PROTON PUMP (H+/K+ ATPASE) INHIBITORS (PPIs) e.g.
(Omeprazole, lansoprazole, pantoprazole, rabeprazole and esomeprazole).
Mechanism of Action
They are prodrugs absorbed from the intestine, then diffuse across gastric parietal cell, they convert into active metabolites in gastric mucosa and bind to parietal cell H+/K+ ATPase ( binds irreversibly to H+/K+ ATPase enzyme) leading to dose-dependent inhibition of both basal and stimulated gastric acid secretion and can reduce acid secretion almost to zero for 1 –2 days.
Full restoration of acid secretion after discontinuing the PPI takes about 3-5 days (time of re-synthesis of H+/K+ ATPase).
Uses
- Gastric and duodenal ulcer.
- Stress ulcer. (drug of choice)
- Gastro- esophageal reflux disease (GERD).
- With ulcerogenic drugs e.g. antirheumatics as a prophylaxis against injury of gastric mucosa. - Prophylaxis
- Pathological hypersecretory syndrome “Zollinger Ellison Syndrome”.
- With antimicrobial regimens to eradicate H. pylori.
- Eradication of H. pylori.
Adverse effects
1. Low incidence of diarrhea, abdominal colic, headache, dizziness, skin rash, leucopenia, transient increase of liver enzymes (Short term use <12 weeks)
2. A dose- dependent decrease in vit B12 absorption has been observed after more than 12 weeks because acid is important for its absorption in a complex with intrinsic factor.
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The PPIs profoundly inhibit gastric secretion and may alter the bioavialability of orally administered drugs, such as ketoconazole, digoxin, iron.
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Omeprazole selectively inhibits hepatic P450 isoenzymes and decreases the elimination of phenytoin, diazepam, warfarin, and cyclosporine.
- 5-In rats’ in high doses induce gastric carcinoid tumor. in humans also mentioned in australia research