Division of Clinical Pharmacology, Department of Medicine, Vanderbilt Autonomic Dysfunction Center, Vanderbilt University Medical Center, Nashville, TN, USA.
Department of Neurology, NYU Langone Medical Center, Dysautonomia Center, 530 1st Avenue, New York, NY, USA.
CNS Drugs. 2017 Nov;31(11):975-989. doi: 10.1007/s40263-017-0473-5.
Cardiovascular autonomic dysfunctions, including neurogenic orthostatic hypotension, supine hypertension and post-prandial hypotension, are relatively common in patients with Parkinson disease. Recent evidence suggests that early autonomic impairment such as cardiac autonomic denervation and even neurogenic orthostatic hypotension occur prior to the appearance of the typical motor deficits associated with the disease. When neurogenic orthostatic hypotension develops, patients with Parkinson disease have an increased risk of mortality, falls, and trauma-related to falls. Neurogenic orthostatic hypotension reduces quality of life and contributes to cognitive decline and physical deconditioning. The co-existence of supine hypertension complicates the treatment of neurogenic orthostatic hypotension because it involves the use of drugs with opposing effects. Furthermore, treatment of neurogenic orthostatic hypotension is challenging because of few therapeutic options; in the past 20 years, the US Food and Drug Administration approved only two drugs for the treatment of this condition. Small, open-label or randomized studies using acute doses of different pharmacologic probes suggest benefit of other drugs as well, which could be used in individual patients under close monitoring. This review describes the pathophysiology of neurogenic orthostatic hypotension and supine hypertension in Parkinson disease. We discuss the mode of action and therapeutic efficacy of different pharmacologic agents used in the treatment of patients with cardiovascular autonomic failure.
心血管自主功能障碍,包括神经源性直立性低血压、仰卧位高血压和餐后低血压,在帕金森病患者中较为常见。最近的证据表明,自主神经早期损害,如心脏自主神经去神经支配,甚至神经源性直立性低血压,发生在与疾病相关的典型运动缺陷出现之前。当神经源性直立性低血压发展时,帕金森病患者的死亡率、跌倒和与跌倒相关的创伤风险增加。神经源性直立性低血压降低生活质量,并导致认知能力下降和身体适应不良。仰卧位高血压的并存使神经源性直立性低血压的治疗变得复杂,因为它涉及使用具有相反作用的药物。此外,由于治疗选择有限,神经源性直立性低血压的治疗具有挑战性;在过去的 20 年里,美国食品和药物管理局仅批准了两种药物用于治疗这种疾病。使用不同药理探针的急性剂量的小型、开放标签或随机研究也表明其他药物也有获益,在密切监测下可在个别患者中使用。本文描述了帕金森病中神经源性直立性低血压和仰卧位高血压的病理生理学。我们讨论了用于治疗心血管自主衰竭患者的不同药物的作用机制和治疗效果。