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1、FactorsthatAffectDrugs’EffectivenessDepartmentofPharmacology,SchoolofPharmacy,LiaoningUniversityofTraditionalChineseMedicineDrugs’factorsIDose,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.Routesofad
2、ministration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).ThestudyofcircadianrhythmofdrugdispositioniscalledChronopharmaco
3、logy2、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.Cushing'ssyndrome(hypercortisolism)causedbyhypothalamuspr
4、oducingcorticotropin-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,sulfamethoxazoleandtrimethopri
5、musedincombination.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
6、苯妥英钠等药代谢加速(3)无关作用IndividualfactorsIndividualvariationcanbecongenitaloracquired.I.AgeChildrenChildrenareatthestageofdevelopingorgans,sotheabilityofdrughepaticmetabolismandrenalclearanceofchildandarelowerthanthatadult.elderlyForelderly,theorganfunctions,e.g.,liverandkidneydecreased,resultingindrugbio
7、transformationinliveranddrugexcretioninkidneydeclinedgradually.PharmacologicalandadverseeffectsofadrugforbothchildrenandelderlyareincreasedII.GenderInPrinciple,therearenoapparentdifferencesbetweenbothgender