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)

During the last 5 years important advances have occurred in the control of gastric acid hypersecretion in Zollinger-Ellison syndrome (ZES). The increased availability of potent gastric acid antisecretory agents such as histamine H2-receptor antagonists and more recently the H+K(+)-ATPase inhibitors such as omeprazole and lansoprazole have made it possible to medically control acid secretion in all patients. Increased understanding of the variation in antisecretory drug dosage between individual patients has led to identification of criteria to ensure effective antisecretory control and to the recognition of subgroups of patients who require special monitoring. Effective regimens for parenteral antisecretory control during surgery have been established. The importance of parathyroidectomy in patients with multiple endocrine neoplasia type I with ZES and the possible usefulness of highly selective vagotomy have been investigated. We review here the new data that led to increased understanding in each of these areas from our studies and studies by others.
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PMID:Control of gastric acid hypersecretion in the management of patients with Zollinger-Ellison syndrome. 836 29

Lansoprazole, a new substituted benzimidazole H+,K(+)-ATPase inhibitor, profoundly inhibits gastric acid secretion and has potential use in the management of diseases such as Zollinger-Ellison syndrome (ZES). In the present study we evaluated the efficacy and safety of lansoprazole in controlling acid hypersecretion in 20 patients with ZES. The starting dose was 60 mg once daily. Control of acid hypersecretion was defined as the dose required to reduce acid secretion to < 10 meq/hr in the last hour before the next dose. Doses were adjusted upwards until effective control was achieved. Patients not controlled with 120 mg once daily were placed on twice daily lansoprazole. Most patients (90%) required lansoprazole once daily. During long-term follow-up (mean 18.5 months), 25% of patients required upward dose adjustments and 25% of patients required twice daily lansoprazole. Following cessation of therapy, the mean time for gastric acid output to reach half basal acid output was 39.1 hr. Lansoprazole was well-tolerated without side effects. Clinical chemistry and hematological studies were unchanged, and no gastric carcinoids developed. These results demonstrate that lansoprazole is a safe and effective inhibitor of gastric acid hypersecretion in patients with Zollinger-Ellison syndrome. Because it has a long duration of action, lansoprazole can be used to control gastric acid hypersecretion in most patients with Zollinger-Ellison syndrome using a once daily dosing schedule.
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PMID:Prospective study of efficacy and safety of lansoprazole in Zollinger-Ellison syndrome. 842 37

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

A 9-year-old male German Shepherd Dog was presented with the primary complaints of vomiting, profuse watery diarrhea, anorexia, and severe weight loss. The dog developed hematemesis and melena, which were unresponsive to treatment with an H2-receptor antagonist and a gastrointestinal protectant. A marked neutrophilia, panhypoproteinemia, hypokalemia, and mildly increased activities of alkaline phosphatase and alanine aminotransferase were the only relevant abnormalities found on a CBC, serum biochemical profile, and urinalysis. An exploratory laparotomy revealed several small nonresectable masses at the root of the mesentery, which were identified histologically as a neuroendocrine neoplasm. Immunohistochemical staining of the neoplasm was positive for gastrin and negative for insulin, glucagon, pancreatic polypeptide, and vasoactive intestinal polypeptide. Fasting serum gastrin concentrations were high. Zollinger-Ellison syndrome was diagnosed, and the dog was treated with omeprazole, an H+,K(+)-ATPase inhibitor. All clinical signs resolved, and the dog remains asymptomatic 2 years later. Omeprazole may be the gastric acid antisecretory drug of choice for dogs with gastrinoma.
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PMID:Omeprazole in a dog with gastrinoma. 947 Jan 66

Zollinger-Ellison syndrome (ZES) is the most common symptomatic pancreatic endocrine tumour in patients with MEN-1. Besides the treatment of the usual endocrinopathies seen in patients with MEN-1, the treatment of the ZES requires attention be paid to controlling the gastric acid hypersecretion, to dealing with the gastrinomas per se which are malignant in 18-60% of cases, and to the diagnosis and treatment of gastric carcinoid tumours, that are increasingly seen in these patients. In this article the current management of each of the areas is reviewed and what is known or uncertain discussed, based on our studies at the NIH and data from others. Data from 231 patients including 45 with MEN-1 and 186 without MEN-1 is contrasted in this report. Gastric acid hypersecretion has been controlled in all patients medically with MEN-1 and ZES at the NIH for up to 22 years. The current drugs of choice are H+-K+ ATPase inhibitors and twice a day dosing is recommended. Periods of parenteral drug therapy (surgery, etc.) and pregnancy require important modifications. The appropriate surgical therapy of the gastrinoma is controversial. Eighty per cent of patients have a duodenal gastrinoma and 20-30% have a pancreatic tumour. Recent studies suggest gastrinoma enucleation combined with duodenotomy rarely results in cure. Aggressive surgery (Whipple resection) can result in cure of gastrinoma but effect on survival is unclear. There are important differences in gastrinoma location, extent, and percentage with aggressive disease in patients with or without MEN-1, which are discussed. Confusion has occurred because of lack of information on the natural history of the gastrinoma compared to the other pancreatic endocrine tumours that occur in MEN-1 and survival data from patients with and without MEN-1 is contrasted. The occurrence of gastric carcinoids in patients with and without MEN-1 with ZES is contrasted and the areas of certainty and disagreement reviewed.
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PMID:Management of the Zollinger-Ellison syndrome in patients with multiple endocrine neoplasia type 1. 968 46

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.
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PMID:Proton pump inhibitors. Pharmacology and rationale for use in gastrointestinal disorders. 977 9

The pharmacology, pharmacokinetics, clinical efficacy, adverse effects, and dosage and administration of pantoprazole are reviewed. Pantoprazole is a gastric hydrogen-potassium adenosine triphosphatase (H+/K(+)-ATPase) inhibitor. It shares the same core structure as other currently available proton-pump inhibitors (PPIs). The FDA-labeled indication is the short-term treatment of erosive esophagitis. PPIs act by selectively inhibiting H+/K(+)-ATPase in the secretory canaliculus of the stimulated parietal cell. Understanding the pharmacodynamics of PPIs is more relevant than knowing their pharmacokinetics, since the duration of action depends on the rate of de novo proton-pump regeneration, not the duration of drug circulation in the body. Pantoprazole is well absorbed, undergoes little first-pass metabolism, and has an absolute bioavailability of approximately 77%. Pantoprazole has been evaluated in more than 100 clinical trials involving more than 11,000 patients. It is effective in treating erosive esophagitis and duodenal and gastric ulcers. It is also effective as adjunctive treatment with antimicrobials in patients infected with Helicobacter pylori. Pantoprazole has been shown to control acid production in Zollinger-Ellison syndrome. Pantoprazole is well tolerated. The most commonly reported adverse effects are headache, diarrhea, and abdominal pain. The recommended oral dosage for erosive esophagitis is 40 mg once a day for up to eight weeks. The recommended i.v. dose is 40 mg given over 15 minutes once a day in patients with gastroesophageal reflux disease who are unable to take oral medication. Pantoprazole appears to be as safe and effective as other PPIs in acid-related disorders.
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PMID:Pantoprazole. 1140 94

Lansoprazole (Prevacid, TAP Pharmaceuticals, Inc.) is a substituted benzimidazole that inhibits gastric acid secretion. This agent is approved for the short-term treatment of erosive reflux oesophagitis, active gastric ulcer, active duodenal ulcer and the treatment of non-steroidal anti-inflammatory drug (NSAID)-induced gastric and duodenal ulcers. It is also approved for the long-term treatment of healed reflux oesophagitis, healed duodenal ulcer, the treatment of hypersecretory conditions such as Zollinger-Ellison syndrome and the eradication of Helicobacter pylori as a component of triple therapy with lansoprazole, clarithromycin and amoxicillin, or dual therapy with lansoprazole and amoxicillin. Its mechanism of action is to selectively inhibit the membrane enzyme H+/K+ ATPase in gastric parietal cells. In clinical trials, lansoprazole is more effective than placebo or histamine (H2)-receptor antagonists in the treatment of reflux oesophagitis. Lansoprazole administered at a dose of 30 mg daily produced faster relief of symptoms and superior healing rates in patients with gastric or duodenal ulcers or reflux oesophagitis than H2-receptor antagonists. A daily dose of 30 mg lansoprazole reduced epigastric pain faster than omeprazole 20 mg daily in patients with peptic ulcer disease but healing rates at 4 and 8 weeks were similar with both agents at these dosages. Lansoprazole was more effective than H2-receptor antagonists in patients with Zollinger-Ellison syndrome and produced similar treatment outcome to omeprazole. Lansoprazole in combination with clarithromycin and amoxicillin produced similar rates of eradication of H. pylori. In clinical trials, lansoprazole is well-tolerated and has a low frequency of side effects similar to that of H2-receptor antagonists or omeprazole.
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PMID:Lansoprazole: pharmacokinetics, pharmacodynamics and clinical uses. 1182 9

The more potent and longer-lasting inhibition of gastric acid secretion provided by proton pump inhibitors (PPIs) as compared with histamine-2-receptor antagonists is caused in large part by differences in their mechanism of action. PPIs block histamine-2-, gastrin-, and cholinergic-mediated sources of acid production and inhibit gastric secretion at the final common pathway of the H+/K+ adenosine triphosphatase proton pump. In contrast, histamine-2-receptor antagonists cannot block receptor sites other than those mediated by histamine. It seems that the rapid loss of acid suppression activity by the histamine-2-receptor antagonists may be attributed to tolerance. Such tolerance has not occurred in patients receiving PPIs because these agents are irreversible inhibitors of the H+/K+ adenosine triphosphatase proton pump. For these reasons, patients who have acid-related disorders that require high levels of acid suppression do not respond well to intravenous histamine-2-receptor antagonists and would be excellent candidates for intravenous PPI therapy. Candidates for intravenous PPIs also include patients who cannot receive oral PPIs and those who may need the higher acid suppression therapy provided by the intravenous rather than the oral route. Clinical studies have demonstrated the efficacy of intravenous pantoprazole in maintaining adequate control of gastric acid output during the switch from oral to intravenous therapy in patients with severe gastroesophageal reflux disease or the Zollinger-Ellison syndrome. Intragastric administration of solutions prepared from oral PPIs has been used as an alternative to the intravenous route in critical care settings. However, decreased bioavailability may limit the value of intragastric delivery of PPIs because of the high frequency of gastric emptying problems in critically ill patients.
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PMID:Pharmacology of acid suppression in the hospital setting: focus on proton pump inhibition. 1207 61


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