Parietal cells inhibition

At neutral pH proton pump inhibitors are chemically stable, lipid-soluble, weak bases that have no inhibitory activity. In an acid environment they become protonated and a sulfenamide is formed. This sulfenamide binds covalently to the K+H+-ATPase proton pump in the gastric parietal cells, inhibiting this enzyme irreversibly and thus the entry of H+ ions into lumen. Omeprazole metabolizes at a pH of about 3.9. 1, whereas rabeprazole metabolizes at a pH of about 4.9. Secretion of acid only becomes possible again after new molecules of K+H+-ATPase are formed. 

Mecfianism of Action A benzimidazole that is converted to active metabolites that irreversibly bind to and inhibit hydrogen-potassium adenosine triphosphatase, an enzyme on the surface of gastric parietal cells. Inhibits hydrogen ion transport into gastric lumen. Therapeutic Effect Increases gastric pH, reduces gastric acid production. Pharmacokinetics ... 

Inhibits histamine action at 112 receptors of parietal cells, inhibiting gastric acid secretion (fasting, nocturnal, or when stimulated by food, caffeine, insulin)... 

The anti-ulcer agents omeprazole, lanzoprazole, and pantoprazole have been introduced during the past decade for the treatment of peptic ulcers. Gastric acid secretion is efficiently reduced by prazole inhibition of H+K+-ATPase in the parietal cells of the gastrointestinal mucosa [75]. The prazoles themselves are not active inhibitors of the enzyme, but are transformed to cyclic sulfenamides in the intracellular acidic compartment of parietal cells [76]. The active inhibitors are permanent cations at pH < 4, with limited possibilities of leaving the parietal cells, and thus are retained and activated at the site of action. In the neutral body compartments the prazoles are stable, and only trace amounts are converted to the active drugs. (For a review on omeprazole, see Ref. [77].)... 

PPIs block gastric acid secretion by inhibiting hydrogen potassium adenosine triphosphatase in gastric parietal cells, which results in profound and long-lasting antisecretory effects. 

Prostaglandins inhibit the secretion of protons by the parietal cells in the stomach, which is normally increased in response to food and the hormone gastrin. Consequently, inhibition of prostaglandin synthesis by aspirin or other similar drugs results in increased secretion of protons by the stomach, which can result in considerable gastric discomfort and can, if chronic, lead to the development of a peptic ulcer. Consequently, there is some conflict between the use of such inhibitors to relieve chronic pain (see below), in diseases such as arthritis, and the risk of development of ulcers. 

Omeprazole is classified as a proton pump inhibitor, as it acts by blocking the hydrogen-potassium adenosine triphosphate enzyme system of the gastric parietal cells. Omeprazole therefore inhibits gastric acid release. Common side-effects associated with omeprazole include diarrhoea, headache, nausea and vomiting. Concurrent administration of omeprazole and phenytoin results in enhanced effects of phenytoin, which may lead to phenytoin toxicity. 

Omeprazole (p. 167) can cause maximal inhibition of HCl secretion. Given orally in gastric juice-resistant capsules, it reaches parietal cells via the blood. In the acidic milieu of the mucosa, an active metabolite is formed and binds covalently to the ATP-driven proton pump (H+/K+ ATPase) that transports H+ in exchange for IC into the gastric juice. Lansoprazole and pantoprazole produce analogous effects. The proton pump inhibitors are first-line drugs for the treatment of gastroesophageal reflux disease. 

Misoprostol is a stable analog of prostaglandin Ei. It reduces acid secretion by inhibiting histamine-stimulated adenyl cyclase activity in the parietal cell. 

Mechanism of Action A proton pump inhibitor that selectively Inhibits the parietal cell membrane enzyme system (hydrogen-potassium adenosine triphosphatase) or proton pump. Therapeutic Effect Suppresses gastric acid secretion. Pharmacokinetics ... 

Mechanism of Action A prostaglandin that inhibits basal, nocturnal gastric acid secretion via direct action on parietal cells. Therapeutic Effect Increases production of protective gastric mucus. 

Mechanism of Action An Hj blocker and gastric acid secretion inhibitor that inhibits histamine action at histamine-2 receptors of parietal cells TherapeuticEffeet Inhibits basal and nocturnal gastric acid secretion. 

The H+-K+-ATPase acts as the proton pump in the parietal cells of the stomach mucosa. It transports protons and Cl ions into the stomach via a K+ antiport. Substituted benzimidazoles, such as omeprazole (8.27) inhibit this enzyme and are 2-12 times as active as cimetidine (8.28) in inhibiting gastric stimulation. 

The H2 antagonists exhibit competitive inhibition at the parietal cell H2 receptor and suppress basal and meal-stimulated acid secretion (Figure 62-2) in a linear, dose-dependent manner. They are highly selective and do not affect H j or H3 receptors (see Chapter 16). The volume of gastric secretion and the concentration of pepsin are also reduced. 

Misoprostol has both acid inhibitory and mucosal protective properties. It is believed to stimulate mucus and bicarbonate secretion and enhance mucosal blood flow. In addition, it binds to a prostaglandin receptor on parietal cells, reducing histamine-stimulated cAMP production and causing modest acid inhibition. Prostaglandins have a variety of other actions, including stimulation of intestinal electrolyte and fluid secretion, intestinal motility, and uterine contractions. 

Inhibit basal and nocturnal gastric secretions by competitively and reversibly inhibiting the action of histamine at the histamine H -receptors of parietal cells... 

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