Omeprazole is a drug used to treat conditions such as gastroesophageal reflux disease (GERD), gastric ulcers, duodenal ulcers, erosive esophagitis, Zollinger-Ellison syndrome and stomach infections caused by Helicobacter pyloribacteria. Omeprazole is a prodrug administered orally but since it degrades rapidly at low pH, the capsule contains enteric-coated granules. After undergoing absorption in the small intestine, it passes from the blood stream into the parietal cells in the stomach, then enters the stomach lumen. It is a weak base and thus, accumulates on the outside of cell in the acidic environment. Its main target is the H+/K+ ATPase in the parietal cells in the stomach. In parietal cells, carbonic anhydrase converts water and carbon dioxide to hydrogen bicarbonate ions and H+. The bicarbonate ions go into the blood via the chloride anion exchanger on the basolateral membrane which exchanges the hydrogen bicarbonate for Cl- ions. There is also the Na+/K+ ATPase which pumps Na+ out of the cell and K+ into the cell. The H+/K+ ATPase is located on the apical membrane and pumps the H+ from the cell into the stomach lumen and K+ from the lumen into the cell. Another transporter, the K+/Cl- symporter transports K+ and Cl- in the stomach lumen. The H+ and Cl- in the stomach lumen forms the HCl acid which, in excess, can cause disorders like ulcers. The acidic environment in the stomach converts the prodrug omeprazole into its active form, sulfenamide. Sulfenamide then covalently binds to the cysteine residues on the alpha subunit of the H+/K+ ATPase via disulfide bridges. This binding of sulfenamide irreversibly inhibits the H+/K+ ATPase, preventing too much acid secretion in the stomach. Less acid in the stomach is favorable for symptomatic relief of disorders caused by the acid. Omeprazole is metabolized in the liver by CYP2C19 to form its main metabolite, 5-hydroxyomeprazole, which is excreted form the body in urine. Side effects of taking omeprazole may include flatulence, abdominal pain, headache, diarrhea, nausea, vomiting, fever, upper respiratory infection

Omeprazole Pathway References