Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0017168 (gastroesophageal reflux disease)
 11,783 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:Functional dyspepsia versus other functional gastrointestinal disorders: a practical approach in Belgian general practices. 851 55

Cisapride is a substituted benzamide compound that stimulates motor activity in all segments of the gastrointestinal tract by enhancing the release of acetylcholine from the enteric nervous system. Cisapride is administered orally in the treatment of gastro-oesophageal reflux disease, functional dyspepsia, gastroparesis, chronic intestinal pseudo-obstruction syndromes and chronic constipation. In gastro-oesophageal reflux disease in both adults and children, cisapride provides symptomatic improvement and mucosal healing. Long term treatment with cisapride is effective in the prevention of relapse of oesophagitis. Cisapride improves gastric emptying rates and improves symptoms in patients with gastroparesis of various origins. Unlike domperidone and metoclopramide, long term administration of cisapride seems to result in persistently enhanced gastric emptying. Cisapride is also effective in improving symptoms in patients with functional dyspepsia. In comparative studies in patients with functional dyspepsia, cisapride was at least as effective as metoclopramide, domperidone, clebopride, ranitidine and cimetidine. Cisapride increases stool frequency and reduces laxative consumption in patients with idiopathic constipation. Severe cases of slow transit constipation seem refractory to cisapride. Clinical studies also indicate that cisapride might be effective in the treatment of chronic intestinal pseudo-obstruction, postoperative ileus, peptic ulcer and irritable bowel syndrome. Further clinical studies are warranted to define the role of cisapride in these conditions. The dosage of cisapride ranges from 5mg 3 times daily to 20mg twice daily. Cisapride is generally well tolerated, both during short and long term treatment. In children, cisapride is also well tolerated in doses of 0.2 to 0.3 mg/kg, 3 to 4 times daily.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:A risk-benefit assessment of cisapride in the treatment of gastrointestinal disorders. 852 13

Patients with pyrosis or regurgitation as the dominating symptoms have gastro-oesophageal reflux disease (GORD). However, patients with more atypical symptoms may also suffer from it. The disease is usually chronic and patients who have additional oesophagitis are at risk of developing complications. The therapeutic goals in GORD are symptom relief, healing of lesions, prevention of complications, and omittance of adverse effects at the lowest possible costs. Patients with functional dyspepsia usually have symptoms of less severe intensity and as, per definition, no organic substrate is demonstrable, complications do not develop in these patients. Therefore, in patients with GORD and functional dyspepsia, treatment of GORD should have the highest priority. Pharmacologic treatment of GORD comprises H2 receptor antagonists, proton-pump inhibitors and cisapride. The pharmacologic treatment of functional dyspepsia is less documented and in most studies the symptomatic pattern could not predict the pharmacologic principle of clinical benefit. This may be because a separation between presence of symptoms and presence of symptoms as a major problem has not been taken into account. Cisapride is the drug that has been proven clinically useful in most randomized studies. This does not, however, rule out that other drugs are better in subgroups of patients with functional dyspepsia.
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PMID:Is this a reflux patient or is it a patient with functional dyspepsia with additional reflux symptoms? 854 27

Cisapride and metoclopramide are used clinically in the treatment of gastro-oesophageal reflux disease and also in a variety of motility disorders of the gastrointestinal tract. Their prokinetic effect is thought to be due to the augmentation of acetylcholine release from the myenteric plexus, an effect likely to be mediated through the stimulation of 5-HT4 receptors. The role of 5-HT4 receptors in the control of intestinal motility in man and animals is not clear, therefore we have investigated their role in the control of small intestinal transit in the rat. Radioactive microspheres were administered into the proximal duodenum of fasted conscious rats through an indwelling cannula. The extent of small intestinal transit was examined by determining the distribution of the microspheres within the intestine. Following i.p. injection small intestinal transit was inhibited (78%) by atropine (3 mg/kg), suggesting the presence of a basal cholinergic influence. Furthermore, in the presence of p-amino clonidine intestinal transit was stimulated (126%) by bethanechol (3 mg/kg). The 5-HT4 receptor agonists cisapride (1.0 mg/kg) and zacopride (1.0 mg/kg) failed to increase small intestinal transit. The 5-HT4 receptor selective antagonist GR125487 (1 mg/kg) was also without effect. These data suggest that 5-HT4 receptors are not involved in the control of small intestinal transit in the fasted conscious rat.
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PMID:5-HT4 receptors are not involved in the control of small intestinal transit in the fasted conscious rat. 869 80

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 severity of GORD, particularly in severe oesophagitis, are the proton pump inhibitors. The substituted benzimidazoles (omeprazole, lansoprazole and pantoprazole), are prodrugs which once trapped and activated in the acid milieu of the gastric glands potently suppress gastric secretion of acid and pepsin. Their long duration of action, more related to the slow turnover of parietal cell H(+)-K+ ATPase molecules, allows once daily administration in most patients. Interindividual variation in bioavailability sometimes calls for higher doses or twice daily administration. Acid suppression is closely related to the AUC. Omeprazole is prone to interaction with the metabolism of other drugs, some of which may e be clinically important. Lansoprazole seems to have an earlier onset of action than omeprazole, ascribed to higher bioavailability during the first days of treatment. Proton pump inhibitors have a slow onset of action, which makes them unsuited for on-demand therapy. Clinical practice in GORD calls for the use of not one but several substances, according to the severity and symptom pattern of the patient. Pharmacokinetic optimisation in the treatment of GORD is a question of selecting the most suitable substances and administration schemes within each group. Cisapride is superior to other prokinetics in terms of longer plasma t1/2 and less toxicity. Amongst H2 receptor antagonists, the more long-acting compounds, ranitidine and famotidine, will improve acidity control througho
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PMID:Pharmacokinetic optimisation in the treatment of gastro-oesophageal reflux disease. 911 86

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.
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PMID:Esophagoprotective potential of cisapride. An additional benefit for gastroesophageal reflux disease. 924 29

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.
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PMID:Prokinetic therapy in gastroesophageal reflux disease. 934 80

Cisapride, a cytochrome P450 3A4 (CYP3A4) substrate, is widely prescribed for the treatment of gastrointestinal motility disorders. Prolongation of QT interval, torsades de pointes, and sudden cardiac death have been reported after concomitant administration with erythromycin or azole antifungal agents, but not with other CYP3A4 inhibitors. A possible drug interaction occurred in a 45-year-old woman who was taking cisapride for gastroesophageal reflux disorder and diltiazem, an agent that has inhibitory effect on CYP3A4, for hypertension. The patient was in near syncope and had QT-interval prolongation. After discontinuing cisapride, the QT interval returned to normal and symptoms did not recur. We suggest that caution be taken when cisapride is prescribed with any potent inhibitor of CYP3A4, including diltiazem.
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PMID:Prolongation of the QT interval related to cisapride-diltiazem interaction. 954 59

Currently available medications for gastroesophageal reflux disease (GERD) vary in mechanisms of action from neutralization or suppression of gastric acid to improving underlying upper gastrointestinal dysmotility. This article reviews the clinical efficacy of pharmacological agents used to treat GERD and provides a rationale for considering a primary prokinetic approach to antireflux treatment which will be applicable to many patients. Treatment trials in acute GERD have demonstrated unexpectedly prolonged maintenance of high esophageal pH with tablet and liquid antacid formulations. However, there are no well-designed placebo-controlled trials of antacids for esophageal mucosal healing. H2 receptor antagonists (H2RAs) at conventional doses relieve reflux symptoms in at least 50% of reported series of GERD patients, and they can also provide endoscopic healing in 27-45% of the cases. Therapy with more potent acid-suppressive agents such as proton pump inhibitors (PPIs) may lead to improved symptomatic relief and to superior healing compared with H2RA therapy, especially in those patients with more advanced erosive esophagitis. Promotility agents, particularly cisapride, offer symptom relief and healing rates which are quite similar to standard H2RA treatment. GERD tends to be a chronic and relapsing condition. Cisapride has been shown to be quite effective in maintaining remission in GERD patients, including endoscopic remission in the lesser degrees of esophagitis. This may be accomplished with relatively low and cost-effective dosing in many individuals. For the small proportion of patients who manifest severe grades of esophagitis, PPI therapy is associated with lower relapse rates than either H2RA or prokinetic treatment. Overall, a strong case can be made for the empirical selection of promotility therapy for the large numbers of GERD patients who do not have documented severe erosive disease.
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PMID:A prokinetic approach to treatment of gastroesophageal reflux disease. 954 35

Cisapride is a substituted piperidinyl benzamide. It is chemically related to metoclopramide but lacks the antidopaminergic properties of metoclopramide that affect the central nervous system and cause extrapyramidal side effects. Cisapride is indicated for the symptomatic treatment of patients with nocturnal heartburn due to gastroesophageal reflux disease. Based on extensive assessment of the drug's pharmacokinetic profile, the currently approved initial oral dosing regimen for cisapride is 10 mg QID. However, the pharmacokinetics of cisapride after oral administration of 20 mg BID have not been investigated. We present here findings from an open-label trial assessing the pharmacokinetics of cisapride 20-mg tablets after a single dose and at steady state (BID dosing). The results indicate that 20-mg BID and 10-mg QID regimens produce similar steady-state concentrations.
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PMID:Pharmacokinetic profile of cisapride 20 mg after once- and twice-daily dosing. 958 20


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