Neurogenic orthostatic hypotension (OH) is a disorder that results from malfunctions of the autonomic compensatory mechanisms that work to maintain blood pressure when upright.
Many patients with this condition will require pharmacologic treatments.
However, non-pharmacologic approaches are always the first step in managing this condition.
(Disclaimer: I am not a medical professional and all information provided in this post is from the article which is available in the “references” section at the bottom of the page. This post is meant only to provide a synopsis of the information covered in the original article.)
Introduction
OH is evidence of a failure of the compensatory autonomic mechanisms that usually regulate blood pressure when a person is upright.
Furthermore, OH is more often than not a condition that is occurring because of either a neurodegenerative disorder such as multiple system atrophy (MSA), pure autonomic failure (PAF), or Parkinson's disease (PD). Also, OH can be caused by a systemic illness that is causing autonomic neuropathies such as paraneoplastic, autoimmune, diabetes, or amyloid disorders.
When treating OH, it should always be assumed that it is a comorbidity of another condition overwhelming the autonomic functioning mechanisms.
Heart failure, diabetes, and hypertension are the most common comorbidities that occur with OH.
The first step in treating OH should be to examine and treat any aggravating factors.
Denervation Hypersensitivity
As a result of denervation hypersensitivity, patients with autonomic impairment have disproportionate responses to both depressor and pressor stimuli.
The denervation hypersensitivity explains the extreme drop in blood pressure in response to digestion (postprandial hypotension), standing (orthostatic hypotension), and other drops in blood pressure associated with seemingly minor stimuli.
In addition to hypotension, this hypersensitivity also contributes to supine hypertension.
Two things can explain these reactions.
One is a loss of baroreflex buffering that typically controls changes in blood pressure.
Two, an upregulation of adrenergic receptors due to a decreased exposure to norepinephrine (NE) caused by the loss of noradrenergic nerve fibers.
Residual sympathetic function
The insufficient release of NE from the sympathetic nerves ultimately causes orthostatic hypotension.
These insufficiencies are caused either by an impairment of the central pathway that typically triggers sympathetic activation or by a loss of peripheral noradrenergic fibers.
The cause is important for selecting medications because a different treatment approach may be necessary depending on what is causing the impaired NE secretion.
Estimation of sympathetic reserve
The sympathetic reserve is the concentration of NE in the blood plasma.
There are a few different methods for determining the sympathetic reserve.
One approach is measuring compensatory orthostatic tachycardia in patients.
Patients with neurogenic OH cannot properly increase their heart rate to compensate for drops in blood pressure.
Another method is to measure the blood pressure response to the Valsalva maneuver to determine the level of sympathetic impairment.
The Valsalva maneuver involves specific breathing patterns which cause sympathetic activity.
Autonomic dysfunction results in a sustained decrease in blood pressure due to strain.
The third method is to measure the concentration of NE in blood plasma, but this can be difficult to do correctly as a result of ever-changing sympathetic activity and differences between patients and conditions.
Physiologic targets to increase blood pressure
NE plays the most crucial role in regulating blood pressure.
Because of this, most pharmacological treatments will work to either replace or enhance NE in OH patients.
These treatments are primarily based on either utilizing the remaining NE by stimulating secretion or preventing degradation (NE enhancement), or direct alpha-receptor activation (NE replacement). These pharmacological interventions include:
Norepinephrine Replacers (Midodrine, Droxidopa)
Non-specific treatments (Fludrocortisone, Octreotide)
Norepinephrine Enhancers (Pyridostigmine, Atomoxetine, Yohimbine)
Supine Hypertension
Many OH patients also present with hypertension when lying down (supine), which may be another manifestation of baroreflex difficulties as it cannot regulate OH or supine hypertension.
For symptom management, supine hypertension has to be treated without worsening OH.
Several treatments have been suggested, such as nitroglycerine patches, nebivolol, sildenafil, losartan, and eplerenone.
Heart Failure
OH often co-occurs with heart failure. Fludrocortisone is generally avoided in heart failure patients because it increases the risk of hospitalizations.
Midodrine is commonly used to treat OH, but supine hypertension is a concern for heart failure patients.
Droxidopa or Droxidopa combined with beta-blockers for treating OH in heart failure patients.
Postprandial Hypotension
Postprandial hypotension is a drop in blood pressure within 2 hours after eating.
This results from splanchnic venous pooling, which is normal in small amounts but worsened by autonomic impairments.
Pharmacological treatments for postprandial hypotension include caffeine, octreotide, and acarbose.
Parkinson's Disease
OH is a premotor symptom of Parkinson's disease, which may manifest with other precursor Parkinson's symptoms such as rigidity, tremors, and bradycardia.
It is very common for OH to occur with Parkinson's disease.
As a result, Parkinson's disease patients may benefit better from NE replacers.
Multiple System Atrophy
Neurogenic OH often occurs along with motor symptoms in multiple system atrophy patients.
Multiple system atrophy is a progressive neurodegenerative disorder that results in central autonomic failure.
If non-pharmacological treatments cannot manage symptoms, NE enhancers may be used.
Atomoxetine has shown some success in managing OH in multiple system atrophy.
Diabetes
Autonomic neuropathy is often a complication of type 1 and 2 diabetes.
Lifestyle modifications and glucose control are the first steps in preventing the progression of OH symptoms (especially in type 1).
Medications such as alpha-adrenoreceptor antagonists, tricyclic antidepressants, and diuretics should be carefully monitored before starting any further pharmacologic treatments.
Conclusion
OH is a complication of numerous illnesses. Non-pharmacologic interventions should be attempted first, but pharmacologic interventions may be necessary if they do not help enough.
Depending on what condition(s) the patient is experiencing, different pharmacologic approaches may be helpful.
References
Park, Jin-Woo, et al. “Pharmacologic Treatment of Orthostatic Hypotension.” Autonomic Neuroscience : Basic & Clinical, U.S. National Library of Medicine, 1 Dec. 2020, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7704612/.
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