DrugsAffectingGastrointestinalFunctionGaoFen-Fei精選課件OUTLINEPepticUlcerDigestionVomitingDiarrheaBileReview-Questions精選課件Ulcer-Background20世紀(jì)初，與應(yīng)激、生活、飲食等有關(guān)，故主張鎮(zhèn)靜、休息、飲食治療。1910年，Schwarz提出”NoAcidNoUlcer”1971年，Black等發(fā)現(xiàn)H2受體。1976年，第一代H2受體拮抗劑西咪替丁用于臨床——第一次革命。諾貝爾獎。20世紀(jì)80年代中期，質(zhì)子泵抑制劑（protonpumpinhibitor，PPI）奧美拉唑問世。1983年，澳大利亞學(xué)者Warren與Marshall分離出Hp，病因觀念轉(zhuǎn)變，再一次革命。根治成為可能。2005年，獲諾貝爾獎。精選課件IntroductionofUlcerEpidemiologyincidenceofadisease:10%-12%EuropeandAmerica:

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

?精選課件Anti-ulcerTargetsHClMucusHp精選課件Anti-ulcerClassificationAntacids---

Neutralize

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

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

Mechanism:PharmacologicEffects:Basalgastricacid

nocturnalsecretionAgents:Cimetidine，Ranitidine，F(xiàn)amotidineAdverseEffect:Gynecomastia,prolactin,CYP450,headache精選課件Ⅱ.1.⑵AntimuscarinicAgentsMechanism:BlockingM3-RonParietalCell,M-RonECLcellandGcellPharmacologicEffects:HCl

spasmolysisAgents:Atropine，ProbanthinePirenzepine-M1,M2-RselectionAdverseEffect:精選課件Ⅱ.1.⑶AntagonistofG-RMechanism:CompetingGastrin-RonParietalCellPharmacologicEffects:HCl

Mucosal

Agents:ProglumideAdverseEffect:精選課件Ⅱ.2.ProtonPumpInhibitorsMechanism:H+,K+-ATPase H+K+

PharmacologicEffects:HCl&Hp

Agents:Omeprazole（losec）LansoprazolePantoprazole，RabeprazoleAdverseEffect:精選課件精選課件Ⅲ.MucosalProtectiveAgentsDerivativesofProstaglandin:Misoprostol(PGE1),EnprostilMechanism:

HCl;PepsinMucus-HCO3-;CytoprotectiveeffectPharmacologicEffects:PreventionofulcersiducedbyNSAIDsContraindication：Womenwithchildbearing精選課件2.

SucralfateMechanism:

Polymerization&gelatinebarrierPGE2

Mucus-HCO3-

HpPharmacologicEffects:EffectiveinDuodenalUlcersNotice:AcidpHEmptystomach精選課件3.

CBS

Mechanism:

PepsinPGE1

Mucus-HCO3-

CoatingHp（disputed）4.

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

AntibacterialDrugsDomesticCBS+PPIorH2-RAntagonist+AntibacterialDrug精選課件DigestionAidsContentsofDigestiveJuice:PepsinPancreatinHelpfulBacteriasinBowel:biofermin精選課件AntiemeticDrugsandDrugsPromotingGastrointestinalMotility精選課件MedullaOblongata

VomitingCenterStimuliChemoreceptorTriggerZoneStomachandAbdomminalMusculaturePathogenesisofVomiting精選課件延髓嘔吐中樞高級中樞催吐化學(xué)感受區(qū)(5-HT3,D2,M1)孤束核(5-HT3,D2,M,H1)咽喉胃腸道（5-HT3）迷走神經(jīng)H1,M小腦內(nèi)耳前庭前庭神經(jīng)刺激刺激化學(xué)刺激物晃動精選課件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↑精選課件AntidiarrhealDrugsand

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

Surface-activeagentsLubricating,StoolsoftenLiquidparaffin精選課件CholereticdrugCholicAcidHMG-CoA

reductase(ratelimitingenzyme)↓