Which medications are used to treat orthostatic hypotension in patients with multiple system atrophy (MSA)?

Updated: Oct 17, 2018
  • Author: André Diedrich, MD, PhD; Chief Editor: Selim R Benbadis, MD  more...
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Answer

Many agents have been advocated for the management of orthostatic hypotension. Table 9, below, shows some of the most widely used drugs. However, drug therapy of orthostatic hypotension is limited by supine hypertension, which affects about 60% of patients with MSA. [41]

In February 2014, droxidopa was approved by the FDA for the treatment of orthostatic hypotension. It is a synthetic amino precursor prodrug and is converted to norepinephrine. [42]

Water is a uniquely powerful pressor agent in the management of orthostatic hypotension in patients with MSA. It acts by increasing sympathetic activity. On average, 16 ounces of water will raise BP about 30 mm Hg. Patients may understandably be skeptical that something so commonplace could help raise their BP, so it does require patient education. No other beverage (not juice or coffee or even Gatorade) is as good as a pressor agent as water in patients with autonomic dysfunction. Its major limitations are a short (1-hour) half-life and increased urination (inconvenient when autonomic impairment makes urination difficult).

Patients should drink 16 ounces of water on awakening each morning, even before they get out of bed. Patients should learn to use water prophylactically; they will be able to do much more in the hour after ingesting water than at other times. A repeat dosing midmorning or at lunch and at midafternoon may give the patient additional capacity for activity during this part of the day. Conversely, since patients with autonomic failure commonly have supine hypertension, we discourage them from drinking large amounts of water within the 2 hours prior to bedtime, although we allow them to drink when they are thirsty.

Table 9. Drugs Used to Manage Orthostatic Hypotension in MSA (Open Table in a new window)

Class

Drug

Description or Mechanism

Corticosteroids

Fludrocortisone (Florinef)

Mineralocorticoid; sodium retention, primarily in extravascular compartment, causes tissue edema to venous capacitance bed in lower extremity. With this edema, venous bed accommodates decreased volume of blood in an upright posture (high doses, late effect); increases sensitivity to norepinephrine (even with small doses)

Sympathomimetic amines

Midodrine

Alpha1-adrenoreceptor agonist acts directly on vasculature, causes venous and arteriolar vasoconstriction

 

Droxidopa

 

Droxidopa is a synthetic precursor of norepinephrine. It acts by conversion to norepinephrine in the body.

Recombinant erythropoietin (EPO)

Epoetin alfa

Increases sensitivity to pressor effects of angiotensin II; increases plasma endothelin level; increases cytosolic free calcium in vascular smooth muscle; increases intravascular volume

NSAIDs

Indomethacin, ibuprofen

Inhibition of vasodilator prostaglandins proposed but not proven

Antihistamines

Diphenhydramine, cimetidine

Reduce vasodilatation caused by histamine release

Somatostatin analogs

Octreotide

Reduce splanchnic capacitance

Vasopressin agonists

Desmopressin (DDAVP)

Vasopressin analogs; no effect on V1 receptors, which are responsible for vasopressin-induced vasoconstriction; acts on V2 receptors on renal tubuli, which are responsible for antidiuretic effect; prevents nocturnal diuresis, raises BP in morning

Other sympathomimetics

Yohimbine

Alpha2-adrenoreceptor antagonist

Caffeine

Adenosine receptor antagonist


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