piperidines and Esophagitis--Peptic

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

Topics: Anti-Ulcer Agents; Cisapride; Combined Modality Therapy; Esophagitis, Peptic; Female; Gastric Acidity Determination; Histamine H2 Antagonists; Humans; Male; Middle Aged; Omeprazole; Piperidines

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

Topics: Cisapride; Esophagitis, Peptic; Histamine H2 Antagonists; Humans; Omeprazole; Piperidines; Serotonin Antagonists; Sucralfate

The various therapeutic approaches for reflux esophagitis are to increase the competence of the antireflux barrier, to enhance esophageal clearance, to improve gastric emptying and pyloric sphincter competence, to coat damaged tissue, and, especially, to reduce the volume and pH of gastric contents. Of the prokinetic agents, cisapride is the only drug with proven benefit. Single-agent therapy with conventional-dose H2-receptor antagonists or sucralfate results in similar degrees of symptom relief and healing. Post-evening meal (PEM) dosing of H2-receptor antagonists appears to be a rational method of suppressing late evening gastric acidity, but on balance the symptomatic response of twice daily dosing is superior to once daily dosing. More rapid symptom relief and healing are achieved with high-dose H2-receptor antagonists and omeprazole. The significance of sustained a(hypo)chlorhydria remains to be established. To prolong the symptomatic and/or endoscopic remission, the therapy has to be continued long-term with high-dose H2-receptor antagonist, cisapride either alone or in combination with H2-receptor antagonist, or sucralfate with or without H2-receptor antagonist. In the elderly or complicated patient long-term omeprazole may be a justified alternative.

Topics: Anti-Ulcer Agents; Cisapride; Esophagitis, Peptic; Histamine H2 Antagonists; Humans; Omeprazole; Piperidines; 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

The various therapeutic approaches for reflux oesophagitis are to enhance oesophageal clearance, to coat damaged tissue, to increase the competence of the reflux barrier, to reduce the volume and pH of gastric contents, and to improve gastric emptying and pyloric sphincter competence. Unfortunately, drug therapy of reflux oesophagitis is not yet ideal. Of the prokinetic agents, cisapride is the only drug with proven benefit. Single-agent therapy with the H2-receptor antagonists or sucralfate results in similar degrees of symptom relief and healing. Rapid symptom relief and healing are achieved by omeprazole; however, the significance of sustained achlorhydria remains to be established. Dinnertime dosing of cimetidine appears to be a rational method of suppressing late-evening gastric acidity. Patients with severe or recalcitrant disease should not be treated with conventional therapy alone; the results of controlled studies of combination therapy with the H2-receptor antagonists and sucralfate or cisapride will be viewed with interest.

Topics: Antacids; Bethanechol; Bethanechol Compounds; Cisapride; Domperidone; Esophagitis, Peptic; Histamine H2 Antagonists; Humans; Metoclopramide; Omeprazole; Piperidines; Serotonin Antagonists; Sucralfate

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: Cisapride; Esophagitis, Peptic; Histamine H2 Antagonists; Humans; Omeprazole; Piperidines

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

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

There has been no study on the efficacy of lafutidine for patients with reflux esophagitis in Korea.. To evaluate the efficacy of a new-generation histamine-2 receptor antagonist, lafutidine, in comparison with famotidine in patients with reflux esophagitis.. This was a randomized, double-blind, non-inferiority trial enrolling patients with erosive esophagitis. The efficacy and safety of 20 mg lafutidine (treatment group) were compared with those of 40 mg famotidine (control group) and 20 mg omeprazole (reference group). The primary endpoint was the complete healing rates of reflux esophagitis on endoscopy after 8 weeks of treatment. The non-inferiority margin was assumed to be -15 %.. The healing rates of reflux esophagitis on endoscopy after 8 weeks of treatment were 70.14 % (101/144) in the lafutidine, 63.45 % (92/145) in the famotidine, and 85.71 % (126/147) in the omeprazole group. The difference in healing rates between the lafutidine and famotidine groups was 6.69 % (95 % confidence interval = [-4.14 to 17.52]). In addition, lafutidine was superior to famotidine in clinical improvement (53.73 % vs. 39.55 %, P = 0.0200).. Lafutidine was non-inferior to famotidine in healing of reflux esophagitis. Lafutidine, however, was superior to famotidine in terms of symptom relief of reflux esophagitis.

Topics: Acetamides; Adult; Aged; Anti-Ulcer Agents; Double-Blind Method; Esophagitis, Peptic; Esophagoscopy; Famotidine; Female; Humans; Male; Medication Adherence; Middle Aged; Omeprazole; Piperidines; Pyridines; Republic of Korea; Severity of Illness Index; Treatment Outcome

To evaluate the efficacy of lafutidine (20mg) , famotidine (40mg) and placebo in patients with mild reflux esophagitis (Grades A and B according to the Los Angeles classification) , a double-blind, multicenter, randomized clinical trial was performed for the first time in Japanese patients. In addition to each physician's evaluation, efficacy was evaluated by judging panels using images submitted by each physician. The healing rate after 8 weeks for lafutidine, famotidine and placebo were 67.7%, 56.6% and 41.2%, respectively. Lafutidine was significantly more effective than placebo (p=0.002, according to the judging panels) . Based on the evaluation of endoscopic images by the judging panels, 91 (27.1%) of 336 images submitted by each physician were judged to not be mucosal breaks. Judging panels are considered one of the ways to resolve the problem of the need to unify the criteria.

Topics: Acetamides; Adult; Aged; Asian People; Esophagitis, Peptic; Famotidine; Female; Histamine H2 Antagonists; Humans; Male; Middle Aged; Piperidines; Pyridines

This randomized, double-blind, controlled study examined whether lafutidine is superior to placebo and non-inferior to famotidine in terms of healing rates as assessed by endoscopy in Japanese patients with mild reflux esophagitis. Safety and improvement in symptoms of heartburn were also assessed.. Patients with an endoscopic diagnosis of grade A or B reflux esophagitis according to the Los Angeles classification were randomly assigned to receive lafutidine (20 mg/day), famotidine (40 mg/day), or placebo for 8 weeks.. Of the 584 patients enrolled in the study, 447 were diagnosed to have grade A or B reflux esophagitis by the Endoscopic Assessment Committee. Healing rates at 8 weeks were 71.0% (115/162) in the lafutidine group, 61.4% (86/140) in the famotidine group, and 9.7% (14/145) in the placebo group. Lafutidine was thus demonstrated to be superior to placebo and non-inferior to famotidine. As compared with placebo, lafutidine significantly improved symptoms of heartburn.. Lafutidine has a high endoscopic healing rate and improves symptoms of heartburn in patients with mild reflux esophagitis. Lafutidine is considered a promising treatment option for mild reflux esophagitis.

Topics: Acetamides; Double-Blind Method; Esophagitis, Peptic; Esophagoscopy; Famotidine; Female; Heartburn; Histamine H2 Antagonists; Humans; Japan; Male; Middle Aged; Piperidines; Pyridines; Treatment Outcome

Saliva plays an important role in esophageal acid clearance. Reduction in salivary function has been considered in the pathogenesis of reflux esophagitis. Cisapride, a prokinetic agent, has been reported effective for treating mild-to-moderate grade gastroesophageal reflux disease. Some studies have shown that cisapride increases saliva volume and acid-buffering capacity. The aim of this study was to evaluate the effect of cisapride on salivary gland function by means of dynamic salivary scintigraphy.. Fifty-five patients with endoscopic reflux esophagitis (Savary-Miller Grades I-II) were enrolled in this study. In Group 1 (n = 29), patients were evaluated during the fasting state, both before and after cisapride treatment (5 mg, 3 times/day, before meals, for 2 wk). In Group 2 (n = 26), patients were evaluated during the postprandial state, both before and after cisapride treatment. Uptake ratio (UR) and excretion ratio (ER) of the salivary gland in each group were compared using the paired Student's t-test.. In Group 1, no significant differences were found in UR or ER after cisapride treatment. However, in Group 2, ER increased significantly after treatment (p < 0.01), but UR did not show any significant change.. Cisapride can increase the secretion function of salivary glands during the postprandial phase but not the fasting phase.

Topics: Cisapride; Esophagitis, Peptic; Fasting; Female; Gastrointestinal Agents; Humans; Male; Middle Aged; Piperidines; Postprandial Period; Radionuclide Imaging; Radiopharmaceuticals; Salivary Glands; Salivation; Sodium Pertechnetate Tc 99m

Topics: Adult; Anti-Ulcer Agents; Cisapride; Drug Therapy, Combination; Esophagitis, Peptic; Esophagoscopy; Female; Humans; Long-Term Care; Male; Middle Aged; Omeprazole; Piperidines; Ranitidine; Treatment Outcome

There are few data on the role of prokinetic agents as maintenance therapy in moderately severe reflux oesophagitis despite the high relapse rate of this condition after healing.. To determine whether cisapride is more effective than placebo as maintenance therapy after healing of moderate erosive oesophagitis in two respects: first, in preventing symptomatic relapse and preserving quality of life; and, second, in improving oesophageal motor function.. Forty-two patients whose grade II-III oesophagitis had been healed with omeprazole were randomized to receive either cisapride 20 mg nocte or placebo for 6 months. Oesophageal pH monitoring and manometry were performed before starting maintenance therapy and after 4 weeks, and symptomatic status and quality of life were assessed at weeks 0, 4, 13 and 26.. After 4 weeks of maintenance therapy, lower oesophageal sphincter pressure improved in the cisapride group (16.4-21.9 mmHg, P = 0.01) but not in the placebo group (25.5-22.7 mmHg, P = 0.2). Oesophageal pH monitoring showed no significant changes in either group. Sixteen (76%) cisapride patients and 12 (57%) placebo patients withdrew within 4 weeks owing to symptomatic relapse (P = 0.2). After 26 weeks, 21 (100%) cisapride and 17 (81%) placebo patients had relapsed (log-rank analysis of survival time P = 0.07). Quality of life parameters deteriorated in both treatment groups to a similar degree.. Maintenance therapy with cisapride 20 mg nocte improves the lower oesophageal sphincter pressure in patients whose oesophagitis has been healed with omeprazole. However, cisapride is no better than placebo in preventing symptomatic relapse or deterioration in quality of life.

Topics: Adult; Anti-Ulcer Agents; Cisapride; Double-Blind Method; Esophagitis, Peptic; Female; Humans; Hydrogen-Ion Concentration; Male; Middle Aged; Piperidines; Quality of Life; Treatment Outcome

In an international, multicentre, double-blind trial, to document the therapeutic equivalence of two dosing regimens of cisapride on endoscopic healing and symptom improvement in patients with proven reflux oesophagitis grade I or II (Savary-Miller).. Four hundred and seven patients were randomly allocated to treatment with either cisapride 10 mg q.d.s. or cisapride 20 mg b.d. for 8-12 weeks depending on whether complete healing was found at endoscopy. The primary parameters of efficacy were cure of oesphagitis and improvement of the reflux symptom score.. The healing rates at endpoint were 73% in both treatment groups. The mean total reflux symptom score decreased from baseline to endpoint from 7.9-2.1 (cisapride 10 mg q.d.s) and 7.9-2.5 (cisapride 20 mg b.d.). Each of the two treatment regimens was well tolerated. The most frequently (6.9%) reported adverse event (diarrhoea) was mild or moderate in most cases and can be explained by pharmacological action of cisapride.. The results of the study demonstrate that cisapride 10 mg q.d.s. and 20 mg b.d. are equivalent in terms of efficacy and safety in the treatment of reflux oesophagitis.

Topics: Adolescent; Adult; Aged; Anti-Ulcer Agents; Cisapride; Dosage Forms; Double-Blind Method; Esophagitis, Peptic; Female; Humans; Male; Middle Aged; Piperidines; Serotonin Antagonists; Treatment Outcome

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

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

Patients with reflux esophagitis have a high rate of relapse within one year after therapy is discontinued.. We enrolled 175 adults with endoscopy-confirmed reflux esophagitis in a prospective study comparing five maintenance therapies. All the patients were initially treated with omeprazole (40 mg orally once a day) for four to eight weeks, and healing was confirmed by endoscopy. Participants were then stratified according to their initial grade of esophagitis and randomly assigned to 12 months of treatment with one of the following: cisapride (10 mg three times a day), ranitidine (150 mg three times a day), omeprazole (20 mg per day), ranitidine plus cisapride (10 mg three times a day), or omeprazole plus cisapride. Endoscopy was repeated after 6 and 12 months of treatment; the endoscopists were blinded to the treatment assignments. Remission was defined as the absence of esophageal lesions on scheduled or unscheduled follow-up endoscopy.. In an intention-to-treat analysis, the numbers of patients in continued remission at 12 months were 19 of 35 (54 percent) in the cisapride group, 17 of 35 (49 percent) in the ranitidine group, 28 of 35 (80 percent) in the omeprazole group, 23 of 35 (66 percent) in the ranitidine-plus-cisapride group, and 31 of 35 (89 percent) in the omeprazole-plus-cisapride group. Omeprazole was significantly more effective than cisapride (P = 0.02) or ranitidine (P = 0.003), and combination therapy with omeprazole plus cisapride was significantly more effective than cisapride alone (P = 0.003), ranitidine alone (P < 0.001), or ranitidine plus cisapride (P = 0.03). Ranitidine plus cisapride was significantly better than ranitidine alone (P = 0.05).. For maintenance treatment of reflux esophagitis, omeprazole alone or in combination with cisapride is more effective than ranitidine alone or cisapride alone, and the combination of omeprazole and cisapride is more effective than ranitidine plus cisapride.

Topics: Adult; Anti-Ulcer Agents; Cisapride; Disease-Free Survival; Drug Therapy, Combination; Esophagitis, Peptic; Esophagoscopy; Female; Histamine H2 Antagonists; Humans; Male; Middle Aged; Omeprazole; Piperidines; Prospective Studies; Ranitidine; Recurrence; Severity of Illness Index; Single-Blind Method; Treatment Outcome

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

Oesophagitis is usually a chronic condition. Healing with omeprazole is often followed by early relapse. Combination treatment and subsequent maintenance treatment with the prokinetic cisapride may be of benefit in relapse prevention.. Patients with endoscopically proven oesophagitis, grade I (n = 120) or grade II (n = 105), were randomized in an open fashion to receive 8 weeks of healing treatment with omeprazole 20 mg daily (OM) followed by 12 months of follow-up without maintenance treatment, or 8 weeks of combined treatment of omeprazole 20 mg daily plus cisapride 5 mg t.d.s. (OMCIS) followed by 12 months of maintenance treatment with cisapride 5 mg t.d.s. (CIS). Only the patients healed after acute treatment were included in the 12-month follow-up study for evaluation of endoscopic relapse.. In the group of patients with oesophagitis grade I (n = 58 receiving OM, n = 62 receiving OMCIS), healing rates were comparable for both acute treatment regimens. In the group of patients with grade II (n = 54 receiving OM, n = 51 receiving OMCIS), the healing rates were slightly but not significantly in favour of OMCIS after 4 and 8 weeks of treatment. During the 12 months of follow-up, CIS maintenance treatment was associated with a significant reduction of relapse. In the group of patients with initial grade I oesophagitis, the relapse rates after 3 months were 20% in the OMCIS group receiving CIS maintenance treatment, compared to 48% in the group healed on OM without further maintenance treatment (P = 0.04). After 6 months, these relapse rates were 31% and 85% respectively (P < 0.001), and after 12 months 40% and 96% (P < 0.001). In the group of patients with initial grade II oesophagitis, they were, respectively, 20% vs. 39% after 3 months (P = 0.056), 41% vs. 78% after 6 months (P < 0.001) and 52% vs. 95% after 12 months (P < 0.001).. The results of this open study indicate that continued treatment with cisapride 5 mg t.d.s. (after initial healing with omeprazole 20 mg daily plus cisapride 5 mg t.d.s.) is beneficial in the long-term management of grade I and II oesophagitis: this treatment approach significantly reduces the high relapse rate observed after stopping healing treatment with omeprazole.

Topics: Adult; Aged; Cisapride; Drug Administration Schedule; Drug Therapy, Combination; Esophagitis, Peptic; Female; Humans; Male; Middle Aged; Omeprazole; Piperidines; Recurrence

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

To compare the efficacy of treatment for 8 or 12 weeks with a combination of 150 mg ranitidine twice daily plus 20 mg cisapride twice daily with ranitidine 150 mg twice daily alone in patients with moderate-to-severe reflux oesophagitis.. A double-blind, randomized, parallel-group clinical trial.. Forty-two out-patient centres in the UK, Germany, Ireland, Denmark and South Africa.. A total of 344 symptomatic patients with endoscopically confirmed reflux oesophagitis (Hetzel grade 3 or 4) were randomly assigned to receive the study medication.. Patients underwent a follow-up endoscopy after 8 weeks' treatment. Healing was defined as Hetzel grade 0 or 1 upon endoscopy. Patients with unhealed oesophagitis continued their allocated treatment regimen for a further 4 weeks before undergoing a repeat endoscopy.. The primary efficacy analysis was based on a comparison of 12-week cumulative healing rates between the two groups.. A statistically significant difference (P = 0.015) in the cumulative healing rate was observed between patients given ranitidine plus cisapride (82%) and those given ranitidine alone (71%). Oesophagitis in patients who received the combination was twice as likely to heal as that in patients who received ranitidine alone.. A combination of 150 mg ranitidine twice daily and 20 mg cisapride twice daily is a safe and effective treatment for moderate-to-severe reflux oesophagitis and offers increased efficacy over ranitidine alone.

Topics: Administration, Oral; Adolescent; Adult; Aged; Aged, 80 and over; Cisapride; Double-Blind Method; Drug Therapy, Combination; Esophagitis, Peptic; Esophagoscopy; Female; Follow-Up Studies; Histamine H2 Antagonists; Humans; Logistic Models; Male; Middle Aged; Piperidines; Ranitidine; Serotonin Antagonists; Treatment Outcome

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

The effect of ranitidine and cisapride on acid reflux and oesophageal motility was investigated in 18 patients with endoscopically verified erosive reflux oesophagitis. Each patient was treated with placebo, ranitidine (150 mg twice daily), and ranitidine (150 mg twice daily) plus cisapride (20 mg twice daily) in a double blind, double dummy, within subject, three way cross over design. Oesophageal acidity and motility were monitored under ambulatory conditions for 24 hours on the fourth day of treatment, after a wash out period of 10 days during which patients received only antacids for relief of symptoms. Acid reflux was monitored by a pH electrode located 5 cm above the lower oesophageal sphincter. Intraoesophageal pressure was simultaneously recorded from four transducers placed 20, 15, 10, and 5 cm above the lower oesophageal sphincter. Upright reflux was three times higher than supine reflux (median (range) 13.3 (3.7-35.0)% v 3.7 (0-37.6)% of the time with pH < 4.0, p < 0.01, n = 18). Compared with placebo, ranitidine decreased total reflux (from 10.0 (3.2-32.6)% to 6.4 (1.2-22.9)%, p < 0.01), upright reflux (p < 0.05), supine reflux (p < 0.001), and postprandial reflux (p < 0.01), but did not affect oesophageal motility. The combination of ranitidine with cisapride further diminished the acid reflux found with ranitidine--that is, cisapride led to an additional reduction of total reflux (from 6.4 (1.2-22.9)% to 3.7 (1.0-12.7)%, p < 0.01), supine reflux (p < 0.05), and postprandial reflux (p < 0.05). Cisapride also reduced both the number (p<0.01) and duration (p<0.05) of reflux episodes and significantly increased amplitude, duration, and propagation velocity of oesophageal contractions (p<0.05) but did not affect the number of contractions. The findings show that the 30% reduction of oesophageal acid exposure achieved by a conventional dose of ranitidine (150 mg twice daily) can be improved to more than 60% by combination with cisapride (20 mg twice daily). The cisapride induced increase in oesophageal contractile force and propagation velocity seems to enhance the clearance of gastro-oesophageal reflux. Combination of a histamine H2 receptor antagonist with a prokinetic agent may therefore provide an alternative treatment for reflux oesophagitis.

Topics: Adult; Aged; Anti-Ulcer Agents; Cisapride; Double-Blind Method; Drug Therapy, Combination; Esophageal Diseases; Esophagitis, Peptic; Esophagogastric Junction; Female; Gastric Acid; Gastrointestinal Motility; Humans; Hydrogen-Ion Concentration; Male; Manometry; Middle Aged; Monitoring, Physiologic; Muscle Contraction; Muscle, Smooth; Piperidines; Ranitidine; Time Factors

We conducted a double-blind study comparing two dosage regimens of a prokinetic drug, cisapride (10 mg q.d.s. and 20 mg b.d.), with a low dose of a H2-receptor antagonist (150 mg ranitidine b.d.) in the treatment of 155 patients with reflux oesophagitis as determined by endoscopy. The active treatment took 8 to 12 weeks depending on whether complete healing was found at endoscopy. Improvement in oesophagitis grades from baseline to endpoint was observed in 68% of patients in the 10 mg cisapride q.d.s. group, 83% in the cisapride 20 mg b.d. group and 81% in the ranitidine group (N.S.). At endpoint, the percentages of endoscopically cured patients with initial grades I or II were 52% for 10 mg cisapride q.d.s., 71% for 20 mg cisapride b.d. and 80% for ranitidine (N.S.). The proportional improvement of the overall reflux symptom score (60%) also showed no significant difference between the three groups. In the treatment of mild reflux oesophagitis (grades I and II) similar results can be expected from 20 mg cisapride b.d. and 150 mg ranitidine b.d. As the results of the two dosage regimens of cisapride were not different, the 20 mg twice daily regimen is preferred because it will improve patient compliance. It is concluded that in reflux oesophagitis grades I and II, the efficacy of 20 mg cisapride b.d. and 150 mg ranitidine b.d. are broadly similar.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Aluminum Hydroxide; Antacids; Cisapride; Double-Blind Method; Drug Administration Schedule; Drug Combinations; Dyspepsia; Esophagitis, Peptic; Esophagoscopy; Humans; Magnesium Hydroxide; Middle Aged; Piperidines; Ranitidine; Serotonin Antagonists; Single-Blind Method

The effect of a prokinetic agent, cisapride, on the relapse of reflux esophagitis was investigated in a randomized, double-blind trial conducted in 443 patients whose esophagitis had previously been healed with an acid antisecretory drug. Patients received cisapride, 20 mg at night, cisapride 10 mg twice daily, or placebo for 12 months or until endoscopic relapse was confirmed endoscopically. In 88% of all patients (respectively 133, 132, and 124), endoscopic data were available at discontinuation of treatment. In comparison with placebo, the two cisapride regimens prolonged both the time to endoscopically confirmed relapse (Kaplan-Meier analysis; P = 0.001) and the time to symptomatic relapse (P = 0.012). The life-table endoscopic relapse rates at 12 months were 51% for placebo, 32% for cisapride 20 mg at night (P = 0.005), and 34% for cisapride 10 mg twice daily (P = 0.02). Patients with more severe esophagitis before healing relapsed more rapidly during maintenance therapy, regardless of the treatment regimen. Adverse events were infrequent in all three groups. These findings indicate that maintenance treatment with the prokinetic drug cisapride prevents the relapse of esophagitis after it has been healed by acid antisecretory therapy.

Topics: Cisapride; Double-Blind Method; Drug Administration Schedule; Esophagitis, Peptic; Esophagoscopy; Female; Humans; Life Tables; Male; Middle Aged; Piperidines; Recurrence; Serotonin Antagonists

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

Maintenance treatment with cisapride was evaluated in 298 patients in whom reflux oesophagitis had been healed with antisecretory drugs. Initially, 34% of the patients had grade-I oesophagitis, 33% had grade II, and 33% had grade III. The patients were treated with 20 mg cisapride twice daily or placebo for 6 months or until endoscopic relapse was shown if this occurred earlier. Survival analysis showed that cisapride significantly prolonged the time to endoscopic relapse in grade-I patients (P = 0.02). The intergroup difference in symptomatic relapse in all patients was also significant (P = 0.010). The effect of cisapride was less clearcut in grade II or III, and/or in patients healed with omeprazole. Factors associated with early relapse were placebo therapy, prior omeprazole therapy, duration of pre-trial symptomatic period, and initial endoscopic severity grade. Adverse experiences were limited; diarrhoea was reported by 9% of the cisapride patients.

Topics: Anti-Ulcer Agents; Cisapride; Double-Blind Method; Esophagitis, Peptic; Female; Humans; Male; Middle Aged; Omeprazole; Piperidines; Recurrence; Serotonin Antagonists; Survival Analysis

Altogether, 138 patients were included in a study aimed at evaluating the effect of cisapride on healing and relapse of oesophagitis shown endoscopically. In the first phase of the study cisapride was given in an open fashion at 10 mg four times a day for 8 to 16 weeks, and healing was obtained in 69% of patients. Healing occurred later in patients with grades II to IV oesophagitis. The total score for reflux symptoms decreased by 67%. Eighty of the healed patients were included in the second phase. They were randomly assigned to double blind treatment with either cisapride 10 mg (n = 37) or placebo (n = 43) twice a day. Control endoscopy was performed when symptoms recurred or at the end of the six month trial. The cumulative percentage of patients in remission was higher (p = 0.06, survival analysis) in the cisapride group than in the placebo group, the relapse rates being 20% and 39%. The duration of remission tended to be longer in patients with a lower initial degree of oesophagitis. Adverse effects were no more frequent with cisapride than with placebo. In conclusion, cisapride is efficacious in healing oesophagitis, and, unlike other gastrointestinal prokinetic drugs or low dose cimetidine (400-800 mg daily) or ranitidine (150 mg daily), it may prevent relapse of oesophagitis.

Topics: Adolescent; Adult; Aged; Cisapride; Double-Blind Method; Esophagitis, Peptic; Esophagus; Female; Humans; Male; Middle Aged; Piperidines; Prospective Studies; Recurrence; Remission Induction

The clinical relevance of cispride's stimulating effects on lower oesophageal motility was studied in 19 patients with documented (endoscopy, biopsy) grade II or III oesophagitis. Patients were treated for 8 or 16 weeks (depending essentially on whether the result was cure or failure) with 10 mg of cisapride four times a day (n = 11) or placebo (n = 8). Cisapride was superior to placebo with regard to mucosal healing (p less than 0.001) and symptomatic improvement (p less than 0.05): at the end of treatment, healing (grade 0) was observed in 8 cisapride patients, against 1 placebo patient, and reflux symptoms had disappeared in 7 and 1 patients, respectively. In conclusion, cisapride was of significant benefit to oesophagitis patients and was well tolerated.

Topics: Adult; Cisapride; Double-Blind Method; Esophagitis, Peptic; Esophagus; Humans; Peristalsis; Piperidines; Randomized Controlled Trials as Topic; Serotonin Antagonists; Stimulation, Chemical

Topics: Adolescent; Adult; Aged; Cisapride; Clinical Trials as Topic; Double-Blind Method; Esophageal Neoplasms; Esophagitis, Peptic; Humans; Middle Aged; Piperidines; Precancerous Conditions; Ranitidine; Serotonin Antagonists

Topics: Adult; Antacids; Cisapride; Double-Blind Method; Esophagitis, Peptic; Female; Humans; Male; Piperidines; Randomized Controlled Trials as Topic; Ranitidine; Serotonin Antagonists

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

The efficacy of cisapride, as compared with cimetidine, in the treatment of erosive esophagitis was studied in a double-blind trial. One hundred and twenty-nine patients were assigned to one of four dosage schedules: cisapride 10 mg b.i.d. (20 mg group) or q.i.d. (40 mg group), or cimetidine 400 mg b.i.d. (800 mg group) or q.i.d. (1600 mg group). Treatment lasted 8 to 12 weeks. The degree of esophagitis and the severity of diurnal and nocturnal heartburn and regurgitation were significantly (p less than 0.01) reduced in the four treatment groups. Endoscopy did not show any significant differences among the four groups, although cisapride tended to be more effective in moderate to severe esophagitis, in which cases mucosal healing (i.e. absence of erosions and ulcers) was observed in 69%, 64%, 55% and 55% of the patients treated with cisapride 40 mg, cisapride 20 mg, cimetidine 1600 mg and cimetidine 800 mg. Improvement in reflux symptoms in the two cisapride groups was not significantly different from that in the cimetidine 1600 mg group, but was better (p less than 0.05) than that in the cimetidine 800 mg patients. The severity score for all reflux symptoms had decreased by 79%, 74% (cisapride 40 mg and 20 mg), 69% and 57% (cimetidine 1600 mg and 800 mg) by the end of treatment. These results show that cisapride is at least as effective as acid-suppressing therapy in patients with reflux esophagitis, and is therefore a valuable alternative to it.

Topics: Cimetidine; Cisapride; Double-Blind Method; Drug Administration Schedule; Esophagitis, Peptic; Female; Gastrointestinal Motility; Humans; Male; Middle Aged; 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

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

The healing effect of the prokinetic drug cisapride (10 mg q.i.d.) on esophageal lesions, and its therapeutic control of gastroesophageal reflux symptoms were compared with the effects of the H2-antagonist ranitidine (150 mg b.i.d. + placebo b.i.d.) in a double-blind trial. In each group, 28 patients with Savary-Miller Grade I or II esophagitis were treated for 6 or 12 weeks. At the end of treatment, follow-up endoscopy showed that mucosal lesions were absent in 89% of the cisapride patients and in 79% of the ranitidine patients. In addition, 86% and 82% of the patients in the cisapride and the ranitidine group, respectively, had no, or only mild, reflux symptoms. Minor side effects were experienced in both groups. From these data, cisapride appears to be as effective as ranitidine in controlling reflux symptoms and in promoting the healing of mucosal lesions in milder forms of reflux esophagitis.

Topics: Cisapride; Clinical Trials as Topic; Double-Blind Method; Esophagitis, Peptic; Female; Humans; Male; Middle Aged; Piperidines; Random Allocation; Ranitidine

In a 6 to 12-week double-blind trial, the effect of cisapride (10 mg q.i.d.) was compared with that of placebo in 63 patients with esophagitis confirmed by endoscopy and/or biopsy. In only one patient (3%) in the cisapride group but in 43% of the placebo patients (p = 0.001), symptoms had not improved after 6 weeks. Forty patients continued treatment until week 12. At that time, control endoscopy showed a significantly (p = 0.005) higher rate of healing (no erosions, ulcers, or bleeding mucosa) in the cisapride patients (63%) than in the placebo patients (12%). At week 12, only three of the 21 cisapride patients still had moderate reflux symptoms, whereas eight of the 19 placebo patients had moderate or severe symptoms (p less than 0.05). Cisapride patients also took significantly (p less than 0.001) less antacids during the trial. These results show that cisapride, 10 mg q.i.d., heals esophagitis lesions and greatly reduces associated symptoms. The treatment was well tolerated.

Topics: Adult; Cisapride; Double-Blind Method; Esophagitis, Peptic; Esophagoscopy; Female; Humans; Male; Middle Aged; Multicenter Studies as Topic; Peristalsis; Piperidines; Placebos; Random Allocation

Combined treatment with cimetidine 1 g daily and cisapride 40 mg daily in patients with endoscopically diagnosed severe reflux oesophagitis was compared with single drug therapy (cimetidine and placebo). At the end of the six to 12 weeks treatment, 11 (46%) of the 24 patients under single drug therapy were endoscopically healed and three were improved. In contrast, 16 (70%) of the 23 patients under combined therapy were healed and all of the remainder were improved (p = 0.025). The severity of diurnal and nocturnal heartburn, decreased significantly more (p less than 0.05) on cimetidine + cisapride than on cimetidine + placebo. The combined treatment was well tolerated. These results suggest that combined therapy with cisapride and cimetidine may be useful in patients with severe reflux oesophagitis.

Topics: Adult; Aged; Cimetidine; Cisapride; Clinical Trials as Topic; Double-Blind Method; Drug Combinations; Esophagitis, Peptic; Esophagoscopy; Female; Heartburn; Humans; Male; Middle Aged; Piperidines; 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

Topics: Benzimidazoles; Clinical Trials as Topic; Domperidone; Double-Blind Method; Esophagitis, Peptic; Gastric Emptying; Gastrointestinal Motility; Humans; Piperidines; Random Allocation

Gastroesophageal reflux disease is considered to be caused primarily by gastric juice refluxed into the esophagus. Here, we investigated the possible involvement of host defense mechanisms in the development of acute reflux esophagitis using lafutidine, a histamine H(2) receptor antagonist (H(2)RA) with proven gastric mucosal protective effects.. The ligation of both the pylorus and the forestomach of SD rats under anesthesia caused hemorrhagic lesions in the esophageal mucosa at 6 h. Lesion formation was significantly inhibited by treatment with H(2)RAs, including the conventional H(2)RAs famotidine and cimetidine as well as lafutidine. The maximum suppressive abilities of these agents were similar to that of the proton pump inhibitor lansoprazole. Interestingly, unlike famotidine, lafutidine at low doses significantly suppressed esophagitis without inhibiting gastric acid secretion. Note that neither lafutidine nor famotidine inhibited hexosamine output in gastric juice samples obtained 3 h after ligation. Additionally, the protective effect of lafutidine, but not of famotidine, was partly attenuated by the denervation of capsaicin-sensitive afferent nerves with a large dose of capsaicin.. The present results indicate that esophageal host-defense via capsaicin-sensitive afferent nerves may contribute to the therapeutic action of lafutidine.

Topics: Acetamides; Acute Disease; Animals; Dose-Response Relationship, Drug; Esophagitis, Peptic; Esophagus; Histamine H2 Antagonists; Male; Neurons, Afferent; Piperidines; Pyridines; Rats; Rats, Sprague-Dawley

We examined the effect of lafutidine, a novel histamine H(2)-receptor antagonist, on acid reflux esophagitis in rats in relation to capsaicin-sensitive afferent neurons. The esophagitis was induced in rats by ligating both the pylorus and forestomach for 4 h. Lafutidine (1 - 30 mg/kg) and cimetidine (100 mg/kg) were administered either intragastrically or intraduodenally, while capsaicin (1 - 30 mg/kg) was administered intragastrically after the dual ligation. Intragastrical administered lafutidine at >3 mg/kg significantly prevented the hemorrhagic esophageal damage induced by the dual ligation, and this effect was mimicked by neither capsaicin nor cimetidine given intragastrically, but totally abolished by sensory deafferentation. In contrast, lafutidine and cimetidine given intraduodenally were both protective against the esophageal damage in a sensory deafferentation-resistant manner. The acid secretion in pylorus-ligated stomachs was significantly inhibited by these agents given intraduodenally, but not intragastrically. Vanilloid receptor subtype 1 (VR1) was expressed abundantly in the stomach, but very weakly expressed in the esophagus as assessed by Western blotting. These results suggest that lafutidine is effective against the esophageal lesions induced by acid reflux through inhibition of acid secretion and capsaicin-sensitive afferent neurons. The latter mechanism, not shared by cimetidine, may be due to the interaction of lafutidine with unidentified sites on sensory neurons other than VR1.

Topics: Acetamides; Animals; Capsaicin; Dose-Response Relationship, Drug; Esophagitis, Peptic; Histamine Antagonists; Male; Neurons, Afferent; Piperidines; Pyridines; Rats; Rats, Sprague-Dawley; Receptors, Histamine H2

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

The mechanisms responsible for the efficacy of cisapride in gastroesophageal reflux disease remain unclear. The current study was designed to test the hypothesis that cisapride decreases esophageal acid exposure by augmenting esophageal motility and improving acid clearance.. Eighteen patients with reflux esophagitis underwent combined 24-h ambulatory esophageal manometry/pH-metry at baseline and then again after 2 wk of cisapride therapy (10 mg q.i.d.).. Esophageal acid exposure was significantly decreased during cisapride therapy (total percentage of time pH was < 4: 8.3 +/- 2.0% at baseline vs 3.8 +/- 0.6% on cisapride). This was not associated with significant changes in contraction amplitude or duration, peristaltic velocity, or the proportion of peristaltic contractions. The number of reflux episodes per hour was unchanged by cisapride therapy; however, cisapride significantly decreased the number of prolonged duration reflux episodes as well as the duration of the longest reflux episode. Although the relative proportion of peristaltic versus nonperistaltic contractions occurring during reflux episodes was unchanged by cisapride therapy, there was a significant increase in the mean number of contractions per minute (both peristaltic and nonperistaltic combined) occurring during reflux episodes.. These data suggest that cisapride decreases esophageal acid exposure by improving esophageal clearance and that this occurs because of an increase in the number of esophageal contractions rather than by augmenting contraction amplitude or duration or the proportion of peristaltic sequences.

Topics: Adult; Aged; Ambulatory Care; Anti-Ulcer Agents; Cisapride; Drug Evaluation; Esophagitis, Peptic; Esophagus; Female; Humans; Hydrogen-Ion Concentration; Male; Manometry; Middle Aged; Peristalsis; Piperidines

Since angina and heartburn can feel the same, excluding cardiac disease may be the first order of business. That done, clinical findings and laboratory tests can help identify the esophageal disturbance. Gastric acid reflux, motility disorders, and visceral nerve hypersensitivity--alone or in combination--can cause chest pain, and each may call for a different pharmacologic regimen.

Topics: Adrenergic Uptake Inhibitors; Algorithms; Amitriptyline; Anti-Ulcer Agents; Atropine; Chest Pain; Cisapride; Diagnosis, Differential; Esophageal Motility Disorders; Esophagitis, Peptic; Female; Humans; Male; Manometry; Middle Aged; Parasympatholytics; Piperidines; Postprandial Period

Topics: Anti-Ulcer Agents; Cisapride; Drug Therapy, Combination; Esophagitis, Peptic; Humans; Omeprazole; Patient Compliance; Piperidines; Ranitidine

Topics: Anti-Ulcer Agents; Cisapride; Drug Therapy, Combination; Esophagitis, Peptic; Humans; Omeprazole; Piperidines

Although oesophagitis is the most common diagnosis made at upper gastrointestinal endoscopy, data on the longterm outcome of affected patients are sparse.. This study assessed the level of reflux symptoms, quality of life, drug consumption, and complications in patients at least 10 years after diagnosis of oesophagitis at one centre.. One hundred and fifty two patients with typical reflux symptoms and a first time diagnosis by endoscopy of grade I-III oesophagitis between 1981 and 1984, were followed up using a postal questionnaire and telephone interview.. Eighteen of 152 patients had died, 33 failed to respond, and 101 replied (mean follow up 11 years, range 121-160 months). Over 70% of patients still had heartburn at least daily (32%) or weekly (19%) or required daily acid suppression treatment (20%). Two patients (2%) had developed oesophageal strictures and one had Barrett's oesophagus. Two of eight quality of life scores (physical function and social function) measured by the Short Form-36 were significantly lower than Northern Ireland population scores.. Nearly three quarters of patients previously diagnosed as having oesophagitis still had significant morbidity related to gastro-oesophageal reflux disease more than 10 years after diagnosis. Some quality of life scores were significantly lower than those of the general population.

Topics: Adult; Aged; Aged, 80 and over; Antacids; Barrett Esophagus; Cisapride; Deglutition Disorders; Disease Progression; Esophagitis, Peptic; Female; Follow-Up Studies; Humans; Male; Metoclopramide; Middle Aged; Omeprazole; Piperidines; Quality of Life

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

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

Topics: Abdominal Pain; Anti-Ulcer Agents; Cisapride; Dyspepsia; Esophagitis, Peptic; Humans; Piperidines

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

A 60-year-old male had visited our hospital periodically, because of perennial moderate atopic asthma, since 53 years of age. His symptoms had stabilized following treatment with oral theophylline 400 mg, tranilast 300 mg and inhalation of beclomethasone dipropionate 400 micrograms and procaterol hydrochloride. His peak expiratory flow rate early in the morning was 465 L/min, %VC was 115% and FEV1.0% was 62.4% in May of 1993. On May 24, 1993, though he had no gastrointestinal symptoms, gastrointestinal fiberscopy revealed a hiatal hernia, reflux esophagitis and active gastroduodenal ulcer. The upper gastrointestinal x-ray films showed gastroesophageal reflux. Therefore, we diagnosed bronchial asthma associated with reflux esophagitis and gastroduodenal ulcer. He was started on omeprazole, as a proton pump inhibitor (PPI), and cisapride. After the treatment with PPI and cisapride, his peak expiratory flow rate early in the morning and in the evening, %VC and FEV1.0 increased. Three months later gastrointestinal fiberscopy revealed improvement in the reflux esophagitis and the gastroduodenal ulcer. We speculate that the improvement in the peak expiratory flow rate is related to that of the gastroesophageal reflux.

Topics: Asthma; Cisapride; Esophagitis, Peptic; Humans; Male; Middle Aged; Omeprazole; Peak Expiratory Flow Rate; Peptic Ulcer; Piperidines

Propulsid is indicated in the treatment of patients with nocturnal heartburn due to gastroesophageal reflux disease. Propulsid administration increases lower esophageal sphincter pressure and increases esophageal acid clearance.

Topics: Cisapride; Drug Interactions; Esophagitis, Peptic; Humans; Piperidines

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

The advent of histamine H2 receptor antagonists (H2-RA) has allowed the treatment of reflux esophagitis (RE) to be controlled over a relatively long term. The authors have experienced some cases resistant to H2-RA, but it was revealed that these cases can be successfully treated with proton pump inhibitors. It has been suggested that esophagogastric dysmotility can lead to RE. RE has been treated for many years by using GI-prokinetic agents, which theoretically inhibit acid reflux and improve esophageal acid clearance. In order to compare the effects on acid reflux of an H2-RA (famotidine), a proton pump inhibitor (omeprazole) and a GI-prokinetic agent (cisapride), we measured the 24-hour pH in the esophagus and stomach simultaneously, before and after treatment in 17 patients with RE. It was found that the proton pump inhibitor was the most effective drug for inhibiting esophageal acidification, followed by famotidine and then cisapride. Furthermore, we found that cisapride often actually exacerbated acid reflux. The differences in inhibitory effects on acidification allowed us to draw conclusions regarding the treatment of RE. It was concluded that the stronger the inhibitory effect of a drug on acid secretion, the more useful it was in the treatment of RE. The GI-prokinetic drug did not inhibit acid reflux as much as we had expected.

Topics: Adult; Aged; Chronic Disease; Cisapride; Esophagitis, Peptic; Esophagus; Famotidine; Female; Humans; Hydrogen-Ion Concentration; Male; Monitoring, Physiologic; Omeprazole; Piperidines; Serotonin Antagonists; Stomach

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: Cimetidine; Cisapride; Drug Therapy, Combination; Esophagitis, Peptic; Humans; Piperidines

Manometric study was performed to investigate the effects of cisapride, a new non-antidopaminergic gastrointestinal prokinetic compound, on interdigestive lower esophageal sphincter pressure (LESP) and gastroduodenal motility using infused catheter technique. The subjects consisted of 9 healthy volunteers and 29 patients with progressive systemic sclerosis (19), reflux esophagitis (8) and others (2). 4 mg of cisapride was given by bolus injection, continuous infusion or oral administration. The following results were obtained: Intravenous and oral cisapride increased LESP compared with basal pressure. Especially, bolus injection of cisapride caused a significant elevation of LESP during 30 minutes after administration. After administration of cisapride, gastroduodenal motility was accelerated gradually, then inducing IMC-like contractions. By bolus injection, IMC-like contractions were induced in healthy subjects more frequently than in patients group. On the other hand, motility index of stomach and duodenum showed persistent increase in patients group compared with healthy subjects. Cisapride-induced IMC-like contractions initiated from LES and upper part of stomach and mediated to duodenum, though aborad migration was not confirmed in the present study.

Topics: Adolescent; Adult; Aged; Cisapride; Duodenum; Electromyography; Esophagitis, Peptic; Esophagogastric Junction; Gastrointestinal Motility; Humans; Manometry; Middle Aged; Piperidines; Scleroderma, Systemic