Chater 17 Treatment of CNS degenerative diseases 治疗中枢神经系统退行性疾病药.

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1 Chater 17 Treatment of CNS degenerative diseases 治疗中枢神经系统退行性疾病药

2 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。

3 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

4 Introduction ----§1 anti PD agents
Parkinson disease 帕金森病 (paralysis agitans 震颤麻痹 ) 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).

5

6 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)…

7 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

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

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

10 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 

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

12 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

13 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；

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

15 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…

16 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)

17 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.

18 （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.

19 ----§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

20 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

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