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

1、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,Drug interaction means the modification of the effect of a drug（object drug）by concurrent administration of other drugs（precipitating drug）.A drug interaction can result in either an increased

2、or decreased effect of the object drug.,E.g.,terfenadine+ketoconazole,object drug,precipitating drug,the objects drugs（目标药物）：在联合用药中，药效发生变化的药物the precipitating drugs（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,Drugs likely to be involved in interactions,Likely to be the precipitating drugs（促发药物）highly protein bo

3、und phenylbutazone,aspirin,sulfonamidesalter the metabolism of other drugs enzyme inducers anticonvulsants,rifampicin,griseofulvin enzyme inhibitors allopurinol,chloramphenicol,cimetidineaffect renal clearance of object drugs diuretics,probenecid,8,Likely to be the objects drugs（目标药物）a steep dose-re

4、sponse curvea low therapeutic indexanticoagulants,anticonvulsants,2022/10/9,9,Types of Drug Interactions,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。Dose addition：A剂量（B剂量）=A剂量+B剂量Effect addition：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

5、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ChemicalPhysiological or functionalCompetitiveNoncompetitive,10,11,InconsequentialDesirable or beneficialincrease the effect of therapydecrease the side effectdecrease tolerancetrea

6、tment complications-Adverse（0 22%）E.g.,terfenadine+ketoconazole,Outcomes of drug interactions,12,Mechanisms of Drug Interactions,Pharmacokinetic interactions（PK）-ADME:Absorption,distribution,metabolism,elimination-A change in serum concentration and the amount of drug available at the site of action

7、Pharmacodynamic interactions（PD）-Molecular target,electrolyte balance or the bioactive system-Without alterations in pharmacokinetic parametersPharmaceutical interactions-the principles to prevent pharmaceutical interactions,13,PK interactions-Absorption,Altering GI tract pH-E.g.,salicylate+NaHCO3,1

8、4,Ketoconazole+Ranitidine,Piscitelli S et al.Antimicrob Agents Chemother 1991;35:1765-1771,15,PK interactions-Absorption,ChelationForming an insoluble complex in the GI tractTetracyclines,quinolone antibiotics+ferrous sulfate（Fe+2）,antacids（Al+3,Ca+2,Mg+2）,dairy products（Ca+2）,16,PK interactions-Abs

9、orption,17,PK interactions-Absorption,Alteration in GI motilityIncrease motility-metoclopramide,cisapride,domperidone E.g.,paracetamol+metroclopramideDecrease motility-anticholinergic drugs（atropine,probanthine）,chlorpromazine,diphenhydramine,18,PK interactions-Absorption,Binding-by cholestyramine E

10、.g.,warfarin+cholestyramine-by charcoal E.g.,carbamazepine+charcoal,19,PK interactions-Absorption,Administration with foodFor many drugs,change the rate of absorption Indinavir fewer is absorbed into systemic circulation together with high fat meal,AUC and Cmax decreased by 80%Saquinavir-administrat

11、ion with high fat meal increases AUC by 57%,for low F drug,20,PK interactions-Distribution,Protein Binding Interactions Competition between drugs for plasma or tissue protein binding sitesWhen drugs with highly affinity for the same protein are used together,a competitive displacement interaction ma

12、y occur,resulting in a transient increase in the free concentration of the displaced drug.E.g.,warfarin+phenylbutazone,21,Protein Binding Interactions,22,PK interactions-Distribution,To cause a clinically significant effect if:-highly protein bound（90%）-a small volume of distribution-a narrow therap

13、eutic index-a rapid onset of action,23,PK interactions-Distribution,Protein Binding Interactions The displaced drugs（the object drugs）warfarin,phenytoin,tolbutamidethe displacing drugs（the precipitant drugs）phenylbutazone,sulfonamides,salicylates,chloral hydrate,24,PK interactions-Metabolism,DRUG,+,

14、25,PK interactions-Metabolism,Enzyme inducer-a drug or substance that increases the metabolic activity of an enzyme usually by increasing the amount of that enzyme expressed in cells.,26,Inducers of enzyme activity,27,PK interactions-Metabolism,Outcome of induction:Active Drug inactive:Resulting in a lower plasma concentration and a decreased effectE.g.,Phenobarbital and warfarin Drug Toxic metabolites:Resulting in an increased toxic effectE.g.,isoniazid acetyl