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.

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

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.

Hello,

I am Anne, a french PwP, I was a MD, specialist in gynaecology and oncology surgery before day of diagnosis of own PD in 1999, at 42 years of age.

I have "some ideas" about dopaminergic drugs optimization as,in fact, I have led a huge work on my own, during several years upon the very subject.

In 2001, I had first worked upon mechanisms of drugs addiction and withdrawal troubles as I wanted to confirm my hypothesis levodopa therapy motor complications may present similar mechanisms.
Then with the knowledge I had acquired from excellent works in toxicology and psychopharmacology of reward circuitries, I "naturally" extended then my works upon dopaminergic drugs in nigrostriatal pathways.
I was then contacted by group of frech engineers who had started a manual method for optimization and they asked me to make somthing from it.
I must say all my admiration for al they had done , it was odf great help to me. But nobody inneurology had agreed to listen to them ;
As nothing was referenced in their work and they had no idea about mechanisms, they encourage me to go on. This is how I led new bibliographic research, still on my own, ran a meta-analysis of almost all the international and multicentric essays for each drug, each presentation, each bi-therapy protocol and same with COMT and MAO B inhibitors and have read and worked upon loads of articles upon same subject.
This is how I succeeded after 3.5 years of really tough work to list with scientific references almost all pharmacokinetic data ((Cmax,T max and half life, whole work is about 500-600 references).
Two french neuropharmacologists I met to compare with their knowledge were absolutely astonished to see I had found all the others, and indeed some were not even listed in the US pharmacologists
database at that time, in November2004. A french engineer PwP’s too and working with me in Mediapark the association I have founded in Lyon has then defined mathematics for a computerized application we have now since end of Spring 2005.
-following lines coming soon-

Reverett,
I’m not familiar with the concept of electrolyte imbalance, thanks for the tip. I will check this out.
Amazing: 32 mg of requip a day. To me Requip works quite well, but to a maximum dose of 15 mg a day or to be more specific, 3 mg per intake. If I take more than 3 mg I get serious side-effects.
Ibby,
I agree that the fact that it isn’t standardized is a serious draw back of mucuna. It increases the amount of variables.
As far as I know there isn’t a formulated blend of the two decarboxylase inhibitors.This may be because the two drugs are patented by different companies.
Bezerazide is a component of Madopar (Dutch name) Carbidopa is a component of Sinemet (Dutch name)
How much Amantadine did you add, and did you omit any Requip at the same time?
Anne,
I’m very curious about the rest of your story
Joop

I started w/ a liquid Amantadine and took 1 tsp (50) daily for a week, upped to 2 tsp daily the 2nd week and am now - 3rd week - at 1 capsule (100 mg) daily. This was prescriibed by my local GP Doctor. I'm going to be away for winter and will see a neurologist soon. There aren't any near where I live. I've been 'self-mediciating' for the past 3-4 years. I was doing very well until a year ago when I had a small oops-slip while exercising and experienced an over-night change for the worse. I strongly believe that there is a musculo-skeletal factor with PD.

I was thinking the same re: no formulated blends of ben-carb w/ l-dopa - ie different manufacturers. ($$ issue)

I have not taken requip... Someone - Ol' CS? - recently said that Amantadine is like a mild dopamine agonist. I don't know. Have absolutely NO bio-chemical background/understanding. Can't speak that language!