Two Questions. 1. Drug Tizanidine 2. Norepinephrine Levels

[bustersacc11]

First question.

Tizanidine, centrally acting α₂ adrenergic agonist, has similar properties to Clonidine and Methyldopa. Has anyone tried this drug to treat his or her hyperadrenergic component?

Second question.

In spite of taking clonidine, methyldopa, has anyone had their catecholamine’s rechecked while on these drugs and still had high norepinephrine levels? If so, what was the explanation?

I recently had my levels rechecked while on Methyldopa and Cozaar and my levels are still high. No explanation other than it wouldn’t change the course of treatment.

[arizona girl]

I've taken tiz and it is actually a muscle relaxer with bp lowering mechanisms. With me it knocked me out, you can't stay awake. I would only take it at night when I had bad spasms. It also totally dried out my eyes, nose and mouth, just sucked the moisture out. I already had issues with that and tiz made that worse. Of course meds can behave different with different people. I would not take it simply to lower bp/hr.

Dr. Grubb prescribed me short acting labetalol which is an alpha/beta, he prescribes when you can't tolerate clonidine. I was on that before I saw him and my body had an addiction like reaction to it, requiring more and more to keep me down. Coming off that was frightening. Labetalol can also be tirated up and down as needed. It has worked fairly well, I can still get a break through rise when in an overly animated situation or being upright for more extended periods. I'm on baby doses and my swings have actually decreased since we have been treating the autoimmune and cvid illnesses that caused my small fiber autonomic neuropathy.

Grubb had my cardio check my supine to standing cats. Only did it once my epi was slightly elevated in both positions, my norepi almost tripled on standing. I've not done the test again.

Please consider if your cats were elevated regardless of position that can point to something else like a pheo.

[bustersacc11]

That is what I am afraid of. I am a SAHD and cannot be in a drunk'in stupor, while trying to take care of a my family. I am not using it for spasms; rather, for BP and adrenaline overload. I have a slow HR. Did it slow your HR much?

Neg. for pheochromocytoma. These elevations with my cats are captured upon standing. I would of thought that I would have seen better results.

[arizona girl]

I'm not sure what you mean by SAHD. I'm trying to follow you, are you already on tiz? I don't recall what tiz did to my bp/hr, if anything. It was the clonidine which lowered me and then was causing excessive rebound spikes in bp/hr when it wore off requiring higher doses to keep me down. I've never taken methyldopa or cozaar, so can't help you there. When I was on atenenol which stayed to long in my body I was waking with low bp/hr. My bp/hr always drops when supine, so that med pushed me lower while sleeping. That is why the short acting labetalol works better for me. As an alpha/beta it works in both directions.

I also get a rise in norepi only on standing and talking. In me this is a compensatory result of my blood pooling and my body's attempt to get blood back up to the brain on standing. My blood pools as a result of small fiber autonomic neuropathy. The nerve damage keeps my blood vessels from normal constriction on standing. Norepi also constricts the blood vessels, so it's a back up system.

If you still have elevations in norepi on standing I am not surprised. The medications you've mention treat symptoms not cause. Do you even know why you have dysautonomia? If you have it due to nerve damage, your body will keep shooting off norepi to constrict blood vessels and may even produce more norepi to overcome what the additional medications are doing. That is what happened to me.

Small fiber autonomic neuropathy is often caused by an autoimmune disease and is common with diabetics. Unless you treat the secondary causes of dysautonomia you may not improve. I am currently treating for 3 auto's and an immune deficiency/cvid. My autonomics are improving from just treating those conditions. At times I don't even need to take the labetalol anymore. I'm not cured by any means, nor will I be cured with what is available today. However, we are managing it and I am slowly improving. Without my current treatment plan though I would back where I started.

I also don't understand when your slow heart rate is occuring, so don't know how to answer that question.

[arizona girl]

Hey Rama,

The way you put things is sometimes very confusing. I wish I fit these particular research theories you keep putting out there, others might, but I don't fit them. On tilt and in life I get significant rises in hypertension/tachy on standing, higher then you've mentioned and a continuous rise until supine again. When I do get a hypotensive drop to near syncope it is sudden without warning with dramatic symptoms. Tilt showed I would have continued to drop into asystole, if they'd left me up. I do not get dizzy like you either until I'm already going down to the ground. Normally when I lay down I have huge drops and at times am hypotensive and brady when supine. I never have supine hypertension. I'm not some research test dummy this is what happens to me and has been medically documented. I agree that because I don't have sustained hypertension/tachy and can drop it fast just by lying down, I have not been worried about the consequences of sustained hypertension. However going back forth from one extreme to the other can't be great for the body.

No one even mentioned hyper pots in this post. However Dr. Grubb did diagnosis me as hyperadrenergic in my medical records. I do not find his diagnostic skills and approach to be erroneous. I did not diagnosis myself with that description he did and I have the supportive testing results to prove it. He also prescribed the labetalol to treat that specific response. Which has worked very well for me. I can't get caught up with conflicting research theories, that don't fit me. I can only speak to what works for me and is happening with me. I know that I am not alone in my particular subset of symptoms. There are others like me. Enough to consider us a particular subset form of dysautonomia, whether the researchers have described it yet or not. So, please don't shoot us down the way you do sometimes, it is not helpful.

I think Grubb knows his stuff and is one of the better research experts in this area. As his treatment plans worked for me and makes logical sense I will stick with his opinion in my case. I also have documented autonomic neuropathy by skin biopsy which in my humble opinion is superior to Qsart as that only tests the sweat nerves not the autonomic ones. I also have obvious pooling with change in skin color and swelling. My rise in norepi cats on standing was also lab documented not subjective and went from 400 to 1300, a significant rise.

When I talk about my symptoms and responses they are my symptoms and responses. I don't fit the descriptions that you keep bringing up in regards to this and other related posts you've made on this topic. Also my point to buster is if you are getting a shoot up of norepi on standing because your body is trying to constrict your blood vessels to get blood to the brain, then interrupting that by trying to lower it might actually make your symptoms worse. So I agree trying to suppress norepi might not be effective in symptom relief. I can speak directly to that as it is what happened to me when I was put on extended release inderal. It was horrid, I was a walking zombie and was in complete brain fog.

The good news for me is that we discovered that my small fiber nerves were being attacked due to autoimmune disease and cvid. If you can stop the attack on the nerves and the inflammation they will regenerate and symptoms will improve. My treatment plan which is directed at cause not symptoms has improved my overall health and symptoms. My labs continue to improve and my wide bp/hr swings are much lower now. BTW I was an athlete in great physical condition, when I first got sick, so for me upright aerobic exercise only became a problem when I started having sudden drop attacks. Upright exercise continues to be difficult for me because of that.

My cardio just told me "Right now there is no cure for what you have, so let go of that, we can however manage it by treating the autoimmune disease and other symptoms and hopefully hold off progression of these disease states. However, If we withdraw your current treatments you will revert back to where you were."

I feel very fortunate to be improving, I hope that give others on here hope that they can turn this confounding condition around. You know rama, I have always supported, encouraged and appreciated the way you look into things, even when they don't fit me. I'd appreciate the same kind of support and respect from you. Of course if you could find some research that describes my subset of symptoms I'd love it. Take care!

[bustersacc11]

I am a stay-at-home-dad. Having two very young children I cannot be a wet noodle and dopey. It would not be very safe option. So, I do have some reservations about it being a muscle relaxer and that possibility of making me really sleepy.

I am not on tizanidine. I am exploring the idea of trying it as an experiment. If I try Tizanidine it will definitely have to be in tablet form, not capsule, at the lowest dose. I see it has a really short peak and duration time, which can be good and bad depending on your situation.

For me, when my dysautonomia (I do not have POTS) came on 5 years ago part of my problem was I developed a very low resting heart rate along with a consistently high BP and terrible adrenaline surges. Subsequently, I had a pacemaker implanted. Unfortunately, while it corrected my slow heart rate it did not provide me symptom relief. For me, medications that can cause bradycardia more often than not effect me. My HR pings at my paced rate and basically causes me a drug induced chronotropic incompetence effect. It is not a good feeling. Exasperates my fatigue and tiredness. Very sluggish. Imagine walking up a steep hill all day when you are actually just moving around your house. That is what chronotropic incompetence can feel like.

The BP side of things, I have been trying different meds the past year because I would like some symptom relief with minimal drug side effects. I have been on Methyldopa for 4 years and I feel it has brought side effects that have worsen my dysautonomia even though the adrenaline overload symptoms have decreased. I have weened off methyldopa off and on over the past year to try Toprol, Propranolol, and last month Losartan. All of them controlled my blood pressure, but I still experienced strong hyperadrenergic symptoms, along with side effects from the meds that forced me to abandon these experiments.

Vandy has followed me for 5 years, along with opinions on my case from Mayo at Rochester and Cleveland Clinic. At the CC, the radionuclide study done back 2008 did note that I have marked venous pooling. We have not been able to identify a cause and probably never will. I have had sweat tests done in the past and my results are not consistent so I have been tagged possible SFN. Further, I have had two skin biopsy sent off to John Hopkins for analysis. Both times my epidermal nerve fiber density was within normal limits. However, second bx did show a few medium sized swellings (nothing major). Further, sweat gland analysis on one was abnormal but the other came back normal. I was told that even though my nerve fiber density test came back normal that doesn’t mean they are working right. The nerve damage could be higher up and possibly at the dorsal root. Just can’t tell. I will say the sweat gland analysis interpretation result process is far from perfect. Nerve fibers they can count but what is a normal amount of sweat glands someone should have. I have been told just because they are absent on one punch spot doesn’t translate into an autonomic dysfunction process is going on. Overall, the skin biopsy is useful tool to help diagnose the presence and stage the severity of a neuropathy, but it has shown to have some draw-backs in my opinion.

4 years I put my efforts into a cause and have come up blank. Now, I am trying to get some symptom relief with an effective treatment plan since Methyldopa has some side effects that I don’t like and it hasn’t improved my overall well-being. Really at this point, I don’t even know anymore what tests to ask for to look for a disease or to monitor the progression of a disease that we don’t even know I have.

[ramakentesh]

Also my point to buster is if you are getting a shoot up of norepi on standing because your body is trying to constrict your blood vessels to get blood to the brain, then interrupting that by trying to lower it might actually make your symptoms worse. So I agree trying to suppress norepi might not be effective in symptom relief. I can speak directly to that as it is what happened to me when I was put on extended release inderal. It was horrid, I was a walking zombie and was in complete brain fog.

The good news for me is that we discovered that my small fiber nerves were being attacked due to autoimmune disease and cvid. If you can stop the attack on the nerves and the inflammation they will regenerate and symptoms will improve.

What i was indirectly trying to say. Sorry my response was actually trying to agree with your post but when i read it now its confusing so I will delete it and try again

This is my point. In the past people assumed that only non hyper POTS could be neuropathic - but this clearly is not correct as you have small fiber neuropathy as do many 'hyper' POTS. So how useful is the label hyper POTS if it doesnt really tell you anything about the underlying etiology.

Perhaps a better scheme might be what Dr Freeman and others are suggesting - neuropathic v non neuropathic POTS based on QSART results. There are definately neuropathic POTS with florid hyper presentations.

I think what i was also trying to say was the point that if small fiber neuropathy is resulting in impaired sympathetic autonomic vasoconstrictive control then suppressing sympathetic activity might not be the best avenue of treatment. But there are always exceptions.

Dr Grubb does have numerous publications stating that Hyper POTS is caused by NET deficiency but it isnt that simple.

[arizona girl]

Wow, yes I can see how tough this has been on you. I know that trying to walk upstream in a creek feeling and I don't have a pace maker. We've had some on here who got worse with a pacemaker. Have you had a chance to look at any of Dr. Blair Grubbs research articles? I'm wondering if maybe the labetalol might be something you ask your docs about before trying tiz. It is also short acting and doesn't knock you out. Grubb first line for those with the hyperandregenic symptoms is usually the clonidine, which you tried already right? I couldn't handle it, so he prescribed the labetalol as it is an alpha/beta. I too go high to low and it helps regulate that swinging, without the side effects of clonidine. I really like it as I can take more if I need to and I don't get adverse reactions when I don't take it, like some beta's.

Are your highs and lows related to your posture, or they do it regardless of position? I kinda think that when it isn't triggered by posture change there is actually something else going on other dysautonomia. I get the exhaustion of trying to figure out cause, it took me decades to get diagnosed. Thing is symptom treatment only helped so much and I really didn't start getting real improvement until we started treating the cause of my sfn. I agree with your doc sfn can be hard to pin down, the biopsies need to be done right with punches on the lower leg and hip. Also overtime if done again they can become more diagnostic as things get worse.

If you do try the tiz, I wouldn't do it when you are watching your kids alone, until you know if it is going to knock you out. It usually knocked me out within a half hour of taking it. Everybody responds differently, so that might not happen to you.

I really hope you find something that improves how you feel, so you can be there fully for your kids.

[ramakentesh]

I am a stay-at-home-dad. Having two very young children I cannot be a wet noodle and dopey. It would not be very safe option. So, I do have some reservations about it being a muscle relaxer and that possibility of making me really sleepy.

I am not on tizanidine. I am exploring the idea of trying it as an experiment. If I try Tizanidine it will definitely have to be in tablet form, not capsule, at the lowest dose. I see it has a really short peak and duration time, which can be good and bad depending on your situation.

For me, when my dysautonomia (I do not have POTS) came on 5 years ago part of my problem was I developed a very low resting heart rate along with a consistently high BP and terrible adrenaline surges. Subsequently, I had a pacemaker implanted. Unfortunately, while it corrected my slow heart rate it did not provide me symptom relief. For me, medications that can cause bradycardia more often than not effect me. My HR pings at my paced rate and basically causes me a drug induced chronotropic incompetence effect. It is not a good feeling. Exasperates my fatigue and tiredness. Very sluggish. Imagine walking up a steep hill all day when you are actually just moving around your house. That is what chronotropic incompetence can feel like.

The BP side of things, I have been trying different meds the past year because I would like some symptom relief with minimal drug side effects. I have been on Methyldopa for 4 years and I feel it has brought side effects that have worsen my dysautonomia even though the adrenaline overload symptoms have decreased. I have weened off methyldopa off and on over the past year to try Toprol, Propranolol, and last month Losartan. All of them controlled my blood pressure, but I still experienced strong hyperadrenergic symptoms, along with side effects from the meds that forced me to abandon these experiments.

Vandy has followed me for 5 years, along with opinions on my case from Mayo at Rochester and Cleveland Clinic. At the CC, the radionuclide study done back 2008 did note that I have marked venous pooling. We have not been able to identify a cause and probably never will. I have had sweat tests done in the past and my results are not consistent so I have been tagged possible SFN. Further, I have had two skin biopsy sent off to John Hopkins for analysis. Both times my epidermal nerve fiber density was within normal limits. However, second bx did show a few medium sized swellings (nothing major). Further, sweat gland analysis on one was abnormal but the other came back normal. I was told that even though my nerve fiber density test came back normal that doesn’t mean they are working right. The nerve damage could be higher up and possibly at the dorsal root. Just can’t tell. I will say the sweat gland analysis interpretation result process is far from perfect. Nerve fibers they can count but what is a normal amount of sweat glands someone should have. I have been told just because they are absent on one punch spot doesn’t translate into an autonomic dysfunction process is going on. Overall, the skin biopsy is useful tool to help diagnose the presence and stage the severity of a neuropathy, but it has shown to have some draw-backs in my opinion.

4 years I put my efforts into a cause and have come up blank. Now, I am trying to get some symptom relief with an effective treatment plan since Methyldopa has some side effects that I don’t like and it hasn’t improved my overall well-being. Really at this point, I don’t even know anymore what tests to ask for to look for a disease or to monitor the progression of a disease that we don’t even know I have.

Doesnt sound like fun. Sure abnormal skin biospy doesnt automatically prove you hacve autonomic neuropathy - but it does provide some support for that hypothesis. NET deficiency is another area getting support for POTS in some cases although the lack of tachycardia in your case wouldnt generally suggest that.

[bustersacc11]

Yes, it may support that hypothesis if they are able to get a punch site that captures an abnormal ENFD and/or SGNFD. ENFD is easier quantified than SGNFD. Many variables involved and other things that have not really been sorted out yet to say this is how many sweat glands one person should have.

[bustersacc11]

Arizona Girl,

Yes, I have read many of Dr. Grubb’s articles. He seems to have the reputation of being one of the elite in this sub-specialty. In addition, he is a world-renowned electrophysiologist. I learned that he likes using Biotronik pacer for people with severe NCS since one of the bells and whistles is it monitors BP. He has articles where he has implanted this device for people with severe NCS have shown to have no syncope episodes post-implant. Great stuff.

I asked the Vandy docs this year about switching to Clonidine and they told me that since Methyldopa and clonidine are in the same class of drugs and both have similar effects of reducing sympathetic tone and would have similar side effects they prefered that I stay on Methyldopa. Vandys experience is they have found methyldopa to provide more steady effects. Clonidine option was not recommended. I feel like the minority taking this drug. I have not come across too many people that were prescribed Methyldopa. Overall, it seems a lot of people with a hyper component are prescribed Clonidine first.

Curious. Do you feel getting the autoimmune issues under control and feeling your autonomic symptoms are improving that it could appear your experiencing less side effects with Labetalol than Clonidine or not? Your experience with Labetalol is nice to hear. I am definitely going to mention it.

Right now, I am on so much BP medication they are running around (lying and sitting) 100-110/50-60’s. With a <10-13pt drop upon standing (90-100/50-60’s). When I come off BP medication I run 140-160/80-90’s regardless of position and no drop with standing. Sometimes higher with upright posture. Was documented with TTT. Off meds, I hate the terrible forceful contractions. It is so unsettling. The adrenaline surges can happen regardless of position. When those adrenaline flood gates open for whatever reason it is awful.

That’s why I like DINET. It is such a great repository for information and place to run things by people that can relate and empathizes.

Thanks again for the advice about Tizanidine. I am going back to the Mayo next month for the second time. Pretty soon I am going to have to start weening off all meds. So, before I try Tizanidine or anything new I am waiting to see if they find anything new.

My desperate search for symptom relief is all for my wife and children. They are my key-drivers!

[arizona girl]

Buster,

Well I was on clonidine first with the patch. Had a site reaction to the patch, which never lasted the week it was suppose to. Then I switched to orals and the nightmare began. Didn't last long on it and getting off it was scary. This was long before the labetalol and before I even new that I had dysautonomia and was swinging up and down. I'd gone through about 6 bp meds none of which worked well or caused side effects.

I was on labetalol about 6mos to a year before we finally were able to start treating the small fiber nerve autonomic issues. I did have some history of autoimmune marker's like +ANA and fibro like symptoms. So my neuro felt the sfn was most likely autoimmune in nature, but might be idiopathic. We then started with pheresis and I had rather rapid improvement of autonomic bp/hr symptoms. That response pretty much proved there was an autoimmune base. My neuro and grubb's diagnostics happened about the same time. Getting treatment with the neuro took longer because of insurance and further testing. That is why I was on the labetalol without autoimmune treatment first. So there is no relationship with my symptoms from clonidine and my autoimmune treatments as they were not on board at the same time.

At the low dose labetalol I'm on I've had no real side effects at all before or since autoimmune treatments started. Can't say what higher doses would do. It does have some beta features which can cause weight gain at higher doses. I've had nothing similar at all to what happened with clonidine. The labetalol did improve symptoms but didn't do anything to treat cause. Like an onion ring autoimmune causes finally became diagnostic. When we realized I was immune deficient we switched to ivig and with that I've had symptom and lab documented improvements. I had further improvement when we started treating the other autoimmune diseases. We are still tweaking that plan. I still have fatigue and bouts with painful spasms. Some of which may have due to car accident injuries. I'm working on that now. It has been a complicated and tiring path. Balancing all the specialists is overwhelming at times. However, I am for sure going in the right direction and feel really close to where maybe I will feel normal again.

I don't know much about mdopa, I think that is the research level drug that vandy is using. Are you one of their research patients? Considering my experience with clonidine, your docs might be right with keeping you on the mdopa. A question you were having these adrenal surges and abnormal bp/hr issues before starting the drug, right?

I've never had those surges or maybe I was having them all my life and didn't know it was abnormal, so I was used to them. The fact that you have symptoms that don't change much with posture really points to something else being off. That is not the typical set of dysautonomia symptoms we see. We do have other members who have this happening, most call them adrenal surges, if you want to search the forum for those discussions.

Also with those bp numbers you are right you may be on too much and that can also cause you to not feel right. Have they ruled out carcinoid syndrome yet? We have a member that has that and may have similar symptoms to you.

I agree at DINET I think we get to see a bigger picture of the many things that can be wrong. I'm so happy that you have a family that keeps you going. If we didn't have them it would be easier to just give up on this confounding condition. Then where would we be. It is why I volunteer here. If I can make it easier for someone else, then maybe my difficult path will have some purpose.