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)

The proton pump, a H+/K(+)-ATPase located on the secretory canalicular membrane of the parietal cell, forms the final pathway for gastric acid secretion. Omeprazole is concentrated in the secretory canaliculus, where it is converted to its active form, which binds covalently with the H+/K(+)-ATPase, thus inhibiting acid secretion arising from any stimulus. Meta-analysis has defined the primary determinants for peptic ulcer healing as the degree of acid suppression, the duration of suppression over 24 hours, and the length of treatment. The longer duration of acid suppression with omeprazole, particularly during the day, when food is ingested and H2-receptor antagonists are less effective, is reflected in the clinical superiority for symptom relief and ulcer healing and especially for the treatment of erosive esophagitis. Extensive clinical experience has proved omeprazole to be safe, and concerns over hypergastrinemia, ECL-cell hyperplasia, and carcinoid formation have not been substantiated in humans. Recent evidence has shown that omeprazole suppresses Helicobacter pylori and, in combination with antibiotics, can eradicate this organism in a substantial proportion of patients. This effect may result from enhancement of antibiotic bioavailability and optimizing host defense mechanisms.
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PMID:Progress with proton pump inhibition. 134 Oct 69

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

Our stomach produces daily a large amount of hydrochloric acid at a pH close to 1. This secretion represents a more than one million-fold in H+ ion concentration as compared to blood and intracellular medium of a pH of 7.4. It is due to a specialized cell, the parietal cell, which contains a unique transport enzyme, the (H+, K+)-ATPase. The parietal cell is itself under the control of several endocrine and paracrine stimuli operating through appropriate receptors. The recent progresses achieved in the knowledge of these key elements of the acid secretion mechanism had led to the development of specific and potent inhibitors of crucial interest in the treatment of ulcer disease and reflux oesophagitis such as histamine H2 and (H+, K+)-ATPase antagonists.
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PMID:Cell physiology and pharmacology of gastric acid secretion. 135 71

Omeprazole is a specific inhibitor of H+,K(+)-ATPase or 'proton pump' in parietal cells. This enzyme is responsible for the final step in the process of acid secretion; omeprazole blocks acid secretion in response to all stimuli. Single doses produce dose-dependent inhibition with increasing effect over the first few days, reaching a maximum after about 5 days. Doses of omeprazole 20mg daily or greater are able to virtually abolish intragastric acidity in most individuals, although lower doses have a much more variable effect. Omeprazole causes a dose-dependent increase in gastrin levels. Omeprazole must be protected from intragastric acid when given orally, and is therefore administered as encapsulated enteric-coated granules. Absorption can be erratic but is generally rapid, and initially the drug is widely distributed. It is highly protein-bound and extensively metabolised. Its elimination half-life is about 1h but its pharmacological effect lasts much longer, since it is preferentially concentrated in parietal cells where it forms a covalent linkage with H+,K(+)-ATPase, which it irreversibly inhibits. Omeprazole binds to hepatic cytochrome P450 and inhibits oxidative metabolism of some drugs, the most important being phenytoin. Omeprazole has produced short term healing rates superior to the histamine H2-receptor antagonists in duodenal ulcer, gastric ulcer and reflux oesophagitis. It has also been shown to be highly effective in healing ulcers which have failed to respond to H2-receptor antagonists, and has been extremely valuable in treating patients with Zollinger-Ellison syndrome.
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PMID:Clinical pharmacology of omeprazole. 202 1

The presence of unbuffered acid appears to be an essential contributory factor in the pathogenesis of peptic ulcer disease. Treatment has concentrated therefore on the reduction of acidity, and the last decade has seen the widespread and effective use of H2 antagonists. They are, at low doses, more successful in improving the natural history of duodenal ulcer disease than of gastric or esophageal ulceration. The H2 receptor plays a central role in activation of parietal cell acid secretion, and antagonists at this receptor block most (but not all) of the acid secretion due to even gastrinergic or muscarinic (vagal) stimulation. In hypergastrinemic states such as Zollinger-Ellison syndrome, or where acid secretion has to be inhibited by more than 20% over a 24-hr period, such as for treatment of esophagitis, NSAID damage, or gastric ulcers, the dose and frequency of administration of the currently available antagonists must be increased to achieve reliable therapy. This has led to a search for an alternative target for acid inhibitory drugs, such as the gastric acid pump, the H+,K(+)-ATPase. This article focuses on the function of this ATPase and suggests that inhibition of this pump will provide a more efficacious means of reduction of acid secretion by the stomach, hence improving and simplifying therapy of acid related diseases.
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PMID:Gastric H+,K(+)-ATPase as a therapeutic target in peptic ulcer disease. 217 66

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

Results of medical therapy of reflux oesophagitis are disappointing, especially compared to the success obtained in peptic ulcer disease. H2-receptor antagonists, with or without the addition of mucosaprotectiva or prokinetica, produce healing only in 50% of the patients. Nowadays, even severe, resistant reflux oesophagitis can be treated successfully with the H+/K+-adenosine triphosphatase antagonist omeprazole. Experience of more than 3 years of continuous treatment with omeprazole, in doses which have been adjusted to prevent recurrences, has also demonstrated its high efficacy in the long-term management of the patients. The use of this drug emphasizes the importance of long-standing, strong acid inhibition for this condition, although careful surveillance of the safety profile of this drug remains obligatory.
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PMID:Treatment of reflux oesophagitis resistant to H2-receptor antagonists. 257 61

The development of H+/K+-adenosine triphosphatase inhibitors with their potent and long-acting antisecretory action raises the question as to whether profound inhibition of gastric acid results in better clinical effects. The answer to this question may be anticipated by extrapolation of the results of studies on the effect of the degree of acid inhibition by the presently available H2-receptor antagonists on the healing of acid-related disorders. These studies suggest that powerful antisecretory drugs may be especially promising for the treatment of reflux oesophagitis, but also for the treatment of various forms of peptic ulcer disease.
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PMID:Is there a need for strong gastric acid inhibition in clinical practice? 269 9

Due to its potent and long-lasting antisecretory properties is omeprazole, the first clinically used H+/K+-adenosine triphosphatase inhibitor, highly effective in healing of duodenal and gastric ulcers and reflux oesophagitis. Omeprazole is superior to all other presently available antiulcer drugs in the treatment of Zollinger-Ellison syndrome and refractory ulcers. Short-term administration of the drug is safe. However, serum gastrin and gastric enterochromaffin-like cells should be carefully monitored during long-term treatment with the drug.
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PMID:H+/K+-adenosine triphosphatase inhibitors. A new approach to the treatment of acid-peptic diseases. 269 16

Omeprazole is the first representative of a new class of gastric acid secretion inhibitors. It acts by specific and prolonged inhibition of H+K+ ATPase, or proton pump, which is the terminal and compulsory stage of acid secretion by the parietal cells. The drug therefore inhibits both basal and stimulated secretion. It appears from therapeutic trials that omeprazole administered in doses of 20 mg a.m. once a day is superior to the H2-receptor antagonists in the healing of active duodenal ulcers and ulcerated reflux oesophagitis. It is as active or slightly more active than histamine inhibitors in gastric ulcers. Finally, it is the treatment of choice to prevent ulcerations in Zollinger-Ellison syndrome. These are the 4 indications for omeprazole at the moment. The use of that drug for periods of a few weeks has not given rise to any significant side-effect.
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PMID:[The second generation of gastric antisecretory agents: omeprazole]. 306 2


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