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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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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 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
DA ACh normal ㈠ (+) Parkinson’s disease DA ACh 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 DA curative effect DC brain <1% L-dopa po. periopheral AADC > 95% DA adverse reaction liver (一) carbidopa
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;
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 withvitamin 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 [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-dopacurative 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.