[soccertese]

i take regular cabidopa/levodopa and the CR version, about 150mg every 3hrs and stop taking meds around 6pm.
lately seem to be doing pretty well in the morning but wearing off in the afternoon. cognitive function affected the most, tough to put my thoughts together, motor skills not affected as much, increasing my dosage doesn't seem to help, just have to suffer thru it and repeat the cycle with sleep fixing the problem. food might be a factor but have fasted and still get the same result. i'm reluctant to add more drugs, agonists make me too sleepy but they did help my motor problems.

just strange how it works so well up until about noon and then peters out.

[reverett123]

Originally Posted by soccertese

i take regular cabidopa/levodopa and the CR version, about 150mg every 3hrs and stop taking meds around 6pm.
lately seem to be doing pretty well in the morning but wearing off in the afternoon. cognitive function affected the most, tough to put my thoughts together, motor skills not affected as much, increasing my dosage doesn't seem to help, just have to suffer thru it and repeat the cycle with sleep fixing the problem. food might be a factor but have fasted and still get the same result. i'm reluctant to add more drugs, agonists make me too sleepy but they did help my motor problems.

just strange how it works so well up until about noon and then peters out.

My experience has been similar to yours and I have figured out a few things but much remains. First of all, the problem is not a "steady state" that we can deal with just by sticking to a schedule. Like you, I do my best in the morning. Up until I eat I do fairly well, but once I break fast I have to stay on my toes. I am on a two-hour interval with a single CR tab plus a single 10/100 tab available at my option each time. If I am not up to speed at a given interval I may take both or if I am rolling then I may skip both. That gives me maximum flexibility.

Gastric transit time can vary greatly and be a real pain in the ***. There has been published work showing that rhubarb root, ginger, and fish oil keep things moving so you can predict things a bit better. Check Medline and let me know if you find something else. There are a lot of things that slow it down but darned little that speed it up.

IMHO, it is best to take enough Ldopa to keep things working and to avoid stressing the system. Above all I want to avoid falling back into the Trench of Doom and go "off" as it takes half a day for recovery.
-Rick

[soccertese]

i have experienced that "trench" too, not fun.
food has always affected my absorption but not until recently has just taking 50 or 100mg not helped and gotten me back to tolerable. could be gastric emptying but i have fasted and still experienced this reduced effectiveness, still could be gastric emptying, can't wait for inhaleable l-dopa, quick way to diagnose the digestive system as a factor.
or even those apomorphine oral strips when they come out, hopefully a quick fix to get over a hump?

certainly curious what this might be if not gastric emptying, and i'm not really off physically but mentally, so something else might be going on.

in the "parkinson's disease treatment book", to paraphrase:
"if you are doing well 1hr after your dose, 2 hrs if taking CR, then you have the correct dose.. you can raise the dose by 1/4 to 1/2 tab increments until you find the dose that works if CR, increase by 1/2 tab.. once you have figure the dose then you can address how often. rarely sees any benefit from higher than 300mg (!!) except taken close to meals. ceiling dose of 25/100CR tab is 4 tablets!!

when you find the dose, calculate how long it takes for the dose to kick in and how long it lasts, then reduce the interval between doses so the effects slightly overlap..

better to shorten time between doses than increase the dose size.

the book goes into taking 1/2 more tablet before meals, drinking a lot of water with each dose, sugar can help but doesn't recommend. and says mysteriously sometimes advanced pd'ers just have a bad day.

[reverett123]

I hesitate to find out, but I can't help but wonder if glucose handling problems might have a role? Particularly if we are using Ldopa as our mainstay.

There is a "charming" phenomenon called hypokalemia where one's potassium flees the serum and seeks refuge within the cell. It is triggered by insulin just like glucose uptake. You might find it interesting. Visit
http://periodicparalysis.blogspot.com/
and remember that this is just one of a number of variants. It could explain the puzzle of the Trench since it is transient and tied to eating. But sudden, vigorous exercise halts the process!

[aftermathman]

Originally Posted by soccertese

i take regular cabidopa/levodopa and the CR version, about 150mg every 3hrs and stop taking meds around 6pm.
lately seem to be doing pretty well in the morning but wearing off in the afternoon. cognitive function affected the most, tough to put my thoughts together, motor skills not affected as much, increasing my dosage doesn't seem to help, just have to suffer thru it and repeat the cycle with sleep fixing the problem. food might be a factor but have fasted and still get the same result. i'm reluctant to add more drugs, agonists make me too sleepy but they did help my motor problems.

just strange how it works so well up until about noon and then peters out.

I have found taking a high dose of 175 mg stalevo at 7am really gets me going well, then 100 mg at 10 am and 12 am.

From there I pretty much wing it, I take stalevo 100 and stalevo 75 and I tend to take the 75 in the afternoon as it hits the tremors but has less chance of dysks.

Sorry I cannot help more, I guess my revelation was that starting the day on a high dose (175 mg) and then attempting to just "surf the wave" by taking a reduced stalevo dosage (75 mg) in the afternoon does for me.

Hope you work something out, cannot believe how trial and error this drug regime really is.

Neil.

[Conductor71]

Hi Guys!

If you are up for sharing, how much of your day is spent "off". I am hyper vigilant of not letting myself go "off" for same reasons as you. I find that I get trapped in this almost on fugue where my motor ability is almost normal but my brain all goes fuzzy and shuts down everything else other than turning on. Gee, that sounds nothing at all like drug addiction, right? :P

This used to be the norm for me, but I can add failed dose the mix. This is on straight Sinemet and Requip XL. (amantadine too). I dose the Sinemet similarly to Rick. This leaves me functional 70%, but I cannot predict any of it anymore.

I have found adding Comtan to really help quite a bit. On a good day it might extend my levodopa by an hour but mostly I benefit from it giving 90% + smooth ons. I like taking it as its own med because I can use only half and better control dyskinesias. It sounds like since this is just at certain times that it might work as a booster. It works well for me.

You might instead or first try adding l-tyrosine supplementation. I did that instead for awhile, but it did not work as well as Comtan. My neuro was okay with it.

Here is how the entacapone (Comtan) works:

When administered in conjunction with dopaminergic agents such as L-DOPA, entacapone prevents COMT from metabolizing L-DOPA into 3-methoxy-4-hydroxy-L-phenylalanine (3-OMD) in the periphery, which does not easily cross the blood brain barrier (BBB). Pharmacologically, entacapone is somewhat similar to carbidopa or benserazide, in that it is an inhibitor of an enzyme that converts L-DOPA into a compound that cannot cross the blood brain barrier.

-Wikipedia


Laura

[soccertese]

hi laura,
interesting that we both separate "ON" into mental and physical. i haven't tried COMTAN, with my IR/CR l-d0pa combo, i'd say i'm physically on - can drive a car, ride a bike, type - as long as i take my l-d0pa on schedule.
like you, i often get mental funks in the afternoon where l-dopa just doesn't help.
the "funk" manifests itself mainly thru trouble getting my thoughts out. so hard to measure that in terms of 'ON", i'd estimate i'm mentally off a little bit most of the day. i admit kind of a vague reply.

[reverett123]

Laura-
On a good day I will be "ON" about 80% of the time. That means that I stay home, unplug the phone, the Wife is out for the day, the politicians have resigned en masse, etc. I can occassionally hit 100% with a fair wind blowing warm out of the South over my shoulder. When Life is going on the number is more like 60% to 70% with the spread being between slow mornings or slow afternoons or slow evenings. This takes a lot of med-awareness with a check every two hours. But it seems to be working for me. I currently am on the following schedule-
6:00 AM Get up and have a 10/100 and a 200 CR (net 150 mgs); total 250 mg;
8:00 AM Have a 200 CR (150 mg); 10/100s are always an option; total 150 mgs;
10:00 AM Have a 200 CR.

Note that this is when I am most at risk of going "OFF" and it is eather strange. I am still investigating it, but it seems for all the world as though it is tied into the observations we made when they accidentally left those gluccometers in reach of we chimps.

Originally Posted by Conductor71

Hi Guys!

If you are up for sharing, how much of your day is spent "off". I am hyper vigilant of not letting myself go "off" for same reasons as you. I find that I get trapped in this almost on fugue where my motor ability is almost normal but my brain all goes fuzzy and shuts down everything else other than turning on. Gee, that sounds nothing at all like drug addiction, right? :P

This used to be the norm for me, but I can add failed dose the mix. This is on straight Sinemet and Requip XL. (amantadine too). I dose the Sinemet similarly to Rick. This leaves me functional 70%, but I cannot predict any of it anymore.

I have found adding Comtan to really help quite a bit. On a good day it might extend my levodopa by an hour but mostly I benefit from it giving 90% + smooth ons. I like taking it as its own med because I can use only half and better control dyskinesias. It sounds like since this is just at certain times that it might work as a booster. It works well for me.

You might instead or first try adding l-tyrosine supplementation. I did that instead for awhile, but it did not work as well as Comtan. My neuro was okay with it.

Here is how the entacapone (Comtan) works:

When administered in conjunction with dopaminergic agents such as L-DOPA, entacapone prevents COMT from metabolizing L-DOPA into 3-methoxy-4-hydroxy-L-phenylalanine (3-OMD) in the periphery, which does not easily cross the blood brain barrier (BBB). Pharmacologically, entacapone is somewhat similar to carbidopa or benserazide, in that it is an inhibitor of an enzyme that converts L-DOPA into a compound that cannot cross the blood brain barrier.

-Wikipedia


Laura

[soccertese]

since people getting a steady blood concentration of l-dopa via a duodopa system have less off times, have to assume dopamine receptors get densensitized by the fluctuation l-dopa, maybe it's just the brain's normal response to high levels of dopamine since our nigral cells are no longer storing dopamine and other areas of the brain are being used to affect our muscles?

keeping in mind less than `10% of l-dopa gets to the brain this doesn't seem like a lot of l-dopa.

that's just a wild guess but you can go back 30 years and read about the "off" problem likely being solved by a long lasting l-dopa, and wonder if DBS therapy has put a damper on companies wanting to develop drugs that extend the "ON", which is why you get only small companies working on it and an IMPAX labs that can't get FDA approval for RYTARY because of unacceptable mfg'ing facility in calif.

[johnt]

soccertese,

You mention that levodopa works well "until about noon" and "repeat the cycle with sleep fixing the problem".

IMHO this strong diurnal relationship suggests that melatonin may be playing a part in your problem.

"Melatonin ... is a naturally occurring compound found in animals, plants, and microbes.... In animals, circulating levels of the hormone melatonin vary in a daily cycle, thereby allowing the entrainment of the circadian rhythms of several biological functions." [1]

"In patients with Parkinson's disease (PD), MT1 and MT2 expression declines especially in the substantia nigra and the amygdala." [2]

Hardeland [2] lists a wide range of symptoms.

References

[1] http://en.wikipedia.org/wiki/Melatonin

[2] "Neurobiology, Pathophysiology, and Treatment of Melatonin Deficiency and Dysfunction"
Rüdiger Hardeland
ScientificWorldJournal. 2012; 2012: 640389
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3354573/

John