Orthostatic hypotension (OH) is characterized by a drop in blood pressure upon standing, with accompanying symptoms including dizziness and lightheadedness. Usually, the autonomic nervous system regulates blood pressure (BP) and increases blood vessel constriction upon standing to keep BP constant. In MSA, disturbances in the autonomic nervous system leads to neurogenic orthostatic hypotension (nOH), defined as a drop in systolic BP ≥ 14 mmHg or in diastolic BP ≥ 6 mmHg. Lying-to-sitting drops in blood pressure can also be used to diagnose OH in patients if standing is not feasible, with drops in sitting systolic BP ≥ 14 mmHg or diastolic BP ≥ 6 mmHg indicating the presence of nOH. (Sun 2016) These drops in blood pressure can lead to dizziness, problems maintaining balance, walking and an increased risk of falls. nOH occurs in anywhere from 54%-81% of patients with MSA.
1. Non-pharmaceutical treatments for OH include correcting aggravating factors and implementing other measures to decrease symptoms and risk of fall. OH has been found to be worse in the morning, in hot weather, after eating large meals (especially carbohydrate-heavy meals) and from lifting heavy objects. Avoiding exposure to these factors can decrease the frequency and severity of OH instances. Other non-pharmaceutical interventions include:
2. Pharmaceutical treatments for nOH try to either increase plasma volume or to increase peripheral resistance through various mechanisms of action. Drugs used to treat MSA are described in Table 1.
Table 1: Medications to Treat Orthostatic Hypotension in MSA
|Drug||How it Works||How It is Used||Side Effects|
|Fludrocortisone||Synthetic adrenal corticosteroid hormone that|
increases sodium and water absorption, increases blood volume, sensitivity to adrenaline, and causes contraction of blood vessels and increases in BP.
|Commonly used in conjunction with a drug that increases blood vessel constriction, such as midodrine, droxidopa or other agents.||Can lead to hypertension and end organ damage, leading to heart and renal failure and has been found to increase risk of hospitalization.|
Side effects include ankle swelling, hypokalemia or low potassium levels, and headache.
|Midodrine||Vasoconstrictive agent that leads to increased BP in laying down, sitting and standing positions.||It has been shown to be effective in the treatment of nOH among MSA patients, with an increase in standing systolic BP of nearly 22mg Hg.||Found to cause an increase in supine hypertension, or dangerous increases in BP while lying down, and should not be taken close to bedtime.|
|Droxidopa||Converted to norepinephrine, a hormone that increases BP and has shown significant reductions in BP in several small clinical trials, while results from larger clinical trials have been mixed.||Patients with a lower level of norepinephrine while lying down tend to have better success with droxidopa and may be used to predict success.||Can have central nervous system side effects including behavioral changes, including memory difficulties, confusion, mania, and irritability. Other side effects include headache, dizziness and nausea.|
|Pyridostigmine||Stops the breakdown of acetylcholine, the main neurotransmitter of the autonomic nervous system, increases the release of adrenalin.||Has been shown to cause an increase of an average of 4mm HG in systolic BP.||Side effects can include stomach pain, nausea, vomiting, diarrhea, blurred vision, muscle cramps and twitching.|
|Epoetin alfa||Recombinant erythropoietin that increases the sensitivity of the blood vessels to the hormone angiotensin, which increases vasoconstriction and consequently BP.||The use of this to treat nOH is not widely recommend as the evidence to support it is weak.|
|Non-steroidal anti-inflammatory drugs||Blocks prostaglandin-mediated vasodilation and has been hypothesized as using this mechanism to prevent OH.||Results haven’t been validated in large trials.||Possible gastrointestinal irritation.|
|Yohimbine||Leads to increases in the activity of the autonomic nervous system through increases in norepinephrine.||Clinical evidence of effective control of OH is scarce.||Side effects can include anxiety, palpitation, tremor and confusion.|
|Desmopressin (DDAVP)||Helps to contract blood vessels and may combat OH by mimicking the action of the hormone vasopressin.||Helps to prevent nocturnal urination thereby improving BP control in the morning. Limited data on this agent make recommendations for the use of this agent weak.||Alternations in blood chemistry, specifically low sodium levels.|
|Atomoxetine||Short acting norepinephrine transport inhibitor, increases BP in nOH.||Especially effective with patients with high levels of norepinephrine.||Side effects can include gastrointestinal and urinary symptoms.|