药物的肝脏毒性，消化系统用药高分飞.ppt

Drugs Affecting Gastrointestinal Function OUTLINE Peptic Ulcer Digestion Vomiting Diarrhea Bile Review-Questions Ulcer-Background 20世纪初，与应激、生活、饮食等有关，故主张镇静、休息、饮食治疗。 1910年，Schwarz提出”No Acid No Ulcer” 1971年，Black等发现H2受体。1976年，第一代H2受体拮抗剂西咪替丁用于临床——第一次革命。诺贝尔奖。 20世纪80年代中期，质子泵抑制剂（proton pump inhibitor，PPI）奥美拉唑问世。 1983年，澳大利亚学者Warren与Marshall分离出Hp，病因观念转变，再一次革命。根治成为可能。2005年，获诺贝尔奖。 Introduction of Ulcer Epidemiology incidence of a disease: 10%-12% Europe and America: DU GU; Japan: GU DU Etiology General consideration: No Acid No Ulcer Main Destroy Factors: ①HCl, ②Pepsin, ③Hp Protective Barrier: Mucus-HCO3- Review How is the secretion of gastric acid adjusted ? What is the mechanism of secretion of gastric acid ? Anti-ulcer Targets HCl Mucus Hp Anti-ulcer Classification Antacids--- Neutralize HCl Gastric Antisecretory Drugs HCl secretion Antagonize Rs. on Parietal Cell--- H2,M3, G Inhibitor of H+-Pump Protectors of Mucosa Agents kill HP Ⅰ. Antacids Mechanism: Alkalizers——To Neutralize HCl Agents: Mg(OH)2 Al(OH)3 CaCO3 NaHCO3 Adverse Effect: Systemic alkalosis, Diarrhea , CO2 Ⅱ.1.⑴ H2-R Antagonists Mechanism: Pharmacologic Effects: Basal gastric acid nocturnal secretion Agents: Cimetidine， Ranitidine， Famotidine Adverse Effect: Gynecomastia, prolactin , CYP450 , headache Ⅱ.1.⑵ Antimuscarinic Agents Mechanism: Blocking M3-R on Parietal Cell, M-R on ECL cell and G cell Pharmacologic Effects: HCl spasmolysis Agents: Atropine ，Probanthine Pirenzepine - M1,M2-R selection Adverse Effect: Ⅱ.1.⑶ Antagonist of G-R Mechanism: Competing Gastrin-R on Parietal Cell Pharmacologic Effects: HCl Mucosal Agents: Proglumide Adverse Effect: Ⅱ.2. Proton Pump Inhibitors Mechanism: H+,K+-ATPase H+ K+ Pharmacologic Effects: HCl Hp Agents: Omeprazole（losec） Lansoprazole Pantoprazole，Rabeprazole Adverse Effect: Ⅲ. Mucosal Protective Agents Derivatives of Prostaglandin: Miso