Chater 17 Treatment of CNS degenerative diseases 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。

1、Parkinson’s disease, PD classification 1、Parkinson’s disease, PD 帕金森病 2、Alzheimer ’ s disease, AD 阿尔茨海默病 3、Huntington disease, HD 亨廷顿病 4、Amyotrophic lateral sclerosis, ALS 肌萎缩侧索硬化症

Introduction ----§1 anti PD agents Parkinson disease 帕金森病 (paralysis agitans 震颤麻痹 ) 1817 British doctor James Parkinson described and reported; It’s a kind of degenerative disease of CNS, causing tremor(震颤) at rest, muscle rigidity (僵直) and hypokinesia, often with dementia (痴呆).

Aetiology(病因学) mostly unknown; toxin induced: MPTP, CO, Mn2+… drug induced: DA-R(-)… rare causes: cerebral ischaemia(脑缺血); encephalitis (脑炎) , stroke (脑卒中)…

Pathophysiology theory of Dopamine: in the nigrostriatal pathway (黑质纹状体通路) dopaminergic neurons degeneration. (多巴胺能神经元变性)  DA concentration

normal Parkinson’s disease DA ACh ACh DA ACh Supply DA Anti ACh ㈠ （+） 相对 DA ACh therapy Supply DA Anti ACh

Treatment of Parkinson ’ s disease Dopamine mimetic drug ： L-dopa Cholinoceptor blocking drug: artane

Usual drugs （一） Dopamine mimetic drug levodopa, L-dopa 左旋多巴 [ pharmacokinetics ] 1、po---absorb rapidly from small bowel， influence factors: 1）gastric emptying 2）gastric acid  3）food of high protein absorption F 

Usual drugs 2、 mostly peripheral decarboxylation (by AADC) DA ;  1%  CNS . 3、used with AADC inhibitors effects ，adverse reactions

Usual drugs L-dopa po. carbidopa DA DC DA curative effect brain < 1% L-dopa po. periopheral AADC > 95% DA adverse reaction liver （一） carbidopa

Levodopa action and uses Treat PD supply DA first choice characters ： 1) light symptom and young patient ； 2) improvement in rigidity、 bradykinesia； tremor inapplicable. 3) act slowly 、 duration is longer. 4) inefficacy : induced by CPZ；

Levodopa adverse reactions 1. Early reactions 1) gastrointestinal ~ (80%)； 2) cardiovascular ~： orthostatic hypotension (30%) 体位性低血压

Levodopa adverse reactions 2. Long term reactions hyperkinesia (运动过多症) on - off response mental confusion (10-15%) [ Drug interaction ] p.148 not used with vitamin B6, CPZ and reserpine…

Other drugs p.148-150 AADC inhibitors: carbidopa(卡比多巴); MAO-B inhibitors：selegiline (司来吉兰) COMT inhibitors：nitecapone (硝替卡朋) DA receptor agonist：lisuride (利修来得) Drugs that release dopamine ： amantadine (金刚烷胺)

Amantadine 金刚烷胺 1、action: 1）antiviral agent(抗病毒药) 2）antiparkinsonian； [characteristics of action ] 1、action: 1）antiviral agent(抗病毒药) 2）antiparkinsonian； 2、used with L-dopa effect ； 3、mechanism complex; 4、adverse reaction: mild and reversible.

（二） cholinoceptor blocking drug benzhexol 苯海索 （安坦，artane） [characteristics of action ] 1、po absorption well， improve tremor obviously ； 2、used with L-dopacurative effect ； 3、 efficacy : PD induced by CPZ ； 4、 side action and contraindications similar to atropine.

----§2 anti AD agents Alzheimer ’s disease, AD Clinical feature： 1) incidence with ages; 2) impairment of cognitive(认知)； 3) impairment of memory； Therapeutic:  CNS cholinergic nerve function

Usual drugs p.152-154 ChE inhibitors tacrine 他克林 donepezil 多奈哌齐 galanthamine 加兰他敏 …… M-R agonists xanomeline 占诺美林

questions 1、Describe the drugs of classification used in PD, name the major agent. 2、 Describe the rationality of L-dopa with carbidopa.