Well Here is From My Care Provider in Regards to Mestinon

[MikeO]

Mike,

The mechanism of action of Mestinon is quite complex and I do not think it is entirely understood. I admittedly feel that my understanding, even after considerable literature review, is inadequate. In terms of orthostatic hypotension, Mestinon prevents the breakdown of acetylcholine, which makes more acetylcholine available to increase sympathetic activity in order to compensate for blood pressure drops, while in the upright position. I apologize, this only skims the surface on Mestinon, but that is my attempt to explain why it may be providing you with some symptom improvement.

You have good data to show that your symptoms are worse with elevated blood sugar readings. No need to continue to send updates on that front.

[MikeO]

@Jyotihere is what i promised for a response from my provider as to why pyridostigmine works. At least it is a honest response.

[Jyoti]

@MikeO--thanks for sharing the above.  It is funny because I was looking up the mechanism of anticholinestertase drugs today.  And while I appreciate that your doctor took the time to look into it I think he got only part of the story.  Or maybe he was trying to simplify for you? 

Here is the definition, from Britannica:

Quote

anticholinesterase, any of several drugs that prevent destruction of the neurotransmitteracetylcholine by the enzyme acetylcholinesterase within the nervous system. Acetylcholine acts to transmit nerve impulses within the parasympathetic nervous system—i.e., that part of the autonomic nervous system that tends to induce secretion, to contract smooth muscles, and to dilate blood vessels. In preventing the destruction of acetylcholine, anticholinesterase permits high levels of this neurotransmitter to build up at the sites of its action, thus stimulating the parasympathetic nervous system and in turn slowing the heart action, lowering blood pressure, increasing secretion, and inducing contraction of the smooth muscles.

Also, from the British Journal of Anesthesia/Oxford:

Quote

Vagal influences on the heart are augmented by anticholinesterases. The effective refractory period of atrial muscle is shortened and the refractory period and conduction time at the sino-atrial (SA) and atrio-ventricular (AV) nodes are prolonged. The predominant effect on the heart is bradycardia caused by the accumulation of acetylcholine. This can result in a decrease in cardiac output and blood pressure. Centrally-acting agents may cause these effects by action on the vasomotor centre.

 

Or maybe no one knows?  Another distinct possibility in our world!

But it looks to me like Mestinon lowers heart rate and potentially BP by increasing parasympathetic activity.  You have HPOTS?  I don't.  So it is curious that we both get benefit.

But, look at this: https://www.healthrising.org/blog/2022/05/29/mestinion-chronic-fatigue-syndrome-exercise/  This makes sense in terms of the benefit I get.  I can exercise with Mestinon. Without it, it is ALL will.  I drag my limbs, step by torturous step. With Mestinon, on good days anyway, I can actually move.  (I am less tachycardic as well, overall, but not dramatically so.)

This study finds that it increases not only acetylcholine (or prevents its loss) but....norepinephrine!  How about that for crazy stuff?  And the theory outlined in the above blog post, if I got it right, is that because of SFN, the linings of our blood vessels (smooth muscles) are damaged and thus do not contract properly.  The acetylcholine causes contraction of the smooth muscles of the blood vessels, aided by norepinephrine.  This latter makes the most sense to my not-terribly scientifically oriented mind.

What do you think?

[MikeO]

Hi @JyotiThanks for sharing the material on Mestinon. I kept pressing my Faint Doc on how the drug works as i too have been seeing benefits outside of just the usual OH and have been reporting it to her. Not sure how much she knows about the drug but i am sure she did simplify the explanation.

So no i don't have HPOTS but have/do experience sudden tachycardia when my Blood Pressure drops too low to quickly (never a good outcome). Like you i see a big difference in my orthostatic tolerance (standing) and moving about it's like a light switch was turned on. Without Mestinon i am more fatigued almost like moving around like the hunchback of notre dame (lol) and have some considerable leg pain. My GI issues have been much better as well along with better blood sugar management and diet. I have also seen more stable blood pressures as well and i walk like a normal person now!

The above improved when i titrated up to 30 mg x4.

I have read some of the same material posted as well and makes sense. I did also read that Mestinon helps with the vagal NS tone and favors the PNS by helping some of the verve pathways to fire. I know that my Ranolazine also favors the PNS tone of the heart and helps with diastolic stretch. It has been suggested that Mestinon also Alleviates Inflammation. Kinda want to believe this as my hip pain has improved 10 fold or maybe it's that my muscles are contracting better and pushing out all that blood sugar out of my microvascular system Haha what a thought. sure my hip is feels better as i and standing more proper and taking the stress of of it Plausible?

Yeah i am not very scientifically minded as well but i do get that a damaged NS not firing well or nerve messages getting where they are supposed to go and a over stimulated sympathetic NS plays havoc on the body.

That's all i got. I am sure my doc will out of the blue update what she thinks about Mestinon.

Have you increased your dosage at all?

 

 

   

  

[Jyoti]

22 hours ago, MikeO said:

Without Mestinon i am more fatigued almost like moving around like the hunchback of notre dame (lol) and have some considerable leg pain.

Hahaha!  I get it.  Same here.  It is really amazing what a difference it makes.   Whatever the reasons!  Maybe sometimes you just say 'thank you.'

But it does make me curious about the various drugs and our various responses to them.  Why beta blockers work for some, why vasodilators worth for others, etc.  Maybe one day we (and the medical establishment) will know.

[MikeO]

@JyotiThank You!

[MikeO]

Hey @Jyotii just had a prescription denied by insurance (kinda did panic a bit) so i called insurance and they said the mfg was discontinuing pyridostigmine. Not sure is this means that pharmacy is no longer carrying it or the med will no longer be available on the market (which would be sad for some of us). Pharmacy did fill one more 30 day supply at a cost to me 32 bucks but i am sure that's it.

I don't need to deal with this right now. Just seeing if you heard of anything.   

[Jyoti]

37 minutes ago, MikeO said:

Hey @Jyotii just had a prescription denied by insurance (kinda did panic a bit) so i called insurance and they said the mfg was discontinuing pyridostigmine. Not sure is this means that pharmacy is no longer carrying it or the med will no longer be available on the market (which would be sad for some of us). Pharmacy did fill one more 30 day supply at a cost to me 32 bucks but i am sure that's it.

I don't need to deal with this right now. Just seeing if you heard of anything.   

Yikes.  I am going to refill my prescription then.  See what I learn.  Thanks for the heads up.  That would be sad!

[MikeO]

35 minutes ago, Jyoti said:

Yikes.  I am going to refill my prescription then.  See what I learn.  Thanks for the heads up.  That would be sad!

Please let me know what you find out. I just am hoping this is just a "whatever event" or just a care provider MyChart mistake. but i will find out. My insurance is good to March 2024 

[MikeO]

update @Jyotimy insurance discontinued one of the mfg's that is a supply to my pharmacy for the pyridostigmine and other drugs so they will not pay for it from them. unfortunately pharmacy is out of stock for the mfg that they will pay for. i am sure i will be looking into the rest of my meds as well. 

just hate to find a new source for meds.

[Jyoti]

Oh, that is a drag, @MikeO.  Always something, no?  Is there another manufacturer of pyridostigmine that your pharmacy may restock in future?  

I was going to mention that I ordered a refill myself and encountered no difficulties, so it definitely looks like it is still generally available--the issue is insurance.  What about some of these independent drug discounters like Good RX or Mark Cuban's enterprise?  Might those obtain you the pyridostigmine at a reasonable price?

[MikeO]

29 minutes ago, Jyoti said:

Oh, that is a drag, @MikeO.  Always something, no?  Is there another manufacturer of pyridostigmine that your pharmacy may restock in future?  

I was going to mention that I ordered a refill myself and encountered no difficulties, so it definitely looks like it is still generally available--the issue is insurance.  What about some of these independent drug discounters like Good RX or Mark Cuban's enterprise?  Might those obtain you the pyridostigmine at a reasonable price?

Thanks Jyoti! i will get this insurance paid for. i still have enough to get me by. $32.00 is not that much. i did reach out to my PCP. hope that helps. 

[MikeO]

@Jyotii did finally get my pyridostigmine paid for. took a couple of messages to the university of wisconsin who was the prescriber and they fixed this. side note pharmacy said that the drug is a rare one for them to dispense.

Best, Mike 

[Jyoti]

Good!  Glad you got it and that it was paid for by your insurance in the end.

13 hours ago, MikeO said:

side note pharmacy said that the drug is a rare one for them to dispense

I just refilled and it took almost a week for the pharmacy to get it.  So this seems to back up that statement.   Good to plan ahead!

[MikeO]

last note @Jyoti my Doc did say she had to co-sign to get this to go thru. not sure what that means but does want me to let her if i have trouble getting the drug filled going forward.

[Jyoti]

Ugh.  Good that your doctor is able and willing to do that, but.....such a drag that we have to jump through these hoops.  You find something that makes a difference and then not infrequently, this sort of complication follows.  It really raises questions about pharmaceutical drugs and all  the different interests that control them.

[MikeO]

well @Jyotipharmacy called today and wanted to know if i was still taking pyridostigmine even tho i have a active prescription. i just hope this drug is not going to the wayside. did see there is a newer myasthenia gravis drug coming out in the market.

[Jyoti]

@MikeO--are you talking about RYSTIGGO?   Or is there an orally administered med that is new as well?  I really hope that we can hold on to pyridostigmine too.  As you know, I don't take much, but the other morning, I forgot my dose and wow....about an hour later I started wondering WHAT IS WRONG WITH ME?  Sometimes I wonder, with all the supplements I take, if anything is really making a difference.  I took the pyridostigmine right away and within a half hour was feeling more like myself.  I do not want to lose that edge, and I know you don't either.

[MikeO]

52 minutes ago, Jyoti said:

are you talking about RYSTIGGO?

yes! For some reason not feeling like the med will be easily available in the future. I know i am like you as well if i mis a dose i know it.

[MikeO]

well @Jyotii stopped my pyridostigmine and sure it's for good. i am so sad cause it does help but the side effects (bad stomach cramps and nausea and aggravated GI) finally kicked in and just is not tolerable.. not sure if there was some other trigger but i stopped yesterday and i feel better.

I hope you do better than i have. 

Edit: whatever you, do not eat popcorn

[Jyoti]

Oh no!  @MikeO--I am sorry that it had such nasty side effects for you.  It really seemed to make a difference, but I know some things are not worth the price.  I take so little compared to the recommended dose--somehow I found a sweet spot with no side effects and some intended effects.  I imagine if I could tolerate more, I might have had even bigger positive results, but I am very grateful for the slight boost I get in physical energy.

So for you, the quest continues?  For the needle in the haystack that will help you feel better without making you feel worse?  I think we all know that one....  Wishing you a fortuitous find!