Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.6.1.3 (ATPase)
65,361 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.
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PMID:Medical treatment of gastroesophageal reflux disease: options and priorities. 134 50

Omeprazole is the first of a new class of gastric antisecretory drugs, proton pump inhibitors. It inhibits the H+,K(+)-adenosinetriphosphatase enzyme of the gastric parietal cell, resulting in potent, long-lasting suppression of basal and stimulated acid secretion. The drug is currently approved for treatment of gastroesophageal reflux disease and Zollinger-Ellison syndrome. In clinical trials, treatment with omeprazole results in rapid healing of duodenal ulcers; it is also effective in treating gastric ulcer disease. It is uniformly well tolerated without significant adverse effects, although animal studies linked profound long-term suppression of gastric acid secretion with the development of gastric carcinoids. Potential future uses include the prophylaxis of ulceration secondary to stress or use of nonsteroidal anti-inflammatory drugs, and the prophylaxis of recurrent peptic ulcer disease.
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PMID:Omeprazole: a new drug for the treatment of acid-peptic diseases. 193 56

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.
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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.
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PMID:Omeprazole. Overview and opinion. 200 54

The management of oesophageal reflux disease can and should be highly individualised, depending on the severity of the disease. Mild occasional symptoms of heartburn can often be controlled with conservative measures or changes in diet and antacids. For patients with erosive or ulcerative oesophageal disease, it is becoming clear that acid plays a crucial role in injury and that suppression of acid enhances healing. Antipeptic dosages of histamine receptor antagonists achieve good relief of symptoms but may not always heal erosive oesophagitis. Healing rates are improved with the use of new hydrogen-potassium adenosine triphosphatase (ATPase) pump inhibitors which suppress virtually all acid production. The recurrence of disease is common after acid suppression therapy is discontinued, suggesting the need for some form of long term maintenance therapy. Promotility drugs, which improve oesophageal motility, have inconsistent results in clinical trials and have been associated with a higher rate of adverse drug effects in comparison with acid-suppressive therapies. Surgical treatment should still be considered for patients with chronic recurrent disease who do not respond well to pharmacological therapies.
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PMID:Treatment approaches to reflux oesophagitis. 219 48

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.
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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.
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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.
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PMID:Gastroesophageal reflux disease. Selecting optimal therapy. 830 65

Proton pump inhibitors (PPIs) are targeted to the gastric acid pump, H+, K(+)-adenosine triphosphatase (ATPase). The drugs accumulate in the acid space of the parietal cell and convert to active sulfenamide by an acid-catalyzed reaction. Consequent covalent inhibition of H+, K(+)-ATPase blocks the final step of acid secretion, hence the PPIs omeprazole, lansoprazole, and pantoprazole are more effective than histamine2-receptor antagonists (H2RAs) in controlling acid secretion. Preclinical short- and long-term clinical surveillance data show these drugs to be well tolerated and safe. The PPIs heal the lesions of gastroesophageal reflux disease and lessen symptoms more effectively and more quickly than the H2RAs, and are effective and faster acting for peptic ulcer disease. Helicobacter pylori is causally implicated in the majority of peptic ulcers and in atrophic gastritis. Since PPIs, but not H2RAs, are synergistic with antibiotics in eradicating H. pylori, their use is appropriate in all acid-related diseases since all patients who are H. pylori positive require eradication as well as healing.
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PMID:Proton pump inhibitors and acid-related diseases. 901 63

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


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