课件：GERD胃食管反流英文版.ppt

Prokinetics Domperidone (Motilium, Costi) Prokinetics Cisapride (Prepulsid, Propulsid) Prokinetics Rarely used because of severe side effects Fatigue Tremors Parkinsonism Tardive Dyskinesia Severe cardiac events New Treatments Cholecystokinin2 receptor antagonists (CCK2) Potassium competitive acid blockers (P-CABs) Treatments Cholecystokinin2 receptor antagonists (CCK2) Block the CCK2 receptors inhibiting acid secretion Still in clinical trials Best use in combination with PPI’s CCK2 Itriglumide CCK2 Z-360 Treatments Potassium competitive acid blockers (P-CABs) Target H+/K+ ATPase Ionically binds to the proton pump Specific for the K+ binding region and prevents acid secretion Binds reversibly Still in clinical trials P-CABs Revaprazan P-CABs Soraprazan Treatment for H. pylori Amoxicillin + clarithromycin + proton pump inhibitor Metronidazole + clarithromycin + proton pump inhibitor Bismuth subsalicylate + metronidazole + tetracycline + proton pump inhibitor Assigned Reading Vesper, J.B. et all, Gastroesophageal Reflux Diesease, Is there More to the Story?, ChemMedChem (2008), 3, 552-559. Homework Questions What is an antagonist and how do the H2RAs (histamine receptor antagonists) act as one? Explain the precise biological mechanism whereby prokinetics achieve their effect, including the receptors they act upon. Are they agonists or antagonists? Of which chemical messenger? What is a prodrug? What causes the PPI’s to become an active drug? Bacteria in the upper GI tract may play a role in GERD. Explain. References Bak, Young-Tae. Management Strategies for Gastroesophageal Reflux Disease. Journal of Gastroenterology and Hepatology (2004), 19, S49-S53. Horn, J. Understanding the Pharmacodynamic and Pharmacokinetic Differences between proton pump inhibitors- focus on pKa and metabolism. APT (2006), 2, 340-350. Pettit, M. Treatment of Gastroesophageal Reflux Disease. Pharm World Sci (2005) 27, 432-435. Vakil, N., New Pharmacological Agents for the Trea