Pyrdostigmine---Mestinon

[akavella]

okay so i have been on midodrine 15mg, 15mg, then 10mg with no luck with raising my bp. avg bp 70-85/40-50. has anyone had any luck with this medicine and did you have any sideeffects? he is going to be staring me on 60mg TID....

thanks

[skiberthoud]

I hope that Mestinon brings some relief to you! If you do a search on here for Mestinon you will come across quite a few posts that may be helpful. It seems as though some benefit greatly from it and others do not. I am someone who responds well to this med. It's actually the only medication I take for my pots symptoms and it makes the difference between not functioning and functioning. I do not have blood pressure issues, so I can't comment on that, but it helps with most everything else. I was started on 60mg tid. I would regularly forget one of the three doses and it was clear that I needed all 3. I switched to the 180mg timespan, which you only take once a day and it seems to work just fine. I have had no side effects from this med. My body loves this drug, now I just want to know why! I hope it brings some relief for you.

[akavella]

i sure hope it works for me also. glad to hear it works well for you...i am hoping i have no side effects from it...i was not able to tolerate florinef...

[heathmcev]

Mestinon has helped raise my BP to be fairly normal (but I also take florinef which deserves some of the credit). I only take 60mg 1x/day. I couldn't tolerate the 180mg timespan - had horrible GI issues. Since you posted about having nausea you might consider a slow start to let your tummy adjust. Mine never did get used to the higher dose, so I get what benefit I can from a lower amount. But do search for older posts as many have commented on successes & frustrations. Good luck - I hope it helps you!!!

[skiberthoud]

See, everyone is different. I had daily nausea and vomiting until I started the mestinon and I stated on the 60 tid, and that is what nearly eliminated the daily nausa and vomiting. There have been some tests I've had that have required me going off med a few days before and the nausea and vomiting come right back. I guess you'll just have to try it to see how it effects you.

[ramakentesh]

Im about to try this medication. I have posural hypertension but also dizziness and reduced blood volume to the brain on standing. Im hoping that since my POTS arrived with and is possibly secondary to another systemic autoimmune illness, it will be helpful - as it seems to be of greatest benefit in these circumstances.

If POTS patients have parasympathetic withdrawal, mestonin is also likely to assist.

[issie]

It wasn't good for me. I felt horrible on it. Everyone is different.

[Neshema1]

I've been on it for a long time with no side effects. In fact, I've decided it's not effective at all. I tend to be very sensitive to medications but cannot find treatment that helps me enough. I think the best thing is saline IVs but they are not very practical. It probably deipends on whether the primary problem (autoimmune, EDS, norepinephrine transport, hypovolemia, etc) can be determined. Mestonn is an acetylcholinesterase inhibitor (the enzyme that breaks down acetylcholine) and is particularly effective for problems involving the parasympathetic nervous system. If your problem is related to issues that involve processes that occur following acetylcholine breakdown, I doubt mestonin will help, but I'm not an expert.

[mwise]

I am on both Mestinon 60mg 3xday along with Midodrine 5mg 3xday. I was started 1st on Florinef alone and had horrible reactions and was taken off of it. Next, I was started on Mestinon which slowly/slightly increased my blood pressure but really relieved my nausea, feeling bloated and helped with my constipation. About 21/2 weeks later, my Cleveland Clinic Neurologist added Midodrine along with the Mestinon which made a world of difference within 2 weeks of being on both for me. I went from being bed, wheel chair & couch bound to being able to walk with a Rollator Walker to walking mostly without the Walker now longer distances, returned to work (I do have a desk job) and doing little chores around the house. I had no side effects from the Mestinon, but do have side effects from the Midodrine-itchy head, skin crawls, goose bumps, feeling cold, parathesia n now & than heart pounds for about 5 seconds. The benefits out way the side effects. I hope the combination will work for you as well as it has for me.

Feel free to email or pm me with questions:)

[TXPOTS]

Dr. Ben Levine (the exercise guy) in Dallas thought the mechanism of my POTS was parasympathetic withdrawal and recommended that I try Mestinon as a next step. I also have postural hypertension (no hypotension) with completely normal catecholamines supine and then after standing and high/ normal overall blood volume. I still haven't taken the leap because I have been feeling much better lately. I'm not 100%, but I am a happy 70%, so I don't want to rock the boat.It may be a good option for select patients.

[sue1234]

So, TXPOTS, if someone is having a problem with the parasympathetic system NOT kicking in and balancing, then Mestinon would help that?

I just looked at the basics of what the parasymp. system does, and I don't think I have one()LOL!

http://www.google.com/imgres?imgurl=http://griffithbiomed.wikispaces.com/file/view/F02_16.gif/35948433/F02_16.gif&imgrefurl=http://griffithbiomed.wikispaces.com/PSynNSRev&h=322&w=377&sz=27&tbnid=qLJPuB5nQYK57M:&tbnh=104&tbnw=122&prev=/search%3Fq%3Dparasympathetic%2Bsystem%26tbm%3Disch%26tbo%3Du&zoom=1&q=parasympathetic+system&usg=__HmrBsePpwV54Rt8lW0JKUzjgdMA=&sa=X&ei=8D2iTfasJdK_0QGF3cn8BA&ved=0CDIQ9QEwBA

Wow, that put a long address. Oh well, if it doesn't work, you can look at any basic picture of what the sympathetic vs. the parasympathetic system does.

I can see in the sympathetic system ALL of our "diagnoses":

1. Eye sensitive to light(due to dilation)

2. Sjogren's(just big word for down flow of our saliva)

3. Tachycardia

4. Angina

5. Gastroparesis(stomach and intestines stop moving)

6. Our odd breathing problems(due to dilated bronchi)

7. For me, pancreas issues and adrenal issues

8. Ummm, "arousal" issues

I am 100% making it on sympathetic and wonder where my para. is??? Now I understand why I can't handle sunlight anymore, as it is soooo blinding to my dark brown eyes(never an issue before). I've always wondered why I felt like I was taking in too much air with a good breath, so preferred to control it by always nose breathing.

So, is Mestinon the go-to drug to make the para. kick in? I will surely ask one of my doctors to give it a try!

[iheartcats]

I'm still on my Mestinon 30mg/ two times a day. I've tried more and less and this seems a happy dose for me.

I think it helps a little. Not tremendously, but if I feel 10% better on it, it's worth it. I had some icky digestive issues for about a week and then things settled down.

[sue1234]

I need serious help with my intestines--I would love to know if Mestinon would help. I read that the para. system relaxes sphincter control. I'm sorry if this is TMI, but I have the hardest time passing gas!! It's like the body won't "relax" and let it pass. And, it works on the other end, too. I get the feeling of needing to burp and it won't come up. I'm kind of thinking that might be why I bloat so much also is the possibility of the small intestinal contents don't move on to the large intestine. All I know is my gi issues are absolutely awful.

[TXPOTS]

Sue- Mestinon may be especially good if you have gastroparesis or slow movement of the GI tract. This is one of the reasons I am opting out of Mestinon for now. I think it's one of those things that you just have to try and judge for yourself.

What I personally don't like about Mestinon is it's broad mechanism of action, especially if POTS is a partial dysautonomia.

[bruc]

Will mestinon help with myopathies of the colon, small bowel, and esophagus?

Sue- Mestinon may be especially good if you have gastroparesis or slow movement of the GI tract. This is one of the reasons I am opting out of Mestinon for now. I think it's one of those things that you just have to try and judge for yourself.

What I personally don't like about Mestinon is it's broad mechanism of action, especially if POTS is a partial dysautonomia.

[TXPOTS]

The approved indication is myasthenia gravis, which as we know may cause profound skeletal weakness.

I don't know if Mestinon is used to treat myopathy of the GI tract, though it definitely may increase peristalsis by ramping up parasympathetic activity. One word of caution Mestinon can actually cause muscle weakness (the very thing it is used to treat). The dose has to be carefully tailored to the patient.

[issie]

Sue,

I'm with you the sympathtic is fully activated and wondering about the para. But, mestinon was the second drug I tried. It made me really angry and agitated - I felt awful on it. Everyone is different. So, you won't know until you try it. My husband said I'd better not take any more - he was on the receiving end of the reaction - poor baby. I've tried so many things. What helps me most for the slowed intestines is Bentyl. A really old drug used for IBS - it's basically a muscle relaxer. Works great for me.

[Kyler]

Mestinon did not improve my son's symptoms and sent us on our first POTS related trip to the ER because it dropped his HR WAY too low. It also gave him muscle spasms, major pooling, diahrrea, and Chest Pain. It took 4 days to build up to this. Perhaps his para is working better than most. It sounds like lots of others have had luck with it - perhaps it helps adults more that kids. Good Luck.

[akavella]

i started it on friday, so far okay, except for it has lowered my hr to 50 from 70-80's...no major problems so far, but no major improvements, i do notice a strange feeling though, i cant exactly pinpoint it yet...i also have noticed my digestive tract seems to be increased..so that is good. i am still having bp drops and nausea associated with that, but not as much nausea all day long. fingers are crossed!

[ramakentesh]

There are some suggested mechanisms of POTS that mestonin would not help at all I think.

I think 41% of POTS patients tested had a good response.

[akavella]

There are some suggested mechanisms of POTS that mestonin would not help at all I think.

I think 41% of POTS patients tested had a good response.

so i am curious...if mestinon helps what type of pots or the root cause do you have? is there a link, like autoimmune etc. is this helping hyperadrenergic pots etc...

[ramakentesh]

They are only speculating as to why it works but the general concensus is that it improves function of the parasympathetic system.

[TXPOTS]

Here is a copy and paste from "Acetylcholinesterase Inhibition Improves Tachycardia in POTS" in the journal Circulation from Raj et al. regarding possible mechanism of action.

The mechanism of the salutary action of pyridostigmine is not entirely clear, but we propose a model based on neurotrans- mission in the autonomic nervous system (Figure 4, top). Acetylcholine is the primary neurotransmitter in the auto- nomic ganglia in both the sympathetic and parasympathetic nervous systems. The parasympathetic nervous system uses acetylcholine again as the neurotransmitter at the postgangli- onic synapse. This results in an inhibitory effect on heart rate. In contrast, the sympathetic nervous system uses norepineph- rine as the postganglionic synaptic neurotransmitter. This results in a direct increase in heart rate and blood pressure (Figure 4, solid lines); however, the increase in blood pressure is modulated by the baroreflex, which leads to a reduction in sympathetic tone, an increase in parasympathetic tone, and a subsequent decrease in heart rate (Figure 4, dashed lines).

In the presence of an acetylcholinesterase inhibitor (Figure 4, bottom), synaptic acetylcholine is increased in the auto- nomic ganglia of both the sympathetic and parasympathetic nervous systems, which results in increased cholinergic transmission in both limbs. At the postganglionic synapse of the parasympathetic nervous system, the augmented level of acetylcholine (due to both increased transmission and de- creased acetylcholine degradation) has a strong inhibitory effect on heart rate. Because the sympathetic nervous system uses norepinephrine as the postganglionic neurotransmitter,

the acetylcholinesterase inhibitor has no effect at this level. There is slightly more sympathetic nervous system traffic (thicker lines) as a result of the ganglionic acetylcholine augmentation. The resulting increase in blood pressure leads to augmented baroreceptor activity, which also contributes to a restraining effect on heart rate. In support of this model, there are recent data that pyridostigmine has been found to increase baroreflex sensitivity in both a murine model22 and in patients with POTS.23

It is likely that the major effect of acetylcholinesterase inhibition in patients with POTS is the reduction in heart rate through augmentation of parasympathetic tone. It is possible, however, that other mechanisms also play a role in the apparent benefit of acetylcholinesterase inhibition. Jacob et al11 have reported that some patients with POTS have a “partial dysautonomia,” with focal impairment of sympa- thetic tone in the lower extremity, which leads to impaired vasoconstriction. Stewart et al6 have shown that intravenous phenylephrine, an -1 adrenoreceptor agonist, acutely im- proved orthostatic tolerance through peripheral vasoconstric- tion in a cohort of patients with POTS. Augmentation of sympathetic tone due to ganglionic acetylcholinesterase inhi- bition might increase peripheral vascular resistance through -1 receptor stimulation. It is tempting to speculate that this “non–heart rate” mechanism may play an important role in the symptomatic improvement seen with acetylcholinesterase inhibition in POTS; however, vascular resistance was not measured in the present study.

The augmentation in sympathetic tone with acetylcholines- terase inhibition has proven clinically useful in patients with orthostatic hypotension. We found that peripheral acetylcho- linesterase inhibition increased blood pressure among pa- tients with autonomic failure in a dose-dependent fashion.8 Singer et al9 reported that pyridostigmine decreased ortho- static hypotension in patients with neurogenic orthostatic hypotension by increasing the peripheral resistance in re- sponse to head-up tilt and consequently improved their orthostatic symptoms.

[ramakentesh]

There is also unpublished work concerning its affects on the nitrergic system.

[skiberthoud]

It does help my tachy trememdously.