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1、药物的肝脏毒性，消化系统用药,1,Drugs Affecting Gastrointestinal Function,Gao Fen-Fei,药物的肝脏毒性，消化系统用药,2,OUTLINE,Peptic Ulcer Digestion Vomiting Diarrhea Bile Review-Questions,药物的肝脏毒性，消化系统用药,3,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
2、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。,药物的肝脏毒性，消化系统用药,4,Introduction of Ulcer,Epidemiology incidence of a disease: 10%-12% Europe and America: DU GU; Japan: GU DU Etiology General consideration: No Acid No
3、 Ulcer Main Destroy Factors: HCl, Pepsin, Hp Protective Barrier: Mucus-HCO3-,药物的肝脏毒性，消化系统用药,5,Pathogenesis of Peptic Ulcer,药物的肝脏毒性，消化系统用药,6,药物的肝脏毒性，消化系统用药,7,Review,How is the secretion of gastric acid adjusted ? What is the mechanism of secretion of gastric acid ?,药物的肝脏毒性，消化系统用药,8,药物的肝脏毒性，消化系统用药,9,药
4、物的肝脏毒性，消化系统用药,10,药物的肝脏毒性，消化系统用药,11,药物的肝脏毒性，消化系统用药,12,How to treat peptic ulcer ?,药物的肝脏毒性，消化系统用药,13,Anti-ulcer Targets,HCl Mucus Hp,药物的肝脏毒性，消化系统用药,14,Anti-ulcer Classification,Antacids- Neutralize HCl Gastric Antisecretory Drugs HCl secretion Antagonize Rs. on Parietal Cell- H2,M3, G Inhibitor of H+-
5、Pump Protectors of Mucosa Agents kill HP,药物的肝脏毒性，消化系统用药,15,. Antacids,Mechanism: AlkalizersTo Neutralize HCl Agents: Mg(OH)2 Al(OH)3 CaCO3 NaHCO3 Adverse Effect: Systemic alkalosis, Diarrhea , CO2,药物的肝脏毒性，消化系统用药,16,Major constituents of antacids,药物的肝脏毒性，消化系统用药,17,.1. H2-R Antagonists,Mechanism: Phar
6、macologic Effects: Basal gastric acid nocturnal secretion Agents: Cimetidine， Ranitidine， Famotidine Adverse Effect: Gynecomastia, prolactin , CYP450 , headache,药物的肝脏毒性，消化系统用药,18,.1. Antimuscarinic Agents,Mechanism: Blocking M3-R on Parietal Cell, M-R on ECL cell and G cell Pharmacologic Effects: HC
7、l spasmolysis Agents: Atropine ，Probanthine Pirenzepine - M1,M2-R selection Adverse Effect:,药物的肝脏毒性，消化系统用药,19,.1. Antagonist of G-R,Mechanism: Competing Gastrin-R on Parietal Cell Pharmacologic Effects: HCl Mucosal Agents: Proglumide Adverse Effect:,药物的肝脏毒性，消化系统用药,20,.2. Proton Pump Inhibitors,Mecha
8、nism: H+,K+-ATPase H+ K+ Pharmacologic Effects: HCl Pepsin Mucus-HCO3- ; Cytoprotective effect Pharmacologic Effects: Prevention of ulcers iduced by NSAIDs Contraindication： Women with childbearing,药物的肝脏毒性，消化系统用药,23,2. Sucralfate Mechanism: Polymerization & gelatine barrier PGE2 Mucus-HCO3- Hp Pharm
9、acologic Effects: Effective in Duodenal Ulcers Notice: Acid pH Empty stomach,药物的肝脏毒性，消化系统用药,24,3. CBS Mechanism: Pepsin PGE1 Mucus-HCO3- Coating Hp （disputed） 4. Teprenone 5. Marzulene,药物的肝脏毒性，消化系统用药,25,. Anti-Hp Drugs,90% DU,70% GU - Helicobacter pylori (G-) Anti-Ulcer Agents: Bismuth Compounds Pro
10、ton Pump Inhibitors sucralfate Antibacterial Drugs: Amoxicillin Gentamicin Metronidazole,药物的肝脏毒性，消化系统用药,26,药物的肝脏毒性，消化系统用药,27,Combination Therapy,Therapy of triad Oversea PPI + two Antibacterial Drugs Domestic CBS + PPI or H2-R Antagonist + Antibacterial Drug,药物的肝脏毒性，消化系统用药,28,Digestion Aids,Contents
11、 of Digestive Juice: Pepsin Pancreatin Helpful Bacterias in Bowel: biofermin,药物的肝脏毒性，消化系统用药,29,Antiemetic Drugs and Drugs Promoting Gastrointestinal Motility,药物的肝脏毒性，消化系统用药,30,Medulla Oblongata Vomiting Center,Stimuli,Chemoreceptor Trigger Zone,Stomach and Abdomminal Musculature,Pathogenesis of Vomi
12、ting,药物的肝脏毒性，消化系统用药,31,延髓呕吐中枢,刺激,晃动,药物的肝脏毒性，消化系统用药,32,Antagonists of Receptors of H1: Nucleus of tractus solitarius, vestibulocerebellar pathwayDiphenhydramine, Dimenhydrinate M : Nucleus of tractus solitarius, CTZScopolamine D2 : CTZ, Nucleus of tractus solitarius, Stomach, Small intestineThiethylp
13、erazine，Metoclopramide 5-HT3 : Stomach, Small intestine, CTZ, Nucleus of tractus solitariusOndansetron，Granisetron Prokinetics： Metoclopramide Blocking Gastrointestinal Domperidone D2-R Cisapride：Ach release,药物的肝脏毒性，消化系统用药,33,Antidiarrheal Drugs and Adsorbents,Opium preparation and Derivatives Opiat
14、e receptors in Gastrointestinal tract tonemotility（），secretion（），Ach release Loperamide： Derivatives of Haloperidol Astringents Tannalbin Bismuth subsalicylate, Bismuth subcarbonate Adsorbants Medicinal Charcoal Kaolin,药物的肝脏毒性，消化系统用药,34,Laxatives,Contact cathartics Irritant or stimulant intestinal m
15、otility Phenolphthalein, Rhubarb, Senna, Castor oil Osmotic laxatives nonabsorbable distending peristalsis MgSO4, Na2SO4, Lactulose, Celluloses Surface-active agents Lubricating, Stool soften Liquid paraffin,药物的肝脏毒性，消化系统用药,35,Choleretic drug,Cholic Acid HMG-CoA reductase (rate limiting enzyme) bile salt，cholesterol Chenodiol (Chenodeoxycholic acid) MgSO4 cholecystokinin Cinametic acid Anethol trithione,药物的肝脏毒性，消化系统用药,36,Review-Questions,The classification of drugs used in the treatment of peptic ulceration. the mechanisms and the agents of each.,药物的肝脏毒性，消化系统用药,37,Good Bye!,