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Methydopa Prescribed Today - Any Info On Vandy Trial


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Dear Buds,

Presently I am sitting here with bp of 210/110. My norepinephrine on a tilt is over 5000 mg, so I have a particular problem with NE. I am already on Kerlone (B1 and B2 beta blocker) maxed out at 20 mg and catapres .2mg patch and .1 oral twice a day (any more clonidine and I fall asleep sitting up).

Went to a new cardiologist today about my POTS and very high BP. I told him that I had been on dimethylene, compounded down into a lower dose, and have great success for awhile, but instead of going with what I know worked for me, he suggested methyldopa, 250 mg twice a day.

I have seen Ram's thread about Vandy doing methydopa trials and apparently they have not started yet and are still taking new people. But I would like to get y'all's input on going this route. I it is part of a trial, that tells me that it is not a standard treatment...or maybe even a safe treatment.

I was particularly concerned that the doctor did not request I get liver testing prior to and while taking this med, as the FDA says "It is important to recognize that a positive Coombs test, hemolytic anemia, and liver disorders may occur with Methyldopa therapy. Before treatment is started, it is desirable to do a blood count (hematocrit, hemoglobin, or red cell count) for a baseline or to establish whether there is anemia. Periodic blood counts should be done during therapy to detect hemolytic anemia."

And, of course, my last physical showed enlarged red blood cells, which is a minor kind of anemia. When I asked my primary care about this, he said "not important in somebody like you." Note that I am already short 20% of my red blood cells per the Cleveland Clinic. Wondering if the doctor even read my test results.

Also I have posted about having CHF and it looks like methydopa can cause edema, so I'm further not so thrilled with this.

And he says it will take a week to lower my BP.

Any thoughts would be appreciated.

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I think he wants to get your blood pressure down.

It really looks like if your dysautonomia is the cause of the high blood pressure that this may solve the problem from what I just saw online.

I guess just give it a try. If you notice any adverse effects I would call right away I wouldn't wait.

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methyldopa is used to reduce sympathetic drive. It could be a wonder drug for POTS - the trial has already commenced (unless im mistaken) but it still recruiting.

I thought the study was involving patients with CFS. I could be wrong. I have a hard time believing methyldopa will be the new wonder when clonidine has been used quite extensively in POTS patients. Clonidine appears to help some, while making others far worse. If the root problem is an overactive sympathetic nervous system, I can certainly see methyldopa and clonidine helping. However, if the increase sympathetic tone is compensatory, are we not blocking the body's back up mechanism to perfuse the brain? I guess that's the purpose of the study, to see.

Just another thought/musing... Some of us have mentioned having abnormalities on our echocardiograms. I have left ventricle hypocontractility and a reduced stroke volume. I am told this is not CHF, but rather a small, stiff, deconditioned heart. Why? I'm not sure. I have been an extremely active athlete my whole life, working out almost every day. I am going to guess some kind of genetic predisposition to a small heart. Who knows? Maybe this is why I have always felt better when working out. If you have a weak heart, common sense would say one's heart is not able to effectively pump blood upstairs. The result would be an increase in sympathetic tone to get blood to essential organs. It seems counter productive to give drugs to block cardiac output if cardiac output is already low. What am I missing? I did try clonidine for 2 weeks after developing supine hypertension.... yuck, disaster! I am happy for those who do find benefit though. Do most patients with POTS have completely normal heart size and ejection fraction?

Elegiamore,

I hope the methyldopa brings some relief to your high bp. How frustrating for you! You certainly have a strong sympathetic response. In an ideal world, baseline blood counts, liver function panel, and a Coombs test would be performed, and then monitored every few months to check for hemolytic anemia when starting methyldopa. I wish you the very best. I have the same frustrations with low blood volume, ECHO changes, and adrenaline surges (though not as strong as yours). Hugs.

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The Vandy study is the studying 'the subset of CFS patients who exhibit POTS' and its based on the contention that sympathetic excess underlies their circulatory abnormalities and causes inflammation (through increased neuropeptide Y release or other mechanisms that are yet to be explained).

Reduced stroke volume is seen in nearly all POTS patients - and can also occur because of reduced venous return to the heart either from impaired vasomotor nerve function, venous pooling or arterial vasoconstriction which could starve venous reservoirs of blood return.

Whether sympathetic excess is the cause or consequence of POTS is the million dollar question - it could be a side effect because of parasympathetic withdrawal, it could be the main problem or it could be a normal reponse to impaired vaso or veno constriction. I guess this study might help to see whether chronic reductions in sympathetic outflow result in symptom improverment in some or all patients.

I see your point with clonodine and methyldopa. Methyldopa has a different action to clonidine and perhaps it might work better than just being an a2 adrenorecptor stimulator.

But I agree with your point - i doubt but hope its that simple. In this case with crazy orthostatic hypertension it might be helpful.

As for the small heart thing - there are CFS doctors who think this might be the problem. Interestingly my dad's cardiologist says that he sees POTS often in families with a history of cardiomyopathy. Perhaps it goes both ways - too big or too weak??

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Thanks so much for the responses.

TX, I ALSO have small heart syndrome. My theory (and also one of my doctor's): I am so dehydrated/hypovolemic that my heart is also dehydrated and therefore appears smaller. This would jive with my mitral valve problem, which is very interesting to me. Sometimes I have a mitral valve prolapse that is leaking, but sometimes I DON'T. Same with the accompanying murmur. Most likely it shrivels up when dehydrated and goes back to normal when I'm not.

Ram, your responses are very valuable and insightful. But my own personal assessment is quite simple:

1. Dibenzyline, which is an NE blocker and prescribed for pheochromocytomas (adrenal tumors which release comparable NE to my own body when standing/tilted), has worked in the past.

Here is the difference in possible side effects:

Side Effects of Dibenzyline:

The following adverse reactions have been observed, but there are

insufficient data to support an estimate of their frequency.

Autonomic Nervous System*: Postural hypotension, tachycardia,

inhibition of ejaculation, nasal congestion, miosis.

Side Effects of Methydopa:

Sedation, usually transient, may occur during the initial period of

therapy or whenever the dose is increased. Headache, asthenia, or

weakness may be noted as early and transient symptoms. However,

significant adverse effects due to ALDOMET (methlydopa) have been

infrequent and this agent usually is well tolerated.

The following adverse reactions have been reported and, within each

category, are listed in order of decreasing severity.

Cardiovascular: Aggravation of angina pectoris, congestive heart

failure, prolonged carotid sinus hypersensitivity, orthostatic

hypotension (decrease daily dosage), edema or weight gain,

bradycardia.

Digestive: Pancreatitis, colitis, vomiting, diarrhea, sialadenitis,

sore or "black" tongue, nausea, constipation, distension, flatus,

dryness of mouth.

Endocrine: Hyperprolactinemia.

Hematologic: Bone marrow depression, leukopenia, granulocytopenia,

thrombocytopenia, hemolytic anemia; positive tests for antinuclear

antibody, LE cells, and rheumatoid factor, positive Coombs test.

Hepatic: Liver disorders including hepatitis, jaundice, abnormal liver

function tests (see WARNINGS).

Hypersensitivity: Myocarditis, pericarditis, vasculitis, lupus-like

syndrome, drug-related fever, eosinophilia.

Nervous System/Psychiatric: Parkinsonism, Bell's palsy, decreased

mental acuity, involuntary choreoathetotic movements, symptoms of

cerebrovascular insufficiency, psychic disturbances including

nightmares and reversible mild psychoses or depression, headache,

sedation, asthenia or weakness, dizziness, lightheadedness,

paresthesias.

Metabolic: Rise in BUN.

Musculoskeletal: Arthralgia, with or without joint swelling; myalgia.

Respiratory: Nasal stuffiness.

Skin: Toxic epidermal necrolysis, rash.

Urogenital: Amenorrhea, breast enlargement, gynecomastia, lactation,

impotence, decreased libido.

------------------

Which one would you try first? Considering that I seldom take a med that doesn't have a side effect for me, I vote for the safest one first and the methyldopa last.

Meanwhile, I am waking up after a few hours with chest pain, trouble breathing and high bp. I feel terrible.

And I am getting very, very tired of trying to moving forward, listening to doctors with horrific, callus bedside manners and no apparent concern for my well-being. The newest doctor said he was requesting a renal study, but has not even called to set it up.

My new CFS doctor will not call me back. My primary refused to get involved yesterday and had me call an associate cardiologist, who when heard what my condition was, suddenly didn't have any openings until September. Sure.

My neurologist seems to be the only sane one and wants me to go to Vandy, but they cannot see me until October or November. Firewalker thinks I should have him send a SOS letter to Vandy for me, but Vandy was EXTREMELY adamant

that no rush patients are ever seen. Even if you get admitted to the Vandy Hospital.

Thanks again! Elegiamore

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Quick synopsis on the 3 drugs.

Dibenzyline: This is actually an alpha antagonist. It is used in pheo and kick starts the renin-angiotensin-aldosterone back into gear. Think of this drug as the opposite as Midodrine. It can actually cause POTS in otherwise healthy individuals. It is generally not used in POTS because it can take the rug out from underneath us by causing significant vasodilation. I've had this conversation with my POTS physician and endocrinologist because I wondered why it was not being used in POTS when renin and aldosterone are so low. That being said... mixed beta and alpha antagonists like labetatol are sometimes used successfully in POTS. I have never dispensed this particular drug in all my years as a pharmacist, so your physician may not have a comfort level with this medication. I have yet to hear of a POTS patient being treated with pure alpha antagonists. However, you've had success with this drug in the past.

Clonidine: This is an alpha agonist, which a high affinity for alpha 2 receptors in the brain stem. This drug tricks the brain into believing catecholamine levels are higher than they are, interfering with the brain's signals to the adrenal medulla. Catecholamine release is lowered.

Methyldopa: Inhibits the enzyme that converts L-DOPA into dopamine. Dopamine subsequently would be converted into norepinephrine and epinephrine which stimulate beta and alpha receptors throughout the body.

These drugs are all blocking the sympathetic nervous system response in different parts of the chain. Methyldopa blocks the production. Clonidine blocks the brain's signal to fire. Dibenzyline blocks the alpha receptors that the catecholamines would be triggering further down in the chain.

I would definitely encourage you to talk with your cardiologist about your concerns. Keep calling until all your questions are answered and concerns are addressed. It is your body, and you certainly have the right to discuss worrisome side effects, follow up lab work, and the fact that you have used dibenzyline in the past.

Rama,

I don't wish POTS on anyone, but I was relieved to here many other POTS patients have low stroke volume. I also recently heard that some researchers are calling POTS "The Grinch Syndrome" because so many POTS patients have small hearts. This would be the opposite of elite athletes who have huge, torpedo shaped hearts. This burns me up because I have spent almost every day of my life exercising (aside from much of the last year, but i'm back at it). I would love to know what on earth the underlying cause is. I resolved myself to stop pondering the research, but alas, it's not my nature.

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I was in the Vanderbilt study for 2 weeks at the end of April. I was impressed with the staff, and glad to be a part of POTS research. I didn't hear anything while there about trying methyldopa... I did just finish trying carvedilol, at the lowest dose, which is similar to labetalol in action, alpha AND beta blocker. It made me unable to function! I felt like a huge lump of lead. If the roof had fallen in on me, I don't think I could have moved! So I stopped it, and am back on propranolol. I have high plasma NE levels: supine 604 pg/ml; standing 1231 pg/ml. I have all the hyperadrenergic POTS symptoms.

I'm curious to see how the methyldopa works... keep us informed! I LOVE my clonidine, can't live without it, and Klonipin added when it gets really bad. Also, Vanderbilt found that melatonin helped me greatly, symptom-wise.

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Melatonin helps my tachycardia, adrenal rushes and most all my symptoms. There was a marked difference on my holter monitor within 30-45 minutes after taking my nightly melatonin. I only take a little, 1.5mg, but I have found it helps tremendously. The problem is that you can't take it all day. At the wrong time it will really mess with your circadian rhythm and even your hormones! It works if you take it at dusk, when your body is supposed to start making it anyway.

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For me, they gave it to me as one of my med trial drugs, so I didn't know what I was taking at the time. My heart rate and bp were not affected, they were as high as usual. But subjectively, I felt less weak, less brain fog, able to stand longer. I don't know why! But Dr. Raj said he wasn't surprised, that a lot of POTS patients had that response to melatonin. It is a major drawback that you can only take it before bedtime, because that doesn't help me get through the day! But I take it anyway, but haven't noticed much difference when I only take it at bedtime.

The thing that helps my jitteriness, chest pain, and anxious feeling is clonidine.

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Thanks for the comments, y'all.

Ram, I don't think I have ever heard of the term "postural anxiety" and I've been around! I can guess that is is panic related to changing positions? In the beginning before I found clonidine and a good beta blocker, I did have panic type attacks, but not anymore.

I am desperate to get somebody to prescribe dibenzyline again but that cardiologist has retired.

Unfortunately, my bp of 220/110 has finally gotten to me; blood vessels are bursting all over my body, violent headaches and I finally went to the ER, was checked into St. Joseph in Atlanta (I have the same problem as firewalker - can't find a cardiologist) and it was a dismal failure. They sent me home last night after starting me on bystolic 10 mg and by this morning, I had BP of 214/100 again. Great.

I think I need to get a week or more of bystolic in me to see if it works, but already I have a weird thing: Sitting my bp is 165/78 but when I stand up, it went to 135/100. WHAT? Normally they drop in unison. And I feel very close to syncope when standing or changing positions on this drug. However, they have also given me a TON of ativan to "calm me down" also.

Love your thoughts on all of this. Elegiamore

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Eligiamore, what you are describing sounds like hyperadrenergic POTS. Sounds like your catecholamine levels are quite high. This is what produces the anxiety-like feelings. Clonidine blocks the norepinephrine response, which helps that feeling.

Hypotension isn't really a part of POTS, it is another form of dysautonomia, NMH (neuromediated hypotension)/ orthostatic intolerance. Part of the definition of POTS is the heart rate increase >30 bpm or 120 bpm within so many minutes of standing "IN THE ABSENCE OF HYPOTENSION." That is what the research articles say anyway...

It is normal with POTS for your systolic bp to remain the same or decrease slightly upon standing, and for the diastolic to increase by about 10 mmHg.

So the blood pressures you reported are consistent with POTS... if you had hypotension you would have another dysautonomic component going on as well...

does that make sense?

Ram... tell me if I'm wrong, please! :)

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E-

Bystolic is cardio-specific, so it shouldn't effect all the other $*%& that your body is spitting out when you stand, there's the problem and why it didn't work well for me. When the pulse pressure narrows, your diastolic will go up and systolic will go down when you stand. When was your last IV? It is a "classic" hypovolemic response. I'm sorry the last cardio didn't work out. Take it easy and try to keep your BP down.

My thoughts and prayers are with you!

Jennifer

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Hey Firewatcher, thanks! I wasn't even thinking about the narrow pulse pressure being classic for hypovolemia!!! The saline bolus I got at vanderbilt did help... but I've read articles saying that drinking oral fluids help more than the IV fluids, if u can get that much water down... guess I'll try to be better at gulping down the pedialyte! I get it in the baby section of Walmart, it comes in those little powder packets u add to water now! less sugar than gatorade... kind of expensive, tho...

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TXPOTS,

How does Wellbutrin compare to Methydopa? At one point, when they thought I had Parkinson's, they tried sinement and It was too strong, so they put me on Welbutrin. I took it for awhile, and in some ways it seemed to help. After time, I went downhill. I got much weaker, my tremors were worse, and it got to where I had to use a cane and needed a wheelchair. I decided that what they were doing was making me worse and stopped taking it. Then went to Mayo and got diagnosised w/POTS. My neurologist, before Mayo, had decided that I must have Multiple System Atrophy because the dopa products didn't work.

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Hi Issie,

Wellbutrin prevents the uptake of norepinephrine and dopamine at the neural synapse, so essentially the drug increases levels of norepinephrine and dopamine at the neurons. In opposition, methyldopa reduces the formation of dopamine to begin with. So, a very simplistic view would be methyldopa=less dopamine (and norepinephrine and epinephrine) and Wellbutrin= more circulating dopamine and norepinephrine at the nerve level. Very, very different drugs. No wonder so many POTS patients have horrid drug reactions. Many of the medications used for POTS have opposing effects in the body.

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Soooo, if I needed less dopamine and was on the Wellbutrin it increased it. So, if this other drug does work for POTS it decreases it. Therefore, NO WONDER it made me worse. Not to mention the sinement. Being treated for a year and a half for something ---I didn't have. OHHHHH!!!!!!!! Okay, will the damage from the mis-treatment, get better? I guess time will tell.

Thanks for explaining.

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Soooo, if I needed less dopamine and was on the Wellbutrin it increased it. So, if this other drug does work for POTS it decreases it. Therefore, NO WONDER it made me worse. Not to mention the sinement. Being treated for a year and a half for something ---I didn't have. OHHHHH!!!!!!!! Okay, will the damage from the mis-treatment, get better? I guess time will tell.

Thanks for explaining.

In the brain...yes, it does increase dopamine and levodopa definitely does. I think the jury is still out on whether methyldopa is helpful for POTS, so I wouldn't say you were mistreated yet. Many patients that have POTS are on SSRIS, SSRIs, and Wellbutrin and find benefit. It's a perplexing condition when the treatments are so different.

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I believe if you have the neurogenic type of POTS things like Wellbutrin may help, I don't know. But if you have the hyperadrenergic type, where you already have too much circulating norepinephrine, then Wellbutrin could likely make the condition worse! I sure wouldn't want to try it!

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I believe if you have the neurogenic type of POTS things like Wellbutrin may help, I don't know. But if you have the hyperadrenergic type, where you already have too much circulating norepinephrine, then Wellbutrin could likely make the condition worse! I sure wouldn't want to try it!

Official guinea pig here. I do believe that's the type of POTS I have the hyperadrenergic type. I really got sooooo much worse in that year and a half before I got my POTS diagnosis and stopped all those medicines. I thankfully stopped the meds. a few months before I went to Mayo. I think that would have messed my test up even worse. I was mis-diagnosised and mis-treated. Trial and error, she was at least trying to help.

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Thanks again, everybody. Overlooked the note on dibenzyline causing pooling, so THANKS for that info.

Started the methyldopa today. My bp dropped to 160/100 but I immediately fell asleep. Woke up three hours later and my BP is now 187/99 sitting, so not any help at all SO FAR. Takes a week to see full effects supposedly.

Fire, the comment on the IV is a crucial observation. The hospital refused to give me an IV until Tuesday. They did such a sorry job of getting a vein that the IV needle was in the crux of my arm and it took seven hours (!) for me to get 500 ml. Not enough.

Thursday a.m. I had 700 ml IV in the morning. Seems to be gone already (it is Saturday morning).

Now I have burning, nerve-damage-ish pain in my right arm and shoulder, like a shingles infection that didn't break out. I can only use my right arm and shoulder for about 10 minutes without having to stop from the severe pain. Have NO IDEA how this is connected unless it is a shingles breakout precipitated by high bp.

Significant chest pain, but the cardiologist of last record (lol) said that as I passed a treadmill test, the pain is not cardiac, even with bp over 200. Say what?

Good weekend to all and thanks again - arm giving out. Elegiamore

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