药物的肝脏毒性消化系统用药(高分飞).ppt
Drugs Affecting Gastrointestinal Function,Gao Fen-Fei,OUTLINE,Peptic UlcerDigestionVomitingDiarrheaBileReview-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,Epidemiologyincidence of a disease:10%-12%Europe and America:DU GU;Japan:GU DU EtiologyGeneral consideration:No Acid No UlcerMain Destroy Factors:HCl,Pepsin,HpProtective Barrier:Mucus-HCO3-,Pathogenesis of Peptic Ulcer,Review,How is the secretion of gastric acid adjusted?What is the mechanism of secretion of gastric acid?,How to treat peptic ulcer?,Anti-ulcer Targets,HClMucusHp,Anti-ulcer Classification,Antacids-Neutralize HClGastric Antisecretory Drugs HCl secretionAntagonize Rs.on Parietal Cell-H2,M3,GInhibitor of H+-PumpProtectors of MucosaAgents kill HP,.Antacids,Mechanism:AlkalizersTo Neutralize HClAgents:Mg(OH)2 Al(OH)3 CaCO3 NaHCO3Adverse Effect:Systemic alkalosis,Diarrhea,CO2,Major constituents of antacids,.1.H2-R Antagonists,Mechanism:Pharmacologic Effects:Basal gastric acid nocturnal secretionAgents:Cimetidine，Ranitidine，FamotidineAdverse Effect:Gynecomastia,prolactin,CYP450,headache,.1.Antimuscarinic Agents,Mechanism:Blocking M3-R on Parietal Cell,M-R on ECL cell and G cellPharmacologic Effects:HCl spasmolysisAgents:Atropine，ProbanthinePirenzepine-M1,M2-R selectionAdverse Effect:,.1.Antagonist of G-R,Mechanism:Competing Gastrin-R on Parietal CellPharmacologic Effects:HCl Mucosal Agents:ProglumideAdverse Effect:,.2.Proton Pump Inhibitors,Mechanism:H+,K+-ATPase H+K+Pharmacologic Effects:HCl&Hp Agents:Omeprazole（losec）LansoprazolePantoprazole，RabeprazoleAdverse Effect:,.Mucosal Protective Agents,Derivatives of Prostaglandin:Misoprostol(PGE1),EnprostilMechanism:HCl;PepsinMucus-HCO3-;Cytoprotective effectPharmacologic Effects:Prevention of ulcers iduced by NSAIDsContraindication：Women with childbearing,2.SucralfateMechanism:Polymerization&gelatine barrier PGE2 Mucus-HCO3-HpPharmacologic Effects:Effective in Duodenal UlcersNotice:Acid pHEmpty stomach,3.CBS Mechanism:Pepsin PGE1 Mucus-HCO3-CoatingHp（disputed）4.Teprenone5.Marzulene,.Anti-Hp Drugs,90%DU,70%GU-Helicobacter pylori(G-)Anti-Ulcer Agents:Bismuth CompoundsProton Pump InhibitorssucralfateAntibacterial Drugs:AmoxicillinGentamicinMetronidazole,Combination Therapy,Therapy of triadOverseaPPI+two Antibacterial DrugsDomesticCBS+PPI or H2-R Antagonist+Antibacterial Drug,Digestion Aids,Contents of Digestive Juice:PepsinPancreatinHelpful Bacterias in Bowel:biofermin,Antiemetic Drugs and Drugs Promoting Gastrointestinal Motility,Medulla Oblongata Vomiting Center,Stimuli,Chemoreceptor Trigger Zone,Stomach and Abdomminal Musculature,Pathogenesis of Vomiting,延髓呕吐中枢,刺激,晃动,Antagonists of Receptors of H1:Nucleus of tractus solitarius,vestibulocerebellar pathwayDiphenhydramine,DimenhydrinateM:Nucleus of tractus solitarius,CTZScopolamineD2:CTZ,Nucleus of tractus solitarius,Stomach,Small intestineThiethylperazine，Metoclopramide 5-HT3:Stomach,Small intestine,CTZ,Nucleus of tractus solitariusOndansetron，Granisetron Prokinetics：Metoclopramide Blocking GastrointestinalDomperidone D2-RCisapride：Ach release,Antidiarrheal Drugs and Adsorbents,Opium preparation and DerivativesOpiate receptors in Gastrointestinal tract tonemotility（），secretion（），Ach release Loperamide：Derivatives of HaloperidolAstringentsTannalbinBismuth subsalicylate,Bismuth subcarbonateAdsorbantsMedicinal CharcoalKaolin,Laxatives,Contact catharticsIrritant or stimulant intestinal motilityPhenolphthalein,Rhubarb,Senna,Castor oilOsmotic laxativesnonabsorbable distending peristalsisMgSO4,Na2SO4,Lactulose,Celluloses Surface-active agentsLubricating,Stool softenLiquid paraffin,Choleretic drug,Cholic AcidHMG-CoA reductase(rate limiting enzyme)bile salt，cholesterol Chenodiol(Chenodeoxycholic acid)MgSO4cholecystokinin Cinametic acidAnethol trithione,Review-Questions,The classification of drugs used in the treatment of peptic ulceration.the mechanisms and the agents of each.,Good Bye!,
