治疗中枢神经系统退行性疾病药 ppt课件

Chater 17 Treatment of CNS degenerative diseases 治疗中枢神经系统退行性疾病药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、Parkinsons 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; Its 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 ACh DA ACh normal Parkinsons disease therapy （+） 相对 DA DAACh Supply DAAnti ACh Dopamine mimetic drug ： L-dopaL-dopa Treatment of Parkinson s disease Cholinoceptor blocking drug: artaneartane 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. brain 95% periopheral AADC DA adverse reaction carbidopa （一） liver Levodopa action and uses Treat PD supply DA first choicefirst 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 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 ago