It's discussion, learning, and so forth. please do so. Very helpful and now I can narrow down and hopefully soon pinpoint what the scenario actually is.

I hate having discussions with myself......don't you?

oops forgot the main thought - Given the inconclusive data, the potential safety concerns that exist with this class of medications in this patient population, and the lack of FDA approval for this indication (reviewed in Sections V.B.1.a.4 and II.C.5.a.1.a), no specific recommendation can be made in favor of routine use of cholinesterase inhibitors in patients with mild cognitive impairment at this time. Nonetheless, individual patients may benefit from their use.

What isn't clear about this? i didn't check the year of that artcle, but nothing has changed that I know of in the area of ACbE drug development and what follows.....it's all on cholinesterase inhibitors.



paula

Paula and Laura,
My patch is called Kentera, and is one of a string of anti-cholinergic drugs I have tried for PD-related OAB. The others have all been tablets, some of them 3 a day, others 1 a day. The patch differs from this in that it is changed every 3-4 days. From the outset with all of these drugs there have been two main side effects. The most bothering has been brain fog and apathy. The other is increase in joint pain, something that I was prepared to live with if it improved OAB. From the outset my urologist has discussed with me that this class of drugs bring some improvement as a side-benefit for PD, and I would agree with this. These side-benefits are with mobility, smoother faster movement, and less wearing off in terms of mobility, though other wearing off signs are more sudden and acute. With all there was this trade off in terms of pain when sinemet wore off, to a degree that does not happen when I am on just the sinemet/entacapone PD regime I use. Taking the anti-ch pills in the night gave me dystonia so I took them in the morning instead, and it resolved. The difference between them and the patch is that it is active over a much longer period. I am now experiencing acute wearing off dystonia, expecially if I leave it too long between sinemet doses, as TMJ type pain, and nocturnal foot dystonias, and I would also correlate early morning lower back dystonia and internal dystonias with this. All resolve when sinemet kicks in. All I had to a degree BEFORE going on sinemet, i.e. when untreated. None were a problem last year when I spent nearly 4 months off anti-ch meds and only on sinemet. I went onto Kentera because the OAB became unbearable. So my conclusion from this was the same as yours Paula, that when sinemet is at it's lowest there is a corresponding increase in acetycholine DESPITE being on the patch. In other words an imbalance. And perhaps taking this medication means my body is no longer regulating acetycholine naturally?? I don't know how to wean myself off this patch, I cannot split it like a pill, leaving it on longer does not seem to work, by the 5th day I am in trouble, and leaving it off is giving me over heating, nausea, headaches, joint pain and a feeling of being very unwell, similar to flu, I have tried this 4 times, and each is pretty much the same. I did not have the same difficulty with oral anti'ch's, I just weaned myself off gradually over a couple of weeks. I had absolutely no idea that there would or could be an issue. So Laura's info made some kind of sense to me. By the third day of trying to get off I am desperate and whack another patch on because otherwise I am losing too many days not functioning, and to put it bluntly I do not have a practical support system other than my 18 yr old son. I am going out a lot less, because on the patch I have this apathy thing where I am rather unmotivated, and off it continence of both kinds as well as the other awfulness makes being away from home difficult. So until I can get advice from someone who knows I am stuck, i.e. waiting for a urology appointment to come through. I think that the patch must be hitting different receptors from the tablets taken previously, and of course the delivery method is different....

Sorry about the length of this, I have tried to include what I think might be useful. I am also not saying that everyone would feel this way on the same medication. It is my belief that the problems do not occur when there is more acetylcholine per se, but rather when the body is unable to balance it with other nt's,

Lindy

Lindy,

Blech, sorry you have to go through this. It seems with every drug it's one step forward, two steps back.

I found this at at the Net Doctor UK site where it explains how Kentera works:

Kentera patches contain the active ingredient oxybutynin hydrochloride, which is a type of medicine called an anticholinergic (or antimuscarinic) muscle relaxant. It works by relaxing the involuntary muscle that is found in the wall of the bladder.

The muscle in the wall of the bladder is called the detrusor muscle. It can sometimes contract in uncontrollable spasms, and this is often referred to as having an overactive or unstable bladder.

Oxybutynin works by relaxing the detrusor muscle in the wall of the bladder. It does this by blocking receptors called cholinergic (or muscarinic) receptors that are found on the surface of the muscle cells. This prevents a natural body chemical called acetylcholine from acting on these receptors.

Normally when acetylcholine acts on these receptors, it causes the detrusor muscle to contract and the bladder to empty. By blocking acetylcholine, oxybutynin helps the muscle in the bladder wall to relax. This reduces unstable, involuntary contractions of the bladder,

I am confused; however, as to why it would cause "more" dystonia or muscular problems. As an anticholinergic it is in the same league as Amantadine which helps lower our acetylcholine levels. This is why it is prescribed because it helps prevent the bladder from spasms which result in overactive bladder issues.

On the other hand, if your doctor also gave you Aricept for some reason, that is an cholinesterase inhibitor and this increases acetyl choline; thus, in essence canceling out effects of the patch.

So I guess I am in the dark as to how this would make your dystonia worse from a neurotransmitter perspective unless it somehow makes things more off balance. If anything, as you experience more mobility with Kentera, I would think that the anti-cholinergic aspect would play in your wearing off too, that you would have less acetyl choline, unless there is some sort of weird symptom rebound going on? I also don't see much out there on side effects...some do report muscle pain. I wonder if because it is fairly new how there may be some negatives that are relatively unknown. Have you asked your neurologist for feedback?

I'm stumped.

Laura

Thanks for reply Laura, like you I try and keep the equation in some kind of balance, and it does not work out - the only thing that made sense really was that you found some research that seems to indicate that an imbalance could give problems. Anecdotally my PD nurse said that very few are able to take this class of drugs for very long, the effects wear off and the side effects outweigh the benefits by a long way. She also said that we should not be taking these, we meaning PwP. BUT acknowledged that for OAB there is little choice, and that people keep stopping and starting them, because without them they are '-------' and with them they are ' ------'.

I wondered if this was another of those things that like dopamine, give problems both when there is too little and too much that have similarities symptomatically, when altered with medication.

Sorry Paula if this is confusing the issue more, though it seems there is more to this chemical than the empirical 'they' let on, some of the stuff you posted earlier is mind-boggling, why do people make some of these things, what do they eat for breakfast.......

...... another thing that I have wondered about is whether we are particularly susceptible as PwP because of the hit and miss nature of the other drugs we take, it seems like very far from exact science.... only a small percentage of levodopa crosses the BBB for instance, and the rest is floating around our system, giving us nausea dyskinesias, and other stuff, while acetylcholine can hook up almost anywhere, and we are trying to either limit it or increase it - how much levodopa and/or acetylcholine attaches to receptors here and there, hooks up in the wrong way, creates imbalances that our own little chemical sweatshops can't compete with, creating even more mess - and that goes for all the other stuff we have to take to make us feel human.....

Lindy

Here's a helpful site that explains how anticholinergic drugs work. They block acetylcholine receptors. Too much acetylcholine causes muscle contraction as we have learned. Our natural cholinesterase enzyme, cleans up the excess acetylcholine.

From webpage: here's what cholinesterase does naturally

"The transmitter is either broken down by enzymes (10%) and removed or taken back up again into the nerve ending (i.e. recycled) - a process known as re-uptake."

and

" the less dopamine activity you have in the extra-pyramidal system, the more acetylcholine is released in the muscles. Acetylcholine is the transmitter in the synapses of the muscles which make them contract. If you block dopamine in the extra-pyramidal system, you get more acetylcholine in the muscles, so they tighten up. Neuroleptics can thus block your ability to relax your muscles. So, your muscles can't relax and stiffen up and you get stiffness, tremor etc.

Anticholinergic drugs (such as procyclidine, benzhexol, benztropine, orphenadrine etc) block the acetylcholine receptors in the muscles, and reduce the effect of having too much acetylcholine, so your muscles are able to relax;"
------

Now i have to go look up the link again. I have heard that anti-cholinergic meds do not have bad side effects. But Cogentin gave me brain fog. Recently an article did come out saying something about anti-cholinergic drugs causing dementia or cognitive loss. They may know this, but i don't take an anticholinergic for any of the reasons talked about. It relieves my leg weakness that I wonder about coming from too much acetycholine. I was wrapping my legs in ace bandages to be able to hold myself up steady and walk. Nortriptyline takes it away, and other benefits are extra, including an antidepressant function and a nerve pain killer.

lindy your dystonia might be an excellent way of telling if the patch works or not. do you see any pattern to your dystonia? at certain points of your med cycle are you more cramped than others? med changes are very difficult. When merck [europe] began playing with sinemet availability, did anyone even think about how hard it is for pwp to quit or change anything? I am sorry to hear about the withdrawal.... Can you start another med at the same time as you titrate down? Maybe you could google that question.

Cogentin made me feel better than anything [took it before i got the muscle weakness]. I could actually relax [pre-sinemet - i was on eldepryl and maybe mirapex by then. I would take it again....the brain fog might be the lesser of the evils someday.

http://www.nmhct.nhs.uk/pharmacy/moa-proc.htm
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