Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P20020 (adenosine triphosphatase)
 3,299 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We tested the hypothesis that the gastric H+/K+ adenosine triphosphatase inhibitor, omeprazole, because of its different mode of action and pronounced inhibitory effect on gastric acid secretion, may be more effective in peptic ulcer that is refractory to histamine H2 receptor antagonist treatment than continuing the same therapy. Altogether 107 patients (duodenal ulcer, n = 88; prepyloric ulcer, n = 14; gastric ulcer, n = 3; mixed sites, n = 2) with refractory peptic ulcer - that is ulcer unhealed after at least two months' treatment with cimetidine 0.8 g or 1 g daily or with ranitidine 0.3 g daily - were randomly allocated to receive either omeprazole 40 mg daily (n = 54) or to continue treatment with the same H2 receptor antagonist and at the same dose (n = 53) for up to eight weeks. The patients in the two treatment groups were well matched demographically. Healing by 'intent to treat' analysis was as follows: at four weeks, omeprazole 46 of 54 (85%), H2 receptor antagonist 18 of 53 (34%) (p less than 0.0001); and at eight weeks, 52 of 54 (96%) and 30 of 53 (57%) respectively (p less than 0.0001). One patient was lost to follow up but of the 22 patients whose ulcers were shown to be unhealed at endoscopy after receiving continued H2 receptor antagonist treatment, 21 healed in four to eight weeks when changed to omeprazole. Daytime epigastric pain cleared at four weeks in 43 of 47 (91%) patients on omeprazole and in 32 of 46 (70%) on H2 receptor antagonists (p=0.01) and relief of all dyspeptic symptoms occurred in 39 of 47 (83%) and 23 of 45 (51%) (p=0.0009) patients respectively. Adverse events occurred in 11 of 54 (20%) patients on omeprazole and in 12 of 35 (34%) on cimetidine but in none on ranitidine. The events were mild and none required treatment withdrawal. The commonest event in patients on omeprazole was loose stools or diarrhoea (n=5). Omeprazole was significantly better than continued H2 receptor antagonist treatment for the short term management of refractory peptic ulcer as judged by healing rate and pain relief, and it was safe.
 ...
PMID:Treatment of refractory peptic ulcer with omeprazole or continued H2 receptor antagonists: a controlled clinical trial. 162 76

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.
 ...
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.
 ...
PMID:Is there a need for strong gastric acid inhibition in clinical practice? 269 9

Lansoprazole is a benzimidazole derivative that effectively decreases gastric acid secretion, regardless of the primary stimulus, via inhibition of gastric H+,K(+)-adenosine triphosphatase (ATPase). It provides effective symptom relief and healing of peptic ulcer and reflux oesophagitis after 4 to 8 weeks of therapy and appears to prevent recurrence of lesions when administered as maintenance therapy. When administered at therapeutic dosages, lansoprazole produced higher healing rates than ranitidine or famotidine in patients with duodenal and gastric ulcers. Lansoprazole heals duodenal ulcers more rapidly than ranitidine or famotidine. Relief of ulcer symptoms in lansoprazole recipients is at least equivalent to, and tends to be more rapid than, that in patients receiving histamine H2-receptor antagonists. In comparisons with omeprazole 20 mg/day, lansoprazole 30 mg/day produced duodenal ulcer healing more rapidly and reduced ulcer pain to a greater extent at 2 weeks, but overall healing rates were similar after 4 weeks of therapy. At therapeutic dosages, lansoprazole produces superior healing and symptom relief of reflux oesophagitis in comparison with ranitidine, and it tends to relieve heartburn more effectively than omeprazole, although both agents produce equivalent healing. Healing of peptic ulcers or reflux oesophagitis refractory to histamine H2-receptor antagonists occurs after 8 weeks in the majority of patients treated with lansoprazole, and lansoprazole and omeprazole demonstrate similar efficacy in patients with refractory peptic ulcers. In patients with Zollinger-Ellison syndrome, lansoprazole effectively controls mean basal gastric acid output. Lansoprazole is generally well tolerated in clinical trials. The incidence of adverse effects is similar to that of omeprazole, ranitidine and famotidine in comparative studies. Combination therapy with lansoprazole and antibacterial agents such as amoxicillin, tinidazole, roxithromycin and/or metronidazole appears to eradicate Helicobacter pylori in 22 to 80% of patients with this organism. Limited data also suggest that lansoprazole may have superior activity against H. pylori in comparison with omeprazole, although the clinical relevance of this preliminary finding requires further confirmation. Thus, lansoprazole may be considered as alternative to existing antisecretory agents available for the treatment of acid-related disorders, particularly because it may provide more rapid healing and relief of symptoms.
 ...
PMID:Lansoprazole. A reappraisal of its pharmacodynamic and pharmacokinetic properties, and its therapeutic efficacy in acid-related disorders. 752 61

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.
 ...
PMID:Lansoprazole and omeprazole in the treatment of acid peptic disorders. 895 52

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.
 ...
PMID:Proton pump inhibitors and acid-related diseases. 901 63

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.
 ...
PMID:Lansoprazole: a comprehensive review. 908 23

Proton Pump Inhibitors (PPIs) are widely used in the treatment of acid-peptic diseases. Their mechanism of action involves inhibition of the H-K-adenosine triphosphatase enzyme present in the parietal cells of the gastric mucosa. Because PPIs are the most potent inhibitors of gastric acid secretion available, they effectively alleviate acid-peptic symptoms and facilitate healing of inflamed or ulcerated mucosa. Although the use of PPIs is nowadays short term in patients with Helicobacter pylori-related peptic ulcer disease, these drugs are increasingly used long term, frequently for a lifetime, in patients with typical or atypical symptoms of gastro-oesophageal reflux disease, and in NSAID or aspirin users at risk for gastrotoxicity and related complications, such as bleeding, perforation and gastric outlet obstruction. This review outlines the essentials of PPI pharmacology, the safety and adverse profiles of the various available agents, and balances them against their clinical short- and long-term benefits. PPI use, prophylactically or with a therapeutic intent may also be combined with other strategies, such as endoscopic therapy, surgery or antibacterial use. Various clinical endpoints, such as symptom relief, mucosal healing, prevention of disease recurrence or complications, and cancer chemoprevention, are discussed and unmet needs are highlighted.
 ...
PMID:Guide to the use of proton pump inhibitors in adult patients. 1845 60

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.
 ...
PMID:Novel approaches to inhibition of gastric acid secretion. 2092 27

Proton pump inhibitors (PPIs) are one of the most commonly prescribed classes of medications in the United States. By inhibiting gastric H/K adenosine triphosphatase via covalent binding to the cysteine residues of the proton pump, they provide the most potent acid suppression available. Long-term PPI use accounts for the majority of total PPI use. Absolute indications include peptic ulcer disease, chronic nonsteroidal anti-inflammatory drugs use, treatment of Helicobacter pylori, and erosive esophagitis. Although PPIs are generally considered safe, numerous adverse effects, particularly associated with long-term use have been reported. Many patients receiving chronic PPI therapy do not have clear indications for their use, prompting consideration for reduction or discontinuation of their use. This article reviews the indications for PPI use, the adverse effects/risks involved with their use, and conditions in which their use is controversial.
 ...
PMID:Proton pump inhibitors: the good, the bad, and the unwanted. 2312 6


1