Monday, August 20, 2012

The Pharmacologic Treatment of Dysautonomia

 For dysautonomia or postural hypotensive tachycardia syndrome (POTS), pharmacologic management may be necessary to optimize cerebral perfusion and minimize complaints of syncope or pre-syncope.

 Black Licorice.   For the hypotension of dysautonomia or POTS, the following may be considered.

     The perennial plant Glycyrrhiza glabra is related to beans and peas.  The root of the plant has been used to treat the common cold, adrenal insufficiency, arthritis, and allergic reactions.  It contains glycyrrhizin that is similar in action to the hormone aldosterone.  Aldosterone increases the secretion of potassium from the body, while increasing both salt and water retention.   Fluid retention and high blood pressure occur.

     A High Salt Diet and/or Na Tablets:  Many patients with dysautonomia crave salt and water in their diets.   Since water is usually ingested at increased rates, the serum Na doe not usually increase to the point of hypernatremia.  For ease of reaching higher serum sodium levels, Salt Tablets may be prescribed.  If steroids are prescribed, there is no need to take sodium tablets, because the steroids help the body hold on to salt.

No doctor wants a patient to go on steroids unless it is absolutely necessary.  Steroid therapy with fludrocortisone is therefore considered to be a serious approach, usually reserved for hypotension that is extremely limiting quality of life.   The drug has a good effect in the treatment of dysautonomia, and lasts a long duration of time such that it is only taken once per day.  It depends on salt intake, and thus changes in salt intake can affect is reliability.  Since fludrocortisone increases intracranial pressure, it should be used with extreme caution in patients with such diagnoses as Chiari malformation.  Any reported headaches should be followed closely.  Some patients complain of lightheadedness, insomnia, weight gain, and nervousness.  Fludrocortisone use for dysautonomia is classified as a non-FDA-approved use, therefore it is given "off-label".

    The peripheral alpha-adrenergic vasoconstrictor midodrine is a good choice of drug therapy for many patients with dysautonomia.  This is usually prescribed by a cardiologist who has evaluated and excluded other intrinsic cardiac abnormalities.   Midodrine is usually started a low doses.   It lasts four hours, so it is not to be taken if the patient is going to sleep (high blood pressure may occur, leading to a stroke).   The dose can be tapered upwards to sustain a mean arterial blood pressure of choice. Common side effects include scalp tingling, chills, and headaches.

      Beta-blockers are relatively easy to dose, making them a good pharmacologic choice.  They should be used cautiously in patients with Mast Cell Deactivation Disorder.   Side effects include hypotension, decreased blood volume, decreased sex drive (impotence in men), nightmares, weigh gain, depression, and either constipation or diarrhea.  Names of beta-blockers include: atenolol, metoprolol, bisoprolol, acebutolol, and propanolol.

     Selective Serotonin Reuptake Inhibitors (SSRI's) supress the sympathetic nervous system, treat anxiety, and are used in small doses for patients with dysautonomia.  The key manner in which these help is by aiding the regulation of serotonin to control blood pressure especially in hyperadrenergic states; this is accomplished by suppression of the sympathetic nervous system.   Normally used for depression at higher doses, SSRI use in dysautonomia does not mean that the patient is "depressed".  Once the patient understands this, compliance with drug therapy should be improved.  Side effects include an increased risk for suicide (as with many anti-depressants), insomnia, tremors, weight change, decreased sex drive, headaches, and increased sweating.  Names of SSRI's include paroxetine, fluoxetine, sertraline, escitalopram. venalafaxine, and duloxetine.

    Pyridostigmine:  At therapeutic doses, pyridistigmine increases blood pressure while standing, not affecting blood pressure while laying down.  The mechanism of action is that it inhibits acetylcholine breakdown and this increases parasympathetic nervous system activity.   Therefore, it is useful if dysautonomoia is due to autoimmune dysfunction or if used for delayed gastric emptying.  Cons include the fact that this drug has a short duration of action, wearing off quickly.  Side effects include increases in parasympathetic autonomic activity: increased salivation, sweating, nausea, warmth, diarrhea, watery eyes, stomach upset and stomach pain.  The trade name is Mestinon.

    Disopyramide:  This is a drug that opposes parasympathetic activity and is useful in cases where severe bradycardia is an issue.  The mechanism of action is that it inhibits the release of epinephrine and norepinephrine.  Side effects include stomach pain, constipation, diarrhea, nausea, headache, drowsiness, and lightheadedness.  The brand name is Norpace.

   Benzodiazepines:   Benzodiazepines are used for relieving panic symptoms associated with autonomic crisis.  In higher doses, hypotension can occur and this may be counterproductive.  Common side effects include insomnia, drowsiness, nausea, headaches, and being clumsy.  Benzodiazepines should not be taken with alcohol or opiods for fear of respiratory depression, especially during sleep.  Common drugs include clonazepam with a trade name of Klonopin, and diazepam with a trade name of Valium.

Intravenous Fluid:   It is not uncommon for patients with dysautonomia to require intravenous fluid replacement therapy to ensure adequate tissue and organ perfusion.   Some patients have required percutaneous intravenous continuous catheter (PICC) line placement and continuous infusion of fluid in order to survive for 3 or more years, including the author.   The usual fluid is 0.9% Normal Saline, as salt replacement is important with dysautonomia.   Patients may present to the ER for fluid management, and iv hydration in some Centers is provided in an Outpatient Clinic, much like chemotherapy fluid is given to those patients.

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