《胃肠病药物治疗》PPT课件

1、胃肠病药物治疗,上海市消化疾病研究所吴叔明教授,.分类（1）.,抗溃疡1:1067,Sulfasalazine(SASP),SASP:5-aminosalicylicacid(5-ASA)和sulfapyridine(SP)二部分2030%SASP在上GI吸收,经胆汁和尿液排泄肠道细菌将SASP裂解为SP和5-ASA脂溶吸收的SP:side-effect脂溶吸收差的SASP留在结肠,AdverseEffectsofSulfasazine,Doserelatednauseavomitinganorexiafolatemal-ab.Headachealopecia,Notdoserelatedsk

2、inrashhemolyticanemiaagrannulocytosisfibrosingalveolitishepatitismaleinfertilitycolitis,溃疡性结肠炎的药物治疗,各种剂型膜包被控释型偶合型AsacolPentasaOsalazineClaversalBalsalazideSalofalkMesalazineRowasa,MechanismsofSteroidAction-IBD,StabilizeslysosomalmembranesReducescapillarypermeabilityFunctionasinhibitorsofchemotaxisan

3、dphagocytosisImpairscell-mediatedimmunityinexperimentalmodels,AdministrationandDosage,OralDosageTaperingIntravenousBolusorcontinuousinfusionTopicalPosition,Dosage,Duration,CommonlyUsedGlucorticoidds,EquivalentMineralo-GlucocorticoidGlucocorticoidcorticoidDuratonofactionPotencyDose(mg)ActionShort-act

4、ingCortisol120yesCortisone0.825yesPrednisone45y/noPrednisolone45y/noMethylpredinisolone54y/noIntermediate-actingTriamcinolone54noLong-actingBetamethasone250.60noDexamethasone300.75no,免疫抑制药物,药名作用适应症不良反应用量mg/kg.d硫唑嘌呤干扰嘌呤的缓解期的胰腺炎、BM12生物合成维持抑制，过敏6-MP肝内转化缓解期的胰腺炎、BM11.5硫唑嘌呤维持抑制，过敏环胞素细胞免役对皮质激素肝毒性口服：5抑制剂疗效不

5、好者静滴:4,UC直肠炎的治疗,推荐治疗：5ASA栓剂或类固醇灌肠的表面治疗。5-ASA有更高的缓解率，激素布地奈的为首选。23周有所缓解。缓解治疗：缓解后减至23次/周栓剂治疗不耐受者口服SASP或美沙拉嗪,远段溃疡性结肠炎（3040厘米处乙结肠）,轻、中度的早期：5ASA栓剂或类固醇灌肠的表面治疗。夜间灌肠（美沙拉嗪4克/天34周后每3天1次。无效时考虑加用氢考晨间灌肠。口服治疗：每天SASP1+美沙拉嗪1.2+奥沙拉嗪0.5。无效时每天SASP46+美沙拉嗪4.8+奥沙拉嗪3。重度：5ASA+强的松4060毫克,左半结肠炎和全结肠炎,治疗效应和剂量相关中度：46克SASP或美沙拉嗪4.8

6、克重度和无效者：强的松4060毫克，710天后减量。,重度和爆发性结肠炎,主治方式：强的松30毫克/BID或甲强龙16毫克TID直肠症状为主：加用5ASA和氢考灌肠类固醇IV1014天无效者：手术或环孢素A治疗。,类固醇治疗无效的UC,最大剂量口服和表面治疗的5-ASA以及类固醇治疗无效者。2/3的这类病人在使用免疫抑制剂后可获缓解。硫唑嘌呤或6-巯基嘌呤50毫克/天渐增至硫唑嘌呤1.5毫克或6-巯基嘌呤1.5毫克/kg/天6个月无效，可改用MTX7.5毫克25毫克，812周见效。,类固醇依赖的UC,类固醇减量后复发病例可应用硫唑嘌呤或6-巯基嘌呤，缓解后撤除类固醇，仍应维持免疫抑制治疗。,C

7、rohns病的药物治疗,口腔Crohns病的治疗,1.含氢考的甲基纤维素、果胶、或明胶作表面治疗，2/3的病人有效。2.硫糖铝表面治疗。,胃十二指肠Crohns病的治疗,甲基纤维素粒剂包裹的缓释美沙拉嗪（Pentasa）部分在近端小肠释放，可用之。Pentasa无效时，类固醇治疗。类固醇依赖或类固醇无效：可应用硫唑嘌呤或6-巯基嘌呤,活动性回肠炎、回结肠炎和结肠炎,SASP作用有限5-ASA治疗：美沙拉嗪4克/天一般有效。从11.6克/天开始。无改善者加用环丙沙星0.5克，一天二次。5-ASA无反应或伴全身症状：强的松4060毫克/天,Crohns病局灶性腹膜炎的治疗,Crohns病局灶性腹膜

8、炎指患者出现发热、腹痛腹膜刺激症状、白细胞增多。甲硝唑+第二代头孢菌素；青霉素+庆大霉素是否使用类固醇药物尚有争议,Crohns病小肠梗阻的治疗,胃肠减压+TPN+类固醇治疗无效者手术治疗,Crohns病的维持缓解治疗,Crohns病的维持缓解治疗：5-ASA、类固醇5-ASA的作用不大类固醇作用不明止泻药支持治疗：上述治疗无反应且无全身症状，洛呱丁胺和消胆胺控制腹泻有效,类固醇无效和依赖的Crohns病,硫唑嘌呤或6-巯基嘌呤：50毫克/天，可每月增加25毫克，直至最大剂量。治疗36个月有效硫唑嘌呤或6-巯基嘌呤无效：MTX或环孢霉素抗肿瘤坏死因子-A嵌合抗体输注,Crohns病瘘管的治疗,

9、复发率高，先试用药物。甲硝唑1020毫克/公斤/天可应用6-巯基嘌呤静注环孢霉素抗肿瘤坏死因子-A嵌合抗体输注,Crohns病肛周病和瘘管的治疗,甲硝唑1020毫克/公斤/天甲硝唑和局部切除无效：可应用6-巯基嘌呤抗肿瘤坏死因子-A嵌合抗体输注,PearlsandPitfall-IBD,IBDflareduringpregnacyIBDflaremaybedetrimentaltotheoutcomeofpregnancy?Steroidshouldbeusedtoenhanceafavorableoutcome:NoperinatalorfetaladverseeffectsNofetal8

10、0:72,PearlsandPitfall-IBD,PatientwitheitherpsychiatricdiseaseNotaffecttheriskofonsetanddevelopHypoalbuminemiaReducethedosagetolowside-effectandtoxicity(nonprotein-boundsteroid)IBDflareduringdosagetaperingDosagereturntoprevioushighlevelNoinprovementinoncedailyusageSplittingregimentcouldbetried,Pearls

11、andPitfall-IBD,RetardgrowthinchildSteroidtherapybeavoidedinkid55岁2）WBC160003）血糖200mg%4）LDH350U/L5）AST250U%,48小时时6）HCT下降10%以上7）BUN升高5mg%血钙低于8ng%PaO260mmHg碱缺失超过4mmol液体积聚量6000ml,急性胰腺炎的CT诊断,CT对重症胰腺炎的早期识别和预后判断有使用价值，“脂肪岛”的出现与继发感染关系密切。,CT分级,A级：正常B级：局限或弥漫的胰腺增大，胰腺内少量液体积聚，轮廓不规则。非出血性腺体增强。C级：胰腺异常显象模糊，条纹样改变。D级：单

12、个胰外液体积聚。E级：两个以上胰外液体积聚F级：大量气体和液体积聚于胰腺和邻近部位，累及腹膜后间隙。,急性胰腺炎,有待证实或有限作用的药物：抗酸剂、抗胆碱能药物、H2-受体拮抗剂镇静剂、胰高糖素、降钙素、生长抑素、加压素、丙基硫氧嘧啶、抑肽酶、加贝脂、肝素、抗生素、激素、前列腺素,慢性胰腺炎,胰腺炎的分类,1963年马赛分类：急性胰腺炎急性复发性胰腺炎慢性复发性胰腺炎慢性胰腺炎,慢性胰腺炎的分类,1988年罗马分类1.慢性钙化性胰腺炎；2.慢性阻塞性胰腺炎3.慢性炎症性胰腺炎,慢性胰腺炎的确诊标准,（1a）腹部B超：胰腺组织内有胰石存在（1b）CT：胰腺内钙化，胰石存在（2）ERCP胰管不规则

13、扩张、不均匀；主胰管部分或完全阻塞（3）分泌试验重碳酸盐胰酶分泌减少（4）组织学检查（5）导管上皮增生不典型增生、囊肿形成,胰脂酶,胰腺外分泌不足导致脂肪泻慢性胰腺炎导致腹痛,Pancrelipase-Pharmacology,脂酶含量:thebasisofproductpotencyforreliefofsteatorrheapH4不可逆性失活Enteric-coatedtablet:thecoatdissolvedatpH6.(Poorbioavailability)Coatedmicrospheresincapsule:affectedbygastricemptyofspheres,Su

14、ggestedRegimenforPancreaticEnzymeReplacement,1.Beginwithapreparationprovidingatotalof20,000to40,000lipaseunitspermeal.2.Enteric-coatedformulationsworkwellforcontrolorsteatorrhea,butthenonentericreleaseproteasebetterintheduodenumandarepreferredforpaincontrol.3.Thepreparationshouldbetakenatthebeginnni

15、ngofamealorthroughoutthemealformal-absorption4.forpaincontrol,anighttimedosebegiven,SuggestedRegimenforPancreaticEnzymeReplacement,5.Ifnonenteric-coatedenzymesareusedandnoclinicalimprovementoccurs,addone500mgtabletofSBbeforeandaftermeals,andwithanynighttimeenzymes.6.Ifthereisstillnoimprovement,consi

16、der:a.AddingaPPIoranH2-blckerb.IstheDxcorrect?c.Small-bowelbacteriaovergrowthmaybepresent,Pearls&Pitfall,1.Tx.ofstearorrheaiseffectivewithhigh-lipasemicrospherepreparations.2.Tx.forpainreliefisbestbytraditionaluncoatedpreparationwithhighproteaseandattentiontogoodacidneutralization.3.Bioavailabilityo

17、ftheuncoatedisuncertaininpostgatrectomyduetorapidgastricempty4.Acidneutralizationisimportantincysticfibrosis.,Pearls&Pitfall,5.Alow-fatdietshouldbegivenforseverepancriticinsufficiency,ifsteatorreaisnotreversedcompletelybyreplacement6.SBmaymakethecoatdissolvedprematurely7.Ahigh-fiberdietmakesreplacem

18、entlesseffective.8.MeasuringTx.responsein34Wkslater.Steatorrheaimproveasmalnutritioncorrected.,Pearls&Pitfall,9.Themagnesiumorcalciumformsoapswithfreefattyacidsworseningsteatorrhea.10.Replacementregimenisalife-longthrerapy,No.oftablets,comlianceandthecostshouldbeconsidered.,乳果糖Lactulose,Asyntheticdi

19、saccharideanalogueoflactaseactsasalaxativebystimulatingcolonicperistalsis.,Lactulose,Themostimportantmeasuresinthemanagementofhepaticencephalopathyareeliminatingexogenoussourcesofammoniabyrestrictingdietaryprotein,controllinggastrointestinalbleedinganereducingthenumberofammonia-producingentericbacte

20、ria.,Lactulose,MechnismItishydrolyzedintogalactoseandfructosebybacteriaincolon.Themonosaccharidesbreakdowntohydrogen,lactate,andshortfreeacids.Acidsenhancedcolonicacidification,stimulatedmotility,inhibitedcoliformgrowthandammoniaproductionandincreasedfecalammoniasecretion.,Lactulose,Dosage&Administr

21、ation1.3040ml3/d,dosagemaybeadjustedsothatpatientproducestwoorthreesoftstoolperday.2.Enemaretention:300mllactulosewith700mlwaterorNSisgavenperrectumandheldatleast20mins.,Lactulose,SideEffectsGaseousness,abdominaldistention,flatulence,belching,andabdominalcramping.,Pearls&Pitfall,Othermeasurementssho

22、uldbeincludedRetentionenemamaybeusedforpatientsatriskofaspirationfromCNSabnormality.TheadditionofneomycinmaybenefitthosewhocontinuesmanifestCNSchanges.Hypokalemia&hypernatremiawasnotedinchronicuse.CautioususageinDM.,AntidiarrhealAgents,AntidiarrhealAgents,Kaolin&PectinNonspecificabsorbentOnlysubjectivebenefitindiarrheaNotusedinintestinalobstructionorkid3yearsAbsorbingconcomitantmedicationElectrolytesdisordersouldbenoticedPectin(tobedietaryfiber)showsinprovementofbloodsugarinDM,Loperamide,Asyntheticantidiarrhealnarcoticanalogue,agonistactivityongut-associatedmu-opiatereceptorAntisecretory