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Lisa Levanderon 11 October 2013
Transcript of Esomeprazole (Nexium)
Gastroesophageal Reflux Disease (GERD)
Helicobacter Pylori Eradication
NSAID-induced ulcer prophylaxis
H+,K+ ATPase enzyme pump
also known as the proton pump
Last step in gastric acid production
While the parietal cell is inactivated, the H+,K+ ATPase are located on vesicles inside the cell.
When the stimulated by gastrin, histamine, or acetylcholine, these vesicles move to and fuse into the acid secretory canaliculus of parietal cell's plasma membrane.
Using ATP for energy, the pump exchanges extracellular potassium (native ligand) with hydrogen ions within the cell.
Alpha subunit of the H, K-ATPase
Forms a disulfide bond with a cysteine
Proton-pump Inhibitor (PPI)
***Acid Pump Antagonist (APA)--is referred to as this, but Dr. Garrison said not really relevant for us***
Esomeprazole. In: Clinical Pharmacology. Tampa, FL: Gold Standard. https://library1.unmc.edu/login?url=http://www.clinicalpharmacology-ip.com?id=852776.
Sachs G, Shin JM. Pharmacology of proton pump inhibitors. Los Angles California: Current Medicine Group LLC; 2008. 10.
Yan D, Hu Y, Li S, Cheng M. A model of 3D-structure of H+, K+-ATPase catalytic subunit derived by homology modeling. Acta Pharmacologics Sinica. 2004;25(4):474.
Prodrug--becomes activated by pH--reaction produces a sulphenamide
Sulphenamide forms a covalent, disulfide bond with the sulfydryl group of a cysteine on the H+,K+ATPase
Binds irreversibly to H+,K+ATPase and inhibits hydrogen ion secretion into the gastric lumen
Lipophilic, weak base, is inactive at neutral pH