NET question for Sophia, Buddy Lee's Wife, Poohbear

[michiganjan]

Thanks to Buddy Lee's Wife, Sophia, and Poohbear for responding to my question about the NET defect. You all three wrote to me and said basically the same thing.

However I am confused again. I swear my brain has been damaged from so many years of POTS!

Here is a quote from PoohBear:

"The high levels of norepinephrine, if you had them, would tell you to stay away from meds that inhibit the reuptake (such as tricyclic antidepressants, amphetamines, etc). I also find that anything that increases my norepinephrine levels makes me feel horrible and this makes sense to me too."

Okay. Isn't wellbutrin a norepinephrine reuptake inhibitor? And yet Dr. Grubb has put POTS patients on it--he had me on it a few years ago.

Also I just saw him last week and he prescribed Cymbalta, which I understand is a balanced seritonin and norephinephrine reuptake inhibitor in one. So how does this make sense? Wouldn't I want to avoid Cymbalta?

[Sophia3]

Jan,

It has been a few years since I read the paper articles sent to me...and I am not sure what house they are currently in so I can't check them for you.

Basically, if we have problems with clearing norepi levels OUT of our system, the SSRi's have a CHANCE to fix those things in some people. We never really know when the SSRI will jump into our systems and block things so it's all a gamble.

Obviously, some folks get great responses to the meds and continue on them. Others, the gamble doesn't pay off because all our bodies are timed differently and the meds work to different degrees.

So, that is what makes this so complex.

I hope this helps Jan, more than confuses.

[DancingLight]

Good question Jan,

I do find this incredibly confusing. My POTS doc says that I am pouring out too much norepinephrine and epinephrine...

Steph and Sophia...those answers really helped. I'm falling behind on my 'research' these days as I can't read anything! Grrrrrr!

Anyways, I have tried Wellbutrin, Effexor XR and Cymbalta...all act on norepihephrine transmitters.

Jan, I just ended up deciding to stop the Cymbalta after the 7 week trial...I will let you know how it goes off of it (if I don't remember...just noodge me and ask me again!).

It is great for those who they really work for and regulate things, but so far I haven had that success! I liked the Effexor the best, but could only tolerate it at small doses. With Effexor and Cymbalta the norepinephrine aspect does not kick in much until you get to higher doses...you mostly get the action on the Serotonin receptors. As I increased the Effexor I became more agitated and had more insomnia and constipation.

I am currently weaning off of the Cymbalta.

As you know, start with the teeniest dose possible! The 20 mg pills and see how it goes!

I hope it helps you!!!!!!!

Lots of good thoughts and hugs your way...

Emily

[Sophia3]

Jan,

I can NOT find all my articles I got many years ago. I must check the next time I am at my mom's.

A GREAT phone friend sent me about 15 articles back in 1999 or 2000. One of those was on the NET transporter deficiency deal. In the earlier days of NDRF, before they went to the current format, some lady used to post with big words and medical terminology that used to talk about that NET thing alot. I often wondered what happend to her.

If I remember correctly, I read the articles with a medical dictionary close by (ANCIENT one ) and what it didn't have I looked up online.

I also read Dr. Low's Book and one of his books I got thru the medical library from hospital nearby before it closed down! The book was HUGE and out of my league but a blast to look thru and check the index and look up things.. There is also a long out of print book by Dr. Streeten I read, but little of it applied to POTS. BUT it was fascinating to read by a guy ahead of his time with curiousity about the ANS, may his SWEET soul rest in peace! I LOVED HIS TALKS on the NDRF Conference tapes! He was a little befuddled at times but such a sweet spirit....towards the end, he was exhausted and sadly, died, not too long after that conference if i remember correctly. SUCH a dedicated soul to come OUT OF RETIREMENT to get the connection between CFS and ANS but I am digressing.

I do remember when I saw Grubb years ago, he gave out articles but maybe they were only his? My brain can't remember.

Basically the NET deal it was all anecdotcal and extrapolation. But its like spaghtetti sticking to the wall. Some sticks, some doesn't.....The SSRI would hitch it's ride to stop or suppress too much this and not enough that. I been there and tried many SSRI. But the side effects were more debilitating. Especially in the capsules you could not cut down on. (That's why I like scored pills to break down the doses)

Also, I now use the "5 year wait period" to do ANY NEW MED. To check it's safety record and after 15 years, not to be negative but I pretty much am sensitive to meds. I keep baby doses of what works and take as needed...some daily, some rarely. So, I wish I had a sure thing for you Jan, I really do.

With ALL you are going thru, I can only imagine the zig zagging your HR and OI symptoms on.

Take care of yourself. And remember to focus on your breath: BREATHE!!

We had a long over do Native American blessing on my friends house where I live. It was beautiful and the guy was great and like a therapy session for us!! Bang, zeroed in on questions we werent sure we wanted to hear but geez, it was all beautiful in a way. He had me close my eyes alot and talk about fears...he had to keep telling me to BREATHE! I keep holding my breath alot which I know. But this evening turned into pretty Powerful stuff.

Sorry this post is so long, I should've PM'd you. To tired to do over.

I hope you got my other PM earlier.

Sophia

[Poohbear]

This is a confusing topic!!

Not everyone with POTS has high levels of these catecholamines. For those that do, it could be an indication of Hyperadrengic form of POTS.

I have high levels of norepinehprine and testing shows my body doesn't clear it well(reuptake it).

So...what happens in my case, is my body releases norepinephrine, then the reuptake doesn't happen so a message gets sent to the brain to release more norepinephrine because it isn't getting any back and thus thinks there isn't enough there. Then the horrible cycle starts.

I was told by Vanderbilt to stay away from any med that inhibits norepinephrine transport (which includes tricyclic antidepressants). SSRI's I would think would be an individual decision to try.... SSRI's, I believe, inhibit the reuptake of serotonin.

I do know for myself, anything that increases my norepinephrine levels makes me feel horrible!!!

High levels of Norepinephrine (if the test is done correctly which is another HUGE problem in most places) could indicate the hyperadrengic form of POTS. So, if you have high levels of catecholamines then taking meds that inhibit the reuptake or increase the norepinephrine levels COULD make you feel worse or not help.

Personally, I found it very helpful to have the catecholamine tests done correctly. It gave me the "clue" to try the meds that target the sympathetic nervous system (because with hyperadrengic form your body is over responding)

[color=#CC0000]This is taken from the book available on NDRF "Another cause of hyperadrengic orthostatic intolerance is decreased function of the cell membrane norepinephrine transporter, also called NET deficiency. The cell membrane norepinephrine transporter plays a key role in inactivating norepinephrine. Normally, most of the norepinephrine released from sympathetic nerve terminals is "recycled," by being taken back up into the nerve terminals. When transporter is underactive, more norepinephrine is delivered to its receptors in the heart and blood vessel walls for a given amount of norepinephrine release, producing exaggerated increase in pulse rate and blood pressure in situations where the sympathetic nervous system is activated"[/color]

I hope this is helpful and not more confusing!!!

Sorry...it's late and I hope I don't have tons of typo's in this!

Not everyone with POTS has the hyperadrengic form.

[BuddyLeesWife]

Maybe these exerpts will help with the explanation

http://www.pediatricnetwork.org/medical/CF...hannonstudy.htm

Measurements of norepinephrine while lying down and standing up revealed "hyperadrenergic" orthostatic intolerance, meaning that there was an excessing blood level of norepinephrine while standing. Further testing revealed reduced norepinephrine clearance from the blood stream, and impaired increase of blood levels of norepinephrine after administration of tyramine. The authors analyzed the sequences of the norepinephrine-transporter gene and found an abnormality that impaired the function of this gene in the patient and her twin. They hypothesized that this specific genetic abnormality was the cause of the OI and that "Genetic or acquired deficits in norepinephrine inactivation may underlie hyperadrenergic states that lead to orthostatic intolerance."

In a paper written in 1988 the symptoms of CFS were compared to cocaine withdrawal1, which still remains as an excellent model for the illness. Interestingly, cocaine inhibits norepinephrine reuptake, thus acting in a similar manner to the gene deficit described in this paper. It is because of this deficit that patients experience symptoms suggestive of not enough norepinephrine (adrenaline) simultaneously with too much norepinephrine, a paradox, which underlies much of the confusion regarding CFS. It may be that a physiologic mishandling of norepinephrine lies at the root of both conditions.

[michiganjan]

Thanks to you all, I am less confused in one way, and more in another. Dr. Grubb does have me labeled as having the adregenatic form of POTS, yet he put me on Cymbalta and also wants me to try Mestinon. I haven't started either one yet.

I am suffering right not with irritible bowel, so if I try a new med, I won't know what is caused by the med and what is there anyway from stress.

When I have tried Prosac, paxil, and lexapro, they all pushed me into hypomania. I sure did get things done! Wellbutrin made my liver function go up. Paxil made me gain weight like crazy and constipated me terribly, terribly, terribly. So now here is this drug, cymbalta that is balanced. I just can't imagine that it will be good for me if all the other SSRIs I tried were not good for me and if wellbutrin pushed my liver function.

I do have blood test orders to get a liver function test before starting the cymbalta and then at 3 month intervals.

I could try the mestion first, I guess. I certainly can' t try them both at once. However, I would like my iritible bowel to settle down first, so right now I am just biding time and reading, trying to get a grasp on what is the best thing to do.

[Sophia3]

Jan

Have you tried activated charcoal tablets for IBS? If you have cramping it can sometimes help.

Also a friend of mine who sees Dr. Robertson at Vandy got this silly tip. When her stomach starts churning, she takes a Tums and it helps calm down the entire GI tract.

I have tried this myself and sometimes it can nip things in the bud, so to speak. Othertimes I wait too long or don't have antacids in the house.

Dont know if you have tried the above but IBS can really wear a person out. No doubt YOU ALREADY know that!!