第四章影响药物作用的因素.ppt

,Chapter4Factorsaffectingthepharmacologicaleffects影响药物作用的因素,object,掌握药物的相互作用;长期用药引起的机体反应性变化：耐受性、耐药性、依赖性，停药症状。熟悉药物制剂及给药途径对药物效应的影响。机体因素（年龄、性别、遗传因素、疾病状态、心理因素)对药物效应的影响。了解配伍禁忌、药物滥用的概念。,Individualvariation（个体差异）,Samedoseofdrug,differentbloodconcentration,Sameconcentration,differenteffects,Pharmacokineticvariation,Pharmacodynamicvariation,Factorsaffectingdrugaction,drug,body,Others,1Drug,Preparationsandrouteofadministration1）preparation(制剂),dosageform,dosage,bioavailability,Newpreparations,sustained-release（缓释制剂）药物非恒速释出以达到较稳定而持久的疗效。如康泰克等。,controlled-release（控释制剂）药物缓慢地恒速释出以达到较稳定而持久的疗效。如萘普生等。,2)Routeofadministration,Differentadministrationproducetherateofabsorptiondifferent.generally：iv.inhalation(吸入)im.sc.po.rectum(直肠)skin,Differentadministrationproducethedifferenteffectsanduses.,Forexample:Magnesiumsulfate(硫酸镁)Injection-降压,抗惊厥po.-导泻,利胆,Combinationandinteractionofdrugs,binationofdrugsacommontherapeuticmethodsproduceresults:synergeticaction(协同作用)1+12antagonisticaction(拮抗作用)1+11,Incompatibility(配伍禁忌)药物在体外配伍时发生的理化反应致药物作用改变而影响疗效的现象.eractionofdrugs(药物相互作用)两种或两种以上药物同时或先后序贯应用时对机体产生的一些不利影响.,2Body,I.physiologicalfactors(生理因素)1.AgeChildrenandoldstera.sensitivity(敏感性)differente.gneonate:morphine(-)respiration;oldster:vasodilator（血管舒张）reflecttachycardia（心动过速）,b.Characteristicsofhepaticandrenalfunctiondifferentnewborns-incompletechloramphenicol氯霉素(graysyndrome)灰婴综合征Oldster-decay(衰退)gentamicin庆大霉素(tprolong30h),RemainingFunctionsAredeclining,2.Sex,1)Pregnancy(妊娠期),药物致畸作用出生前诊断,华法林点状软骨发育不全、面部畸形、严重的CNS畸形不可能苯妥英颅面部畸型、肢体畸形生长缺陷可能卡马西平(抗惊厥药，镇痛药)颅面部畸形、指甲畸形可能,2)Lactation(哺乳期)secretingfrombreastmilk(乳汁):diazepam(地西泮)morphine(吗啡)tetracycline(四环素)cimetidine(西米替丁),3.Geneticfactors(遗传因素),1)geneticpolymorphism(遗传多态性)a、氧化代谢多态性异喹胍20400mg/d强代谢型(extensivemetabolism,EM)，弱代谢型(poormetabolism,PM)b、乙酰化代谢多态性INH快、慢乙酰化型产生不同的临床效应和不良反应,轻、中度高血压,2)Racialdifferencesindrugresponse(药物反应种族差异)3)idiosyncrasy(特异质反应)琥珀胆碱敏感症AChE缺乏-常用剂量，呼吸停止1h,II.pathologicfactors(病理因素),Headache(头痛),fever(发热)aspirineffectual!Hepaticandrenalfunctionimpaireddrugeliminationcumulation(蓄积)toxicity,III.placeboeffects(安慰剂效应),placebo-不含药理活性成分的,外形与临床用药相似的制剂.placeboeffectresultmainlyfrommentalfactor(心理因素)forexample:cancerpatient,ChangesofReactivityafterlongadministration,1.ToleranceandresistanceTolerance(耐受性)-反复用药机体对药物的敏感性降低，需增加药量才能达到原有效应.acutetolerance(快速耐受性)crosstolerance(交叉耐受性)Resistance(耐药性)-病原体或肿瘤细胞对反复应用的化疗药物的敏感性降低.,2.dependenceandwithdrawalsymptoms,dependence,physical(躯体依赖性)psychological(精神依赖性),Physicaldependence(addiction成瘾性)连续多次用药,机体对药物产生依赖,一旦停药可出现戒断症状。e.gmorphine,Psychologicaldependence(habituation习惯性)连续多次用药,精神上对药物产生依赖,一旦停药有主观不适感。,withdrawalsymptoms(停药症状),长期连续用药后突然停药,导致原有病情复发或恶化。如：高