In response to a change in posture from supine or sitting to standing, autonomic reflexes normally maintain blood pressure (BP) by selective increases in arteriovenous resistance and by increased cardiac output, ensuring continued perfusion of the central nervous system. In neurogenic
orthostatic hypotension (NOH), inadequate vasoconstriction and cardiac output cause BP to drop excessively, resulting in inadequate perfusion, with predictable symptoms such as
dizziness,
lightheadedness and falls. The condition may represent a central failure of baroreceptor signals to modulate cardiovascular function, a peripheral failure of
norepinephrine release from cardiovascular sympathetic nerve endings, or both. Symptomatic patients may benefit from both non-pharmacologic and pharmacologic interventions. Among the latter, two pressor agents have been approved by the US Food and Drug Administration: the
sympathomimetic prodrug midodrine, approved in 1996 for symptomatic
orthostatic hypotension, and the
norepinephrine prodrug droxidopa, approved in 2014, which is indicated for the treatment of symptomatic neurogenic
orthostatic hypotension caused by primary autonomic failure (
Parkinson's disease,
multiple system atrophy and
pure autonomic failure). A wide variety of off-label options also have been described (e.g. the synthetic
mineralocorticoid fludrocortisone). Because pressor agents may promote supine
hypertension, NOH management requires monitoring of supine BP and also lifestyle measures to minimize supine BP increases (e.g. head-of-bed elevation). However, NOH has been associated with
cognitive impairment and increases a patient's risk of
syncope and falls, with the potential for serious consequences. Hence, concerns about supine
hypertension - for which the long-term prognosis in patients with NOH is yet to be established - must sometimes be balanced by the need to address a patient's immediate risks.