药物的肝脏毒性消化系统用药(高分飞)

DrugsAffectingGastrointestinalFunction,GaoFen-Fei,OUTLINE,PepticUlcerDigestionVomitingDiarrheaBileReview-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”NoAcidNoUlcer”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（protonpumpinhibitor，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。,IntroductionofUlcer,Epidemiologyincidenceofadisease:10%-12%EuropeandAmerica:DUGU;Japan:GUDUEtiologyGeneralconsideration:NoAcidNoUlcerMainDestroyFactors:HCl,Pepsin,HpProtectiveBarrier:Mucus-HCO3-,PathogenesisofPepticUlcer,Review,Howisthesecretionofgastricacidadjusted?Whatisthemechanismofsecretionofgastricacid?,Howtotreatpepticulcer?,Anti-ulcerTargets,HClMucusHp,Anti-ulcerClassification,Antacids-NeutralizeHClGastricAntisecretoryDrugsHClsecretionAntagonizeRs.onParietalCell-H2,M3,GInhibitorofH+-PumpProtectorsofMucosaAgentskillHP,.Antacids,Mechanism:AlkalizersToNeutralizeHClAgents:Mg(OH)2Al(OH)3CaCO3NaHCO3AdverseEffect:Systemicalkalosis,Diarrhea,CO2,Majorconstituentsofantacids,.1.H2-RAntagonists,Mechanism:PharmacologicEffects:BasalgastricacidnocturnalsecretionAgents:Cimetidine，Ranitidine，FamotidineAdverseEffect:Gynecomastia,prolactin,CYP450,headache,.1.AntimuscarinicAgents,Mechanism:BlockingM3-RonParietalCell,M-RonECLcellandGcellPharmacologicEffects:HClspasmolysisAgents:Atropine，ProbanthinePirenzepine-M1,M2-RselectionAdverseEffect:,.1.AntagonistofG-R,Mechanism:CompetingGastrin-RonParietalCellPharmacologicEffects:HClMucosalAgents:ProglumideAdverseEffect:,.2.ProtonPumpInhibitors,Mechanism:H+,K+-ATPaseH+K+PharmacologicEffects:HClPepsinMucus-HCO3-;CytoprotectiveeffectPharmacologicEffects:PreventionofulcersiducedbyNSAIDsContraindication：Womenwithchildbearing,2.SucralfateMechanism:Polymerization&gelatinebarrierPGE2Mucus-HCO3-HpPharmacologicEffects:EffectiveinDuodenalUlcersNotice:AcidpHEmptystomach,3.CBSMechanism:PepsinPGE1Mucus-HCO3-CoatingHp（disputed）4.Teprenone5.Marzulene,.Anti-HpDrugs,90%DU,70%GU-Helicobacterpylori(G-)Anti-UlcerAgents:BismuthCompoundsProtonPumpInhibitorssucralfateAntibacterialDrugs:AmoxicillinGentamicinMetronidazole,CombinationTherapy,TherapyoftriadOverseaPPI+twoAntibacterialDrugsDomesticCBS+PPIorH2-RAntagonist+AntibacterialDrug,DigestionAids,ContentsofDigestiveJuice:PepsinPancreatinHelpfulBacteriasinBowel:biofermin,AntiemeticDrugsandDrugsPromotingGastrointestinalMotility,MedullaOblongataVomitingCenter,Stimuli,ChemoreceptorTriggerZone,StomachandAbdomminalMusculature,PathogenesisofVomiting,延髓呕吐中枢,刺激,晃动,AntagonistsofReceptorsofH1:Nucleusoftractussolitarius,vestibulocerebellarpathwayDiphenhydramine,DimenhydrinateM:Nucleusoftractussolitarius,CTZScopolamineD2:CTZ,Nucleusoftractussolitarius,Stomach,SmallintestineThiethylperazine，Metoclopramide5-HT3:Stomach,Smallintestine,CTZ,NucleusoftractussolitariusOndansetron，GranisetronProkinetics：MetoclopramideBlockingGastrointestinalDomperidoneD2-RCisapride：Achrelease,AntidiarrhealDrugsandAdsorbents,OpiumpreparationandDerivativesOpiatereceptorsinGastrointestinaltracttonemotility（），secretion（），AchreleaseLoperamide：DerivativesofHaloperidolAstringentsTannalbinBismuthsubsalicylate,BismuthsubcarbonateAdsorbantsMedicinalCharcoalKaolin,Laxatives,ContactcatharticsIrritantorstimulantintestinalmotilityPhenolphthalein,Rhubarb,Senna,CastoroilOsmoticlaxativesnonabsorbabledistendingperistalsisMgSO4,Na2SO4,Lactulose,CellulosesSurface-activeagentsLubricating,StoolsoftenLiquidparaffin,Cholereticdrug,CholicAcidHMG-CoAreductase(ratelimitingenzyme)bilesalt，cholesterolChenodiol(Chenod