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Expert Opin Pharmacother. 2019 Feb;20(2):187-199. doi: 10.1080/14656566.2018.1543404. Epub 2018 Nov 8.

Chemical pharmacotherapy for the treatment of orthostatic hypotension.

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a Department of Neurology , Mayo Clinic , Jacksonville , FL , USA.



Orthostatic hypotension (OH) is a common yet often overlooked condition. Particularly debilitating is neurogenic orthostatic hypotension (nOH) caused by deficient neurotransmission of norepinephrine, which is the primary neurotransmitter released at sympathetic peripheral vascular nerve terminals in response to orthostatic stress.


In this review, the author summarizes and critiques established and emerging pharmacologic approaches for the management of nOH. Two drugs are currently approved. Midodrine, an α1-adrenoreceptor agonist, acts on capacitance vessels to increase peripheral vascular tone, thus increases arterial pressure. Droxidopa, an orally administered prodrug of norepinephrine, increases circulating norepinephrine levels, causes peripheral vasoconstriction, and increases standing blood pressure. Preliminary studies support the selective use of several off-label drugs in difficult cases. All of these drugs can potentially unmask or exacerbate neurogenic supine hypertension (nSH), which occurs in about half of patients with nOH.


Chemical pharmacotherapy of nOH is best individualized to the needs and condition of each patient and guided by the underlying pathophysiology, severity of orthostatic incapacity, and minimization of comorbidities such as nSH. The goal of therapy is to maintain cerebral perfusion and increase the patient's ability to engage in upright daily activities. Advances in pharmacogenetics and ambulatory devices hold promise.


Orthostatic hypotension; droxidopa; fludrocortisone; midodrine; pyridostigmine; supine hypertension

[Indexed for MEDLINE]

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