About medication

As a member of the Science and Ethics group of the Dutch Parkinson association, I had to judge a study that was investigating the usability of a drug made from mucuna pruriens.
The seed powder of Mucuna pruriens has long been used in traditional Ayurvedic Indian medicine for Parkinson-like diseases. The seeds contain levodopa and seemed to work as good as modern medication where ldopa is combined with a decarboxylase inhibitor.

There has been a study (Katzenschlager R J Neurol Neurosurg Psychiatry. 2004 Dec;75(12):1672-7.), but this was not very usable to us because the study has only a very limited number of respondents. Further the main conclusion was negated by an obviously faulty figure that actually proofed that mucuna was the worst alternative while the text stated the opposite.

Still there is something about the mucuna project that I think we can learn from. It is what in recent publications is called the dirty drug concept. A drug composed of different active components may work better than the components separately administered.

In pharmacokinetics three important parameters are used to describe the characteristics of a drug:
- Cmac, which is the maximum plasma concetration
- Tmax or the time to reach Cmax
- Half-life, the time that is needed to reach half of Cmax.

The problem with PD is what they call the therapeutic window. If you take too much medicine you get side effects, if you don’t take enough the symptoms are not controlled adequately. This therapeutic window narrows during the development of the disease. It becomes a problem to keep levels of L-dopa within the therapeutic window.

A method that I use for myself, and that seems to work, is to use a diversity of drugs at the same time. I use levodopa together with benserazide and carbidopa. further I take a dopamine agonist (ropinerol) and I’m planning to use amantadine.

One reason why this concept works is that the medicines I use have different values for Tmax. So the top of the graph is reached at different moments in time. The tops aren’t high enough to cause side effects. An old report (Menek Goldstein a.o http://www.neurology.org/cgi/content/abstract/34/2/227) from the University New York wrote the following on combined us benserazide and carbidopa at Parkinson’s disease:
"The pharmacokinetics of levodopa differs when it is combined with benserazide or carbidopa. Peak dopa levels are higher, occur sooner, but decline more rapidly with benserazide. ..... Benserazide was combined with carbidopa in 38 patients who were experiencing a diminished response to carbidopa, .... Ten of the patients improved on the combination of benserazide and carbidopa, with a 30% decline in disability. .... The combination of carbidopa with benserazide is useful in some parkinsonian patients.

Further the time that is needed to metabolise the drug is considerably different in levodopa and dopamine agonists (Half-life). This spreads the effects of the medication in time.
Another method that in my opinion is equally important is to spread the use of medication evenly throughout the day. By taking less medicine, more often, plasma levels don’t get too high or too low.

I would appreciate some feed-back on this matter. Tell me what is wrong or right in my reasoning. In my opinion patients should actively try and fight this disease. And we have a definite advantage in the fact that we can feel what medication or therapy does to us. Something healthy researchers lack. If you have time please visit http://www.parkinsonhuis.nl/parkinso...estionaire.htm and fill in the questionnaire and become a member of our patients panel. Every six months your symptoms will be recorded. The aim is to find correlations both in symptoms and patients, and eventually to predict the development of the disease.

Have you ever done some experimenting with your medication?
Because sometimes my medication didn’t seem to work I’ve done some tests to find out what might cause this annoying phenomenon.
If I eat a copious meal before I take medication it will sometimes take more than 2 hours before the pills take effect. Sometimes it feels like I haven’t had anything at all.
If I eat a small snack, rich of carbohydrates, right after taking my pills I get the fastest response.
I get a better result if I take my pills with enough water.
The reason for this all is that levodopa is metabolised in the stomach. Sometimes there is not much left over when the medicine has reached the duodenum. It is only here where the Parkinson medication is absorbed in the blood.
Duodopa is administered directly into the duodenum, but a clever patient may not need this for a few years.

Joopoele,

"If I have a copious meal before I take medication it will sometimes take more than 2 hours before the pills take effect. Sometimes it feels like I haven’t taken anything at all."

"If I eat a small snack, rich of carbohydrates, right after taking my pills I get the fastest response.

I get a better result if I take my pills with enough water."

Recently I had started eating a breakfast in the morning just before taking my first dose not realizing what I was doing, and I ended up feeling so sick to my stomach I thought I was going to pass out. To add insult to injury, the medication was taking longer to kick in! This is as you indicated the absorbtion issue with the Sinemet. (Carbo/Levo) So now, after I learned the hard way, I now take the medication on an empty stomach and with plenty of water with no ill effects. This gets progressively difficult through out the day as I consume meals, but I did find that the carbohydrates do help the absorbtion better. I think it's because the higher protein meals tend to stay in the gut a lot longer than the carbs, which burn up quickly.

If I can maintain the empty stomach prior to pill taking, it would be a wonderful thing, but I'm thin enough as it is at 132 lbs (60 kg); down from 147 lbs (67 kg) a few years ago and my doctor wants me to keep eating to bring my weight up. With my increased dose schedule, this has proved to be more difficult.

John

John,
To survive parkinson's disease you must adapt. I now have five light meals, as I have five moments during the day that I take my pills.
It is not as difficult as it looks. Have a light breakfast at eight in the morning, some crunchy stuff at 11 dinner left-overs at 14.00, again some snack at five and dinner at eight. Plenty of opportunities to gain some weight I would say. Strangely I lost two kilo's.
Joop

I am an active experimenter and will share what I can.

First and foremost, because it is current and because it could skew any other results, is the matter of electrolyte imbalence. In my case, a routine physical two weeks ago showed low potassium. I began with just 200 mg and was startled by the effect. Twenty-four hours before, I had ended my day as I had been doing increasingly frequently for two years by crawling to bed at midnight - primarily due to balance and lower leg weakness plus freezing. Less than 24 hrs after the first potassium I walked to bed more or less normally and have not crawled since. Further, I have reduced my Requip dosage from 32 mg/day (too much) to 24 mg/day and Sinemet CR (200/50) from 4x/day to 3x. Also, my blood pressure is under better control and my early morning dystonia in my left foot was missing this morning. Pretty good for two weeks.

Some points about this- 1) Despite my study I made the basic mistake of assuming that I was getting sufficient electrolytes. My neuro seemingly was too. Only my sturdy GP was sensible enough to check the basics. So, beware of initial assumptions. 2) The symptoms of electrolyte imbalance are uncannily like those of advanced PD as are some of the other nutrients (B12 in particular). 3) Since it only required 200 mg to make a difference and the daily amount suggested is 20x that, one cannot assume a smooth curve as things gradually worsen. Instead, there is a threshold effect. In my case, that means that for the last several months and maybe over a year I was slipping above and below that threshold. I would have a bad day for no obvious reason just because my diet had slipped the day before. A difficult situation.

Finally, while one might test this at home, caution is advised. If you have any kidney problems (and don't assume you would know) potassium levels can build up to fatal levels. This is one where you need a doc monitoring you system since your heart can stop.

I'll return to topic in a following post, but keep in mind that some of my data may be screwed.

Mucuna- Ron Hutton and I tested this one somewhat, both the raw powder and a standardized extract form. It definitely worked, sometimes too well (dystonia) in the case of the extract. It is on my list to retry the powder as I, too, see an advantage in "dirty" drugs. Mucuna has a lot more than ldopa in it. The biggest problem was that it stained everything black.

Acetyl-L-Carnitine plus Alpha Lipoic Acid plus L-Carnosine- I have had measurable success with this combination. Purportedly the combo boosts mitochondrial function. In my case, I used a timed balance on each foot to test before and after. As I recall, time on each side increased by a factor of five within 48 hours.

Panax Ginseng - "Red" processing method - Although this one may have been affected somewhat by my potassium problem, at least two others have reported similar results. A definite lessening of symptoms and purported protective action.

I've been taking mucuna powder w/ carbidopa (lodosyn)for about a year and a half and lately have been wondering if I'm taking too little or too much of either or both as 'on' time is getting tricky. I also NOW take a Sinemet CR - which helps smooth things out. Sometimes I take a little Sinemet in addition or instead of the mucuna. Add in the food factor and things are further complicated. Oh, also the Mucuna isn't standardized AND my original source has changed/substituted the product. Too many variables and unknowns.

I had not heard of benserazide. Now I am wondering if there is a formulated blend of the two carbidopas w/ l-dopa since that study showed that some patients benefitted from such a mix in the study. And if not, why not! ??

Two weeks ago I added Amantadine and am seeing some improvements in balance and tremor control and have noticed that I'm not sleeping the same.

I know this whole thing is trial and error (mostly that!) as each person is different but lately I am becoming more befuddled about it all. Feeling quite stupid, really. Just can't figure it out!

Like John, weight loss is a problem. I don't have much appetite but dutifully eat to try to gain/keep what I have. The constant need to regiment drugs and food is maddening. Spontaneity has disappeared from my lifestyle, much to my displeasure.

I will get to your survey when I am able. Too much stuff going on these days so it may take awhile.

Ibby

I have not noted a mention of protein in this discussion. Any protein injested less then 2 hours before taking your SInemet or less than one hour after taking it will greatly diminish its effect.
There is a Scandinavian company that has a duodenum pump that continually
dispenses minute amounts of levadopa into the duodenum. It appears to work pretty well.
My friend Nkki O'Brien, takes liquid sinemet on an hourly basis. That regime works well for her.You cannot even tell she has PD when she is on, which is just about all the time. OFF She needs a wheelchair!

Charlie

The protein problem seems to vary with the individual. Somewhere along the line I read something by Dr. Lieberman saying that only a minority (25% ?) had to worry about it. I do not remember the actual processes involved.

For myself, protein is good. I do much better if I start off with meat and eggs. A couple of possible explanations- 1) Protein provides the building blocks for production of dopamine, so having a surplus helps; 2) Meat is also a good source of potassium, so maybe I was benefiting from that. (You see why this is a mixed blessing. I have to doubt everything that I had thought figured out.); 3) Protein stabilizes blood sugar levels; 4) There may be something to the idea that your blood type relates to your dietary needs.

Regarding the advantages of slow, continuous delivery of ldopa into the system- one of the reasons I want to revisit the mucuna question is to experiment with the water bottle and mucuna mix as a delivery system. The constant spiking of ldopa in the system is not good. Mixing a set quantity into a bottle of water in the morning would allow one to minimize that.

Another factor about mucuna is that for those of us without insurance it sure is cheap. Twenty bucks will last you two to three months.

This brings up a question I have been wondering about. When I was trying mucuna powder, I assumed a certain percentage was ldopa - ten percent as I recall. The literature suggested a range of five to fifteen. Simple math gave me the equivalent to the Sinemet I was taking and the mucuna did, indeed, have a similar effect.

Why? The mucuna had no carbidopa to preserve it against degradation. Why did the simple math equivalent work? What am I missing here? Should it not have been wiped out by enzyme action long before it made it to the brain?

I have been wondering lately (as my sinemet and mirapex don't seem to be lasting as long) which is worse - having variations in the amount of dopamine available OR taking too much sinemet. ie should I increase the number of doses in a day and increase my risk of dyskinesia later but keep the dopamine more level. Or should I put up with the somewhat off periods so I don't have to take so much sinemet, but that will cause whatever problems uneven dopamine causes.

Anne, I'm waiting eagerly for the rest of your post, hoping you have some information that will help me make the most of my present meds so I don't have to change anything. Thanks for all your research.