[AnnieB3]

You wrote:

Thanks, Annie, that helps a lot. So when they talk about the "half-life," they only mean that typically, or on the average, it's at half-strength after three or four hours--but even that varies a lot by patient. And even if it's at half-strength after four hours for a particular patient, it doesn't mean that the strength decreases at a steady rate, before or after. I'm catching on! Thanks for all your help,

Abby

Nope, that's not it either.

Talking about a half-life of a drug is deceptive. Jump in here anytime, Mrs. D.

Mestinon COMPLETELY wears off by four hours. For me, it's done working at the 2-1/2 hour point - that is, 2-1/2 hours after I take it. At that point, my body needs more but I have only been "approved" by my neuro to take it every three hours. And that is EVERY THREE hours, round the clock. Or 8 doses in one, 24-hour day. Theoretically, I suppose some people - like those who are hypothyroid and have a slower metabolic rate - could have Mestinon in their body longer than four hours. But for most people, it's gone in at least 4 hours.

Yes, the strength of Mestinon does vary within that "four hour period." It is not a constant strength. That is why some patients with MG are on Mestinon every three hours or 2-1/2 hours or 2 hours. Again, you can't decide that on your own, it has to be a decision between your and your neuro.

And this makes it even more interesting. If your body needs more acetylcholine, like when it's doing something, it can "use up" that Mestinon even faster. That's why you can get weaker the more you do things. It's a "supply and demand" issue.

I don't know where you are getting the information about Mestinon but I hope others aren't getting the same. When in doubt, contact the drug manufacturer: Valeant Pharmaceuticals. Or hope that your pharmacist knows about it and ask them.

Forget about "half-life" of drugs. Think about the full life of them. The full life of Mestinon is FOUR HOURS. Within that period of time, how strong it is or when it kicks in or wears off is different for people.

With people who are just starting Mestinon, doctors will not often allow them to take it more than every four hours or three or four times a day. They want to see how they do on the drug before they up the dose amount (the number of milligrams) or the dose frequency (how many hours in between they take it). Because it is easy for someone who isn't used to a disease or drug to understand all the parameters and how it works for them, it can be easy for them to overdose. That is called a "cholinergic crisis." That's when you get too much acetylcholine.

When you get too little acetylcholine (to clarify, too little to the muscle), it's called a "myasthenic crisis," because it's not the drug causing the weakness but the disease. Make sense?

That's why the dose Kasper's doc was giving her, the 60/90/60/90 was kind of crazy. Then it's hard to tell when you are getting too much or not enough of a drug.

And to confuse you even more, recent studies show that while the drug Mestinon may wear off within four hours (or less), it's effects can last up to two weeks or more. The effects I'm talking about are not how Mestinon gives you more acetylcholine for four hours. It's the effects on the immune system that seem to last longer. They believe Mestinon actually has a suppressing effect on the humoral immune system that produces antibodies. Not enough studies have been done on this, however, to "prove" that.

There is a natural "checks and balances" system in the body with regards to acetylcholine (ah-seat-ill-co-lean). Normally, the body produces acetylcholine, uses it in the neuromuscular junction and then the little "PacMen" enzyme called acetylcholinesterase (ah-seat-ill-co-linn-ess-ter-ase) comes and eats up the "used" acetylcholine. Since people with MG don't have enough acetylcholine (getting to the muscle), we need Mestinon to "fend off" the enzyme so we can use the acetylcholine longer. Kind of like how there are long lines while you wait to buy a popular movie or book (if you go to a store, instead of on-line). It takes a while for all the acetylcholine waiting in line to help your muscles because there aren't as many "receptor cashiers" to receive it. BTW, my "sounds like" of those words are not dictionary accurate but how they sound when you say them.

Extremes of heat and cold (well, actually, not that extreme), will increase the workings of that little enzyme that eats up acetylcholine. That will overwhelm the acetylcholine and you simply get weaker, no matter how much of it you've taken. I dread the summer months because of that. If you are bad off going into hot weather, you have to be VERY careful not to overheat.

If you have more questions of anyone here, please ask. This is a lot to take in and understand. Not to mention the other issues of drug interactions, relatively contraindicated drugs, what triggers MG to be worse, etc.

I hope this helps. I think a conversation with your neuro is in order too!

Annie

Sorry about the length, guys. I tried to break up paragraphs as much as possible.

[Stellatum]

Annie,

I really appreciate your taking all the trouble to explain this.

I couldn't remember where I heard about the half-life of Mestinon being three to four hours, but that's what I find when I type "Mestinon half-life" into Google. For example:

http://www.medsafe.govt.nz/Profs/dat...estinontab.htm
http://www.flexyx.com/M/Mestinon.html
http://emc.medicines.org.uk/medicine...+60mg+Tablets/ (see 5.2)

However, I do understand that the there are so many variables here that speaking of the drug's half-life might be worse than useless. Thanks for that. I had been worried that taking the drug every three hours, as I've been doing, might make it pile up in my system. That seems unlikely to me now, since I get weak at about 2 1/2 horus after each dose. So your explanation is very helpful to me.

Thank you for the invitation to ask questions! I have some more. Tell me if this sounds reasonable: it seems to me that the Mestinon takes care of two problems for me very well: my double vision, which hasn't bothered me at all since I started the drug; and the side muscles of my neck. My head flops from side to side only when it's almost time for my next dose. However, it doesn't seem to strengthen the back muscles of my neck at all--seems like that gives me trouble without regard to when I've taken the drug. Also, the drug seems to help me not to tilt when I walk or stand, but only somewhat--on a bad day, it doesn't seem to help at all.

Is that possible, or am I definitely imagining things?

Thanks for what you said about the heat and cold. I wonder if my sense that I am better on sunny days is really a matter of warm, not sunny. Our house isn't well heated in the winter (wood stove, big house). I will also remember what you said about the heat, because it's amazing how long it sometimes takes me to put two and two together!

Thanks again, Annie, for taking the trouble to share all this knowledge with us. You're helping me a lot.

Abby

[Stellatum]

Annie, can I ask you another question, since you've been so generous? This is another I-thought-I-understood-but-now-I'm-not-sure question.

My understanding was that we myasthenics produce normal amounts of acetylcholine, but the receptor cells that bind to it are damaged by our immune systems. So although we have normal amounts of acetylcholine, not enough of it is able to get through to the muscles. I was assuming that when the Mestinon allows the acetylcholine to hang around longer, that means the receptor cells we have that are working can do double duty, to make up for the ones that aren't working.

But, I realized I was just sort of vaguely guessing. Will you correct and fine-tune that for me, too? Is it that myasthenics produce what would be enough acetylcholine for a normal person, but not for a person with damaged muscle receptor cells?

Thanks again,

Abby

[AnnieB3]

I'm glad I can help, Abby. There is a lot to know about MG and all the drugs.

Think of Mestinon as having a very short "half-life," if you still want to think in those terms. It can wear off quickly. I just didn't want you to get stuck on terminology but understand how the drug works and when it wears off. Any MG expert will tell you how fast the drug wears off. It stinks. I wish they had the other drug, Monarsen (which I believe they renamed), on the market. It is supposed to last 24 hours.

Mestinon is a "helper" drug. It doesn't do anything to address the immune process that creates the antibodies that attack your neuromuscular junction (with the exception of a couple studies that say Mestinon does suppress the humoral immune system).

Imagine you have a slight pain in your back and a raging headache. You take acetaminophen for it. It will probably get rid of your back pain but not all of your headache. When you take Mestinon, it's sort of the same. It may help the "lesser" weakness or areas that you haven't used as much but it won't help the weakest areas get "all better." Don't ever think MG gets "all better" with Mestinon. Never does. So that is in answer to your question about Mestinon not helping all muscles equally.

Have you ever noticed that when you walk a lot, those muscles are weaker in the next couple of days? Or when you sit at the computer a lot, your neck and arm muscles, and possibly chest wall muscles, get weaker? The more you use a muscle, the more acetylcholine you use up. The more you use up the weaker it gets.

And you don't want to target the weakest muscles for getting better via Mestinon because that's when you can take too much Mestinon and overdose, leading to a cholinergic crisis. That's why so many people have to take Pred or other drugs to do better. Mestinon is useful but it is not going to get you back to "normal." EVER.

This takes a while to get, Abby. You are very new at this. It's been a long time for me and I'm still in denial about what I can't do. No one wants to stop doing what they want to!!!

If anyone else has any other good tips, please chime in.

Just go easy on yourself and try not to do too much.

Annie

[AnnieB3]

I missed that second question.

There are some who disagree that someone with MG has a normal amount of acetylcholine "produced" by the body. Without getting you a bunch of articles, which I really don't have the energy for right now (anybody else?), it has to do with the vagus nerve. Interesting nerve, that one is. And you can't separate body parts, like the nerves and muscles. Sort of a yin-yang situation.

Yes, the reason we don't get enough acetylcholine into our muscles is because the neuromuscular junction is damaged. There are fewer places for the acetylcholine to go into to get to the muscles. Mestinon keeps what we have around there longer so that we can use it, otherwise it gets eaten up by the enzyme. Too much acetylcholine in that area, and you have a cholinergic crisis or signs of an overdose.

It's easier sometimes to talk in more basic terms. I like the fact that you "want more, please!" It's good to really "get" all of this.

I should note that, as Alice has said, there are a lot of things that can go wrong in that neuromuscular junction. They don't know everything about it and have not delineated all of the possibilities. Or all of the potential disease states, which is my opinion.

Thanks for asking me to clarify that. My MG is pretty bad right now and I'm not certain my brain is working properly!! I'll have more coffee the next time I answer.

Annie

[Stellatum]

Annie,

Thanks, this is really helpful. I am going to pay attention to the temperatures in my house for a while, especially.

Thanks for the lead on the articles. I can search through the internet just fine if I know what I'm looking for! Just the lead is enough.

That makes a lot of sense, what you say about the Mestinon helping the lesser weaknesses better. I will take your warning about possible overdose from trying to "dose-up" to the toughest cases.

I hope you feel better soon,

Abby

[AnnieB3]

This might help.

http://faculty.washington.edu/chudler/chnt1.html

This too.

http://users.rcn.com/jkimball.ma.ult...ges/P/PNS.html

The immune system, central nervous system and the body in general are COMPLICATED. One thing leads to another leads to another. Reading about it can drive you batty or it can make you want more. It's all quite fascinating.

[allen L]

annie, I was never aware that extreme heat or cold stimulates acetylcholinesterase.
if anyone is interested, some colleges that offer pharmacy have drug information centers set up. Mostly physicians and pharmacists contact them, but Im quite sure theyd answer anyone about a specific drug.

[AnnieB3]

Allen, It's funny but I only know of a couple neuros who know about this. It's like this biochem info never crossed over with the neuromuscular info. I have to wonder how much information out there about other diseases never gets to those who have them because of how "compartmentalized" medicine/science is.

It's quite helpful for someone with MG to know that extremes of heat and cold can make MG worse!

[Brennan068]

Originally Posted by AnnieB3

You wrote:

And to confuse you even more, recent studies show that while the drug Mestinon may wear off within four hours (or less), it's effects can last up to two weeks or more. The effects I'm talking about are not how Mestinon gives you more acetylcholine for four hours. It's the effects on the immune system that seem to last longer. They believe Mestinon actually has a suppressing effect on the humoral immune system that produces antibodies. Not enough studies have been done on this, however, to "prove" that.

Hey Annie,

Do you have any references for this? From what I understand Mestinon is not an immunosupressant. I like to keep on top of any new information...

Thanks,

jbr