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Chater 17

Treatment of CNS degenerative diseases. Chater 17. 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 、 Parkinson’s disease, PD 帕金森病 2 、 Alzheimer ’ s disease, AD 阿尔茨海默病

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Chater 17

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  1. Treatment of CNS degenerative diseases Chater 17 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. 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) • 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).

  5. 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)…

  6. 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

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

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

  9. 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 

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

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

  12. Levodopa action and uses Treat PD supply DAfirst 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；

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

  14. 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 withvitamin B6, CPZ and reserpine…

  15. 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)

  16. Amantadine 金刚烷胺 [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.

  17. （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.

  18. ----§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

  19. 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 ……

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

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