基礎(chǔ)醫(yī)學導(dǎo)論 影響因素學習課件

Chapter3

FactorsInfluencingDrugEffectsandRationalTherapeutics

影響藥物效應(yīng)的因素及合理用藥DrugFactorsPatientFactorsRationaltherapeuticsDrugPatientDoctorefficacy/adverseeffectsdrugconcentrationsAdjustmentDosageregimendrugs,doses,intervals,duration藥劑學過程藥動學過程藥效學過程PartA

DrugFactors1.Physic-chemicalpropertiesofdrugs2.Doseforms3.Administration4.Multiple-drugtherapy5.Long-termdrugtherapy

PartA

DrugFactors1.Physic-chemicalpropertiesofdrugsStabilityMolecularsizeLipid-andwater-soluble……PartA

DrugFactors2.Doseforms

slowreleaseformulationcontrolledreleaseformulationtransdermalpatchinhalationPartA

DrugFactors3.Administration

DosesRoutes

oralintramuscularinjectionsubcutaneousinjectionintravenousinjectionorinfusion

AdministrationtimeDosingintervalsDosingdurationPartA

DrugFactors4.Multiple-drugtherapy(drugcombination)

Drug-druginteractionspharmacypharmacokineticspharmacodynamicsDrugeffectsincombination

synergism:

potentiation/additionantagonismEfficacy:↓,↑Toxicity:↓,↑PartA

DrugFactors藥物在ADME上的相互作用（1）影響胃腸道藥物吸收的相互作用

藥物在胃腸道內(nèi)吸收時相互影響表現(xiàn)在：影響藥物解離度、影響胃排空速度、影響腸蠕動、改變胃腸道環(huán)境、在胃腸道內(nèi)相互結(jié)合等。（2）影響藥物血漿蛋白結(jié)合率的相互作用

當兩種藥物合用時，它們對血漿蛋白結(jié)合部位產(chǎn)生競爭，結(jié)合力強的藥物將結(jié)合力弱的藥物置換出來，后者血漿游離型濃度增加，藥理活性也相應(yīng)增強，增加的程度還受分布容積(Vd)的影響。PartA

DrugFactors（3）肝藥酶誘導(dǎo)（酶促）和抑制（酶抑）以及影響肝藥酶的藥物

一些藥物反復(fù)應(yīng)用可誘導(dǎo)肝微粒體酶活性增加，這稱為肝藥酶誘導(dǎo)作用（酶促作用），如苯巴比妥、利福平、苯妥英等；也有些藥物可抑制肝微粒體酶的活性，稱為肝藥酶抑制作用（酶抑作用），如西米替丁、氯霉素、異煙肼等。（4）影響藥物排泄的相互作用

①腎小球濾過，改變腎血流量的藥物可改變?yōu)V過率；②腎小管主動分泌，可在弱酸性或弱堿性藥物載體（轉(zhuǎn)運體）上相互干擾；③腎小管重吸收，藥物改變尿液pH值可改變其他弱酸或弱堿類藥物的重吸收。PartA

DrugFactors藥物在藥效學上的相互作用（1）生理性拮抗或協(xié)同中樞抑制/興奮；凝血/抗凝血（2）受體水平的協(xié)同或拮抗激動劑/拮抗劑（3）作用機制上的協(xié)同或拮抗磺胺類/TMP；抑菌/繁殖期殺菌（4）干擾神經(jīng)遞質(zhì)轉(zhuǎn)運或代謝TCA/MAOI

PartB

PatientFactors1.

PhysiologicalFactors1.1AgeChildrenSensitivitytodrugsPharmacokineticpropertiesElderlySensitivitytodrugsPharmacokineticpropertiesAge-relatedfactorsinfluencingpharmacokineticprocessesPartB

PatientFactors1.2BodyWeightVolumeofdistributionFat/skeletalmuscleslipid-soluble/water-solubledrugsPartB

PatientFactors1.3SexWomen

Pregnancy-malformationanddysfunctionofthefetuses

Lactation-milk:effectsoninfantsPartB

PatientFactors2.

PsychologicalFactorsPlaceboeffectsPlaceboeffectscommonlyaremanifestedasalterationofmood,othersubjectiveeffects,andobjectiveeffectsthatareunderautonomicorvoluntarycontrol.安慰劑（placebo）是指沒有藥理活性的物質(zhì)（如乳糖、淀粉等），被制成與試驗藥外觀、氣味相同的制劑，作為臨床對照試驗中的陰性對照物。

PartB

PatientFactorsOverallresponsesPharmacologicaleffectsNon-specific

drugeffectsNon-specific

medicationeffectsNaturalrecoveryNottreatmentAbsoluteplaceboeffectsPlaceboeffectsPartB

PatientFactors3.

PathologicalFactorsHeartdiseasesHepaticdiseasesRenaldiseases

GastrointestinaldiseasesMalnutritionImbalancesofacid-baseorelectrolytesPartB

PatientFactors4.

GeneticFactorsPharmacogenetics

abnormalityofdrugresponses

example:

toleranceofwarfarin

abnormalityofpharmacokineticproperties

example:

fastorslowacetylationPartB

PatientFactors5.

LifeStylesandEnvironmentFactorsNutritionDrinking&smokingEnvironmentalpoisonsPartB

PatientFactors6.

Individualvariation(個體差異)(1)SensitivitytodrugsHypersensitivityHyposensitivity(tolerance)(2)AbnormalresponsestodrugsIdiosyncracy(geneticabnormality)Allergy(immunologicalabnormality)Onegoalinthepost-genomicmedicine:

IndividualizedMedicineIndividualvariationofeffectivedosesofamytal←hypersensitivitytolerance→PartB

PatientFactors7.

Changed

responsesafterlong-termdruguse

(長期用藥后機體對藥物反應(yīng)的變化)(1)Toleranceandtachyphylaxis(2)Resistancetochemotherapy(3)DrugdependencePartB

PatientFactorsDependenceAnadaptivestatethatdevelopsinresponsetorepeateddrugadministration.Psychologicdependence

ismanifestedbycompulsivedrug-seekingbehavior.Physiologicdependence

ispresentwhenwithdrawalofdrugproducessymptomsandsigns.Drugaddiction

isdefinedasthecompulsive,out-of-controldruguse,despitenegativeconsequences.Drugabuse:

anyuseofadrugfornon-medicalpurposes.(amaladaptivepatternofdruguseleadingtoclinicallysignificantimpairmentordistress)PartC

Rationaltherapeutics1.Makinganaccuratediagnosis（正確診斷）2.Understandingthepathophysiologyofdisease