Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0847097 (acidity)
 15,165 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Omeprazole inhibits H+,K+-ATPase, the enzyme responsible for the exchange of H+ and K+ in the final step in the acid secretory process within the parietal cell. It has been shown to produce a marked and long-lasting inhibition of acid secretion with a decrease in 24-hour intragastric acidity after repeated daily dosing. Omeprazole has been shown to give significantly higher healing rates than ranitidine or cimetidine in patients with duodenal ulcer and gastric ulcer. Similarly, a more pronounced effect on ulcer symptoms has been observed. In patients with reflux esophagitis, omeprazole has been shown to decrease the time with an acid milieu in the esophagus. Omeprazole has consistently given about twice as high healing rates and faster decrease in symptoms than with ranitidine. In patients with Zollinger-Ellison syndrome, omeprazole has been found to have a rapid and long-lasting effect on acid secretion and acid-induced symptoms.
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PMID:Clinical utility and safety of omeprazole. 265 79

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

Helicobacter pylori is susceptible to many antibacterial drugs in vitro but has proved difficult to eradicate in vivo. The macrolide clarithromycin has good activity against H. pylori in vitro and has demonstrated the highest eradication rate for any antibacterial monotherapy in vivo. However, it is clear that antibacterial monotherapy is not a sufficiently effective treatment for patients with H. pylori infection. The suggestion that high intragastric acidity impairs the action of antibacterial drugs led to the evaluation of combination H. pylori eradication regimens including H+,K+-ATPase inhibitors and antibacterial drug(s) with or without bismuth compounds. Noncomparative studies evaluating the efficacy of dual therapy with clarithromycin plus omeprazole in patients with H. pylori infection have reported eradication rates of between 58 and 83% > or = 4-weeks after therapy. In comparative studies, clarithromycin plus omeprazole was at least as effective as amoxicillin plus omeprazole. However, direct comparisons have shown that eradication rates achieved by dual therapy are not as high as those achieved by triple therapy. Indeed, triple therapy with clarithromycin plus omeprazole in combination with amoxicillin or a nitroimidazole has achieved eradication rates of up to 100%. Although 14-day triple drug regimes were initially considered necessary for effective eradication, it now seems clear that 7-day regimes are equally effective. Factors known to influence response to H. pylori eradication therapy include bacterial resistance and patient compliance. A review of 4 studies evaluating the efficacy of dual eradication therapy with clarithromycin plus omeprazole reported an overall incidence of adverse events (patient or investigator reported, whether related to treatment or not) of 45%. The most common adverse event was taste disturbance (an adverse event commonly reported during the development of clarithromycin); nausea, headache, diarrhoea, vomiting and abdominal pain occurred less frequently. Although dual therapy might be expected to cause fewer adverse events than triple therapy this has not been the case in direct comparisons conducted to date. Thus, although clarithromycin plus omeprazole is associated with an H. pylori eradication rate of approximately 70%, 1 week of triple therapy with these 2 drugs together with amoxicillin or a nitroimidazole, which eradicates the organism in approximately 90% of cases, may represent optimal H. pylori eradication therapy.
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PMID:Clarithromycin and omeprazole as helicobacter pylori eradication therapy in patients with H. pylori-associated gastric disorders. 874 Dec 37

Current therapies to treat gastroesophageal reflux disease (GERD), peptic ulcer disease (PUD), and other acid-related diseases either prevent stimulation of the parietal cell (H2 receptor antagonists, H2RAs) or inhibit gastric H+,K+-ATPase (e.g., proton pump inhibitors, PPIs). Of the 2 approaches, the inhibition of the final step in acid production by PPIs provides more effective relief of symptoms and healing. Despite the documented efficacy of the PPIs, therapeutic doses have a gradual onset of effect and do not provide complete symptom relief in all patients. There is scope for further improvements in acid suppressive therapy to maximize healing and offer more complete symptom relief. It is unlikely that cholecystokinin2 (CCK2, gastrin) receptor antagonists, a class in clinical trials, will be superior to H2RAs or PPIs. However, a new class of acid suppressant, the potassium-competitive acid blockers (P-CABs), is undergoing clinical trials in GERD and other acid-related diseases. These drugs block gastric H+,K+-ATPase by reversible and K+-competitive ionic binding. After oral doses, P-CABs rapidly achieve high plasma concentrations and have linear, dose-dependent pharmacokinetics. The pharmacodynamic properties reflect the pharmacokinetics of this group (i.e., the effect on acid secretion is correlated with plasma concentrations). These agents dose dependently inhibit gastric acid secretion with a fast onset of action and have similar effects after single and repeated doses (i.e., full effect from the first dose). Animal studies comparing P-CABs with PPIs suggest some important pharmacodynamic differences (e.g., faster and better control of 24-hr intragastric acidity). Studies in humans comparing PPIs with P-CABs will help to define the place of this new class in the management of acid-related diseases.
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PMID:Potassium-competitive acid blockade: a new therapeutic strategy in acid-related diseases. 1600 Feb 24

Oxynticopeptic cells of fish stomach are thought to secrete less acid than the specialized parietal cells of mammalian stomach. Gastric acidity, however, has not been directly compared between fish and mammals. We therefore fed rainbow trout and rats the same meal, and found that the lowest postprandial pH of trout stomach was 2.7, which was only transiently sustained for 1 h, whereas that of rat stomach was 1.3, which was sustained for 3 h. Postprandial pH of the small intestine was slightly higher in trout (approximately 8.0) than in rats (approximately 7.6), but pH of the large intestine was similar (approximately 8.0). Addition of acids to fish feeds, in an attempt to aid the weak acidity of fish stomach, has been known to improve phosphorus digestibility, but its physiological effect on fish stomach is not known. Exogenous acids did improve phosphorus digestibility but also decreased steady-state mRNA expression of trout H(+)/K(+)-ATPase (ATP4A, the proton pump) as well as Na(+)/bicarbonate cotransporter (NBC), and had no effect on gastrin-like mRNA and somastostatin (SST) mRNA abundance. Gastrin-like mRNA and SST-2 mRNA were equally distributed between corpus and antrum. ATP4A mRNA and NBC mRNA were in the corpus, whereas SST-1 mRNA was in the antrum. Trout gastrin-like EST had modest homology to halibut and pufferfish gastrin, whereas trout ATP4A mRNA had > or = 95% amino acid homology with mammalian, Xenopus and flounder ATP4A. Although ATP4A seems highly conserved among vertebrates, gastric acidity is much less in trout than in rats, explaining the low digestibility of bone phosphorus, abundant in fish diets. Dietary acidification does not reduce acidity enough to markedly improve phosphorus digestibility, perhaps because exogenous acids may inhibit endogenous acid production.
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PMID:Dietary acidification enhances phosphorus digestibility but decreases H+/K+-ATPase expression in rainbow trout. 1698 89

Anti-ulcer potential and proton pump inhibitory activity of kolaviron (KV) isolated from Garcinia kola Heckel has been evaluated using different ulcer models. Cold-restraint (CRU), aspirin (ASP), alcohol (AL), pyloric ligation (PL) induced gastric ulcer models were used to assess anti-ulcerogenic activity of KV in rats. Effects of KV on gastric juice for free and total acidity, peptic activity and mucin secretion were also evaluated. The H+, K+-ATPase activity was assayed in gastric microsomes, spectrophotometrically. Results of this study showed that KV (200 mg/kg) reduced the incidence of ulcers in CRU (69.0%), PL (67.6%), ASP (68.6%) and AL (51.5%). Reductions were also observed in free acidity (32.6%), total acidity (56.2%) and peptic activity (35.4%) with increase in mucin secretion by 40.1%. KV inhibited the H+,K+-ATPase activity with IC50 of 43.8 microg/ml compared with omeprazole with IC50 of 32.3 microg/ml. KV showed both cytoprotective and anti-secretory potentials against peptic ulcer models, and a proton pump inhibitory activity. KV may emerge as a potent anti-ulcer compound.
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PMID:Anti-ulcerogenic and proton pump (H+, K+ ATPase) inhibitory activity of Kolaviron from Garcinia kola Heckel in rodents. 2170 26