Drugs for Orthostatic Intolerance

Drugs for Orthostatic Intolerance

Dr. Peter Rowe of the Johns Hopkins Children’s Center notes that the effectiveness of most orthostatic intolerance effecting drugs have not undergone treatment trials in chronic fatigue syndrome or POTS and that it may take time for ME/CFS/POTS patients and their doctors to find the drug or combination of drugs. Because these drugs effect basic processes in the body careful monitoring is needed.

Drugs That Increase Blood Flows by ‘Tightening’ Blood Vessels
Blood Volume Enhancers
  • Fludrocortisone (Florinef) - is used to treat neurally mediated hypotension (NMH) and postural orthostatic tachycardia syndrome (POTS). By helping the kidneys retain more sodium, Florinef increases blood volume and vasoconstricts the blood vessels. (Dilated blood vessels are a problem in one form of POTS)
    Two studies did not find Florinef effective but doctors report this drug can be very helpful in the right patient. Dr. Bell, for instance, found it helpful in about 25% of his patients.
    Dr. Rowe emphasizes that salt intake must be increased for this drug to work and that Florinef is often helpful when used with low dose beta blockers in his adolescent patients. (People with low plasma rennin levels should not take Florinef)
    Salt and fluid intake should be increased prior to taking the drug. Starting with a low dose (1/4 table a day: 0.025 mg), Dr. Rowes increases the dosage by ¼ table every 4-7 days to a maximum of 1 ½-2 tablets a day (.2 mgs). Because florinef reduces potassium levels potassium supplements (8-20- mEq) should be taken. If the lactose in Florinef is a problem compounding pharmacies can produce formulations without it. Find out more about Florinef here.
  • Erythropoietin (Procrit, Epoietin-alpha)
  • Saline Solution
  • Oral rehydration solution - Oral rehydration solution is currently being testing in ME/CFS/POTS. It's much, much cheaper than saline and can be made at home. Found out how here.
  • Desmopressin (DDAVP) - by increasing water absorption by the kidneys desmopressin increases fluid retention and thus increases blood volume. A 2012 and a larger 2015 study found that DDAVP decreased the heart rates upon standing and improved symptoms. About 2/3rd's of patients in the larger study were able to tolerate the drug. Of those about 40% experienced significant symptom relief upon standing including reductions in dizziness, fainting, fatigue, anxiety and palpitations. Find out more about DDAVP here.
  • Clonidine
  • Oral Contraceptive Pills
  • Vasopressin - has much the same effect as desmopressin but also triggers sympathetically mediated vasoconstriction.
Drugs That Effect Epinephrine/Norepinephrine Release
  • Atenolol (Tenormin) - a beta blocker, Tenormin reduces heart rates by inhibiting epinephrine activity and can be effective in neutrally mediated hypotension or POTS. Beta blockers are contraindicated in patients with low blood volume or who experience increased heart rates as a consequence of blood pooling in their lower body. Dr Rowe recommends 12-25 mgs a day or 1 mg. for every kg. of body weight (for NMH). Those with heart rates greater than 50 bpm higher doses may not tolerate higher doses.
  • Propanolol (Inderal)- is a beta blocker that reduces sympathetic nervous system activity by blocking epinephrine and/or norepinephrine. Reduced heart rates and blood pressure can occur. Because propanolol can also reduce water retention it may also reduce blood volume. Raj et. al found that low doses (20 mg) significantly reduced heart rates and improved symptoms in POTS. Higher doses could have negative effects. Raj reported
    "Of more clinical importance, however, is that low doses of propranolol also significantly improved symptom burden in these patients. The clinician should be careful not to be too aggressive by targeting complete beta blockade as this may not further improve symptoms, and may paradoxically worsen some symptoms. The findings from this controlled study match our clinical experience. Many of our patients are clinically prescribed propranolol 10–20 mg per dose, and most patients tolerated this dose quite well.
    In an email, fatigue and pain researcher Dr. Light, suggested another reason why low doses of propanolol may be more effective than high doses.
    “Theoretically, beta and alpha blockers should actually make CFS patients worse, because the prevailing theory (with some pretty good evidence) is that vascular smooth muscle alpha and beta receptors are DOWN regulated (are effectively non-functional) due to an “overdrive” of the sympathetic nervous system.
    Activation of these receptors is essential for proper control of blood flow in skeletal muscles and perhaps also the brain. Without proper control, the amount of metabolites signaling fatigue and muscle pain could swing wildly, leading to the sensation of fatigue with even modest movement, and even at rest. Worse, it could lead to orthostatic hypotension (a very common symptom in CFS patients) that could cause the patient to faint when standing, or even sitting upright.
    What we found is that there are also alpha and beta receptors on both the muscle sensory neurons that signal fatigue and also those that signal muscle pain, as well as on circulating immune cells. We further found that the receptors on the sensory neurons and immune cells were blocked at lower doses (1 tenth the dose) than is necessary to block alpha and beta receptors on vascular smooth muscle.
    This means that low doses of propranolol (again 1/5 to 1/10 the dose that is prescribed for blood pressure control) can block the sensory receptors, reducing the total signal to the sympathetic nervous system, allowing the normal sympathetic reflexes to be re-established, leading to much more normal control of metabolite levels in muscle and brain.
    (Much of this last section is still speculation-only inferred from the data we have on blood pressure and vascular control in FM patients, published in Adrenergic dysregulation and pain with and without acute beta-blockade in women with fibromyalgia and temporomandibular disorder. Light KC, Bragdon EE, Grewen KM, Brownley KA, Girdler SS, Maixner W.J Pain. 2009 May;10(5):542-52.).
  • Disopyramide (Norpace)
  • Angiotensin converting enzyme inhibitors/angiotensin receptor blockers
Others

  • Mestinon - (Pyridostigmine bromide) - reduces tachycardia (high heart rates) by decreasing the degradation of acetylcholine, the neurotransmitter used by the vagus nerve to stimulate the parasympathetic nervous system. A 2005 study found that Mestinon both reduced heart rate and improved symptoms in POTS. Mestinon is Dr. David Systrom's go to drug for POTS/ME/CFS. Check out a Mestinon ME/CFS success story - A Mestinon Miracle
  • Ivrabadine - With it's reported 70% success rate in POTS Ivrabadine - introduced to the U.S. in 2015 - may be the most effective drug for this condition. It also appears to produce fewer side effects than beta blockers which are used to reduce heart rates.
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