临床药理学精品课件之药物相互作用英文课件PPT文档格式.ppt

临床药理学精品课件之药物相互作用英文课件PPT文档格式.ppt

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联合用药品种偏多，使药物相互作用的发生率增加，影响药物疗效或毒性增加。

因此在给病人用药时，应十分小心，应尽量减少用药种类，减少药物相互作用引起的药物不良反应。

2022/10/9,4,5,Introduction,Druginteractionmeansthemodificationoftheeffectofadrug（objectdrug）byconcurrentadministrationofotherdrugs（precipitatingdrug）.Adruginteractioncanresultineitheranincreasedordecreasedeffectoftheobjectdrug.,E.g.,terfenadine+ketoconazole,objectdrug,precipitatingdrug,theobjectsdrugs（目标药物）：

在联合用药中，药效发生变化的药物theprecipitatingdrugs（促发药物）：

在联合用药中，引起其他药物发生变化的药物。

6,7,Drugslikelytobeinvolvedininteractions,Likelytobetheprecipitatingdrugs（促发药物）highlyproteinboundphenylbutazone,aspirin,sulfonamidesalterthemetabolismofotherdrugsenzymeinducersanticonvulsants,rifampicin,griseofulvinenzymeinhibitorsallopurinol,chloramphenicol,cimetidineaffectrenalclearanceofobjectdrugsdiuretics,probenecid,8,Likelytobetheobjectsdrugs（目标药物）asteepdose-responsecurvealowtherapeuticindexanticoagulants,anticonvulsants,2022/10/9,9,TypesofDrugInteractions,Addition：

作用强度等于单独用药的作用强度之和阿托品与氯丙嗪可引起胆碱能神经功能过度低下的中毒症状；

氨基糖甙类抗生素与硫酸镁合用，可加强硫酸镁引起的呼吸麻痹。

Doseaddition：

A剂量（B剂量）=A剂量+B剂量Effectaddition：

AB联合用药强度=A作用强度+B作用强度Synergism：

联合用药的效果大于单独用药效应的总和镇静催眠药与抗精神病药合用的中枢抑制作用。

AB联合用药A效应+B效应,Potentiation：

指一种药物可使组织或受体对另一药物的敏感性增强排钾性利尿剂使心脏对洋地黄的敏感性增强，导致心率失常。

Antagonism：

一种药物部分或全部阻断另一药物的作用，合用时引起药效降低ChemicalPhysiologicalorfunctionalCompetitiveNoncompetitive,10,11,InconsequentialDesirableorbeneficialincreasetheeffectoftherapydecreasethesideeffectdecreasetolerancetreatmentcomplications-Adverse（022%）E.g.,terfenadine+ketoconazole,Outcomesofdruginteractions,12,MechanismsofDrugInteractions,Pharmacokineticinteractions（PK）-ADME:

Absorption,distribution,metabolism,elimination-AchangeinserumconcentrationandtheamountofdrugavailableatthesiteofactionPharmacodynamicinteractions（PD）-Moleculartarget,electrolytebalanceorthebioactivesystem-WithoutalterationsinpharmacokineticparametersPharmaceuticalinteractions-theprinciplestopreventpharmaceuticalinteractions,13,PKinteractions-Absorption,AlteringGItractpH-E.g.,salicylate+NaHCO3,14,Ketoconazole+Ranitidine,PiscitelliSetal.AntimicrobAgentsChemother1991;

35:

1765-1771,15,PKinteractions-Absorption,ChelationForminganinsolublecomplexintheGItractTetracyclines,quinoloneantibiotics+ferroussulfate（Fe+2）,antacids（Al+3,Ca+2,Mg+2）,dairyproducts（Ca+2）,16,PKinteractions-Absorption,17,PKinteractions-Absorption,AlterationinGImotilityIncreasemotility-metoclopramide,cisapride,domperidoneE.g.,paracetamol+metroclopramideDecreasemotility-anticholinergicdrugs（atropine,probanthine）,chlorpromazine,diphenhydramine,18,PKinteractions-Absorption,Binding-bycholestyramineE.g.,warfarin+cholestyramine-bycharcoalE.g.,carbamazepine+charcoal,19,PKinteractions-Absorption,AdministrationwithfoodFormanydrugs,changetherateofabsorptionIndinavirfewerisabsorbedintosystemiccirculationtogetherwithhighfatmeal,AUCandCmaxdecreasedby80%Saquinavir-administrationwithhighfatmealincreasesAUCby57%,forlowFdrug,20,PKinteractions-Distribution,ProteinBindingInteractionsCompetitionbetweendrugsforplasmaortissueproteinbindingsitesWhendrugswithhighlyaffinityforthesameproteinareusedtogether,acompetitivedisplacementinteractionmayoccur,resultinginatransientincreaseinthefreeconcentrationofthedisplaceddrug.E.g.,warfarin+phenylbutazone,21,ProteinBindingInteractions,22,PKinteractions-Distribution,Tocauseaclinicallysignificanteffectif:

-highlyproteinbound（90%）-asmallvolumeofdistribution-anarrowtherapeuticindex-arapidonsetofaction,23,PKinteractions-Distribution,ProteinBindingInteractionsThedisplaceddrugs（theobjectdrugs）warfarin,phenytoin,tolbutamidethedisplacingdrugs（theprecipitantdrugs）phenylbutazone,sulfonamides,salicylates,chloralhydrate,24,PKinteractions-Metabolism,DRUG,+,25,PKinteractions-Metabolism,Enzymeinducer-adrugorsubstancethatincreasesthemetabolicactivityofanenzymeusuallybyincreasingtheamountofthatenzymeexpressedincells.,26,Inducersofenzymeactivity,27,PKinteractions-Metabolism,Outcomeofinduction:

ActiveDruginactive:

ResultinginalowerplasmaconcentrationandadecreasedeffectE.g.,PhenobarbitalandwarfarinDrugToxicmetabolites:

ResultinginanincreasedtoxiceffectE.g.,isoniazidacetyl