Trumeprazole Mechanism of Action

Pharmacology: Pharmacodynamics: Mechanism of Action: Omeprazole suppress gastric acid secretion by specific inhibition of the H⁺/K⁺ ATPase enzyme system at the secretory surface of the gastric parietal cell. Because this enzyme system is regarded as the acid (proton)pump within the gastric mucosa, Omeprazole is characterized as the gastric pump inhibitor as it blocks the final step of acid production.
Site and Mechanism of Action: Omeprazole is a weak base and is concentrated and converted to the active form in the acid environment of the intracellular canaliculi within the parietal cell, where it inhibits the enzyme H⁺, K⁺-ATPase- the acid pump. This effect on the final step of the gastric acid formation process is dose-dependent and provides for effective inhibition of both basal acid secretion and stimulated acid secretion irrespective of the secretagogue.
Omeprazole has no effect on acetylcholine or histamine receptors and no clinically significant pharmacodynamic effects have been observed other than those explained by the effect of omeprazole on acid secretion. Effect of Helicobacter pylori: Helicobacter pylori is associated with acid peptic disease including duodenal and gastric ulcer in which about 95% and 70% of patients, respectively, are infected with this bacterium. H. pylori is the major factor in development of gastritis and ulcers in such patients.
Recent evidence also suggest a causative link between H. pylori and gastric carcinoma.
Other Effects Related to Acid Inhibition: During long-term treatment, gastric glandular cysts have been reported in a somewhat increased frequency. These changes are physiological consequence of pronounced inhibition of acid secretion, are benign and appear to be reversible.
Pharmacokinetics: Absorption and Distribution: Omeprazole is acid-labile and is administered as enteric granules in capsules. Absorption takes place in the small intestine and usually completed within 3-6 hours. The systemic bioavailability of omeprazole from a single-oral dose is approximately 35%. After repeated once-daily administration, the bioavailability increases to about 60%. Concomitant intake of food has no influence in the bioavailability. The plasma protein-binding of omeprazole is about 95%.
Elimination and Metabolism: The average half-life of the terminal phase of the plasma concentration-time curve is approximately 40 mins. There is no change in half-life during treatment. The inhibition of acid secretion is related to the area under the plasma concentration-time curve (AUC) but not to the actual plasma concentration at a given time.
Omeprazole is entirely metabolized, mainly in the liver. Identified metabolites in the plasma are the sulfone, the sulfide and hydroxyomeprazole, these metabolites having no significant effect on acid secretion. About 80% of the metabolites are excreted in the urine and the rest in the feces. The 2 main urinary metabolites are hydroxyomeprazole and corresponding carboxylic acid.
The systemic bioavailability of omeprazole is not significantly altered in patients with reduced renal function. The area under the plasma concentration-time curve is increased in patients with impaired liver function, but no tendency to accumulation of omeprazole has been found.