Obering Crystal D, Chen Jack J, Swope David M
School of Pharmacy, University of Missouri-Kansas City, and the Department of Pharmacy, Kansas City Veterans Affairs Medical Center, Kansas City, Missouri 64108, USA.
Pharmacotherapy. 2006 Jun;26(6):840-52. doi: 10.1592/phco.26.6.840.
As Parkinson's disease progresses, fluctuations between akinesia, or hypomobility ("off" times), and mobility ("on" times) increase in frequency despite optimized pharmacotherapy. Motor fluctuations include predictable shortening of therapeutic effects, nocturnal or early morning akinesia, random hypomobility, and delayed mobility (variable responses to individual doses of drugs). Current oral antiparkinson drugs are inadequate for rapid and consistent relief of symptoms during hypomobility. Apomorphine, an injectable dopamine agonist recently introduced in the United States, is indicated for the management of hypomobility associated with advanced Parkinson's disease. Subcutaneous apomorphine is effective for rapid and consistent rescue from hypomobility, with a magnitude of motor improvement similar to that of levodopa. The effect begins within 20 minutes after dosing and lasts approximately 100 minutes. Therapeutic rescue doses are 2-6 mg, and patients typically require approximately three rescue doses/day. Apomorphine is associated with a clinically significant potential to cause nausea and orthostatic hypotension. These potential effects can be managed with antiemetic prophylaxis and appropriate determination of the therapeutic rescue dose.
随着帕金森病的进展,尽管药物治疗已优化,但运动不能或运动减少(“关”期)与运动状态(“开”期)之间的波动频率仍会增加。运动波动包括治疗效果可预测的缩短、夜间或清晨运动不能、随机运动减少以及运动延迟(对单次药物剂量的可变反应)。目前的口服抗帕金森病药物在运动减少期间无法快速、持续地缓解症状。阿扑吗啡是一种最近在美国推出的注射用多巴胺激动剂,适用于治疗与晚期帕金森病相关的运动减少。皮下注射阿扑吗啡可有效快速、持续地缓解运动减少,运动改善程度与左旋多巴相似。给药后20分钟内起效,持续约100分钟。治疗性解救剂量为2 - 6毫克,患者通常每天需要约三次解救剂量。阿扑吗啡有引起恶心和体位性低血压的显著临床可能性。这些潜在影响可通过预防性使用止吐药和适当确定治疗性解救剂量来处理。