Midodrine vs Droxidopa vs Mestinon

[Gingergrrl]

I know there are other threads on these meds but I am interested in hearing from people who have tried some of these meds, specifically with the goal to raise their BP, and how they compare to each other.

I have been on different doses of Midodrine since the end of Sept and for whatever reason it is not only NOT raising my BP but it seems to be lowering it and makes me incredibly sedated more than a sleeping pill!

Both last Fri and today after taking Midodrine, my BP is back in the 80's/50's making it impossible to function and tomorrow is Thanksgiving (in the US.)

My cardio's office is really pushing this new drug Droxidopa (also called Northera) which just got FDA approval this year (in the US.). They got me onto a list and now the drug rep keeps calling me.

I called back today and she was gone but the person I spoke with said my co-pay was over $800 per month, which not only can I not afford, but I don't even think I want this med! You cannot get this med at a regular pharmacy and it is a big production to obtain. There is some program where you can try it for free and they said I qualify but I have a bad feeling about the whole thing.

I googled Droxidopa and found horrible potential rare side effects which seem to always happen to me. Plus it seems to have no better effectiveness than Midodrine. It also seems to be for a specific diagnosis which I don't have.

On the third hand, several people from PR have now mentioned Mestinon but no doctor has recommended it for me. It is for myesthenia gravis (which I do not have) but seems to also raise BP if I am understanding it correctly.

My BP usually does not drop when I stand, it is just very low all of the time. This week I have had no tachycardia due to changing Atenolol dosing and no chest pain or pressure. I really feel if I could get my BP consistently in the upper 90's/upper 60's I would feel a lot better.

So my questions are for people who have tried Droxidopa and/or Mestinon in order to raise their BP and how this compared to Midodrine (if you have also tried Midodrine.)

I have referrals to 4-5 dysautonomia websites and have a serious goal to read through them or even post on their boards when I am feeling more alert.

But I would love to hear some feedback here from those who have tried these meds.

Thanks very much!

 

[Sushi]

@Gingergirl from dinet/POTSplace:

Mestinon works by inhibiting the breakdown of acetylcholine. Acetylcholine is the main chemical messenger of the parasympathetic nervous system. Some POTS patients may have immune systems that are mistakenly making antibodies that are plugging up acetylcholine receptors (Grubb, 2002). Mestinon works to unplug these receptors by allowing more acetylcholine to remain at the neuromuscular junction. Mestinon is particulary useful in patients who have the postviral, paraneoplastic or autoimmune forms of POTS. Mestinon is usually started at 30 mg orally twice a day, titrating to 60 mg orally twice daily, if necessary (Grubb, Kanjwal & Kosinski, 2006).

You will probably find the most information about these meds from patients on the dinet forum.

I remember that my autonomic doc said that he didn't often prescribed mestinon as it was only helpful to a certain profile of patient. I don't remember what that profile was though.

Sushi

 

[Gingergrrl]

@Sushi thanks and I will look at the Dinet forum. Was your autonomic doctor a cardiologist or from another specialty? Did he or she also have an understanding of ME/CFS and people who had no autonomic problems prior to having a viral trigger? Is that person still in practice? I don't want you to post the name but will ask you later.

 

[Sushi]

@Sushi thanks and I will look at the Dinet forum. Was your autonomic doctor a cardiologist or from another specialty? Did he or she also have an understanding of ME/CFS and people who had no autonomic problems prior to having a viral trigger? Is that person still in practice? I don't want you to post the name but will ask you later.

He is an internist who had to quit his practice due to developing severe POTS after mono. He used to pass out on his hospital rounds! He then went back to medical school to study the autonomic nervous system and now only sees patients with dysautonomia. He is the doc with the southern accent in the YouTube Changes.

He is still in practice, though very part-time as he is on disability. We used to talk a lot about ME/CFS, so yes, he is very familiar with it.

Sushi

 

[Gingergrrl]

@Sushi thank you and I watched part of the video but didn't have time to see the whole thing yet. Can I ask what state or city he is in? I tried to find real autonomic specialists here in CA, but literally could not find one!

 

[adreno]

Overall, acetylcholine tends to lower BP, while norepinephrine raises it.

 

[Gingergrrl]

@adreno, so does that mean that Mestinon would lower BP? I want to make sure I am understanding it correctly. Is Mestinon in a totally different class or mechanism than Midodrine & Droxidopa?

 

[adreno]

@adreno, so does that mean that Mestinon would lower BP? I want to make sure I am understanding it correctly. Is Mestinon in a totally different class or mechanism than Midodrine & Droxidopa?

Yes, and yes. I would expect that it could lower your BP.

 

[Valentijn]

@Gingergrrl - Droxidopa is a precursor to norepinephrine, which I know at least some of us are low in. I think the ones who are high in norepinephrine tend to have both POTS and high blood pressure.

It's a drug pretty much targeted to the types of OI which ME patients are likely to have - neurally mediated hypotension, or neurogenic orthostatic hypotension. It's been used for 25 years in Asia, so should have a good record of its effects there, though it's only just made it into the US market.

It has a very targeted effect, so there shouldn't be much in the way of side effects. It's also designed to cross the blood brain barrier (BBB), which also might (or might not) indicate that ME/CFS patients are less likely to have an extreme reaction to it - one possible theory for those extreme reactions to some meds is that they are crossing the BBB when they shouldn't be. But since Droxidopa is expected to cross the BBB, there shouldn't be an extra effect from that in us.

The main side effects are headaches, tachycardia, and high blood pressure. Those side effects will result from EVERY hypotension drug taken by someone who does not have hypotension, or who takes too much of it to rectify their problem. For example, I get a headache if I take a full dose of Yohimbe (increases norepinephrine), yet a quarter dose is extremely helpful.

Droxidopa is one of those drugs with a lot of potential which I've been following for a while ... I wish it was available years ago. And at a reasonable cost

 

[Sushi]

@Sushi thank you and I watched part of the video but didn't have time to see the whole thing yet. Can I ask what state or city he is in?

Sent you a PM.

 

[Gingergrrl]

@Sushi Thank you so much for the info and I will respond to it later this evening or tomorrow. Hope you have a nice Thanksgiving!

 

[Sushi]

@Gingergrrl

That video, Changes, has a lot of excellent POTS information. Two dys specialists are speaking as well as several patients. I recommend it even if you have to watch it 10 minutes at a time.

And thanks, very nice Thanksgiving. Hope yours was too!

Sushi

 

[xks201]

80/50 blood pressure means either your body is not making enough aldosterone, ADH, cortisol, or thyroid. The likelihood of each scenario is probably in that order. I don't think anything else will do much of anything for anyone with that low of blood pressure assuming you don't have the genetic defect...dopamine beta hydroxylhydroxylase deficiency that requires that droxidopa if I remember correctly. Just trying to help.

 

[Gingergrrl]

@Valentijn

Droxidopa is a precursor to norepinephrine, which I know at least some of us are low in. I think the ones who are high in norepinephrine tend to have both POTS and high blood pressure.

When I was tested a few months ago my norepinephrine level was supposedly normal but I have always had low blood pressure my entire life (and now it is extra low!)

It's a drug pretty much targeted to the types of OI which ME patients are likely to have - neurally mediated hypotension, or neurogenic orthostatic hypotension. It's been used for 25 years in Asia, so should have a good record of its effects there, though it's only just made it into the US market.

I am not sure that I have neurally mediated hypotension b/c I have never fainted (or even been remotely close to fainting) in my life. Without a beta blocker, I get severe tachycardia (up to the 160's and 170's) which occurs in my sleep or when I stand up or do a positional change. It has been labeled "inappropriate sinus tachycardia" and also "POTS" by different doctors. With the Atenolol, the tachycardia disappears 100% but every time I have tried to stop it, it returns.

My other symptoms are low blood pressure that can often be in the 80's/50's but does not drop when I stand, at least not consistently. Sometimes it raises when I stand, sometimes it remains the same, and sometimes drops. I also have been told by every doctor that I have low blood volume. I also get a lot of shortness of breath and had been getting chest pressure/pain but the last few weeks this has, thank God, improved.

As far as Droxidopa being on the market in Asia for 25 years, my concerns here are that it is new to the US and my cardiologist has no experience with prescribing it. He seems to think it is the new miracle drug and is prescribing it for everyone through this special protocol and now the drug reps are leaving me constant messages. I can ask them questions, but their feedback will not be objective b/c they are trying to sign people onto this program. Since there is no generic, it is thousands per month and they said my co-pay would be $836 per month which I cannot pay! I can get generic Midodrine for $5 per month and not sure Droxidopa will be any better.

The main side effects are headaches, tachycardia, and high blood pressure.

I am confident it will not give me high BP as no med has ever really raised my BP, no matter how hard I've tried! The tachycardia is what scares me and is part of why I do not want this med as my tachy is under control with Atenolol. I read the whole packet from my doctor and it has some black box warnings that Droxidopa can cause heart attacks, arrythmia's and neuroleptic malignant syndrome (all three of which can be fatal.) Also, with the program they would be enrolling me in, I would have to take the med per a strict schedule which increases it to a very high dose that I would never tolerate. Unless I were to not follow the protocol and lie but either way it puts me in a weird position.

Those side effects will result from EVERY hypotension drug taken by someone who does not have hypotension, or who takes too much of it to rectify their problem. For example, I get a headache if I take a full dose of Yohimbe (increases norepinephrine), yet a quarter dose is extremely helpful.

Is Yohimbe a supplement and how did you know you needed it? I know your symptoms are different than mine but was just curious?

Droxidopa is one of those drugs with a lot of potential which I've been following for a while ... I wish it was available years ago. And at a reasonable cost

The cost is insane and the amount of hoops I would have to jump through to get it are overwhelming. I wish my cardio had some experience with prescribing it b/c I feel like I would be a guinea pig taking it.

Val, I wanted to add if I sound defensive in my responses re: Droxidopa it is NOT toward you, and is only with the experience that I am going through to find answers!

 

[Gingergrrl]

That video, Changes, has a lot of excellent POTS information. Two dys specialists are speaking as well as several patients. I recommend it even if you have to watch it 10 minutes at a time.

@Sushi Thank you for all the info and I am definitely going to watch the video. I watched about 20 min of it so far and it was excellent.

 

[Gingergrrl]

80/50 blood pressure means either your body is not making enough aldosterone, ADH, cortisol, or thyroid. The likelihood of each scenario is probably in that order. I don't think anything else will do much of anything for anyone with that low of blood pressure assuming you don't have the genetic defect...dopamine beta hydroxylhydroxylase deficiency that requires that droxidopa if I remember correctly. Just trying to help.

@xks201 On most days my BP is in the 90's/60's but maybe once a week dips into the 80's/50's. My aldosterone and cortisol are normal on tests (and I even had the ACTH stim test which was normal.) My thyroid is not normal b/c of Hashimoto's but with low dose Armour Thyroid, all the numbers (TSH, T3, T4, etc) have been in the perfect range for over a year. I still have the antibodies but was told this will be life-long and trying to lower them by being gluten free for almost a full year and about to start Selenium.

Is ADH the same as vasopressin? If so, mine is very low (un-measureable on blood test) and my doctor wants me to repeat this test to make sure it was accurate. I googled the genetic defect you mentioned but the symptoms do not match my experience and I don't think it pertains to me.

 

[Valentijn]

@Gingergrrl - I started taking Yohimbe because a study came out showing that ADRA2A is over-expressed in ME patients following exertion. ADRA2A can inhibit the release of norepinephrine, which is something I've consistently tested low in. So I gave it a try.

Before that I was on Strattera, which is a Norepinephrine Reuptake Inhibitor (NRI) that worked very well, but was ridiculously expensive. Yohimbe is a tree bark, and much cheaper, in addition to being the most potent and specific antagonist of ADRA2A.

I wish you could get more testing to find out exactly why your blood pressure is so low

 

[Gingergrrl]

I wish you could get more testing to find out exactly why your blood pressure is so low

@Valentijn What kind of testing would this involve? I am totally open to it but feel like my doctors have done all the testing that they can think of!

My TTT at the hospital in Sept was a waste of time IMO b/c the entire test was less than 15 min. They couldn't get the IV in my arm for the test (four people tried) so they had to re-schedule me for later in the day and then they were really rushed when I returned.

At one point during the test they realized the blood pressure cuff wasn't even working correctly so they disregarded some of the measurements. I had also been taking Atenolol in the hospital so none of the tachycardia showed on the test. But in the standing position of the test, I felt light-headed, short of breath, dizzy, and very uncomfortable but did not faint and have never fainted in my life.

My cardio said the test was "abnormal" but did not add anything new to what he already knew (which is that I have inappropriate sinus tachy without Atenolol, I have low BP, and low blood volume.) He doesn't understand ME/CFS (and he really has no stigma toward it) he just doesn't know about it.

What tests did you have to determine which type of low BP you had?

 

[Ema]

My aldosterone and cortisol are normal on tests (and I even had the ACTH stim test which was normal.

Most doctors (including endos) are absolutely abysmal at interpreting their most important tests.

It would be interesting to see what your actual numbers are because the "normal" range for cortisol includes a whole lot of frank adrenal insufficiency. A healthy person should have an AM cortisol of 20+. Below 6 is diagnostic of adrenal insufficiency on it's own. Everything in between is basically indeterminate.

If one doesn't start at around 20 on a stim test and double, it's a fail. But most doctors forget about needing to start from a good baseline and just remember the doubling part. And then compound their errors by administering the test improperly (ie not fasting, with multiple sticks, not at 8am, etc).

Aldosterone typically needs to be midrange or higher to be sufficient.

If you have low blood volume, aldosterone is very likely implicated. Did you try Florinef?

How are your electrolytes? Sodium 140-144 and potassium 4.2-4.4? Sodium at 136 is technically normal but I always have symptoms at that level.

 

[Gingergrrl]

@Ema, these are good questions and I will have to pull up my results b/c I had these tests done at different dates and places. But I am curious and am going to post the answers when I get a chance. The saliva cortisol was done by my former ND much earlier in the year (maybe Feb or March?) and then ACTH done in hospital in Sept by an Endo (not my own Endo) and the hospital screwed up part of the test but she said it was still normal.

My aldosterone was done over a year ago (Oct 2013) so not sure what the current result would be. My electrolytes vary a lot but the most recent at the ER was Sodium 137 and Potassium 3.8 which were both considered normal. Only my calcium was quite below normal and I am now supplementing with calcium as of this week (I already take prescription Potassium, OTC magnesium, and salt stick tablets.)

I did try Florinef for three months from my former cardio and it never raised my BP and made me feel worse and gave me headaches/pressure in my head.