Omevex Mechanism of Action

Pharmacology: Omeprazole is a racemic mixture of a pair of active optical antipodes which reduces gastric acid secretion through a high target mechanism of action. It is a specific inhibitor of the gastric proton pump in the parietal cell. It is rapidly acting and produces reversible control of gastric acid secretion with once daily dosing.
Omeprazole is a weak base, which is concentrated in the intracellular canaliculi of the parietal cell. Due to the acidic environment in these cells, omeprazole is converted to the active form, where it acts as an inhibitor of the enzyme H+, K+ -ATPase - the proton pump. There is a dose dependency on this final step in the formation of gastric acid, which provides for effective inhibition of the secretion of both basal acid and stimulated acid irrespective of the secretory enhancer. But the inhibition has nothing to do with the stimulus.
Intravenous administration of omeprazole results in dose related inhibition of acid secretion. 40 mg i.v. dose of omeprazole is recommended for the first time in order to produce similar effect immediately on intragastric acidity as repeated oral dosing with 20 mg. The IV injection produces an immediate decrease in intragastric acidity and a mean decrease over 24 hours of approximately 90%. The inhibition of acid secretion is related to the area under the plasma concentration-time curve (AUC) and not to the actual plasma concentration at a given time.
Acid digestive diseases are concerned with Helicobacter pylori, including 95% of duodenal and 70% of gastrohelcoma. Helicobacter pylori are the main factor leading to gastritis. The chief ingredients in causing peptic ulcer are Helicobacter pylori along with gastric acid. Omeprazole can eradicate Helicobacter pylori combined with proper antibiotics. This treat is related to quick relief of symptoms, high reparation rate of gastric mucosa and the long-term mitigation of peptic ulcer disease, which thus reduces the complications of gastrointestinal bleeding and cuts down the long-term need of antacid at the same time.
Decreased gastric acidity due to any means including proton pump inhibitors, increases gastric counts of bacteria normally present in the gastrointestinal tract. Treatment with acid-reducing drugs may lead to a slightly increased risk of gastrointestinal infections, such as Salmonella and Campylobacter.
Pharmacokinetics: Distribution: The apparent volume of distribution in healthy subjects is approximately 0.3 L/kg and a similar value is also seen in patients with renal insufficiency. In elderly patients, and in patients with hepatic insufficiency, the volume of distribution is slightly decreased. The plasma protein binding of omeprazole is about 95%.
Metabolism and Excretion: The average half-life of the terminal phase of the plasma concentration-time curve following IV administration of omeprazole is approximately 40 minutes. The total plasma clearance is 0.3 to 0.6 L/min. There is no change in half-life during treatment.
Omeprazole is completely metabolised by the cytochrome P450 system (CYP), mainly in the liver. The major part of its metabolism is dependent on the polymorphically expressed, specific isoform CYP2C19 (S-mephenytoin hydroxylase), responsible for the formation of hydroxyomeprazole, the major metabolite in plasma. In accordance with this, as a consequence of competitive inhibition, there is a potential for metabolic drug-drug interactions between omeprazole and other substrates for CYP2C19.
No metabolite has been found to have any effect on gastric acid secretion. Almost 80% of an intravenously given dose is excreted as metabolites in the urine, and the remainder is found in the faeces, primarily originating from bile secretion.
There is no significant change in the systemic bioavailability of omeprazole in patients with impaired renal function. Although the area under the plasma concentration-time curve is increased in patients with reduced liver function, no apparent accumulation of omeprazole has been found.
Toxicology: Gastric ECL-cell hyperplasia and carcinoids have been observed in long-term studies in rats treated with omeprazole, H2-recepter blocking agent or proton pump inhibitor, or subjected to partial fundectomy. These changes are the result of sustained hypergastrinaemia secondary to acid inhibition, and not from a direct effect of any individual drug.