帕金森病诊疗进展与展望.ppt

* Bhidayasiri R, Truong DD. J Neurol Sci 2008;266(1-2):204-215.: Long-term dopaminomimetic therapy, not limited to levodopa, is complicated by the emergence of variations of motor response in a majority of PD patients. * * In the early stages of PD there is a large therapeutic window, and the response to levodopa is excellent. At this stage the antiparkinsonian benefits are associated with a low incidence of dyskinesia. As the disease progresses, even in moderate disease, the long-duration response to levodopa diminishes and the response to levodopa begins to more closely reflect its short half-life (~1.5 hours). Antiparkinsonian control becomes increasingly governed by fluctuations in plasma levodopa levels. In more advanced PD, the short-duration response to levodopa predominates. The therapeutic window narrows, and adequate control of symptoms becomes increasingly difficult. Initially this is manifested by an end-of-dose deterioration, where PD symptoms return before the next scheduled medication dose. Patients are often either off, or on with dyskinesia and other complications. Olanow, C. W., R. L. Watts, et al. (2001). An algorithm (decision tree) for the management of Parkinsons disease (2001): treatment guidelines. Neurology 56(11 Suppl 5): S1-S88. * 1st bullet: This often delays effective treatment that can provide excellent symptom relief and allow patients to remain functional and able to care for themselves for years. 2nd bullet: this leads to unneeded expenditures and unfulfilled expectations. * * 左旋多巴制剂和激动剂治疗进展期PD 药物导致的运动波动的演变特点 Bhidayasiri R, Truong DD. J Neurol Sci 2008;266(1-2):204-215. 初期 晚期 清晨少动 剂末现象 中期 剂量峰（或“开” 期）异动症 双相异动症 “关”期肌张力异常 “开/关”现象 无“开”期 “开”期延迟 僵住 剂末现象是症状波动的开始！ 药物并发症及相关因素 运动波动、剂末现象、运动障碍 相关因素: 左旋多巴的使用、服用时间、总服药剂量 多巴胺受体的脉冲性刺激* 黑质退变的严重程度 患者年龄 随时间变化对左旋多巴的反应 平稳，持续临床反应 运动并发症发生率较低 症状控制时间缩短 运动并发症发生率增加 临床症状控制较差 “开”期时间与运动并发症相关 早期PD 中期PD 晚期PD 良好的症状控制 运动并发症风险 症状控制欠佳 目前治疗中存在的问题 如何推迟或预防左旋多巴治疗合并的剂未或开关现象？ 如何减少和控制异动症，但不影响左旋多巴疗效的药物和方法？ 运动波动