Pharmacotherapy of Cardiovascular Autonomic Dysfunction in Parkinson Disease
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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.
C.A.S. was supported by a Doris Duke Foundation Career Development Award. C.A.S. and H.K. received grant support from the Office of Orphan Products Development, Food and Drug Administration, Grant #FD-R-04778-01-A3.
Compliance with Ethical Standards
The authors did not receive funding for the preparation and writing of the present manuscript.
Conflict of interest
CA.S. has received research a grant from the Doris Duke Foundation. C.A.S. and H.K. received grant support from the Office of Orphan Products Development, Food and Drug Administration, Grant #FD-R-04778-01-A3. C.A.S. has received speaker honorarium from Lundbeck Pharmaceuticals. C.A.S. and H.K. received consulting honoraria from Lundbeck and Theravance Biopharma. C.A.S is a member of the Board for the American Autonomic Society.
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