治疗帕金森病的药物.pptVIP

* PD - Classification 1.Primary PD：unknown 2.Secondary: Parkinsonism Cerebral arteriosclerosis Encephalitis(脑炎) Drug poison:氰化物、利舍平、吩噻嗪类抗精神病药等 Chemicals: Mn2+、除草剂、杀虫剂等 * 1. Dopamine (DA) theory PD- Pathophysiology (1) DA neuronal degeneration in substantia nigra reduced or lack of dopamine in the striatum ↓function of DA in nigro-striatal DA pathway ↑the function of Ach muscular tension * Normal PD substantia nigra 正常人中脑有一条狭长的黑色素沉着部位，是正常数量的黑质神经元聚集的部位。而在帕金森病人中脑的相应部位则颜色浅淡，是黑质神经元减少的缘故. * Dopamine theory Ach 黑质 纹状体 DA DA (—) (＋) 调节运动功能 脊髓前角运动神经元 GABA * DA氧化代谢 H2O2、O2- · ·OH Fe2+ 促进神经膜类脂氧化 破坏DA神经细胞膜功能 ComplexⅠ 抗氧化物（谷胱甘肽） 黑质 2. Oxidative stress - free radical theory PD- Pathophysiology (2) 抗氧化治疗(MAO-BI, Vit E): 早期PD首选治疗方案。尽量延缓使用L-DOPA。是PD治疗较大的进展和传统观念的转变 * PD - Animal model MPTP 6-OHDA Rotenone Paraquat * PD - Treatment No cure for PD Dopaminergic medication Non-dopaminergic medication Other strategies Surgical intervention (外科手术) Regular exercise (定期训练) * Antiparkinsonism drugs DA Ach Dopaminomimetic Drugs Central Anticholinergic Drugs * AADC TH:酪氨酸羟化酶 TH AADC:L-芳香族氨基酸脱羧酶 * Ⅰ Dopaminomimetic Drugs 1. Precursor of DA 2. Synergetic agents of L-dopa　(左旋多巴的增效药） 3. DA receptor agonists 4. Drugs enhancing DA release * 1. Precursor of DA　 levodopa（L-dopa, 左旋多巴） Levodopa Dopamine * 【Pharmacological actions and mechanism】 Penetrate BBB into the brain Decarboxylated (脱羧) by AADC to DA Supply DA to striatum * 【Clinical use】 widely used for almost all types of PD patients 1. Parkinson’s disease: symptomatic treatment (1) early stage: good and stable effect 80% can be significantly improved, of which 20% recoverd to the normal state (2) later stage: effect gradually decreased, little effect after 3-5 years 用药初期和用药后期疗效差距很大 * Characteristics: (1) have good effect on mild and younger patients, less effect on severe and elderly patients (2) more effective for muscular rigidity and akinesia (运动不能), less e