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

Proton pump inhibitors (PPIs) [omeprazole, lansoprazole, pantoprazole, rabeprazole and esomeprazole] are widely utilised for the treatment of gastro-oesophageal reflux disease, as well as other acid-related disorders. All PPIs suppress gastric acid secretion by blocking the gastric acid pump, H(+)/K(+)-adenosine triphosphatase (ATPase), but the physicochemical properties of these drugs result in variations in the degree of acid suppression, as well as the speed of onset of acid inhibition. Such differences may impact on the clinical performance of PPIs, and this manuscript discusses data that may help clinicians choose between the available PPIs for specific clinical situations and indications. The characteristics of PPIs that have been developed subsequent to omeprazole offer several advantages over this prototype PPI, particularly with respect to the onset of acid suppression and reduced potential for inter-individual pharmacokinetic variation and drug interactions. Newer agents inhibit H(+)/K(+)-ATPase more rapidly than omeprazole and emerging clinical data support potential clinical benefits resulting from this pharmacological property. Although key pharmacokinetic parameters (time to maximum plasma concentration and elimination half-life) do not differ significantly among PPIs, differences in the hepatic metabolism of these drugs can produce inter-patient variability in acid suppression, in the potential for pharmacokinetic drug interactions and, quite possibly, in clinical efficacy. All PPIs undergo significant hepatic metabolism. Because there is no direct toxicity from PPIs, there is minimal risk from the administration of any of them - even to patients with significant renal or hepatic impairment. However, there are significant genetic polymorphisms for one of the cytochrome P450 (CYP) isoenzymes involved in PPI metabolism (CYP2C19), and this polymorphism has been shown to substantially increase plasma levels of omeprazole, lansoprazole and pantoprazole, but not those of rabeprazole. Hepatic metabolism is also a key determinant of the potential for a given drug to be involved in clinically significant pharmacokinetic drug interactions. Omeprazole has the highest risk for such interactions among PPIs, and rabeprazole and pantoprazole appear to have the lowest risk.Thus, whereas all PPIs have been shown to be generally effective and safely used for the treatment of acid-mediated disorders, there are chemical, pharmacodynamic and pharmacokinetic differences among these drugs that may make certain ones more, or less, suitable for treating different patient subgroups. Of course, the absolute magnitude of risk from any PPI in terms of drug-drug interactions is probably low - excepting interactions occurring as class effects related to acid suppression (e.g. increased digoxin absorption or inability to absorb ketoconazole).
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PMID:Clinical pharmacology of proton pump inhibitors: what the practising physician needs to know. 1466 53

Omeprazole is a proton pump inhibitor which reduces both basal and stimulated gastric acid secretion by inhibiting the parietal cell enzyme H(+)-K(+)-adenosine triphosphatase. Typical adverse effects of proton pump inhibitors are nausea, diarrhea, constipation and endocrinologic abnormalities such as gynecomastia. Cutaneous side effects are rare but may include contact dermatitis, lichenoid eruption, leukocytoclastic vasculitis or toxic epidermal necrolysis; anaphylaxis is rare. We identified omeprazole as the causative agent by oral challenge test in a patient who had developed anaphylaxis while taking several drugs.
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PMID:[Anaphylaxis caused by omeprazole]. 1639 10

Proton pump inhibitors (PPIs) are widely used for the treatment of gastroesophageal reflux disease, as well as other acid-related disorders. Omeprazole, lansoprazole, pantoprazole, rabeprazole and esomeprazole effectively suppress gastric acid secretion by blocking the gastric acid pump, H+/K+ -adenosine triphosphatase (ATPase). Understanding the pharmacokinetic properties of PPIs and examining the pharmacogenetic differences may help clinicians to optimize PPI therapy and to perform individual treatment, especially in non-responder patients with GERD or ulcer or after failed eradication therapy.
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PMID:[Clinical pharmacological aspects of the proton pump inhibitor therapy: importance of pharmacogenetic differences in the clinical practice]. 1744 20


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