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)

Omeprazole is a new hydrogen-potassium adenosine triphosphatase antagonist with indications for severe reflux esophagitis and Zollinger-Ellison syndrome. Side effects involving the liver have consisted of minimal elevations of hepatocellular enzymes with higher dosages. We present what we believe is the first reported case of fulminant hepatic failure related to omeprazole.
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PMID:Fulminant hepatic failure related to omeprazole. 155 42

The H+K+-ATPase is supposed to be the terminal step in the acid-secreting pathway in the parietal cell. Omeprazole blocks this enzyme, resulting in a marked inhibition of basal and stimulated acid secretion. With omeprazole 20 mg daily, 24-hour intragastric acidity is decreased by about 90%. Several clinical studies have now been published in which omeprazole has been compared with the H2-receptor antagonists cimetidine and ranitidine. Omeprazole in doses between 20 and 40 mg daily resulted in healing rates between 65% and 82% after treatment for 2 weeks and between 90% and 100% after treatment for 4 weeks. Treatment with omeprazole also gave faster and more pronounced pain relief. One comparative study in gastric ulcer has also been published showing healing rates equal to those with ranitidine. Placebo-controlled trials have also shown very pronounced therapeutic effect in reflux esophagitis. Omeprazole seems to be the drug of choice in Zollinger-Ellison syndrome, giving beneficial clinical effects and pronounced and long-lasting reduction in gastric acid secretion.
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PMID:Clinical perspectives of drugs inhibiting acid secretion--H+K+-ATPase inhibitors. 302 57

The pharmacology, pharmacokinetics, clinical efficacy, adverse effects, and dosage and administration of omeprazole are reviewed. Omeprazole, a substituted benzimidazole, has a unique site and mechanism of action because it inhibits the proton pump--i.e., hydrogen, potassium adenosine triphosphatase (H+,K+-ATPase)--and consequently blocks the final common step in the gastric acid secretory pathway. Omeprazole inhibits basal and histamine-, gastrin- and pentagastrin-stimulated gastric hydrochloric acid secretion. It produces a dose-dependent reduction in gastric acidity, gastric acid output, and gastric juice volume and has variable effects on pepsin secretion. Omeprazole has no documented effect on esophageal motility or lower esophageal sphincter pressure. Omeprazole is variably absorbed from the gastrointestinal tract, and food appears to decrease the rate, but not the extent, of drug absorption. The drug is approximately 95% bound to plasma proteins and is metabolized to inactive components that are enterohepatically or renally eliminated. Omeprazole is more effective (in most studies) than H2-receptor antagonists in treating duodenal ulcer, at least as effective in treating benign gastric ulcer, and more effective in treating reflux esophagitis. Omeprazole has been used successfully in patients with Zollinger-Ellison syndrome refractory to treatment with H2-receptor antagonists. Gastrointestinal complaints (nausea and diarrhea) are the most commonly reported adverse effects associated with omeprazole therapy. The most frequently reported laboratory abnormality occurring with omeprazole use is elevation of serum aspartate aminotransferase and alanine aminotransferase concentrations. Omeprazole will serve a valuable role in the management of gastrointestinal tract ulcers and hypersecretory conditions.
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PMID:Therapeutic evaluation of omeprazole. 306 85

This multicenter, randomized, double-blind, 8-wk study compared the new H+/K(+)-ATPase inhibitor, lansoprazole, 30 mg daily, to ranitidine 150 mg bid for treatment of erosive reflux esophagitis resistant to histamine-2 receptor antagonists (H2RA). Patients were evaluated after 2, 4, 6, and 8 wk of treatment by symptom assessment and endoscopy. Healing rates for lansoprazole were 71%, 80%, 88%, and 89% at 2, 4, 6, and 8 wk, respectively, compared to 21%, 33%, 45%, and 38% for ranitidine (p < 0.001 at all points). Lansoprazole was significantly more effective than ranitidine for relief of heartburn and reduction of antacid tablet use. Increases in serum gastrin concentrations between the baseline and the 8-wk visit were greater in lansoprazole-treated than in ranitidine-treated patients. Lansoprazole was safe and well tolerated. In patients with erosive reflux esophagitis resistant to standard doses of H2RA, lansoprazole 30 mg/day is more effective than continuation of an H2RA (ranitidine 150 mg bid) for healing of esophagitis and improvement of symptoms.
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PMID:Treatment of reflux esophagitis resistant to H2-receptor antagonists with lansoprazole, a new H+/K(+)-ATPase inhibitor: a controlled, double-blind study. Lansoprazole Study Group. 810 95

The pharmacology, pharmacokinetics, efficacy, safety, and dosage and administration of lansoprazole and omeprazole are reviewed. Lansoprazole and omeprazole are proton-pump inhibitors (PPIs). These agents bind covalently to hydrogen/potassium-exchanging adenosine triphosphatase in gastric parietal cells, rendering the molecule nonfunctional and inhibiting the secretion of gastric acid. The bioavailability of lansoprazole is 85%; that of omeprazole is 54%. Although lansoprazole and omeprazole have a plasma half-life of less than 2 hours, the duration of action is more than 24 hours. Clinical trials have shown lansoprazole and omeprazole to be effective in the treatment of duodenal ulcers, gastric ulcers, peptic ulcer disease involving Helicobacter pylori infection, recurrent ulcers, ulcers induced by nonsteroidal anti-inflammatory drugs, reflux esophagitis, Barrett esophagus, and Zollinger-Ellison syndrome. In many cases, these PPIs were more effective than histamine H2-receptor antagonists or worked when the latter failed. Lansoprazole and omeprazole have similar adverse-effect profiles and are well tolerated in both long- and short-term therapy. The dosage and duration of therapy vary with the condition being treated or the individual patient. Dosage adjustments should be considered only in the case of lansoprazole in patients with severe liver disease. Lansoprazole and omeprazole are highly specific in blocking a critical step in gastric acid production and have been found to be safe and effective in the treatment of many acid peptic disorders.
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PMID:Lansoprazole and omeprazole in the treatment of acid peptic disorders. 895 52

Lansoprazole is the second member of the substituted benzimidazole class of antisecretory agents approved for use in the United States. These drugs decrease parietal cell acid secretion by inhibiting H+, K(+)-adenosine triphosphatase, the final step in the secretion of acid. Lansoprazole has been studied extensively for the short-term treatment of duodenal and gastric ulcers, reflux esophagitis, and Helicobacter pylori-positive peptic ulcer disease; long-term treatment of Zollinger-Ellison syndrome; and maintenance treatment of erosive esophagitis. A dosage of 30 mg/day produced higher healing rates and equivalent or faster relief of ulcer symptoms than ranitidine or famotidine in patients with duodenal or gastric ulcers and reflux esophagitis. Compared with omeprazole 20 mg/day, that dosage provided faster epigastric pain relief in these patients after 1 week, although healing rates for the two agents were equivalent at 4 and 8 weeks. In patients with peptic ulcer refractory to 8-week therapy with histamine2-receptor antagonists, healing rates were not significantly different between lansoprazole and omeprazole. In patients with Zollinger-Ellison syndrome, lansoprazole was superior to histamine2-receptor antagonists and was similar in efficacy, safety, and duration of action to omeprazole. Combinations of lansoprazole or omeprazole with one or two antibiotics produced equivalent eradication of H. pylori. In clinical trials, lansoprazole was well tolerated, with frequency of adverse effects similar to that reported with ranitidine, famotidine, and omeprazole.
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PMID:Lansoprazole: a comprehensive review. 908 23

Hydrochloric acid (HCl) secretion into the gastric lumen is a specialized process driven primarily by H(+)/K(+)-ATPase or proton pump, a unique enzyme expressed in high quantities by the parietal cells. Physiological regulation of this secretion involves central signals conveyed by the vagus nerve and local mechanisms mediated by cholinergic and peptidergic fibers of the gastric wall, as well as amine or peptide secreting cells located in the fundic and antral epithelia. Among these cells, the enterochromaffin-like (ECL) cell plays a major role: it responds to gastrinic, cholinergic and adrenergic stimulations to secrete histamine, which in turn activates an H(2) receptor on the parietal cell. The H(2) receptor is responsible for intracellular production of cAMP, a second messenger critical for the secretory machinery to be triggered. The blockade of this receptor by specific antagonists results in a dramatic albeit surmountable inhibition of HCl output. The blockade of the proton pump is an alternative means of inhibition. This can be achieved by a series of benzimidazole derivatives which specifically accumulate in the parietal cell secretory canaliculus and covalently bind to ATPase extracellular sites. The resulting inhibition is stronger and lasts longer than with the H(2) antagonists. Furthermore, it is effective regardless of the stimulatory status. Therefore, proton pump inhibitors (PPIs) are of special interest in the treatment of acid-related diseases such as gastric and duodenal ulcer, as well as reflux esophagitis.
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PMID:Cellular mechanisms and inhibitors of gastric acid secretion. 1297 69

The gastric H,K-ATPase is the primary target for the treatment of acid-related diseases. Proton pump inhibitors (PPIs) are weak bases composed of two moieties, a substituted pyridine with a primary pK(a) of about 4.0, which allows selective accumulation in the secretory canaliculus of the parietal cell, and a benzimidazole with a second pK(a) of about 1.0. PPIs are acid-activated prodrugs that convert to sulfenic acids or sulfenamides that react covalently with one or more cysteines accessible from the luminal surface of the ATPase. Because of covalent binding, their inhibitory effects last much longer than their plasma half-life. However, the short half-life of the drug in the blood and the requirement for acid activation impair their efficacy in acid suppression, particularly at night. PPIs with longer half-life promise to improve acid suppression. All PPIs give excellent healing of peptic ulcers and produce good results in reflux esophagitis. PPIs combined with antibiotics eradicate Helicobacter pylori.
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PMID:Pharmacology of proton pump inhibitors. 1900 6

The gastric H,K-adenosine triphosphatase (ATPase) is the primary target for treatment of acid-related diseases. Proton pump inhibitors (PPIs) are weak bases composed of two moieties, a substituted pyridine with a primary pK(a) of about 4.0 that allows selective accumulation in the secretory canaliculus of the parietal cell, and a benzimidazole with a second pK(a) of about 1.0. Protonation of this benzimidazole activates these prodrugs, converting them to sulfenic acids and/or sulfenamides that react covalently with one or more cysteines accessible from the luminal surface of the ATPase. The maximal pharmacodynamic effect of PPIs as a group relies on cyclic adenosine monophosphate-driven H,K-ATPase translocation from the cytoplasm to the canalicular membrane of the parietal cell. At present, this effect can only be achieved with protein meal stimulation. Because of covalent binding, inhibitory effects last much longer than their plasma half-life. However, the short dwell-time of the drug in the blood and the requirement for acid activation impair their efficacy in acid suppression, particularly at night. All PPIs give excellent healing of peptic ulcer and produce good, but less than satisfactory, results in reflux esophagitis. PPIs combined with antibiotics eradicate Helicobacter pylori, but success has fallen to less than 80%. Longer dwell-time PPIs promise to improve acid suppression and hence clinical outcome. Potassium-competitive acid blockers (P-CABs) are another class of ATPase inhibitors, and at least one is in development. The P-CAB under development has a long duration of action even though its binding is not covalent. PPIs with a longer dwell time or P-CABs with long duration promise to address unmet clinical needs arising from an inability to inhibit nighttime acid secretion, with continued symptoms, delayed healing, and growth suppression of H. pylori reducing susceptibility to clarithromycin and amoxicillin. Thus, novel and more effective suppression of acid secretion would benefit those who suffer from acid-related morbidity, continuing esophageal damage and pain, nonsteroidal anti-inflammatory drug-induced ulcers, and nonresponders to H. pylori eradication.
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PMID:Novel approaches to inhibition of gastric acid secretion. 2092 27

Melatonin is implicated in sustaining the esophageal integrity in gastro-esophageal reflux disease. However, the role of its synthetic precursor l-tryptophan is not clear in this pathology. The present study was designed to explore the effects of l-tryptophan on esophageal damage following reflux esophagitis (RE)-establishment and concurrent alterations in factors possibly influencing esophageal integrity such as esophageal melatonin level, luminal acidity, H(+)K(+)-ATPase activity, mucin and gastric PGE(2) levels. RE was established in rats by simultaneous ligation of pylorus region and fore-stomach. RE significantly decreased the esophageal-melatonin level and the expression of its synthesizing enzymes: arylalkylamine-N-acetyltransferase (AA-NAT) and hydroxyindole-O-methyltransferase (HIOMT). Administration of l-tryptophan significantly decreased the RE-induced esophageal mucosal damage, without altering the levels of melatonin. l-Tryptophan pretreatment also normalized the esophageal mucosal damage caused by melatonin receptor antagonist-luzindole. Simultaneously, l-tryptophan significantly increased the RE-decreased expression of AA-NAT with insignificant effect on HIOMT gene expression. In contrast, l-tryptophan per se caused a significant elevation in the esophageal melatonin level, with no significant effect on the expression of AA-NAT and HIOMT enzymes. Further, l-tryptophan significantly normalized the RE-induced changes in the gastric juice volume, acidity and pH. However, it did not significantly inhibit the H(+)K(+)-ATPase activity in vitro. Also, l-tryptophan significantly increased the RE-reduced mucin level, COX-2 activity and thereby PGE(2) levels. Interestingly, indomethacin (PGE(2) synthesis blocker), aggravated the RE-induced tissue injury with simultaneous changes in the gastric volume, acidity, pH and mucin content, which l-tryptophan failed to reverse, suggesting that the attenuating effect of l-tryptophan on gastric secretions could be PGE(2) driven. Thus the current study provide evidences that protective functions of l-tryptophan against RE is independent of its conversion into melatonin, and possibly involve mobilization of factors such as COX-2 derived PGE(2) and mucin that counterbalance the detrimental effect of gastric acid on esophageal mucosa, signifying the therapeutic efficacy of l-tryptophan against the esophageal pathologies.
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PMID:Melatonin independent protective role of l-tryptophan in experimental reflux esophagitis in rats. 2152 45


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