第4篇影响药物效应因素.ppt

FactorsthatAffectDrugsEffectiveness,DepartmentofPharmacology,SchoolofPharmacy,LiaoningUniversityofTraditionalChineseMedicine,Drugsfactors,IDose,andPhysicalnatureofdrugsForinstance,drugpowdersize,formulation,electricalcharge,andshape.剂量不同，同一药物对机体作用的强度也不一样。例：注射剂、片剂不同剂型吸收程度不同，同一剂型也因制剂工艺不同而不同.,Routesofadministration口服:吸收慢而不规则；注射:不方便、经济与安全；舌下与直肠：无首过效应,但吸收率不高；吸入：适用于麻醉药和气管扩张药局部用药,给药时间、给药间隔时间及疗程1、给药时间Acycleofactiveandnon-activeperiodsinbodydeterminedbytheinternalmechanismsadrepeatedaboutevery24hoursiscalledcircadianrhythm(biologicalclock).ThestudyofcircadianrhythmofdrugdispositioniscalledChronopharmacology2、给药间隔时间应用抗菌药治疗感染性疾病时尤为突出，因为血药浓度在有效和无效之间波动可导致细菌产生抗药性。3、疗程指为达到一定的治疗目的而连续用药的时间。,Suddencardiacdeathparallelsthoseofhypertension,heartmuscleischemia,angina,andheartattack-a70%greaterriskbetweenthehoursof7a.m.and9a.m.,comparedtotherestoftheday.,Cushingssyndrome(hypercortisolism)causedbyhypothalamusproducingcorticotropin-releasinghormone(CRH),CRHstimulatesthepituitaryreleaseofadrenocorticotropichormone(ACTH)whichstimulatestheadrenalglandstoproducecortisol,反复用药1、耐受性快速耐受性：交叉耐受性：2、耐药性,联合用药药物相互作用(Druginteraction)DrugplasmaproteinbindingSynergism(potentiation)Forinstance,sulfamethoxazoleandtrimethoprimusedincombination.药物配伍禁忌,药物在体内的相互作用包括药动学和药效学两个方面。1、药动学方面（1）妨碍吸收（2）竞争血浆蛋白结合（3）影响生物转化（4）影响药物排泄,2、药效学方面（1）协同作用相加作用：如阿司匹林与对乙酰氨基酚合用，解热镇痛作用增加增强作用：如磺胺甲噁唑与甲氧苄定合用，抗菌作用增加增敏作用：如可卡因抑制交感神经末梢对去甲肾上腺素的再摄取，出现去甲肾上腺素或肾上腺素作用增强（2）拮抗作用药理性拮抗：如纳洛酮拮抗吗啡的作用生理性拮抗：如组胺作用于H1受体，肾上腺素作用于受体化学性拮抗：如重金属或类金属中毒可用二硫基丙醇解救生化性拮抗：如苯巴比妥诱导肝药酶，使苯妥英钠等药代谢加速（3）无关作用,Individualfactors,Individualvariationcanbecongenitaloracquired.I.AgeChildrenChildrenareatthestageofdevelopingorgans,sotheabilityofdrughepaticmetabolismandrenalclearanceofchildandarelowerthanthatadult.elderlyForelderly,theorganfunctions,e.g.,liverandkidneydecreased,resultingindrugbiotransformationinliveranddrugexcretioninkidneydeclinedgradually.Pharmacologicalandadverseeffectsofadrugforbothchildrenandelderlyareincreased,II.GenderInPrinciple,therearenoapparentdifferencesbetweenbothgendersresponsetodrugs.However,(a)inmenstruation,drugsaffectinguteruscontractionshouldbeavoidedtopreventfromoverbleeding;(b)inpregnancy,extremecarefulnessshouldbetakenforthesafetyofbothmotherandfetus;and(c)duringlactation,attentionshouldbepaidtosomedrugsthatexcreteviathemilk.,III、个体差异（1）高敏性：对药物反应特别敏感，很小量就能产生其他人常用量时的作用。（2）低敏性：对药物反应特别不敏感，需加大剂量才能有效（3）特异质反应药物代谢酶异常：慢乙酰化型、快乙酰化型非药物代谢酶异常：药物吸收障碍、高铁血红蛋白缺乏,IV、种族不同人种或民族的人群，对某些药物的反应会产生明显差异。大约有半数日本人和中国人肝内ALDH2缺乏，但在白种人和黑人中，未发现这种酶功能缺乏着。GeneticfactorsTheaimofpharmacogeneticsistostudytheinfluenceofgeneticdifferenceandhereditarydiseaseonthepharmacokineticsandpharmacodynmicsofdrugs.,V.PsychologicalfactorsPlaceboeffect:(a)Thebeneficialeffectinapatientfollowingaparticulartreatmentthatarisesfromthepatientsexpectationsconcerningthetreatment(non-specificplaceboeffect)ratherthandrugspecificpharmacologiceffects.Psychologicalfactorsnotonlyincludenon-specificplaceboeffectbutalsoincludePatient-DoctorInteraction(relationship)whichmayinfluencepatientsmoodandothersubjectiveandobjectiveeffectscontrolledbyautonomicnervesandhormones.,VI.PathologicfactorsTheliveristhemainorganofdrugmetabolism.Hepaticdysfunctiondecreasesdrugmetabolism,drugactionwillbeprolonged.However,somedrugsaretransformedtotheactiveformsintheliver,inthissituation,drugeffectswillbedecreased.Renalexcretionplaysakeyroleinfinaldrugelimination.Renalfailurewillresultindrugaccumulationinthebody,prolongingitseffect.,CardiacdiseaseCardiacdisease,bylimitingbloodflowtotheliver,maydepresstheeliminationofdrugswhosemetabolismisflow-limitedandtheclearanceisperfusion-limited,其他因素,一、营养状态营养不良：高蛋白及低蛋白饮食：禁食和饥饿：二、嗜好和环境1、长期饮酒和吸烟2、环境中存在多种化学物质3、环境温度、湿度、噪音、通气条件等,练习题,联合应用两种药物，其总的作用大于各药单独作用的代数和，这种作用叫做：A、增强作用B、相加