not received the pharmacological treatment. From the clinical viewpoint, cough disappeared in 64.5% of cases without significant statistical differences between the two groups. Gammagraphy became normal in 20/55 cases, improved in 10/55 cases and was unchanged in 25/55. Although there was no significant difference, gammagraphy development was better in children who received domperidone. The agreement between clinical progress and gammagraphy was 60% with a large number of false positives in the gammagraphy. We believe that the simple introduction of the postural-dietetic measures may improve the clinical control in the type of patients who present with a chronic nocturnally predominant cough that does not yield to conventional treatment.

Topics: Adolescent; Child; Child, Preschool; Cisapride; Cough; Domperidone; Female; Gastroesophageal Reflux; Humans; Infant; Male; Piperidines; Prospective Studies; Radionuclide Imaging

Forty patients with gastro-oesophageal reflux disease and oesophagitis, documented by endoscopy (grades I to III by the Savary-Miller classification) were randomized to participate in a comparative double-blind trial to receive cisapride (10 mg q.d.s.) or ranitidine (150 mg b.d.) for an 8-week period. Upper gastrointestinal endoscopy was performed immediately before the entry to the trial and after the 8-week period at the completion of the trial. The evaluable cohort included 37 patients who completed the trial, 18 in the cisapride group and 19 in the ranitidine group. Three patients were withdrawn from the trial; one on ranitidine developed severe anaphylactic reaction, one on cisapride severe dizziness and one on cisapride did not wish to continue on the trial. The results of the trial, regarding symptomatic and endoscopic improvement were comparable in the two groups. Both drugs were effective in controlling symptoms, such as acid regurgitation, retrosternal pain, retrosternal burning, epigastric fullness and discomfort (pain, burning, sense of pressure) and resulted in endoscopic healing of oesophagitis. With few exceptions, symptoms remained in remission 1 month after treatment in the majority of patients. Globally, both drugs were tolerated comparably, and adverse effects other than those which resulted in the withdrawal from the trial were minimal in both groups. The results of this trial indicate that cisapride and ranitidine, although of different pharmacological action, are comparable in their therapeutic effect in symptomatic improvement and endoscopic healing in patients with mild to moderate gastro-oesophageal reflux disease.

Topics: Adult; Anti-Ulcer Agents; Cisapride; Double-Blind Method; Female; Gastric Acid; Gastroesophageal Reflux; Humans; Male; Middle Aged; Piperidines; Ranitidine

The purpose of a single-subject randomized trial is to assess objectively the efficacy of a specific therapeutic intervention in an individual patient. Treatment is randomly alternated with placebo over a number of study periods. Specific outcome measures are recorded blindly and later compared via paired statistical analysis. Single-subject trials have long been successfully performed in adults, but rarely in children. We present single-subject trials of two pediatric patients done to assess the effect of cisapride on symptoms arising from gastroesophageal reflux. In the first patient, the drug affected neither vomiting nor gagging, although stool frequency increased. Since the symptoms of concern were unaffected, cisapride was discontinued. In the second patient, use of cisapride led to a significant decrease in vomiting and wheezing; the drug was therefore incorporated into the therapeutic regimen. Single-subject randomized trials are inexpensive and simple and can be used by the family physician, pediatrician, or pediatric surgeon in daily practice. They permit the rational use of effective therapy and the abandonment of ineffective measures.

Topics: Adult; Child; Child, Preschool; Cisapride; Gagging; Gastroesophageal Reflux; Humans; Infant; Male; Piperidines; Respiratory Sounds; Treatment Outcome; Vomiting

The efficacy and tolerability of Cisapride effervescent granules for treatment of gastroesophageal reflux disease were compared to a metoclopramide-dimeticone combination. The double-blind study was performed in two groups of 10 patients each who received 3 sachets daily of either drug for 8 weeks. Cisapride effervescent granules induced a statistically significant improvement of 75% of symptoms (6/8) while this improvement was obtained with the reference drug for only 60% (3/5). Statistical evaluation showed Cisapride effervescent granules to be more effective than the reference drug for 2 of 5 evaluable symptoms; mean global improvement amounted to 83 vs 58%. Final physician opinion was more favorable to Cisapride effervescent granules than to the reference drug (p < 0.005). Treatment did not have to be withdrawn nor were clinically significant changes of laboratory values observed. Both drugs were found to be well tolerated without differences between the two groups. Three patients treated with Cisapride effervescent granules complained of short-lasting mild abdominal discomfort the relations of which to the drug was doubtful, and which subsided spontaneously without need to withdraw treatment or to apply other types of therapy.

Topics: Adult; Aged; Cisapride; Double-Blind Method; Drug Combinations; Drug Tolerance; Female; Gastroesophageal Reflux; Humans; Male; Metoclopramide; Middle Aged; Piperidines; Powders; Serotonin Antagonists; Simethicone; Time Factors

Prokinetic agents are being used increasingly in medical therapy for gastro-oesophageal reflux disease (GERD). This study examined the effect of 10 mg q.d.s., oral cisapride, or placebo, taken for 12 weeks, on 48 patients with symptoms and endoscopic evidence of GERD. Objective evaluation of benefit was obtained by endoscopy and biopsy, oesophageal manometry, acid reflux provocation test and 24-h oesophageal pH monitoring. Cisapride significantly increased lower oesophageal sphincter pressure (P = 0.003) against baseline and also against placebo, in patients (n = 9) with an hypotensive lower oesophageal sphincter pressure (P < 0.01). The frequency of dyspeptic symptoms was significantly improved in the cisapride group (P = 0.03). Antacid intake, global evaluation of symptoms and a VAS score for symptoms were all better than placebo but failed to reach significance (global evaluation by patients, P = 0.07). Overall, there was no significant improvement in oesophagitis at either 6 weeks (P < 0.05 > 0.3) or 12 weeks (P = 0.07). However, if patients with grades I and II oesophagitis at entry were excluded, cisapride had a significantly greater effect than placebo, 6 weeks (P = 0.05), 12 weeks (P = 0.04). In those with oesophageal ulceration, cisapride was significantly more effective than placebo in inducing healing. Gastro-oesophageal reflux was very variable on both 24-h pH monitoring and acid reflux provocation test. In spite of a 50% decrease in acid exposure on 24-h pH monitoring (cisapride group, mean % pH < 4 day: entry 18.9%, 12 weeks 9.6%), there were no significant intra- or intergroup differences for percentage of time < pH 4, or frequency and duration of episodes, neither pre- or post-prandially, day or night, except for the number of post-prandial episodes during acid reflux provocation tests, which decreased significantly more with cisapride than with placebo (P < 0.05). Thus, oral cisapride when taken for 12 weeks promoted healing of oesophagitis and improved symptoms in patients with GERD; although an increase in lower oesophageal sphincter pressure was observed and a reduction in acid reflux was measured, no significant decrease of acid exposure was seen.

Topics: Adult; Aged; Cisapride; Double-Blind Method; Endoscopy, Digestive System; Esophagitis, Peptic; Female; Gastroesophageal Reflux; Humans; Hydrogen-Ion Concentration; Male; Manometry; Middle Aged; Piperidines; Serotonin Antagonists

The results of a multicentre inquiry started in 1988 in reference centres of sudden infant death are presented. This study concerns the sudden and unexplained mortality of infants under 1 year of age who were treated with atropinics for an alleged risk of sudden death. The 7,851 infants involved were divided into 2,605 siblings, 1,067 premature babies and 4,179 infants who experienced malaises. Only one of the 2,034 infants treated with atropinics (385 siblings, 435 prematures, 1,214 with malaise) died, as opposed to 27 deaths among the 5,817 infants who where not treated (10 deaths among 2,220 siblings, 6 among 632 premature and 11 among 2,965 infants with malaise); P = 0.005. These results are encouraging, but they suffer from the limitations and biases inherent in all large inquiries. They certainly do not allow us to conclude without reservation that vagal hyperreflectivity is the mechanism responsible for sudden infant death and that atropinics must be systematically given to all infants at risk. Wide and randomized prospective studies are highly desirable in this particular field.

Topics: Drug Evaluation; Female; Gastroesophageal Reflux; Humans; Infant; Infant, Newborn; Male; Parasympatholytics; Piperidines; Risk Factors; Sudden Infant Death; Surveys and Questionnaires

Topics: Alginates; Aluminum Hydroxide; Antacids; Bicarbonates; Cisapride; Drug Combinations; Drug Therapy, Combination; Galactans; Gastroesophageal Reflux; Humans; Infant; Mannans; Piperidines; Plant Gums; Polysaccharides; Serotonin Antagonists; Silicic Acid; Sodium Bicarbonate

We compared the efficacy of the prokinetic agent cisapride with that of Gaviscon (an alginate/alkaline compound) plus Carobel (carob seed flour) in the treatment of gastrooesophageal reflux (GOR). Fifty infants with confirmed GOR received either oral cisapride (0.8 mg/kg/day) or Gaviscon plus Carobel for one month in a randomised, parallel group study. Parental evaluations, diary scores, and 24 hour lower oesophageal pH recordings before and at the end of each treatment were compared. In the cisapride group 14/26 (53%) were considered better by their parents compared with 19/24 (79%) of those who received Gaviscon plus Carobel. Diary scores, range (0.00-1.00), improved in both groups with the median change being greater in the Gaviscon plus Carobel group (-0.21) than the cisapride group (-0.15). Five of 17 pH variables had significantly improved from baseline in infants who had received cisapride compared with 11/17 in those receiving Gaviscon plus Carobel. However, unpaired analysis of diary and pH data showed no significant differences between the two groups. We conclude that first line treatment of GOR with cisapride is no more effective than conventional treatment with Gaviscon plus Carobel.

Topics: Alginates; Aluminum Hydroxide; Antacids; Bicarbonates; Cisapride; Drug Combinations; Drug Therapy, Combination; Galactans; Gastroesophageal Reflux; Humans; Hydrogen-Ion Concentration; Infant; Mannans; Piperidines; Plant Gums; Polysaccharides; Serotonin Antagonists; Silicic Acid; Sodium Bicarbonate

Some patients with gastro-oesophageal reflux disease have delayed gastric emptying. This study investigates the effect of cisapride on gastric emptying in 34 patients with proved reflux and delayed gastric emptying of solids. They were enrolled in a double blind controlled crossover study. Placebo or cisapride (10 mg) tablets were given three times a day for three days followed by further assessment of gastric emptying. The protocol was repeated with the crossover tablet. Gastric emptying was assessed by a dual radionuclide technique. The percentage of a solid meal remaining in the stomach at 100 minutes (% R100 minutes) and the time taken for 50% of the liquid to empty (T50 minutes) were calculated and analysed by the Wilcoxon matched pairs signed ranks test and expressed as medians (ranges). For gastric emptying of solids the initial % R100 minutes (70 (60-100)%) was not significantly different from placebo (71 (35-100)%). After cisapride treatment a significant acceleration (p less than 0.001) in gastric emptying occurred (% R100 minutes, 50.5 (28-93)%). Similarly with gastric emptying of liquids, the initial T50 minute value was 26.5 (12-82) minutes, after placebo the value was 28 (11-81) minutes, but this was significantly accelerated with cisapride (p less than 0.03) to 22.5 (6-61) minutes. The acceleration in gastric emptying occurred in the proximal portion of the stomach for gastric emptying of both solids and liquids suggesting that this is the principal site of action of cisapride. We conclude that cisapride significantly accelerates gastric emptying of both solids and liquids in patients with gastro-oesophageal reflux disease and delayed gastric emptying.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Cisapride; Double-Blind Method; Female; Gastric Emptying; Gastroesophageal Reflux; Humans; Male; Manometry; Middle Aged; Piperidines; Serotonin Antagonists; Stimulation, Chemical; Time Factors

Twenty-nine infants (2-4 months old), with pathological gastroesophageal reflux assessed by 24-h esophageal pH monitoring, were studied. Cisapride or placebo was randomly added to positional treatment, prone-antiTrendelenburg position, which was applied to all infants. The pH monitoring was repeated after 13-16 days of treatment and revealed a significant improvement in both groups for most parameters. But the number of reflux episodes lasting longer than 5 min and the total number of reflux episodes had not decreased significantly in the placebo group. Only in the number of reflux episodes lasting longer than 5 min was improvement during treatment significantly greater in the cisapride group. This suggests cisapride both prevented reflux and improved esophageal clearance. These results suggest that in addition to other therapeutic measurements, such as positional treatment (which was previously demonstrated to be effective in this age group), cisapride might be of benefit in the treatment of gastroesophageal reflux disease.

Topics: Cisapride; Gastroesophageal Reflux; Gastrointestinal Contents; Humans; Hydrogen-Ion Concentration; Infant; Piperidines; Pronation; Serotonin Antagonists

Controlled studies showed that cisapride is effective in non-ulcer dyspepsia. Its prokinetic properties are not complicated by dopamine inhibition. In our study the dose of 5 mg t.i.d. was adequate for the treatment of patients with gastric symptoms, while for patients with reflux symptoms the preferred dose is 10 mg t.i.d. cisapride. The average improvement after 1 month of treatment was 68%. Additional medication with antacids was not of benefit. Side effects such as abdominal cramps or diarrhea were minimal (less than 4%). 1071 patients were selected according to the principles described by Talley et al. in 1987. This method was well accepted by investigators and patients and is recommended for similar studies.

Topics: Antacids; Cisapride; Dose-Response Relationship, Drug; Dyspepsia; Female; Gastroesophageal Reflux; Humans; Male; Middle Aged; Piperidines; Serotonin Antagonists

The effect of cisapride, a new gastrointestinal prokinetic drug, on oesophageal motility and acid reflux was studied in 14 children with gastro-oesophageal reflux disease, receiving either placebo or cisapride 0.15 mg/kg intravenously. Cisapride significantly (p less than 0.01) increased the lower oesophageal sphincter pressure (+124%), the amplitude (+84%) and duration (+24%) of oesophageal peristaltic waves, whereas the placebo treatment did not produce any changes. Subsequently, all 14 children underwent 24 hour oesophageal pH-monitoring before and after four weeks of treatment with oral cisapride 0.2 mg/kg tid given in addition to postural therapy and thickened feedings. The 24 hour intraoesophageal pH recordings and symptomatic scores were compared with those of 10 control patients treated only by postural therapy and thickened feedings. When compared with baseline pH data, cisapride significantly reduced the oesophageal acid exposure time, the mean duration of each reflux episode, the duration of the longest reflux episode and the number of long lasting reflux episodes; the number of reflux episodes was not influenced. The effect of cisapride was marked and consistent during fasting and sleep periods. Oesophageal acid exposure was reduced more significantly in patients given cisapride (-61%) than in controls (-24%; p less than 0.001). Symptom improvement was greater after four weeks of cisapride treatment (score reduction: 61%) than after postural and dietary therapy alone (score reduction: 42%; p less than 0.01). No adverse effects occurred. These findings suggest that cisapride is a valuable drug in the management of gastro-oesophageal reflux disease in children.

Topics: Administration, Oral; Child, Preschool; Cisapride; Clinical Trials as Topic; Double-Blind Method; Esophagus; Gastroesophageal Reflux; Gastrointestinal Motility; Humans; Hydrogen-Ion Concentration; Infant; Injections, Intravenous; Peristalsis; Piperidines

Topics: Cisapride; Clinical Trials as Topic; Constipation; Dyspepsia; Gastroesophageal Reflux; Gastrointestinal Diseases; Gastrointestinal Motility; Humans; Intestinal Pseudo-Obstruction; Piperidines; Serotonin Antagonists; Stomach Ulcer

The influence of Cisapride on food-stimulated gastro-oesophageal reflux mechanisms was studied in a double-blind cross-over investigation in 24 consecutive patients selected by endoscopy, 12 with microscopical evidence of gastro-oesophageal reflux and 12 with additional macroscopic oesophagitis. 63% had food-stimulated gastro-oesophageal reflux, and Cisapride significantly reduced the tendency to gastro-oesophageal reflux and mucosal contact time between gastric content and the oesophageal mucosa in 73% of these patients. It is concluded that Cisapride could be valuable in the treatment of gastro-oesophageal reflux.

Topics: Adult; Aged; Barium Sulfate; Cisapride; Clinical Trials as Topic; Double-Blind Method; Esophagitis, Peptic; Female; Gastroesophageal Reflux; Humans; Male; Middle Aged; Piperidines; Radiography; Serotonin Antagonists

In a double-blind, randomized, comparative trial of the prokinetic drug cisapride and the H2-blocker cimetidine, mucosal healing and changes in symptoms of gastroesophageal reflux were evaluated in patients with erosive reflux esophagitis. The patients were treated with either cisapride, 10 mg four times a day (N = 36) or cimetidine, 400 mg four times a day (N = 37) for six weeks, or for 12 weeks if mucosal healing was not obtained by week 6. Upon entry, two thirds of the patients in each group had grade I (Savary-Miller) esophagitis, and the remainder grade II or III. At the end of treatment, endoscopy showed mucosal healing in 56% (38-72%; 95% confidence interval) of cisapride and 57% (39-73%; 95% confidence interval) of cimetidine patients. After six weeks, both drugs significantly (P less than 0.01) decreased the intensity and frequency of heartburn, regurgitation, and the postural syndrome. No significant intergroup differences were found regarding endoscopic parameters or the improvement of heartburn and regurgitation. Concomitant antacid use was also comparable. Adverse effects were reported by four cisapride and nine cimetidine patients. These results indicate that the effects of cisapride compare well with those of cimetidine in terms of both esophageal mucosal healing and symptom relief.

Topics: Adult; Cimetidine; Cisapride; Double-Blind Method; Drug Evaluation; Esophagitis; Esophagoscopy; Female; Gastroesophageal Reflux; Humans; Male; Middle Aged; Piperidines; Random Allocation; Serotonin Antagonists

Gastro-oesophageal reflux occurs when the pressure barrier of the lower oesophageal sphincter (LOS) fails due to a low basal pressure (less than or equal to 6 mm Hg), sphincteric relaxations or a noncompensated increase in intragastric pressure. This reflux becomes pathological when it leads to symptoms severe enough for the patient to seek medical help or results in reflux oesophagitis or its complications. Damage to the oesophageal mucosa develops when the balance between aggressive and defensive factors is no longer in equilibrium. The main aggressive factor is acid-pepsin or alkaline bile secretion. Defence against this aggression is based on rapid removal of the refluxate from the oesophagus (oesophageal clearance) and on poorly understood mucosal resistance. The length of time acid is in contact with the oesophageal mucosa is shortened by adoption of an upright position, by swallow-induced oesophageal peristalsis and saliva. Treatment of pathological reflux aims (1) to decrease acid aggression by means of H2-receptor antagonists or proton pump inhibitors; (2) to strengthen the anti-reflux barrier and improve oesophageal clearance by prokinetic drugs that increase the LOS pressure and enhance peristaltic contractions; and (3) to boost mucosal resistance by sucralfate or prostaglandin analogues. Initial treatment of gastro-oesophageal reflux disease may be symptomatic provided that there are no alarming symptoms, such as dysphagia, anaemia or weight loss. Usually either H2-receptor blockers or prokinetic drugs are used. Endoscopy is indicated whenever alarming symptoms are present and when there is insufficient symptomatic improvement after a 4-6-week therapeutic trial. Moderate oesophagitis may be treated in the same way.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Anti-Ulcer Agents; Cisapride; Clinical Trials as Topic; Esophagitis, Peptic; Esophagogastric Junction; Gastroesophageal Reflux; Histamine H2 Antagonists; Humans; Omeprazole; Piperidines; Serotonin Antagonists

We studied the effect of cisapride on oesophageal motor function and postprandial gastro-oesophageal reflux in a randomised, double blind, placebo controlled crossover study. In 16 patients with symptomatic gastro-oesophageal reflux, cisapride 10 mg orally and placebo were studied on separate days according to identical protocols. Cisapride and placebo were given 30 minutes before a standard meal. Each study day was preceded by corresponding three day oral loading of cisapride (10 mg tds) or placebo. Lower oesophageal sphincter pressure, oesophageal body motility and oesophageal pH were monitored for 30 minutes before and three hours after the meal. Plasma cisapride concentrations were measured before and after dosing on both study days. With cisapride treatment, the plasma cisapride levels ranged from 48.1 (5.0) to 75.9 (6.9) ng/ml. Plasma levels were undetectable during placebo treatment. Cisapride enhanced acid clearance but had no significant effect on the duration of acid exposure, the rate of reflux episodes, the pattern of lower oesophageal sphincter pressure associated with the reflux episodes, basal lower oesophageal sphincter pressure or oesophageal peristalsis. These findings do not suggest a major role for cisapride, at the dosage tested, for the control of troublesome postprandial gastro-oesophageal reflux.

Topics: Adult; Aged; Cisapride; Double-Blind Method; Esophagus; Female; Food; Gastroesophageal Reflux; Humans; Male; Middle Aged; Piperidines; Randomized Controlled Trials as Topic; Serotonin Antagonists

Since gastro-oesophageal reflux disease is due to disturbances of oesophageal motility, motor and pH measurements are an important means to test a new anti-reflux drug, cisapride. In oesophageal manometry cisapride increased the pressure of the lower oesophageal sphincter in healthy volunteers and patients, and in the majority of studies it also strengthened the amplitude of oesophageal contractions. Cisapride lowered the total duration of acid exposure in the lower oesophagus in both volunteers and reflux patients. Thus cisapride may be useful in the treatment of gastro-oesophageal reflux disease.

Topics: Administration, Oral; Cisapride; Clinical Trials as Topic; Esophagogastric Junction; Gastric Acidity Determination; Gastroesophageal Reflux; Humans; Injections, Intravenous; Metoclopramide; Peristalsis; Piperidines; Serotonin Antagonists

Cisapride is a new drug which stimulates gastrointestinal motility via facilitation of acetylcholine release from myenteric nerves. European studies have addressed its clinical efficacy in treating gastro-oesophageal reflux disease in three areas. 1) Symptom relief: Cisapride, usually at a dose of 10 mg t.i.d., was superior to placebo and metoclopramide in relief of daytime and night-time heartburn and regurgitation. 2) Healing oesophagitis: Six studies showed that cisapride 10 mg q.i.d effectively heals oesophagitis over 6-16 weeks. Cisapride was superior to placebo and as effective as H2-antagonists in healing grades I-III oesophagitis. Combination therapy with H2-antagonists may be superior to H2-blocker alone. 3) Paediatric efficacy: Cisapride 1 mg/kg/day was effective in the treatment of infants and children with oesophagitis and pulmonary symptoms related to acid reflux. In conclusion, cisapride offers a promising alternative for the treatment of gastrooesophageal reflux disease without the troubling side effects of existing promotility drugs.

Topics: Adult; Child; Cisapride; Clinical Trials as Topic; Dose-Response Relationship, Drug; Double-Blind Method; Esophagitis, Peptic; Gastroesophageal Reflux; Humans; Piperidines; Serotonin Antagonists; Wound Healing

In a double-blind, randomized study, the clinical effects of 5 mg and 10 mg of cisapride three times daily were compared with those of 10 mg of metoclopramide three times daily in 114 patients with symptoms of gastroesophageal reflux, mainly diurnal and nocturnal heartburn and regurgitation. The symptoms significantly (P less than 0.001) improved in the three groups; the mean severity score decreased by at least 78% after four weeks of treatment. Initial symptoms were more severe in the cisapride-treated patients, especially in those receiving 10 mg three times daily; however, the patients' condition after four weeks was similar in the three groups. Central nervous system side effects were reported by one patient from each of the cisapride-treated groups and by nine of the 43 metoclopramide-treated patients (P less than 0.02). Six metoclopramide-treated patients and one cisapride-treated patient dropped out of the study because of side effects. These findings favor the use of cisapride when prokinetic treatment of gastroesophageal reflux is considered.

Topics: Adult; Aged; Cisapride; Dose-Response Relationship, Drug; Double-Blind Method; Female; Gastroesophageal Reflux; Humans; Male; Metoclopramide; Middle Aged; Multicenter Studies as Topic; Piperidines; Randomized Controlled Trials as Topic; Serotonin Antagonists

The effect of the new prokinetic drug cisapride on the resting lower oesophageal sphincter pressure and on the strength of peristaltic contractions was studied in 10 healthy controls and in 10 reflux patients with abnormally low (less than 10 mm Hg) basal lower oesophageal sphincter pressure. A slow intravenous injection of cisapride 10 mg significantly increased the sphincter pressure in the controls but even more in the patients in whom it almost doubled the resting lower oesophageal sphincter pressure of 8.7 (0.5) mm Hg to between 15 and 20 mm Hg for at least 90 min. Results are expressed as mean (SE). Cisapride also significantly increased the amplitude of peristaltic contractions in controls and reflux patients. Therefore, cisapride might be useful in the treatment of reflux.

Topics: Adult; Cisapride; Clinical Trials as Topic; Double-Blind Method; Esophagogastric Junction; Female; Gastroesophageal Reflux; Humans; Male; Middle Aged; Peristalsis; Piperidines; Pressure; Random Allocation

Twenty children (age range 75 days-47 months) with reflux oesophagitis entered a random double blind trial in which they received either Cisapride (Janssen Pharmaceutical Ltd), a new prokinetic agent, or an identical placebo syrup. Diagnosis of gastro-oesophageal reflux was made by measurement of intraluminal oesophageal pH combined with manometry. Oesophagitis was assessed in all patients by histological examination of mucosal specimens taken during oesophagogastroduodenoscopy. Manometry, pH test, and endoscopy with biopsy examination were repeated at the end of the treatment period. Seventeen patients completed the trial, eight of whom were taking the drug and nine the placebo. Mean total clinical score and post-prandial reflux time (% of reflux) significantly improved in patients in the group given Cisapride but not in the group given placebo. Furthermore, there was a significant improvement of the histological oesophagitis score only in the children in the group given Cisapride, whereas placebo was ineffective. It is concluded that Cisapride is a useful agent both for the relief of symptoms of gastro-oesophageal reflux and for the healing of peptic oesophagitis in infancy.

Topics: Child, Preschool; Cisapride; Clinical Trials as Topic; Double-Blind Method; Esophagitis, Peptic; Female; Gastroesophageal Reflux; Humans; Infant; Male; Piperidines; Random Allocation

A preliminary, double-blind placebo controlled trial of cisapride in reflux oesophagitis was conducted. Eighteen patients were allocated to treatment with either placebo or cisapride, 10 mg three times daily, orally, before meals. Gastric emptying of a scrambled egg meal, oesophageal transit of a liquid bolus and ambulatory monitoring of oesophageal pH were assessed before and after four weeks' therapy. Overall, gastric emptying rates were not influenced by cisapride, although a small but significant reduction in gastric isotope retention, 20 minutes after meal ingestion was observed in patients on the active drug. Oesophageal transit times were not altered by cisapride. A small but significant reduction in the duration of gastro-oesophageal reflux followed cisapride therapy when compared with placebo.

Topics: Adult; Aged; Cisapride; Clinical Trials as Topic; Double-Blind Method; Esophagitis, Peptic; Female; Gastric Acidity Determination; Gastric Emptying; Gastroesophageal Reflux; Humans; Male; Middle Aged; Piperidines

A zone of increased intraluminal pressure exists at the gastroesophageal junction in man and is believed to act as a physiologic sphincter. Increasing this lower esophageal sphincter (LES) tone is an accepted and useful method in preventing gastroesophageal reflux. The effects of LES tone were studied in 10 healthy volunteers receiving sequential intravenous injections of atropine, 0.6 mg, or domperidone, 10 mg, followed by domperidone, 10 mg, or atropine, 0.6 mg. The order of drug administration was randomized during the first study. Each volunteer was studied a second time, 1 week later, when the order of drug administration was reversed from the first. Administration of atropine decreased mean LES pressure by 12.6 cm H2O (p < 0.001). Subsequent injection of domperidone restored LES tone to near normal. In contrast, initial injection of domperidone approximately 1 week later in the same subjects, mean LES pressure increased by 18.5 cm H2O (p < 0.001). Intravenous injection of atropine, thereafter, failed to decrease mean LES pressure significantly, LES pressure being sustained at a mean of 14.8 cm H2O above basal control levels (p < 0.005). Results of this study suggest that domperidone given prior to atropine, before induction of general anesthesia, may counteract the potentially deleterious effect of atropine on LES tone, and thereby reduce the chances of regurgitation and pulmonary aspiration of acid gastric contents.

Topics: Adult; Antiemetics; Atropine; Benzimidazoles; Domperidone; Esophagogastric Junction; Gastroesophageal Reflux; Humans; Muscle Contraction; Muscle Relaxation; Piperidines; Preanesthetic Medication; Pressure

This double-blind and cross-over study was designed to compare the effect of domperidon, metoclopramide and bromopride on esophageal motility. A stimulating effect on lower esophageal sphincter pressure (LESP) was shown after i.v. bolus of all three substances, not after saline (control period). LESP was rised significantly up to 50 min above basal levels. Motility pattern of the esophagus was also stimulated up to 50 min.

Topics: Adult; Benzimidazoles; Domperidone; Esophagogastric Junction; Female; Gastroesophageal Reflux; Humans; Male; Metoclopramide; Piperidines

Forty-seven infants and children suffering from chronic vomiting or regurgitation, participated in a two-week double-blind trial comparing 1% drops of domperidone, 1% metoclopramide drops or placebo. The dose was 0.3 mg/kg given t.d.s. before meals. Both active medicaments were significantly more effective than placebo in controlling the symptoms and domperidone was also significantly superior to metoclopramide. It is concluded, in view of the good safety margin with domperidone, that this drug could become the treatment of choice in such cases.

Topics: Antiemetics; Benzimidazoles; Child; Child, Preschool; Chronic Disease; Clinical Trials as Topic; Double-Blind Method; Female; Gastroesophageal Reflux; Humans; Infant; Infant, Newborn; Male; Metoclopramide; Nausea; Piperidines; Vomiting

Intraluminal manometry has been used in a series of five studies on healthy volunteers and patients, to examine the action of domperidone on lower oesophageal sphincter pressure (LOSP), on peristaltic contraction, amplitudes and on antral, pyloric and duodenal motility. Furthermore, the effect on gastric acid secretion, pH, secretory volume and serum gastrin levels was studied. It was found that domperidone increased LOSP significantly but was less effective in patients with symptomatic gastro-oesophageal reflux than in normal volunteers. The drug also increased the amplitude of oesophageal and duodenal peristalsis but had no effect on endogenous gastrin release or on gastric acid secretion. The results suggest that this drug may be useful in the treatment of gastro-oesophageal and gastroduodenal reflux. This potential benefit is enhanced by the absence of side effects even when given in high doses.

Topics: Adult; Aged; Antiemetics; Benzimidazoles; Clinical Trials as Topic; Dose-Response Relationship, Drug; Double-Blind Method; Drug Evaluation; Duodenum; Esophagogastric Junction; Esophagus; Gastric Juice; Gastroesophageal Reflux; Gastrointestinal Motility; Humans; Middle Aged; Piperidines

To evaluate gastrointestinal (GI) perforation in rheumatoid arthritis (RA) patients receiving tofacitinib, tocilizumab, or other biologic agents.. Using health plan data from 2006 through 2014, RA patients without prior GI perforation were identified. Those in whom treatment with tofacitinib or a biologic agent was being initiated were followed up for incident GI perforation with hospitalization. Crude incidence rates were calculated by exposure. Adjusted Cox proportional hazards models were used to evaluate the association between GI perforation and exposures. Hazard ratios (HRs) with 95% confidence intervals (95% CIs) were calculated.. A cohort of 167,113 RA patients was analyzed. Among them, 4,755 began treatment with tofacitinib, 11,705 with tocilizumab, 115,047 with a tumor necrosis factor inhibitor (TNFi), 31,214 with abatacept, and 4,392 with rituximab. Compared to TNFi recipients, abatacept recipients were older, tofacitinib and rituximab recipients were younger, and tocilizumab recipients were similar in age. Patients beginning treatment with a non-TNFi agent were more likely to have previously received biologic agents than patients beginning treatment with a TNFi. The incidence of GI perforation per 1,000 patient-years was 0.86 (tofacitinib), 1.55 (tocilizumab), 1.07 (abatacept), 0.73 (rituximab), and 0.83 (TNFi). Most perforations occurred in the lower GI tract: the incidence of lower GI tract perforation per 1,000 patient-years was 0.86 (tofacitinib), 1.26 (tocilizumab), 0.76 (abatacept), 0.48 (rituximab), and 0.46 (TNFi). Lower GI tract perforation risk was significantly elevated with tocilizumab treatment, and numerically elevated with tofacitinib treatment, versus treatment with TNFi. Adjusted HRs were 2.51 (95% CI 1.31-4.80) for tocilizumab and 1.94 (95% CI 0.49-7.65) for tofacitinib. Older age (HR 1.16 per 5 years [95% CI 1.10-1.22]), diverticulitis/other GI conditions (HR 3.25 [95% CI 1.62-6.50]), and prednisone use at >7.5 mg/day (HR 2.29 [95% CI 1.39-3.78]) were associated with lower GI tract perforation. The incidence of upper GI tract perforation was similar among all drug exposures.. The risk of lower GI tract perforation associated with tocilizumab treatment, and possibly tofacitinib treatment, is elevated compared to that associated with TNF blockade.

Topics: Abatacept; Adult; Age Factors; Aged; Antibodies, Monoclonal, Humanized; Antirheumatic Agents; Arthritis, Rheumatoid; Biological Products; Databases, Factual; Diverticulitis; Esophageal Perforation; Female; Gastroesophageal Reflux; Glucocorticoids; Humans; Incidence; Intestinal Perforation; Male; Medicare; Middle Aged; Peptic Ulcer; Piperidines; Prednisone; Proportional Hazards Models; Pyrimidines; Pyrroles; Risk Factors; Rituximab; Tumor Necrosis Factor-alpha; United States

The SRS(TM) Endoscopic Stapling System (Medigus, Tel Aviv, Israel) is a new tool capable of creating a totally endoscopic fundoplication, combined with an endoscope, endoscopic ultrasound and a surgical stapler. SRS(TM) endoscopic stapling for gastro-esophageal reflux disease is a minimally invasive, outpatient procedure, which requires general anesthesia with positive-pressure ventilation. Keeping the patient on positive end-expiratory pressure (PEEP) may minimize the pressure gradient between the esophagus and the mediastinum, as well as help to prevent air from leaking around the screws and causing pneumomediastinum. In addition, in patients with hiatal hernia, higher PEEP levels may be required to increase intra-thoracic pressure and to force the stomach to slide into the abdomen for ease of endoscopy. We advise smoother emergence from anesthesia, taking precautions for retching, postoperative nausea and vomiting (PONV), while coughing and gagging during extubation and PONV may affect the success of the procedure. Total intravenous anesthesia with propofol and remifentanil seems to be a good choice for these reasons.

Topics: Anesthetics, Intravenous; Comorbidity; Endoscopy, Gastrointestinal; Fundoplication; Gastroesophageal Reflux; Hernia, Hiatal; Humans; Piperidines; Positive-Pressure Respiration; Postoperative Nausea and Vomiting; Propofol; Remifentanil; Retrospective Studies; Sutures; Ultrasonography

It is still controversial which drugs, proton pump inhibitors (PPI) or histamine-2 receptor antagonists (H2RA), are more effective for dyspepsia in the Japanese population.. Patients with uninvestigated dyspepsia (n = 104; male/female 41/63) were treated with either rabeprazole 10 mg o.d. (n = 62) or lafutidine 10 mg b.i.d. (n = 42) for 4 weeks. Questionnaires (modified Frequency Scale for the Symptoms of Gastroesophageal Reflux Disease [mFSSG] and quality of life [QOL], SF-8) were administered before and after therapy. The mFSSG was classified into a total score (Q-T), reflux score (Q-R), dyspepsia score (Q-D) and pain score (Q-P). The SF-8 had a physical component summary (PCS) and mental component summary (MCS). The predominant type of symptom was reflux (R-S), pain (P-S) or dysmotility (D-S).. R-S was 19.2%, P-S 48.1%, D-S 24.0% and overlap 8.7%. In the R-S, Q-T and Q-R significantly improved with rabeprazole, but neither scale improved with lafutidine. MCS significantly improved with rabeprazole. In P-S, Q-T, Q-R, Q-D and Q-P significantly improved with both drugs. PCS significantly improved with both, whereas the MCS significant improved with rabeprazole. In D-S, Q-R and Q-D significant improved with rabeprazole, but neither improved with lafutidine. QOL did not improve with either. With overlap, neither scale nor the QOL reached a significant difference.. Both PPI and H2RA have a positive effect on P-S, but H(2)RA therapy is limited for R-S and D-S, whereas PPI therapy is generally effective. Therefore, careful prescription based on symptoms is important.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Acetamides; Adult; Dyspepsia; Esophageal Motility Disorders; Female; Gastroesophageal Reflux; Histamine H2 Antagonists; Humans; Japan; Male; Middle Aged; Pain; Pain Measurement; Piperidines; Proton Pump Inhibitors; Pyridines; Rabeprazole; Retrospective Studies; Severity of Illness Index; Surveys and Questionnaires; Treatment Outcome

The pharmacological profile of PF-00885706, a selective 5-HT(4) receptor partial agonist, was investigated. PF-00885706 displayed a high binding affinity for the human 5-HT(4d) receptor with a K(i) of 3.7 nM that translates to functional agonist activity in vitro with EC(50) values of 4.0 nM and 6.6 nM in cell-based assays of human recombinant 5-HT(4d) receptors and rat tunica muscularis mucosae tissues, respectively. In both assays, partial agonism was confirmed with E(max) values of 84% and 78%, respectively. Notably, PF-00885706 was highly selective, displaying >1000-fold higher affinity for 5-HT(4d) receptors compared to 5-HT(1A), 5-HT(1B), 5-HT(1D), 5-HT(2A), 5-HT(2B), 5-HT(2C), 5-HT(3), 5-HT(7), and D(2long) receptors. Furthermore, in vitro binding assays demonstrated that PF-00885706 had no biologically significant interaction with physiologically important enzymes, ion channels including hERG channel, or receptors at concentrations up to 10 microM except for binding to the sigma(2) receptor. PF-00885706 exhibited weak binding affinity for the sigma(2) receptor yielding a K(i) value of 3 microM, which is more than 800-fold weaker than that for the 5-HT(4d) receptor. Oral administration of PF-00885706 to dogs resulted in marked and long-lasting stimulation of gastric motility with a minimum effective dose of 0.001 mg/kg. Pharmacokinetic analysis revealed that PF-00885706 has a low to moderate volume of distribution and the complete absorption in dogs. Pharmacokinetic and pharmacodynamic analysis of PF-00885706 in the dog gastric motility model showed a correlation between plasma concentrations and enhancement of gastric motility. Thus, PF-00885706 is an orally active, highly selective partial agonist for 5-HT(4) receptors that is expected to be effective for the treatment with gastrointestinal dysmotility disorders with reduced adverse effects mediated by other related receptors.

Topics: Animals; Benzimidazoles; Cell Line; Cyclobutanes; Dogs; Esophagus; Ether-A-Go-Go Potassium Channels; Gastroesophageal Reflux; Gastrointestinal Motility; Humans; Male; Muscle, Smooth; Piperidines; Protein Binding; Rats; Receptors, Serotonin, 5-HT4; Serotonin 5-HT4 Receptor Agonists

Gastro-oesophageal acid reflux may cause airway responses such as cough, bronchoconstriction and inflammation in asthmatic patients. Studies in humans or in animals have suggested that these responses involve cholinergic nerves. The purpose of this study was to investigate the role of the efferent vagal component on airway microvascular leakage induced by instillation of hydrochloric acid (HCl) into the oesophagus of guinea-pigs and the subtype of muscarinic receptors involved. Airway microvascular leakage induced by intra-oesophageal HCl instillation was abolished by bilateral vagotomy or by the nicotinic receptor antagonist, hexamethonium. HCl-induced leakage was inhibited by pretreatment with atropine, a non-specific muscarinic receptor antagonist, and also by pretreatment with either pirenzepine, a muscarinic M(1) receptor antagonist, or 4-DAMP, a muscarinic M(3) receptor antagonist. Pirenzepine was more potent than atropine and 4-DAMP. These antagonists were also studied on airway microvascular leakage or bronchoconstriction induced by intravenous administration of acetylcholine (ACh). Atropine, pirenzepine and 4-DAMP inhibited ACh-induced airway microvascular leakage with similar potencies. In sharp contrast, 4-DAMP and atropine were more potent inhibitors of ACh-induced bronchoconstriction than pirenzepine. Methoctramine, a muscarinic M(2) receptor antagonist, was ineffective in all experimental conditions. These results suggest that airway microvascular leakage caused by HCl intra-oesophageal instillation involves ACh release from vagus nerve terminals and that M(1) and M(3) receptors play a major role in cholinergic-mediated microvascular leakage, whereas M(3) receptors are mainly involved in ACh-induced bronchoconstriction.

Topics: Animals; Atropine; Capillary Permeability; Diamines; Female; Ganglionic Blockers; Gastroesophageal Reflux; Guinea Pigs; Hexamethonium; In Vitro Techniques; Male; Muscarinic Antagonists; Nicotinic Antagonists; Parasympatholytics; Piperidines; Pirenzepine; Receptor, Muscarinic M1; Receptor, Muscarinic M2; Receptor, Muscarinic M4; Receptors, Muscarinic; Receptors, Nicotinic; Regional Blood Flow; Respiratory System

Topics: Abnormalities, Multiple; Acidosis; Anesthesia; Anesthetics, Inhalation; Anesthetics, Intravenous; Atracurium; Blood Gas Analysis; Child, Preschool; Chromosome Disorders; Chromosomes, Human, Pair 9; Female; Fundoplication; Gastroesophageal Reflux; Humans; Intellectual Disability; Intubation, Intratracheal; Laryngoscopy; Methyl Ethers; Neuromuscular Nondepolarizing Agents; Piperidines; Propofol; Rare Diseases; Remifentanil; Sevoflurane

Cannabinoids have been shown to inhibit sensory nerve activation in guinea-pigs and humans. Their effects are mediated by specific activation of two types of receptors, named CB(1) and CB(2). The purpose of this study was to investigate the effects of WIN 55,212-2, (R)-(+)-[2,3-dihydro-5methyl-3-[(4-morpholino)methyl]pyrrolo-[1,2,3-de]-1,4-benzoxazin-6-yl](1-naphthyl)methanone, a non selective agonist of cannabinoid receptors, and JWH 133, (6aR,10aR)-3-(1,1-dimethylbutyl)-6a,7,10,10a-tetrahydro-6,6,9-trimethyl-6H-dibenzo[b,d]pyran a selective cannabinoid CB(2) receptor agonist, on the sensory nerve component of intraoesophageal (i.oe.) HCl-induced airway microvascular leakage and bronchoconstriction in guinea-pigs. We also tested the effect of WIN 55,212-2 on substance P-induced plasma extravasation and bronchoconstriction. Airway microvascular leakage and bronchoconstriction induced by i.oe. HCl was inhibited by the cannabinoid CB(1)/CB(2) agonist WIN 55,212-2 (0.3-3 mg/kg i.p.) in a dose-dependent manner (maximal inhibition at the dose of 3 mg kg(-1), P<0.01). The effect of WIN 55,212-2 was inhibited by a cannabinoid CB(2) receptor antagonist SR 144528, [N-[(1S)-endo-1,3,3-trimethylbicyclo[2,2,1] heptan-2yl]-5-(-4-chloro-3-methylphenyl)-1-(4-methylbenzyl)pyrazole-3-carboxamide], but not by a CB(1) receptor antagonist, SR 141716, [N-(piperidin-1yl)-5-(-4-chlorophenyl)-1-(2,4dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide hydrochloride]. The cannabinoid CB(2) agonist JWH 133 (0.3-3 mg/kg i.p.) mimicked the inhibitory effect of WIN 55,212-2 on HCl-induced microvascular leakage. Under similar conditions, WIN 55,212-2 (1 mg kg (-1) i.p.) was unable to counteract the airway microvascular leakage and bronchoconstriction induced by substance P. These results suggest that inhibition by WIN 55,212-2 of airway plasma extravasation and bronchoconstriction induced by i.oe. HCl instillation in guinea-pigs is mediated through cannabinoid CB(2) receptor activation.

Topics: Airway Obstruction; Animals; Benzoxazines; Bronchi; Bronchoconstriction; Camphanes; Cannabinoids; Capillary Permeability; Disease Models, Animal; Dose-Response Relationship, Drug; Esophagus; Extravasation of Diagnostic and Therapeutic Materials; Gastroesophageal Reflux; Guinea Pigs; Hydrochloric Acid; Male; Morpholines; Naphthalenes; Piperidines; Pulmonary Edema; Pyrazoles; Receptor, Cannabinoid, CB1; Receptor, Cannabinoid, CB2; Respiratory Function Tests; Rimonabant; Trachea

1. Gastro-oesophageal acid reflux may cause airway responses such as cough, bronchoconstriction and inflammation in asthmatic patients. Our previous results suggest that microvascular leakage induced, in the guinea-pig airways, by intra-oesophageal hydrochloric acid (HCl) infusion was mainly dependent on the release of tachykinins. Nociceptin, an endogenous ligand of the opioid receptor NOP, has been shown to inhibit bronchoconstriction and cough in guinea-pig or cat by inhibiting tachykinin release. 2. The purpose of this study was to investigate the effects of nociceptin on the intra-oesophageal HCl-induced airway microvascular leakage evaluated by Evans blue dye extravasation measurement in anaesthetised guinea-pigs pretreated with propranolol, atropine and phosphoramidon. 3. Infusion of intra-oesophageal HCl led to a significant increase in plasma extravasation in the main bronchi and trachea. This increase was abolished when animals underwent a bilateral vagotomy. 4. Airway microvascular leakage was inhibited by nociceptin (3-30 microg x kg(-1) i.v.) in a dose-dependent manner (maximal inhibition at the dose of 30 microg x kg(-1): 19.76+/-1.13 vs 90.92+/-14.00 ng x mg(-1) tissue for nociceptin and HCl infusion, respectively, in the main bronchi, P<0.01). The NOP receptor agonist [Arg(14),Lys(15)]N/OFQ mimicked the inhibitory effect of nociceptin, but at a 10-fold lower dose (3 microg x kg(-1) i.v). The NOP receptor antagonist J-113397 had no effect on plasma protein extravasation by itself, but was able to block the inhibitory effect of nociceptin. 5. Morphine (1 mg x kg(-1)) had a similar inhibitory effect as that of nociceptin. Naloxone pretreatment abolished the effect of morphine, but was enable to block the inhibitory effect of nociceptin. 6. Under similar conditions, nociceptin, in the previous range of concentration, was unable to counteract the airway microvascular leakage induced by substance P (SP). 7. These results suggest that airway plasma extravasation induced by intra-oesophageal HCl instillation might be inhibited by specific stimulation of the NOP receptor with nociceptin. Nociceptin is likely to act at a pre-junctional level, by inhibiting tachykinin release, since it was unable to prevent SP-induced airway plasma extravasation.

Topics: Animals; Benzimidazoles; Bronchi; Capillary Permeability; Disease Models, Animal; Gastroesophageal Reflux; Guinea Pigs; Hydrochloric Acid; Male; Morphine; Naloxone; Narcotic Antagonists; Narcotics; Nociceptin; Opioid Peptides; Piperidines; Receptors, Opioid; Substance P; Trachea; Vagotomy; Vasodilator Agents

Gastro-oesophageal reflux is a common clinical disorder associated with a variety of respiratory symptoms, including chronic cough and exacerbation of asthma. In this study, the potential role of acid-induced tachykinin release was examined in guinea pigs and rabbits, by examining the effects of the tachykinin NK1 and NK3 receptors antagonists (SR 140333 and SR 142801, respectively) (1-10 mg x kg(-1)) on plasma protein extravasation induced in airways by hydrochloric acid (HCl) infusion in the oesophagus. Guinea pigs were anaesthetised with urethane, while rabbits were subject to neuroleptoanalgesia with hypnorm. Airway vascular leakage was evaluated by measuring extravasation of Evans blue dye. All animals were pretreated with atropine (1 mg x kg(-1) i.p.), propranolol (1 mg x kg(-1) i.p.), phosphoramidon (2.5 mg x kg(-1) i.v.) and saline or tachykinin receptor antagonists (1-10 mg x kg(-1) i.p.). Infusion of 1 N HCl into the oesophagus led to a three- and five-fold increase in plasma extravasation in the main bronchi and trachea, respectively. This increase was largely prevented by the tachykinin NK1 and NK3 receptor antagonists SR 140333 and SR 142801 (1-10 mg x kg(-1)). These results suggest that protein extravasation in the airways, as induced by intraoesophageal HCl infusion, is mainly dependent on the release of tachykinins, and that both NK1 and NK3 tachykinin receptors are involved. The results suggest that HCl-induced sensory nerve stimulation may act in the periphery on intermediate neurons and/or ganglia where NK3 receptors have been shown to play an important role.

Topics: Animals; Asthma; Capillary Permeability; Disease Models, Animal; Esophagus; Female; Gastroesophageal Reflux; Guinea Pigs; Hydrochloric Acid; Instillation, Drug; Male; Neurokinin-1 Receptor Antagonists; Piperidines; Quinuclidines; Rabbits; Receptors, Neurokinin-1; Receptors, Neurokinin-3

Transient lower esophageal sphincter relaxations (TLESRs) are the major cause of gastroesophageal acid reflux, and are triggered by postprandial gastric distention. Stimulation of GABA(B) receptors potently inhibits triggering of TLESR by gastric loads. The functional similarity between GABA(B) and cannabinoid receptors (CBRs) prompted us to study the role of CBRs on mechanisms of gastric distention-induced TLESRs.. Gastric nutrient infusion and air insufflation was performed during gastroesophageal manometry in conscious dogs. The effects of the CBR agonist WIN 55,212-2 were assessed alone and in combination with the CBR1 antagonist SR141716A or the CBR2 antagonist SR144528. The effects of WIN 55,212-2 were also studied on firing of gastric vagal mechanosensitive afferents in an isolated preparation of ferret stomach.. WIN 55,212-2 (57 nmol/kg) inhibited the occurrence of TLESR after gastric loads by 80% (P < 0.01). The latency to the first TLESR after the load was prolonged (P < 0.001), and the occurrence of swallowing was reduced (P < 0.05). The CBR1 antagonist SR141716A reversed the effects of WIN 55,212-2, whereas the CBR2 antagonist SR144528 did not. The CBR1 antagonist alone increased occurrence of TLESR (P < 0.05). The responses of gastric vagal mechanoreceptors to distention were unaffected by WIN 55,212-2 at a concentration of 3 micromol/L.. Exogenous and endogenous activation of the CBR1 receptor inhibits TLESRs. The effects of CBR1 are not mediated peripherally on gastric vagal afferents, and therefore are most likely in the brain stem.

Topics: Analgesics; Animals; Benzoxazines; Dogs; Esophagogastric Junction; Female; Ferrets; GABA-B Receptor Agonists; Gastroesophageal Reflux; Ligands; Male; Mechanoreceptors; Morpholines; Muscle Relaxation; Naphthalenes; Neurons, Afferent; Piperidines; Pyrazoles; Receptors, Cannabinoid; Receptors, Drug; Rimonabant; Vagus Nerve

Previous evaluation of the cost effectiveness of antireflux medication used in gastro-oesophageal reflux disease (GORD) have been based on results obtained in controlled clinical trials. Unfortunately such an approach does not necessarily identify the therapeutic option which provides the greatest benefit from available resources in real life situations. To make an informed choice requires a recognition that the costs and benefits of therapy in practice may differ from those identified in trials.. To evaluate, based on a retrospective prescription database analysis, the cost effectiveness of alternative treatment options for patients with uncomplicated GORD. The analysis assesses health service resource use during the first six months of treatment in three groups of patients initially prescribed cisapride (CIS), ranitidine (RAN), or omeprazole (OME).. The MediPlus UK database was used to identify all health care resources consumed by patients in the three treatment groups during their first six months of treatment. Patients with more complicated GORD, as indicated by initial referral to a specialist or outpatient hospital visit (< 13%), were excluded from the analysis.. The average cost per patient for the initial six months of treatment for CIS, RAN, and OME based therapies was 136 Pounds, 177 Pounds, 189 Pounds per patient, respectively. A major element underlying this cost variation was the acquisition cost and quantity of antireflux medication required by patients. The average number of one month equivalent prescriptions consumed during this six month period was 1.85 (CIS), 2.57 (RAN), and 2.96 (OME) with associated costs of 49 Pounds (CIS), 67 Pounds (RAN), and 105 Pounds (OME). Antacid and alginate/antacid use was higher in the CIS and RAN groups (about 1.0 antacid prescription per patient versus 0.4 for OME), but their contribution to the total cost per patient was less than 2%. The number of general practitioner consultations over the six month period for each treatment group was 2.4 (CIS), 2.9 (RAN), and 2.6 (OME) with associated costs of 60.31 Pounds (CIS), 73.06 Pounds (RAN), and 65.52 Pounds (OME). The average number of non-drug interventions (referrals, outpatient visits, endoscopies, barium meals, or x rays) was 0.34 in the RAN group compared with less than 0.2 in the CIS and OME groups. The costs associated with such interventions were 23.80 Pounds (RAN), 9.60 Pounds (CIS), and 11.10 Pounds (OME) per patient.. The data indicate that the "step up" approach, starting with a prokinetic or H2 receptor antagonist, represents the most cost effective initial therapeutic strategy for a primary care physician to adopt when faced with a patient with first diagnosis of uncomplicated GORD.

Topics: Anti-Ulcer Agents; Cisapride; Cost-Benefit Analysis; Databases, Factual; Family Practice; Gastroesophageal Reflux; Humans; Omeprazole; Piperidines; Practice Patterns, Physicians'; Ranitidine; Retrospective Studies; Treatment Outcome

Topics: Barrett Esophagus; Bethanechol; Cisapride; Gastric Emptying; Gastroesophageal Reflux; Gastrointestinal Agents; Gastrointestinal Motility; Humans; Parasympathomimetics; Piperidines; Proton Pump Inhibitors; Recurrence

Topics: Adult; Aged; Anti-Ulcer Agents; Barium Sulfate; Chest Pain; Cisapride; Contrast Media; Esophagitis, Peptic; Esophagoscopy; Female; Gastrectomy; Gastric Acid; Gastroesophageal Reflux; Gastrointestinal Agents; Heartburn; Humans; Hydrogen-Ion Concentration; Lymph Node Excision; Male; Manometry; Middle Aged; Patient Selection; Piperidines; Radiography; Stomach Neoplasms; Vagotomy, Truncal

Dysphonia associated with bulimia has been described in the literature associated with vocal fold edema and polypoid changes. Laryngopharyngeat reflux (LPR) has been documented to cause reflux vocal fold pathology including edema and polypoid changes. We studied eight singers with bulimia and documented vocal fold pathology, including edema, posterior commissure hypertrophy, ventricular obliteration, and telangiectasia. Reflux was demonstrated in all eight. The results of this study showed that LPR may be a contributing factor to vocal disorders in singers with bulimia.

Topics: Adult; Anti-Ulcer Agents; Bulimia; Cisapride; Female; Gastroesophageal Reflux; Humans; Omeprazole; Piperidines; Voice Disorders

Apnea in the neonatal period frequently is associated with prematurity. Full-term infants who develop apnea usually have associated clinical conditions such as infection, shock, metabolic disorders, neonatal abstinence syndrome, intracranial pathology, and gastroesophageal reflux. Gastric ulcer also is a rare phenomenon in the neonatal period. We describe a full-term infant presenting with apnea. Upon investigation, a 6-channel pneumocardiogram revealed central apnea and multiple episodes of low esophageal pH (< 4), which is suggestive of gastroesophageal reflux. This was confirmed by an upper gastrointestinal series. A small antral ulcer crater also was demonstrated. When assessing the etiology of apnea in a full-term infant, gastroesophageal reflux and gastric ulcer should be considered.

Topics: Anti-Ulcer Agents; Apnea; Cisapride; Esophagus; Gastroesophageal Reflux; Humans; Hydrogen-Ion Concentration; Infant, Newborn; Male; Nose; Oxygen; Piperidines; Pulmonary Ventilation; Pulse; Ranitidine; Respiration; Stomach Ulcer

Topics: Cisapride; Gastroesophageal Reflux; Humans; Infant; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Long QT Syndrome; Piperidines

Topics: Cisapride; Drug Overdose; Female; Gastroesophageal Reflux; Humans; Infant; Long QT Syndrome; Piperidines

Topics: Administration, Oral; Anti-Ulcer Agents; Cimetidine; Cisapride; Colic; Esophagus; Female; Follow-Up Studies; Gastroesophageal Reflux; Humans; Hydrogen-Ion Concentration; Infant; Male; Piperidines; Prospective Studies

Cisapride is frequently used in the newborn and infant for treatment of gastroesophageal reflux. Twisting-spikes have been reported in adults due to overdosage or therapeutic interaction. We report seven cases of QT prolongation in infants treated with cisapride.. Seven children (one full-term, two mature preterms, four preterm babies), aged (mean, range) 41.8 +/- 21 days (14-79) weighing 2.1 +/- 1.1 kg (1.2-4), free from any cardiac abnormality, except one patent ductus arteriosus, have been studied by ECG and Holter monitoring. They received cisapride at a mean dose of 1.31 +/- 0.2 mg/kg/d (between 1 and 1.7 mg/kg/d).. The corrected QT (QTc: N < 450 ms) was increased to 486 ms (450-540) with a notched T-wave pattern. No arrhythmia was detected. In five cases, cisapride was stopped and changed to metoclopramide. Cisapride dosage was reduced to 0.8 mg/kg/d in the two others. No other therapeutic modification was done. A control ECG performed 48 hours after therapeutic changes showed a QTc shortening of 74 +/- 18 ms (45-90) and the disappearance of the notches independent of any heart rate changes, leading to normal QTc values: 413 +/- 21 ms (390-440).. High cisapride dosage in preterm, newborns and infants seems to favor QT prolongation which is reversible when dosage is reduced or drug is stopped. The use of cisapride in combination with other drugs known to increase QT should be done with extreme caution.

Topics: Anti-Ulcer Agents; Cisapride; Dose-Response Relationship, Drug; Electrocardiography; Female; Gastroesophageal Reflux; Humans; Infant; Infant, Newborn; Long QT Syndrome; Piperidines; Retrospective Studies

Cardiotoxicity of cisapride may increase when this drug is associated with ranitidine.. A 37-day old term infant, treated with cisapride (1.2 mg/kg/d) and ranitidine for regurgitations, was hospitalized for malaise. A prolonged QT interval (with isolate ventricular extrasystoles), noted at admission, disappeared rapidly after cisapride withdrawal. Linkage to cisapride was probable, promoted by high dosage and cisapride metabolism inhibition by ranitidine, but its plasma concentration was not measured.. This case report stresses the problem of cisapride dosage in infants and the question of an interaction between cisapride and ranitidine.

Topics: Anti-Ulcer Agents; Cisapride; Dose-Response Relationship, Drug; Drug Therapy, Combination; Gastroesophageal Reflux; Histamine H2 Antagonists; Humans; Infant; Long QT Syndrome; Male; Piperidines; Ranitidine; Syncope

Cisapride is a novel prokinetic agent that releases acetylcholine at the level of the myenteric plexus. Acetylcholine also plays a role in the secretory function of salivary glands evoked by intraesophagal mechanical and chemical stimulation, mediated through the esophagosalivary reflex. The impact, however, of cisapride on salivary protective components mediated by esophagosalivary reflex remains unknown. Therefore, we have studied salivary pH, bicarbonate, nonbicarbonate, glycoconjugate, protein, EGF, TGF-alpha, and PGE2 before and after the administration of cisapride. The study was conducted in 20 asymptomatic volunteers (9 women and 11 men, mean age 36, range 26-52). Salivary secretions were collected under basal conditions and during masticatory, mechanical, and chemical stimulation before and after four days of cisapride administration (10 or 20 mg four times a day). Cisapride administration resulted in a 45% increase in salivary volume during the basal condition (P < 0.01), a 32% increase during mastication (P < 0.05), a 53% increase during mechanical (P < 0.05), and a 51% increase during chemical (P < 0.01) stimulation. Cisapride administration resulted also in a significant increase in salivary protein output (P < 0.05), salivary bicarbonate (P < 0.05), and nonbicarbonate buffers (P < 0.05), and salivary EGF (P < 0.05). Salivary glycoconjugate significantly increased only during mechanical stimulation with the catheter and at the end of the esophageal perfusion procedure (P < 0.05). Although a similar trend was also recorded during the analysis of salivary PGE2, this difference did not reach statistical significance. Salivary pH and TGF-alpha before and after cisapride administration remained unchanged. The stimulatory impact of cisapride on salivary volume and inorganic (bicarbonate and nonbicarbonate buffers) and organic (protein, glycoconjugate, and EGF) protective components would benefit patients with GERD and would also be potential therapy for xerostomia.

Topics: Adult; Catheterization; Cisapride; Esophagus; Female; Gastroesophageal Reflux; Gastrointestinal Agents; Humans; Hydrogen-Ion Concentration; Male; Perfusion; Piperidines; Saliva; Salivary Proteins and Peptides; Time Factors

It is not known whether antireflux surgery is more effective than medical therapy to control respiratory symptoms (RS) in gastroesophageal reflux disease (GERD).. In 21 GERD patients with RS, reflux was assessed by endoscopy, manometry, and pH monitoring. Patients had proton pump inhibitor therapy and cisapride for 6 months. After GERD relapsed following withdrawal of medical therapy, 7 patients with normal esophageal peristalsis had a laparoscopic Nissen fundoplication and 14 with impaired peristalsis a Toupet fundoplication. Respiratory symptoms were scored prior to treatment, at 6 months following medical therapy, and at 6 months after surgery.. Heartburn and esophagitis were effectively treated by medical and surgical therapy. Only surgery improved regurgitation. Respiratory symptoms improved in 18 patients (85.7%) following surgery and in only 3 patients (14.3%) following medical therapy (P <0.05). Esophageal peristalsis improved following the Toupet fundoplication.. Medical therapy fails to control reflux since it does not inhibit regurgitation. Surgery controls reflux and improves esophageal peristalsis, which contributes to its superiority over medical therapy in the treatment of RS associated with GERD.

Topics: Adult; Aged; Anti-Ulcer Agents; Cisapride; Drug Therapy, Combination; Female; Gastroesophageal Reflux; Humans; Male; Middle Aged; Omeprazole; Piperidines; Respiratory Tract Diseases

Heartburn, the major symptom of gastrointestinal reflux disease (GERD), is a common condition that is usually self-treated with over-the-counter products. For patients with severe or recurrent symptoms of GERD, pharmacologic therapy includes acid suppression with H2-receptor antagonists and proton pump inhibitors, and, alternatively, the use of prokinetic agents. While all of these are efficacious, given its high efficacy in nonerosive and mild-to-moderate erosive esophagitis, the prokinetic agent cisapride deserves significant consideration in this patient population.

Topics: Cisapride; Disease Management; Gastroesophageal Reflux; Gastrointestinal Agents; Humans; Life Style; Managed Care Programs; Piperidines; Quality of Life; United States

A 2-month-old infant with gastroesophageal reflux was treated with cisapride. Bradycardia developed and an electrocardiogram revealed 2:1 atrioventricular conduction and a prolonged QT interval. After cessation of cisapride therapy, both the rhythm and the QT interval returned to normal. Prolonged QT interval during treatment with cisapride may occur in children as in adults.

Topics: Adult; Age Factors; Bradycardia; Cisapride; Electrocardiography; Female; Gastroesophageal Reflux; Humans; Infant; Long QT Syndrome; Piperidines

The aim of the study was to evaluate, in 42 children with gastroesophageal reflux disease, the predictive value of both esophageal manometry and gastroesophageal intraluminal pH on the responsiveness of the disease to medical therapy.. Motility of lower esophageal sphincter and esophageal body was carried out through a perfused pediatric sleeve-probe; prolonged recording of the sphincteric profile was evaluated at the occurrence of reflux episodes as detected by an esophageal electrode; intraluminal pH of the esophagus and stomach was also measured for 24-h through portable equipment. Children were treated for 8 wk with cisapride and ranitidine and were classified as healed or refractory after endoscopy and clinical evaluation.. Twenty one children healed, and 21 were refractory. Compared with healed patients, refractory patients showed, at basal evaluation, an increased esophageal acid exposure (p < 0.05), a reduced basal sphincteric pressure and peristalsis amplitude (p < 0.01), an increased rate of sphincteric pressure drifts (p < 0.01), and a higher rate of transient lower esophageal sphincter relaxations (p < 0.01). The following parameters contributed significantly (p < 0.01) to a multivariate discriminant analysis: peristalsis amplitude, basal sphincter pressure, rate of transient relaxations of the sphincter, and rate of sphincteric pressure drifts. A correct classification of virtually all cases (97.62%) was reached.. Motor dysfunctions of both lower esophageal sphincter and esophageal body are the major factors predicting refractoriness of reflux disease in children to a standard medical treatment. Of the two main mechanisms of reflux, i.e., transient lower esophageal sphincter relaxation and lower esophageal sphincter pressure drift, the latter had the highest predictive value for the refractoriness of reflux disease.

Topics: Anti-Ulcer Agents; Case-Control Studies; Child; Cisapride; Discriminant Analysis; Esophagogastric Junction; Esophagus; Evaluation Studies as Topic; Female; Gastroesophageal Reflux; Humans; Hydrogen-Ion Concentration; Male; Manometry; Monitoring, Physiologic; Peristalsis; Piperidines; Predictive Value of Tests; Pressure; Prognosis; Ranitidine; Treatment Outcome

A total of 3409 patients with gastro-oesophageal reflux disease were treated with roxatidine acetate. 60.7% of the patients received a daily dose of 2 x 75 mg roxatidine acetate, and the median duration of treatment was 5 weeks. Symptoms improved in about 90% of patients. For 1687 patients, endoscopic findings were available at the beginning and end of the treatment period. The overall endoscopic healing rate was 65.3%, and, depending on the initial finding (if), decreased from 92.9% (if: Savary-Miller stage I) to 67.5% (if: stage II), 40.7% (if: stage III), and to 22.5% (if: stage IV). Twenty-one patients experienced adverse events during the course of treatment, which, however, were either only minor or not related to the use of roxatidine acetate.

Topics: Anti-Ulcer Agents; Dose-Response Relationship, Drug; Drug Administration Schedule; Esophagoscopy; Female; Gastroesophageal Reflux; Humans; Male; Middle Aged; Piperidines

Topics: Anti-Ulcer Agents; Child; Cimetidine; Cisapride; Cytochrome P-450 Enzyme System; Drug Interactions; Gastroesophageal Reflux; Humans; Piperidines; Ranitidine

Case of an infant with chronic cough is reported. The most frequent causes of chronic cough were ruled out. Twenty-four hour oesophageal pH-monitoring showed a close correlation between gastro-oesophageal reflux episodes and cough attacks. The patient was successfully treated with cisapride (0.3 mg/kg t.i.d.). These findings show that irritable oesophagus syndrome can cause chronic cough.

Topics: Chronic Disease; Cisapride; Cough; Esophagitis, Peptic; Gastroesophageal Reflux; Humans; Hydrogen-Ion Concentration; Infant; Male; Piperidines; Sympathomimetics; Syndrome

Long-term follow-up examination with esophagogastroduodenoscopy was performed on seven patients who had undergone successful delayed anastomosis for isolated esophageal atresia. The follow-up period ranged from 1.2 to 11.3 years (mean, 5.3). All patients had undergone fundoplication because of symptomatic gastroesophageal reflux (GER). Three anastomotic strictures had to be resected. At the time of the last follow-up examination, the subjective results were excellent for five patients and good for two. The last endoscopy showed macroscopic esophagitis in three and normal mucosa in four. The fundoplication was partly disrupted in two patients. In three patients the fundoplication was competent but partly intrathoracic. Histological examination showed moderate esophagitis in one, mild esophagitis in one, and normal mucosa in five patients; however, four patients were on continuous medication for esophagitis. In conclusion, the subjective results of patients with isolated esophageal atresia treated with esophageal anastomosis are good. However, long-term complications caused by GER are common in these patients. Therefore, active search and treatment of reflux is necessary for these patients.

Topics: Anastomosis, Surgical; Anti-Ulcer Agents; Cisapride; Constriction, Pathologic; Endoscopy, Digestive System; Esophageal Atresia; Esophageal Diseases; Esophagitis; Follow-Up Studies; Fundoplication; Gastroesophageal Reflux; Gastrointestinal Agents; Humans; Infant; Piperidines; Postoperative Complications; Sucralfate

Topics: Antacids; Child; Child, Preschool; Cisapride; Esophagoscopy; Gastroesophageal Reflux; Humans; Hydrogen-Ion Concentration; Infant; Piperidines; Posture

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

Chronic hiccup is a rare but potentially severe condition, that can be symptomatic of a variety of diseases, or idiopathic. Many therapeutic interventions have been reported, most often as case reports. Among other drugs, baclofen has been suggested as a therapy for chronic hiccup. In a large series of patients, we have evaluated its therapeutic position. In patients with chronic hiccup, defined as hiccup spell or recurring hiccup attacks lasting more than 7 days, investigation of the upper gastro-oesophageal tract (fibroscopy, manometry, and pH monitoring) was systematically performed. Most patients had tried numerous drugs in the past, without success. Baclofen was used as a first treatment in patients without evidence of any gastro-oesophageal disease (n = 17), and was undertaken only after full treatment of such disease (n = 55) had failed to solve the hiccup problem (n = 20). Baclofen has, therefore, been administered to 37 patients with chronic hiccup (average duration 4.6 yrs). Baclofen produced a long-term complete resolution (18 cases) or a considerable decrease (10 cases) of hiccups in 28 of the 37 patients. There was no significant difference between patients with or without gastro-oesophageal disease. We conclude that so-called idiopathic chronic hiccup often results from gastro-oesophageal abnormalities. Also, if controlled studies confirm our encouraging results, baclofen can be a major element in the treatment of chronic hiccup that is idiopathic, or that cannot be helped by treatment of gastro-oesophageal diseases.

Topics: Anti-Ulcer Agents; Baclofen; Chronic Disease; Cisapride; Dose-Response Relationship, Drug; Female; Gastroesophageal Reflux; Hiccup; Humans; Male; Middle Aged; Omeprazole; Piperidines; Treatment Outcome

A 43-year-old woman with gastroesophageal reflux disease developed a dystonic-like reaction approximately 3 days after starting oral cisapride therapy. Office evaluation revealed a patient who moved her head rhythmically from side to side as she stared into space, generally unresponsive to external stimuli. She had increased tone of the sternocleidomastoid muscles bilaterally, with occasional tongue protrusion, and a slow shuffling gait. Following discontinuation of cisapride, the patient recovered completely.

Topics: Adult; Cisapride; Diphenhydramine; Dystonia; Female; Gastroesophageal Reflux; Humans; Parasympathomimetics; Piperidines

Respiratory complications of gastroesophageal reflux disease that have been reported include hoarseness, wheezing, bronchospasm, stridor, laryngitis, and chronic cough. Syncope as a manifestation of gastroesophageal reflux disease-induced cough has not been described in the literature. We present an unusual case of gastroesophageal reflux that resulted in frequent cough-induced syncope. Treatment ultimately consisted of a laparoscopic Nissen fundoplication which resulted in sustained relief from both cough and syncope.

Topics: Adult; Cisapride; Cough; Drug Therapy, Combination; Gastroesophageal Reflux; Humans; Male; Monitoring, Physiologic; Omeprazole; Piperidines; Syncope

Gastro-oesophageal reflux (GOR) has been implicated in such clinical phenomena as aspiration pneumonia, bronchospasm or wheezing, apnea, stridor, and hoarseness. Various tests have been used as an aid to diagnosing patients with chronic respiratory disease where GOR is a causal factor. Different forms of conservative treatment have been tried for GOR, including cisapride. Several studies have evaluated its effect on the pH profile and respiratory symptoms in patients with chronic respiratory disease and have demonstrated improvement of nocturnal wheezing, cough, and irritability. Our experience with cisapride is positive in children with GOR. Patients refractory to medical treatment have been surgically treated with good results.

Topics: Anti-Ulcer Agents; Asthma; Child; Child, Preschool; Chronic Disease; Cisapride; Gastroesophageal Reflux; Humans; Infant; Piperidines; Pneumonia, Aspiration; Respiratory Sounds; Respiratory Tract Diseases

The healing of oesophagitis, both symptomatic and endoscopic, can be obtained with cisapride, the results being equivalent to what has been achieved with H2RAs. For many patients, however, GORD is a chronic relapsing disease.. At least 40-50% of patients relapse within a year of initial healing. Important predictors for relapse are the severity of symptoms, the degree of mucosal damage, and the time it takes for the initial lesions to heal. Another important predictor of relapse, as shown in the cisapride maintenance studies, is the need for PPIs, probably because the most recalcitrant patients were selected for this therapy.. Patients with mild or moderate disease should be treated with intermittent or prolonged therapy with cisapride or H2RAs. Patients with severe disease should be given prolonged or permanent therapy with a PPI or with cisapride in combination with either an H2RA or a PPI. For the latter group, antireflux surgery should also be considered, especially in younger patients who have a completely incompetent closing mechanism of the lower oesophageal sphincter.

Topics: Anti-Ulcer Agents; Cisapride; Gastroesophageal Reflux; Histamine H2 Antagonists; Humans; Piperidines; Recurrence

Topics: Adolescent; Adult; Cisapride; Female; Gastroesophageal Reflux; Humans; Male; Parasympatholytics; Piperidines; Sympatholytics; Vomiting

Renal patients often complain of vague abdominal symptoms compatible with a gastric motility disorder. Cisapride is a recently available prokinetic agent that improves motility and emptying of the upper gastrointestinal tract in patients on long-term dialysis. The drug is extensively metabolized in the liver producing metabolites with minimal pharmacologic activity. Adverse reactions are primarily gastrointestinal in nature and include abdominal cramps, flatulence, and diarrhea.

Topics: Cisapride; Gastroesophageal Reflux; Humans; Piperidines; Renal Dialysis; Renal Insufficiency

Topics: Cisapride; Clinical Trials as Topic; Esophagitis, Peptic; Gastroesophageal Reflux; Heartburn; Humans; Piperidines; Posture

Topics: Cisapride; Drug Approval; Gastroesophageal Reflux; Humans; Piperidines; Serotonin Antagonists; United States; United States Food and Drug Administration

In this paper the authors review the main prokinetic drugs analyzing their pharmacological properties, therapeutic indications and adverse effects. In addition, some more recently introduced substances are taken into consideration which, although they were not initially used for digestive tract dyskinesias, can nevertheless be used in certain conditions. From this point of view, calcium blocking agents employed in spastic conditions of the esophagus and the new antiserotoninergic drugs for treatment of anticancer chemotherapy-induced vomiting are of particular interest.

Topics: Antineoplastic Agents; Cisapride; Domperidone; Esophageal Motility Disorders; Gastroesophageal Reflux; Gastrointestinal Motility; Humans; Metoclopramide; Piperidines; Serotonin Antagonists; Vomiting

We evaluated the prevalence of gastroesophageal reflux in 36 children, 22 (61.2%) male and 14 (38.8%) female (median age, 75.5 months; range, 18-178), with noncontrolled asthma by means of prolonged (22-24 h) esophageal pH monitoring. None of the children had gastrointestinal symptoms suggesting gastroesophageal reflux. Atopy was seen in 21 of 36 (58.3%) patients. Pathological gastroesophageal reflux was present in 27 (75%) children. All patients were given cisapride (0.2 mg/kg q.i.d.) for 3 months. A clinical and pharmacological score was determined, and a second pH-metric study was made at the end of the follow-up period. The following pH-metric parameters were evaluated: the total percentage of time pH was < 4, the number of reflux episodes, the number of reflux episodes lasting > 5 min, the length of the longest single reflux episode, and the percentage of time the esophageal pH was < 4 during sleep. The study was completed in 11 of 27 children. The percentage of time that esophageal pH was < 4 improved in nine of 11 (81.8%) patients (p = 0.013). The percentage of time that esophageal pH was < 4 during sleep showed the most significant decrease (p = 0.002) after treatment. Improvement in both clinical and pharmacological scores was highly significant (p < 0.0001) in 19 of 27 patients, eight of whom did not want to repeat the pH study. We conclude therefore that gastroesophageal reflux is frequently associated with noncontrolled asthma and that medical therapy for reflux may improve the further course of respiratory disease.

Topics: Adolescent; Asthma; Child; Child, Preschool; Cisapride; Esophagus; Female; Gastroesophageal Reflux; Humans; Hydrogen-Ion Concentration; Infant; Male; Piperidines; Prevalence; Serotonin Antagonists

This paper identifies the symptom profile associated with the four main diagnoses of functional digestive disorders (dyspepsia, gastro-oesophageal reflux disease (GORD), gastritis, and constipation) made by general practitioners in Belgium. Results are also presented from a multicentre study in which the effects of cisapride, administered as an oral tablet or suspension, were evaluated in patients with these functional digestive disorders. Analysis of symptom patterns revealed that early satiety and postprandial abdominal bloating were the most prominent symptoms, followed by eructation (belching), heartburn, regurgitation, postprandial epigastric burning or discomfort, and nausea. These symptoms occurred in all diagnostic groups. However, different symptom patterns were associated with each of the disorders; for example, heartburn and regurgitation were the core symptoms in patients diagnosed as having GORD, early satiety and abdominal bloating were characteristic of patients diagnosed with dyspepsia, and fasting or postprandial pain were characteristic of patients given the diagnosis of gastritis. Therefore, it appears that these diagnoses used by general practitioners in Belgium closely correspond to reflux-like, dysmotility-like and ulcer-like dyspepsia, as defined by an international working party. Cisapride improved the core symptoms in about 80% of patients with GORD or dyspepsia, relieved all epigastric symptoms in about 80% of patients with gastritis, and significantly decreased the use of laxatives and increased stool frequency in constipated patients. Cisapride was well tolerated and thus appears to be a useful option in the treatment of functional digestive disorders in a general practice setting.

Topics: Adult; Aged; Belgium; Cisapride; Cluster Analysis; Constipation; Dyspepsia; Family Practice; Female; Follow-Up Studies; Gastritis; Gastroesophageal Reflux; Gastrointestinal Diseases; Gastrointestinal Motility; Humans; Male; Middle Aged; Piperidines; Treatment Outcome

To evaluate the effectiveness of administration of oral cisapride in patients with gastro-esophageal reflux, we studied 25 children, aged 1 month-7 years (mean 16.2 months) affected with GER. At the time of diagnosis and 8 weeks after treatment, patients were clinically evaluated and underwent a 24-hour continuous esophageal pH-monitoring. After treatment a complete regression of symptoms was observed in 20/25 patients. Moreover we recorded a significant reduction in the percentage of reflux time (p < 0.0001) and in the Jolley score (p < 0.0001), a very accurate scoring system to evaluate the pH-metric tracing, after treatment. It is concluded that cisapride is a useful agent both for the relief of symptoms and for the improvement of pH-metric parameters in children with GER disease.

Topics: Child; Child, Preschool; Cisapride; Evaluation Studies as Topic; Female; Gastroesophageal Reflux; Humans; Infant; Infant, Newborn; Male; Piperidines; Selective Serotonin Reuptake Inhibitors

The present study aimed to evaluate gastric emptying in children with gastroesophageal reflux (GER) by means of real-time ultrasonography, on the basis of measurements of the cross-sectional area of the gastric antrum. Twelve children with GER were studied (seven males, five females; age range, 3-13 months) and compared with 12 normal control children (six males, six females; age range, 3-13 months). The diagnosis of GER was confirmed by 24-h esophageal pH-monitoring. The GER patients had a significantly greater antral area than the controls at 90, 105, and 120 min after eating a standard meal (cow's milk formula, 300 ml/m2 body surface area); in addition, final gastric emptying time was significantly greater in the patients than in the controls (145 +/- 36.9 versus 78.7 +/- 19.3 min; p less than 0.0025). After 8 weeks of treatment with cisapride (0.3 ml/kg, three times a day) 24-h esophageal pH-monitoring and ultrasonography studies were repeated in the patients. The total percentage reflux time was significantly lower (p less than 0.038), and ultrasonography showed a decreased antral area at all the various study times, with no significant difference between patients and controls; final gastric emptying time was also significantly lower than before treatment (p less than 0.009). Furthermore, in the GER patients there was a significant correlation between gastric emptying time and the sum of the various reflux times recorded in the 2 h after all meals over the 24 h.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Cisapride; Female; Gastric Acidity Determination; Gastric Emptying; Gastroesophageal Reflux; Humans; Infant; Male; Piperidines; Serotonin Antagonists; Stomach; Ultrasonography

Topics: Antacids; Cisapride; Diseases in Twins; Female; Gastroesophageal Reflux; Humans; Infant; Male; Piperidines; Serotonin Antagonists; Twins, Dizygotic; Twins, Monozygotic

Topics: Cisapride; Drug Therapy, Combination; Gastroesophageal Reflux; Omeprazole; Piperidines; Ranitidine

Gastro-esophageal reflux (GER) in infants was studied using 24-hour esophageal pH monitoring. Gastro-esophageal reflux was detected in 32/41 subjects. In our patients the main symptoms were vomiting, regurgitation, failure-to-thrive, chronic respiratory problems such as asthma, apnea, recurrent pneumonia. All patients with GER were treated appropriately with prone positioning and medical therapy (prokinetic agent and, eventually, ranitidine). Successful treatment of the reflux was obtained in all patients. In our opinion the 24-hour intraesophageal pH monitoring is a highly diagnostic test to identify the presence of GER and evaluate its gravity.

Topics: Antiemetics; Benzamides; Child; Child, Preschool; Cisapride; Esophagus; Female; Gastroesophageal Reflux; Humans; Hydrogen-Ion Concentration; Infant; Infant, Newborn; Male; Monitoring, Physiologic; Piperidines; Posture; Serotonin Antagonists; Time Factors

Topics: Cisapride; Contraindications; Drug Interactions; Gastroesophageal Reflux; Gastrointestinal Diseases; Gastrointestinal Motility; Humans; Piperidines; Serotonin Antagonists

A higher frequency (25%) of gastrooesophageal reflux (GOR) has been previously reported in patients over 5 years old with cystic fibrosis compared with controls without cystic fibrosis. It was believed that GOR was caused by the complications of cystic fibrosis. We looked for GOR in all 26 children younger than 60 months who had cystic fibrosis diagnosed. They had a classical genetic profile and the usual scattered clinical manifestations for age. GOR was confirmed in 21 (81%): 20 by abnormal pH tracings and in one on a clinical basis. After at least one month of adjusted cystic fibrosis treatment, antireflux treatment (cisapride) was given to 16 patients and variables of GOR improved dramatically. Weight gain was significant and recurrent cough and wheeze disappeared. One year later half of the patients still suffered from GOR. GOR is a major problem in the early life of those with cystic fibrosis and is not the consequence of either respiratory or gastrointestinal complications as it improves with age whereas cystic fibrosis becomes worse with age.

Topics: Child, Preschool; Cisapride; Cough; Cystic Fibrosis; Female; Follow-Up Studies; Gastroesophageal Reflux; Humans; Hydrogen-Ion Concentration; Infant; Infant, Newborn; Male; Piperidines; Respiratory Sounds; Serotonin Antagonists; Weight Gain

Topics: Cisapride; Depression, Chemical; Female; Gastroesophageal Reflux; Heart Rate; Humans; Infant; Infant, Newborn; Male; Piperidines; Serotonin Antagonists

Topics: Administration, Oral; Cisapride; Gastroesophageal Reflux; Humans; Infant; Kidney Failure, Chronic; Piperidines; Serotonin Antagonists; Vomiting

Abnormal degrees of gastro-oesophageal reflux (GOR) were detected by 24 hour intraoesophageal pH measurement in 12 of 14 children (mean age 7.9 years; range 5 months-16 years) affected by cystic fibrosis and complaining of symptoms suggesting GOR. These patients underwent combined recording of distal oesophageal motility and intraluminal pH in order to investigate mechanisms of GOR. Inappropriate lower oesophageal sphincter relaxation was the most common mechanism of reflux in all patients. Other mechanisms (appropriate relaxation or lowered pressure of the lower oesophageal sphincter, increased intragastric pressure) were detected less frequently. Frequency of inappropriate lower oesophageal sphincter relaxations was significantly higher in patients with cystic fibrosis than in other study groups (symptomatic GOR, GOR disease complicated by respiratory complaints). Inappropriate lower oesophageal sphincter relaxations occurred with the same frequency in patients with cystic fibrosis and in a group of children with GOR disease complicated by oesophagitis. Abnormalities of distal oesophageal contractions such as decreased amplitude or uncoordinated waves were also recorded in cystic fibrosis patients. Seven patients with cystic fibrosis completed a therapeutic trial for eight weeks consisting of postural treatment and oral cisapride, a new prokinetic drug. The oesophageal acid exposure improved in only three patients. We conclude that pathologic GOR is commonly associated with cystic fibrosis. The predominant reflux mechanism in these patients is a transient inappropriate lower oesophageal sphincter relaxation rather than a low steady state basal lower oesophageal sphincter pressure.

Topics: Adolescent; Child; Child, Preschool; Cisapride; Cystic Fibrosis; Drainage, Postural; Esophagogastric Junction; Esophagus; Female; Gastroesophageal Reflux; Humans; Hydrogen-Ion Concentration; Infant; Male; Manometry; Peristalsis; Piperidines; Serotonin Antagonists; Time Factors

Topics: Child; Cisapride; Gastroesophageal Reflux; Gastrointestinal Diseases; Gastrointestinal Motility; Humans; Piperidines; Serotonin Antagonists

Cisapride was used to treat gastro-oesophageal reflux in seven children with neurodevelopmental disorders and in 15 children who were neurologically normal. 24-hour lower-oesophageal pH monitoring was carried out before and after treatment. The neurologically normal group had a statistically significant decrease after treatment in percentage time pH less than 4, but children with neurological abnormalities did not have a comparable improvement in reflux scores.

Topics: Acetylcholine; Brain Damage, Chronic; Cerebral Palsy; Child; Child, Preschool; Cisapride; Down Syndrome; Gastric Acidity Determination; Gastroesophageal Reflux; Humans; Infant; Myenteric Plexus; Piperidines; Serotonin Antagonists

Cisapride is a new prokinetic agent that acts at gastric emptying, esophagic peristalsis and the pressure of the low esophagic sphincter. In the present study we grave Cisapride for 12 weeks to 34 patients with severe pathologic gastroesophageal reflux and/or peptic esophagitis. The results show an important improvement of the clinic, pH monitoring, endoscopic and histologic alterations.

Topics: Cisapride; Esophagitis, Peptic; Female; Gastric Emptying; Gastric Juice; Gastroesophageal Reflux; Humans; Hydrogen-Ion Concentration; Male; Peristalsis; Piperidines; Serotonin Antagonists

Topics: Cholestasis; Cisapride; Gastroesophageal Reflux; Humans; Infant, Newborn; Infant, Premature; Piperidines; Serotonin Antagonists

Topics: Aged; Cisapride; Female; Gastric Acid; Gastroesophageal Reflux; Gastrointestinal Motility; Humans; Hydrogen-Ion Concentration; Male; Middle Aged; Piperidines; Time Factors

Topics: Cisapride; Dyspepsia; Gastric Emptying; Gastroesophageal Reflux; Humans; Intestinal Pseudo-Obstruction; Piperidines; Serotonin Antagonists

Topics: Acetylcholine; Cisapride; Dyspepsia; Gastric Emptying; Gastroesophageal Reflux; Gastrointestinal Motility; Humans; Peptic Ulcer; Piperidines; Serotonin Antagonists

Topics: Acetylcholine; Cisapride; Dose-Response Relationship, Drug; Dyspepsia; Gastric Emptying; Gastroesophageal Reflux; Humans; Myenteric Plexus; Piperidines; Serotonin Antagonists; Stomach

Topics: Cisapride; Gastric Emptying; Gastroesophageal Reflux; Humans; Piperidines; Serotonin Antagonists

Clinical evaluation and prolonged esophageal pH monitoring were performed before and during treatment with cisapride (0.3 mg/kg t.i.d.) for 1 month in 19 children with reflux-associated bronchopulmonary disease. Results (mean +/- SEM) show that cisapride significantly decreases the frequency of long duration (greater than 5 min) reflux episodes (from 9.7 +/- 0.7 to 5.7 +/- 1.2), the percentage of total time pH was less than 4 (from 15.9 +/- 2.5 to 7.7 +/- 1.1%), the percentage of time pH was less than 4 at night (from 18.0 +/- 3.9 to 4.9 +/- 1.5%), the duration of the longest reflux episodes (from 44.5 +/- 6.4 to 19.7 +/- 2.7 min), as well as the duration of reflux at night (from 100.1 +/- 28.0 to 28.2 +/- 10.1 min). The frequency of reflux episodes, however, remains unaffected by cisapride. Cough fits at night disappeared completely in 12 out of 13 children. We conclude that cisapride given for 1 month significantly decreased gastroesophageal reflux as well as cough episodes at night.

Topics: Bronchial Diseases; Child; Child, Preschool; Cisapride; Female; Gastroesophageal Reflux; Humans; Hydrogen-Ion Concentration; Infant; Lung Diseases; Male; Monitoring, Physiologic; Piperidines; Serotonin Antagonists

We studied the effects of positional treatment and cisapride (a new prokinetic agent) on the incidence and duration of gastroesophageal reflux in 22 infants (4-26 weeks old) in asleep, awake, fasted, and postcibal periods. In addition to gastroesophageal reflux (assessed by 24-h continuous esophageal pH monitoring), all infants presented with a disrupted irregular sleep pattern ("respiratory dysfunction") (assessed by a simultaneously performed cardiopneumogram). Reflux was particularly prominent during the sleep and fasted periods. Investigations (cardiopneumogram and esophageal pH monitoring) in the study population were repeated under treatment conditions (cisapride) after 13-16 days. All pH monitoring data with regard to the total investigation time decreased significantly (p less than 0.001). The treatment-related differences were largest in the asleep and fasted periods, but treatment data were not completely within normal ranges (established in age-matched asymptomatic infants), as they were for the awake periods. Associated symptoms of gastroesophageal reflux (belching, cough, nocturnal wheezing, irritability, and restlessness at night) were evaluated before and during treatment by history. A combination of positional treatment and cisapride seemed effective (objectivated by pH monitoring data and clinical improvement); cisapride did not cause adverse reactions. The disrupted sleep pattern improved significantly or disappeared (p less than 0.001) in all infants. These data suggest that in a number of young infants, gastroesophageal reflux may be associated with a disturbed, irregular sleep of poor quality, which is characterized by a typical breathing pattern (multiple, irregularly repeated, short apneas).

Topics: Cisapride; Gastroesophageal Reflux; Humans; Infant, Newborn; Piperidines; Posture; Sleep Apnea Syndromes

Ten infants and newborns with recently and successively diagnosed cystic fibrosis (CF) were investigated for possible gastroesophageal reflux (GER) by means of pH monitoring over a period of about 20 h. All these patients showed abnormal GER. These patients had a scattered clinical profile of either respiratory or gastrointestinal (GI) manifestations, a poor weight gain, or a combination of these under classical CF treatment. Eight patients underwent treatment with cisapride, a new, potent GI prokinetic drug. This treatment was successful, as documented by almost normal pH monitorings, performed during cisapride therapy, in seven infants. The previous clinical disturbances were evaluated on clinical follow-up study. These significantly improved during cisapride, suggesting that GER can trigger many complications in CF. Anti-reflux therapy could be an important part of the treatment of young CF patients.

Topics: Child, Preschool; Cisapride; Cystic Fibrosis; Female; Follow-Up Studies; Gastroesophageal Reflux; Humans; Hydrogen-Ion Concentration; Infant; Infant, Newborn; Male; Monitoring, Physiologic; Piperidines

Foregut drug receptors permit inotropic manipulation of the dysmotility pattern associated with gastroesophageal reflux (GER). Two prokinetic agents, ie, Metoclopramide and Cisapride were assessed in 18 infants with severe GER (mean age 6.5 months) by means of 18-hour continuous intraesophageal pH monitoring. Six parameters were recorded, and the results compared before and during pharmacologic stimulation. Both agents improved the parameters measured, but Cisapride was found to be more effective in enhancing lower esophageal sphincter competence and esophageal motor function. Long-term assessment of both agents in the management of GER in infants is indicated.

Topics: Cisapride; Esophagus; Gastroesophageal Reflux; Humans; Hydrogen-Ion Concentration; Infant; Metoclopramide; Piperidines

Topics: Benzamides; Chemical Phenomena; Chemistry; Cisapride; Dexamethasone; Digestive System; Domperidone; Gastric Emptying; Gastroesophageal Reflux; Gastrointestinal Diseases; Gastrointestinal Motility; Humans; Kinetics; Metoclopramide; Naloxone; Phenytoin; Piperidines; Proglumide; Vomiting

The important nervous and hormonal regulation mechanisms which play a role in the prevention of esophageal reflux are discussed. By manometry of the inferior esophageal sphincter, esophageal pH-metry and acid clearance it is possible to demonstrate disturbance of the continency function in most patients with reflux esophagitis. The value of these methods is compared with other conventional methods in 40 patients. The medical means of restoring esophageal continency are reviewed.

Topics: Alginates; Benzimidazoles; Diagnostic Errors; Diet, Reducing; Dietary Fats; Domperidone; Electrodes; Endoscopy; Esophagogastric Junction; Female; Gastroesophageal Reflux; Hernia, Hiatal; Humans; Hydrogen-Ion Concentration; Male; Metoclopramide; Middle Aged; Muscle Tonus; Piperidines; Pressure; Radiography

Increasing the resting lower esophageal sphincter (LES) tone is a useful method of preventing gastroesophageal reflux. The effects of a new antiemetic, domperidone, on LES were studied in 28 subjects. Group I included eight normal nonpregnant control subjects. The remaining 20 pregnant women were divided into two groups, Group II and III--ten parturients without and ten with symptoms of heartburn. Domperidone increased LES pressure by 19, 11 and 10 cm H2O in Groups I, II and III, respectively (P less than 0.05). Domperidone may be a valuable premedicant in some patients to decrease the chance of gastro-esophageal reflux.

Topics: Adolescent; Adult; Anesthesia, Obstetrical; Benzimidazoles; Domperidone; Esophagogastric Junction; Female; Gastroesophageal Reflux; Heartburn; Humans; Muscle Tonus; Piperidines; Preanesthetic Medication; Pregnancy; Pressure