治疗中枢神经系统退行性疾病药

Chater17,TreatmentofCNSdegenerativediseases,治疗中枢神经系统退行性疾病药,objective,掌握左旋多巴药动学特点、临床应用与不良反应;苯海索的作用特点等。熟悉抗帕金森病药的分类，卡比多巴的作用特点和应用。了解其他抗帕金森病药及治疗阿尔茨海默病的药物作用与应用。,classification,1、Parkinsonsdisease,PD帕金森病2、Alzheimersdisease,AD阿尔茨海默病3、Huntingtondisease,HD亨廷顿病4、Amyotrophiclateralsclerosis,ALS肌萎缩侧索硬化症,Introduction-1antiPDagents,Parkinsondisease帕金森病(paralysisagitans震颤麻痹)1817BritishdoctorJamesParkinsondescribedandreported;ItsakindofdegenerativediseaseofCNS,causingtremor(震颤)atrest,musclerigidity(僵直)andhypokinesia,oftenwithdementia(痴呆).,Aetiology(病因学),mostlyunknown;toxininduced:MPTP,CO,Mn2+druginduced:DA-R(-)rarecauses:cerebralischaemia(脑缺血);encephalitis(脑炎),stroke(脑卒中),Pathophysiology,theoryofDopamine:inthenigrostriatalpathway(黑质纹状体通路)dopaminergicneuronsdegeneration.(多巴胺能神经元变性)DAconcentration,ACh,DA,ACh,normal,Parkinsonsdisease,therapy,（+）,相对,DA,DA,ACh,SupplyDA,AntiACh,Dopaminemimeticdrug：L-dopa,TreatmentofParkinsonsdisease,Cholinoceptorblockingdrug:artane,Usualdrugs,（一）Dopaminemimeticdruglevodopa,L-dopa左旋多巴pharmacokinetics1、po-absorbrapidlyfromsmallbowel，,influencefactors:1）gastricemptying2）gastricacid3）foodofhighprotein,absorptionF,Usualdrugs,2、mostlyperipheraldecarboxylation(byAADC)DA;1%CNS.3、usedwithAADCinhibitorseffects，adversereactions,Usualdrugs,L-dopapo.,brain,95%,periopheral,AADC,DAadversereaction,carbidopa,（一）,liver,Levodopaactionanduses,TreatPDsupplyDAfirstchoicecharacters：1)lightsymptomandyoungpatient；2)improvementinrigidity、bradykinesia；tremorinapplicable.3)actslowly、durationislonger.4)inefficacy:inducedbyCPZ；,Levodopaadversereactions,1.Earlyreactions1)gastrointestinal(80%)；2)cardiovascular：orthostatichypotension(30%)体位性低血压,Levodopaadversereactions,2.Longtermreactionshyperkinesia(运动过多症)on-offresponsementalconfusion(10-15%),Druginteractionp.148notusedwithvitaminB6,CPZandreserpine,Otherdrugsp.148-150,AADCinhibitors:carbidopa(卡比多巴);MAO-Binhibitors：selegiline(司来吉兰)COMTinhibitors：nitecapone(硝替卡朋)DAreceptoragonist：lisuride(利修来得)Drugsthatreleasedopamine：amantadine(金刚烷胺),Amantadine金刚烷胺,characteristicsofaction1、action:1）antiviralagent(抗病毒药)2）antiparkinsonian；2、usedwithL-dopaeffect；3、mechanismcomplex;4、adversereaction:mildandreversible.,（二）cholinoceptorblockingdrugbenzhexol苯海索（安坦，artane）characteristicsofaction1、poabsorptionwell，improvetremorobviously；2、usedwithL-dopacurativeeffect；3、efficacy:PDinducedbyCPZ；4、sideactionandcontraindicationssimilartoatropine.,-2antiADagents,Alzheimersdisease,ADClinicalfeature：1)incidencewithages;2)impairmentofcognitive(认知)；3)impairmentofmemory；Therapeutic:CNScholinergicnervefunction,Usualdrugsp.152-154,ChEinhibitorstacrine他克林donepezil多奈哌齐galanthamine加兰他敏M-Rago