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

Gastroesophageal reflux disease (GERD) represents a spectra of symptoms and of reflux damage to the esophagus. This reflux damage is due to a prolonged acid exposure of the esophagus arising from an imbalance between protective motility factors and aggressive acid secretory factors. Initially, patients may be managed by modifying their food intake and by supportive anti-gravity measures. However, many individuals will require drug therapy. Symptomatic relief can be achieved with pro-kinetic agents, antacids, sucralfate suspension, H2-receptor antagonists and H(+)-K+ ATPase pump blockers. There are limitations in the study design of experiments which have compared one agent with another. Accepting these design limitations, it would appear that pump blockers lead to higher rates of endoscopic healing than the use of standard doses of H2-receptor antagonists. However, higher doses of H2-receptor antagonists will likely give higher rates of symptomatic relief and endoscopic healing of GERD. Recurrence of symptoms and esophagitis occur in a high proportion of patients with GERD, and some patients may need to be considered for maintenance therapy.
 ...
PMID:Medical treatment of gastroesophageal reflux disease: options and priorities. 134 50

Omeprazole, a benzimidazole compound which inhibits H+/K+ ATPase in the gut, is used in the treatment of gastroesophageal reflux disease. Clinical and experimental use of omeprazole has been associated with inhibition of the cytochrome P450-dependent metabolism of a few drugs both in vivo in man and in vitro in animals. In these experiments, in vivo administration of omeprazole to rats failed to inhibit the cytochrome P450-dependent metabolism of four prototypic drugs, testosterone or estradiol.
 ...
PMID:Omeprazole and cytochrome P450-dependent hepatic metabolism: a comparison of endogenous and exogenous substrates in male rats. 194 96

Omeprazole, a substituted benzimidazole, is a specific inhibitor of the enzyme H+/K(+)-ATPase, which is found on the secretory surface of the parietal cell. This enzyme, the "proton pump," catalyzes the final step in acid secretion. Omeprazole is a powerful inhibitor of gastric acid secretion. At the time of writing, omeprazole has been licensed in the United States for the treatment of severe grades of gastroesophageal reflux disease (GERD) as well as GERD unresponsive to treatment with currently available agents, and for the treatment of Zollinger-Ellison syndrome and other gastric hypersecretory states. Most recently, it has been recommended by the FDA advisory committee for approval as first-line therapy in duodenal ulcer disease.
 ...
PMID:Omeprazole. Overview and opinion. 200 54

Until recently, suppression of gastric acid secretion in patients with peptic ulcer was empirical and of unproven value. Anticholinergic drugs had only modest inhibitory effects on acid secretion, many side effects, and uncertain efficacy. Controlled trials using antacids demonstrated the value of reducing gastric acidity for healing duodenal ulcer. The discovery of histamine-2 (H2) receptor antagonists in the 1970s and the introduction of H+,K(+)-ATPase inhibitors in the 1980s made reduction of acid secretion the first-choice modality for healing and preventing recurrences of duodenal and gastric ulcers. The demonstration in the late 1980s and early 1990s that Helicobacter pylori (Hp) was a major risk factor for duodenal and gastric ulcer recurrences suggested that peptic ulcer could be cured by eradicating this organism from the stomach. However, antibiotic eradication of Hp can be difficult, often requiring simultaneous administration of a drug that suppresses acid secretion. Therefore, H2 and proton pump inhibitors continue to play a role in the management of duodenal and gastric ulcers associated with Hp and also play a primary role in the therapy of other acid-related disorders, such as gastroesophageal reflux diseases, stress ulcers, ulcers associated with nonsteroidal anti-inflammatory drugs, and gastrinoma (Zollinger-Ellison syndrome) and other acid hypersecretory states.
 ...
PMID:Suppression of acid secretion in peptic ulcer disease. 767 7

Lansoprazole is an inhibitor of gastric H+,K(+)-ATPase, commonly referred to as the 'proton pump'. The pharmacodynamic effect of proton pump inhibition is to reduce gastric acid secretion. Long experience with H2 antagonists and more recently proton pump inhibitors has demonstrated the value of reducing gastric acid secretion in conditions where acid plays a key role in the pathogenesis of gastrointestinal inflammation and ulceration. The pharmacokinetics, pharmacodynamics and clinical safety of lansoprazole are discussed elsewhere in this supplement, and so this review will focus upon the European and American experience of the efficacy of lansoprazole in the treatment of peptic ulceration and gastro-oesophageal reflux.
 ...
PMID:Clinical review of lansoprazole. 806 Aug 2

An understanding of the pathophysiology of gastroesophageal reflux disease should aid selection of appropriate therapy. Symptoms of mild reflux disease may be controlled by traditional management (ie, elevating the head of the bed, dietary and other lifestyle changes, antacid use). These conservative measures also should be encouraged in patients with complicated disease. Prescription histamine2 (H2) receptor blockers remain the mainstay of antireflux medical therapy. Use of prokinetic drugs and H+,K(+)-ATPase inhibitors may be considered in refractory cases. A small percentage of patients may require antireflux surgery. If over-the-counter preparations of H2 blockers become available, they would likely become a popular component of conservative therapy.
 ...
PMID:Gastroesophageal reflux disease. Selecting optimal therapy. 830 65

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
 ...
PMID:Pharmacokinetic optimisation in the treatment of gastro-oesophageal reflux disease. 911 86

Rabeprazole is a proton pump inhibitor with antisecretory properties. In vitro animal experiments have indicated that the inhibition of the proton pump by rabeprazole is partially reversible. Rabeprazole has 2- to 10-fold greater antisecretory activity than omeprazole in vitro. However, it dissociates more readily from H+,K(+)-ATPase than omeprazole, resulting in a shorter duration of action. In comparative clinical trials rabeprazole was significantly more effective than placebo, famotidine or ranitidine and as effective as omeprazole in the treatment of patients with erosive or ulcerative gastro-oesophageal reflux disease or gastric or duodenal ulcers. Healing rates with rabeprazole were independent of Helicobacter pylori status. Rabeprazole in combination with either clarithromycin and metronidazole or clarithromycin and amoxicillin or amoxicillin and metronidazole or clarithromycin for 7 days produced eradication of H. pylori in 100, 95, 90 and 63% of patients. The tolerability profile of rabeprazole 20mg once daily was similar to that of famotidine 20mg twice daily, ranitidine 150mg 4 times daily or omeprazole 20mg once daily in comparative trials. The adverse events reported with once daily administration of rabeprazole 20mg include malaise, nausea, diarrhoea, headache, dizziness and skin eruptions in 0.7 to 2.2% of patients.
 ...
PMID:Rabeprazole. 950 45

Proton pump inhibitors (PPIs) are drugs which irreversibly inhibit proton pump (H+/K+ ATPase) function and are the most potent gastric acid-suppressing agents in clinical use. There is now a substantial body of evidence showing improved efficacy of PPIs over the histamine H2 receptor antagonists and other drugs in acid-related disorders. Omeprazole 20 mg/day, lansoprazole 30 mg/day, pantoprazole 40 mg/day or rabeprazole 20 mg/day for 2 to 4 weeks are more effective than standard doses of H2-receptor antagonists in healing duodenal and gastric ulcers. Patients with gastric ulcers should receive standard doses of PPIs as for duodenal ulcers but for a longer time period (4 to 8 weeks). There is no conclusive evidence to support the use of a particular PPI over another for either duodenal or gastric ulcer healing. For Helicobacter pylori-positive duodenal ulceration, a combination of a PPI and 2 antibacterials will eradicate H. pylori in over 90% of cases and significantly reduce ulcer recurrence. Patients with H. pylori-positive gastric ulcers should be managed similarly. PPIs also have efficacy advantages over ranitidine and misoprostol and are better tolerated than misoprostol in patients taking nonsteroidal anti-inflammatory drugs (NSAIDs). In endoscopically proven gastro-oesophageal reflux disease, standard daily doses of the PPIs are more effective than H2-receptor antagonists for healing, and patients should receive a 4 to 8 week course of treatment. For severe reflux, with ulceration and/or stricture formation, a higher dose regimen (omeprazole 40 mg, lansoprazole 60 mg, pantoprazole 80 mg or rabeprazole 40 mg daily) appears to yield better healing rates. There is little evidence that PPIs lead to resolution of Barrett's oesophagus or a reduction of subsequent adenocarcinoma development, but PPIs are indicated in healing of any associated ulceration. In Zollinger-Ellison syndrome, PPIs have become the treatment of choice for the management of gastric acid hypersecretion.
 ...
PMID:Proton pump inhibitors. Pharmacology and rationale for use in gastrointestinal disorders. 977 9

Rabeprazole sodium is a new substituted benzimidazole proton pump inhibitor with several differences compared with existing proton pump inhibitors. In vitro and animal studies have demonstrated that rabeprazole is a more potent inhibitor of H+,K(+)-ATPase and acid secretion than omeprazole, and is a more rapid inhibitor of proton pumps than omeprazole, lansoprazole, or pantoprazole. This probably reflects rabeprazole's faster activation in the parietal cell canaliculus. In human studies, once-daily doses of 5-40 mg of rabeprazole inhibit gastric acid secretion in a dose-dependent fashion. A once-daily dose of 20 mg has consistently achieved profound decreases in 24-h intragastric acidity in single and repeat dosing studies, in healthy volunteers and patients with either peptic ulcer disease or gastro-oesophageal reflux disease. Significantly greater decreases in intragastric acidity are achieved on day 1 of dosing with rabeprazole 20 mg than with omeprazole 20 mg. As with other proton pump inhibitors, rabeprazole has in vitro antibacterial activity against Helicobacter pylori, with greater activity against this organism than either lansoprazole or omeprazole. In addition to inhibiting bacterial urease activity, rabeprazole binds to several molecules on H. pylori. Clinical trials are needed to assess the clinical importance of these findings, as well as to assess whether the potential advantages of rabeprazole result in clinical benefit for patients with acid-related diseases.
 ...
PMID:Review article: the pharmacology of rabeprazole. 1049 23


1 2 3 4 5 Next >>