药物的肝脏毒性消化系统用药

DrugsAffectingGastrointestinalFunctionGaoFen-Fei精选课件OUTLINEPepticUlcerDigestionVomitingDiarrheaBileReview-Questions精选课件Ulcer-Background20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。精选课件IntroductionofUlcerEpidemiologyincidenceofadisease:10%-12%EuropeandAmerica:

DU>GU;Japan:GU>DUEtiologyGeneralconsideration:NoAcidNoUlcerMainDestroyFactors:①HCl,②Pepsin,③HpProtectiveBarrier:Mucus-HCO3-精选课件PathogenesisofPepticUlcer精选课件精选课件ReviewHowisthesecretionofgastricacidadjusted?Whatisthemechanismofsecretionofgastricacid?精选课件精选课件精选课件精选课件精选课件Howtotreatpepticulcer

?精选课件Anti-ulcerTargetsHClMucusHp精选课件Anti-ulcerClassificationAntacids---

Neutralize

HClGastricAntisecretoryDrugsHClsecretionAntagonizeRs.onParietalCell---H2,M3,GInhibitorofH+-PumpProtectorsofMucosaAgentskill

HP精选课件Ⅰ.AntacidsMechanism:Alkalizers——ToNeutralizeHClAgents:Mg(OH)2Al(OH)3CaCO3NaHCO3AdverseEffect:Systemicalkalosis,Diarrhea,CO2精选课件ConstituentNeutralizingCapacitySaltFormedinStomachSolubilityofSaltAdverseEffectsNaHCO3HighNaClHighSystemicalkalosis,fluidretentionCaCO3ModerateCaCl2ModerateHypercalcemia,nephrolithiasis,milk-alkalisyndromeAl(OH)3HighAlCl3LowConstipation,hypophosphatemia;drugadsorptionreducesbio-availabilityMg(OH)2HighMgCl2LowDiarrhea,hypermagnesemia(inpatientswithrenalinsufficiency)Majorconstituentsofantacids精选课件Ⅱ.1.⑴H2-RAntagonists

Mechanism:PharmacologicEffects:Basalgastricacid

nocturnalsecretionAgents:Cimetidine，Ranitidine，FamotidineAdverseEffect:Gynecomastia,prolactin,CYP450,headache精选课件Ⅱ.1.⑵AntimuscarinicAgentsMechanism:BlockingM3-RonParietalCell,M-RonECLcellandGcellPharmacologicEffects:HCl

spasmolysisAgents:Atropine，ProbanthinePirenzepine-M1,M2-RselectionAdverseEffect:精选课件Ⅱ.1.⑶AntagonistofG-RMechanism:CompetingGastrin-RonParietalCellPharmacologicEffects:HCl

Mucosal

Agents:ProglumideAdverseEffect:精选课件Ⅱ.2.ProtonPumpInhibitorsMechanism:H+,K+-ATPase H+K+

PharmacologicEffects:HCl&Hp

Agents:Omeprazole（losec）LansoprazolePantoprazole，RabeprazoleAdverseEffect:精选课件精选课件Ⅲ.MucosalProtectiveAgentsDerivativesofProstaglandin:Misoprostol(PGE1),EnprostilMechanism:

HCl;PepsinMucus-HCO3-;CytoprotectiveeffectPharmacologicEffects:PreventionofulcersiducedbyNSAIDsContraindication：Womenwithchildbearing精选课件2.

SucralfateMechanism:

Polymerization&gelatinebarrierPGE2

Mucus-HCO3-

HpPharmacologicEffects:EffectiveinDuodenalUlcersNotice:AcidpHEmptystomach精选课件3.

CBS

Mechanism:

PepsinPGE1

Mucus-HCO3-

CoatingHp（disputed）4.

Teprenone5.Marzulene精选课件Ⅳ.Anti-HpDrugs90%DU,70%GU---Helicobacterpylori(G-)Anti-UlcerAgents:BismuthCompoundsProtonPumpInhibitorssucralfateAntibacterialDrugs:AmoxicillinGentamicinMetronidazole精选课件精选课件CombinationTherapyTherapyoftriadOverseaPPI+two

AntibacterialDrugsDomesticCBS+PPIorH2-RAntagonist+AntibacterialDrug精选课件DigestionAidsContentsofDigestiveJuice:PepsinPancreatinHelpfulBacteriasinBowel:biofermin精选课件AntiemeticDrugsandDrugsPromotingGastrointestinalMotility精选课件MedullaOblongata

VomitingCenterStimuliChemoreceptorTriggerZoneStomachandAbdomminalMusculaturePathogenesisofVomiting精选课件延髓呕吐中枢高级中枢催吐化学感受区(5-HT3,D2,M1)孤束核(5-HT3,D2,M,H1)咽喉胃肠道（5-HT3）迷走神经H1,M小脑内耳前庭前庭神经刺激刺激化学刺激物晃动精选课件AntagonistsofReceptorsof

H1:

Nucleusoftractus

solitarius,vestibulocerebellarpathway——

Diphenhydramine,DimenhydrinateM:Nucleusoftractus

solitarius,CTZ——ScopolamineD2

:CTZ,Nucleusoftractus

solitarius,Stomach,Smallintestine——Thiethylperazine，Metoclopramide

5-HT3

:Stomach,Smallintestine,CTZ,Nucleusoftractus

solitarius——Ondansetron，Granisetron

Prokinetics：Metoclopramide

BlockingGastrointestinalDomperidone

D2-RCisapride：Achrelease↑精选课件AntidiarrhealDrugsand

AdsorbentsOpiumpreparationandDerivativesOpiatereceptorsinGastrointestinaltract→tone↑motility↓（μ），secretion↓（δ），Achrelease↓Loperamide：DerivativesofHaloperidolAstringentsTannalbinBismuthsubsalicylate,BismuthsubcarbonateAdsorbantsMedicinalCharcoalKaolin精选课件LaxativesContactcatharticsIrritantorstimulant→intestinalmotility↑Phenolphthalein,Rhubarb,Senna,CastoroilOsmoticlaxativesnonabsorbable→distending→peristalsisMgSO4,Na2SO4,Lactulose,Celluloses

Surface-activeagentsLubricating,StoolsoftenLiquidparaffin精选课件CholereticdrugCholicAcidHMG-CoA

reductase(ratelimitingenzyme)↓