PROTON PUMP INHIBITORS – Mechanism, Uses, Adverse effects, Pharmacokinetics, Drug Interactions.

Proton pump inhibitors act on potassium/hydrogen ATPase enzyme system which is present on the luminal side of parietal cells in mucosal lining of stomach. This cause Decrease HCl and pepsin activation in lumen of the stomach. After inhibition these agents require 18 hours to be resynthesised. Omeprazole, Esomeprazole, Delaxsoprazole, Lansoprazole, Rabeprazole, Pantoprazole all are prodrugs and require Alkaline pH for absorption, and its absorption occur in duodenum and enteric coating is done to avoid premature degradation. Sodium bicarbonate also facilitate its absorption. Therapeutic uses are for the treatment of stress ulcer, duodenal ulcer, GERD, erosive esophagitis, NSAID-induced ulcers, Eradicate Helicobacter pylori and pathological hypersecretory conditions like Zollinger-Ellison syndrome in which tumor cause increase gastrin production thus stimulate gastric acid secretion. PPI’s should be taken before H2 antagonists. pharmacokinetics are; orally effective, take 30-60 mins before meal. Half life of a few hours. Excreted through urine and feces. Adverse effects are it inhibits CYP2C19 which cause clopidogrel conversion to active metabolites. thus increase cardiovascular events. Increase risk of fracture, diarrhea, hypomagnesimia, pneumonia can occur. decrease absorption of Vitamin B12 and calcium carbonate.

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