ML-Gacid Mechanism of Action

Pharmacological Classification: Medicines acting on gastro-intestinal tract.
Pharmacology: Pharmacodynamics: Omeprazole is a specific inhibitor of the gastric proton pump in the parietal cell and thus reduces the secretion of gastric acid. Reversible control of gastric acid secretion is produced with single daily doses of omeprazole.
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.
Omeprazole has no pharmacological effect on acetylcholine, histamine or gastrin receptors.
Effect on Gastric Secretion: When omeprazole is given daily as a single oral dose, the gastric acid secretion is inhibited with a maximum effect reached within four days of treatment. In patients with duodenal ulcers, a mean decrease of approximately 80% in intragastric acidity is then maintained over a 24-hour period, with the mean decrease in peak acid output after pentagastrin stimulation being approximately 70%, twenty-four hours after initiating treatment with omeprazole.
Pharmacokinetics: Due to the acid lability of omeprazole, the oral formulation consists of enteric-coated granules in capsules.
Omeprazole is usually completely absorbed from the small intestine within three to six hours.
After a single oral dose the systemic bioavailability of omeprazole is approximately 35% which can be increased to about 60%, after repeated once-daily administration.
The simultaneous intake of food has no influence on the bioavailability. Omeprazole is approximately 95% bound to plasma proteins.
The average terminal phase half-life of the plasma concentration-time curve is approximately forty minutes. 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 (AUG) and not to the actual plasma concentration at a given time.
Omeprazole is completely metabolised mainly in the liver. The sulphone, the sulphide and hydroxy omeprazole are the metabolites detected in plasma. These metabolites are inactive and have no significant effect on acid secretion.
Approximately 80% of the metabolites are excreted in the urine and the balance in the faeces. The two main metabolites in the urine are hydroxy-omeprazole and the corresponding carboxylic acid.
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.