Aan 25-01-97 1:25, [log in to unmask] schreef:

> Aan 21-01-97 14:10, in bericht
> You wrote
>
> cipient neck movements and body swaying all reasonably controllable
> although an outside observer might guess that I was having a bad go of
> indigestion!Also more often than not my left leg goes rigid and I find it
> harder to walk than if I had not taken Sinemet.So here is a drug induced
> problem which seems to more or less fit the term diphasic dyskinesia which
> I first came upon in the 'Algorithm for Parkinsons'Disease' a very worthy
> paper published in Neurology and obtainable from our archives.
>
> In the Algorithm the authors discuss the more usual peak dose dyskinesia
> and the narrowness of the therapeutic window and the causes of which Brian
> Collins has described graphically in a number of postings.Then follows
> '
> Choreodystonic dyskinesias are also seen in a second distinct pattern, in
> which these adventitious movements occur just at the beginning and again at
> the end of the levodopa response cycle. This has been termed "diphasic
> dyskinesia" or D-I-D response, a shorthand for "dyskinesia-improvement-dys-
> kinesia"). The end-of-dose period of dyskinesias is typically more prolon-
> ged and troublesome than the initial dyskinetic period of the levodopa
> cycle.
>
> So I find that after getting up at 5.00am I can manage well for several
> hours and then pop a couple of CR 25/1100 mid morning and a couple more
> early afternoon and these will cover me for the period I need to be physi-
> cally active.
>
> All of which brings me to some final points;
>
> 1. I can find no explanation of how this end of dose overdosing occurs.What
> is the mechanism?
>
> 2.  How does all this tie up with the theory expounded so admirably by
> Brian Collins that the therapeutic window narrows with progress of the
> disease. I don't regard myself as far progressed in pd yet as soon as I
> started on Sinemet I began to experience the overdose effects aslbeit not
> during the "on" and this indicates to me that problems with sinemet do not
> always arise just through narrowing of the theraputic window due to progres
> sion of the disease.
>
> Any input would be gratefully received (Back to Basics has my support)
>
> David Langridge
> David
>
> Your second question first. The amount of dopamine you need may fluctuate
> somewhat during the day. A healthy person has always a store of dopamine.
> When the cells in the substantia nigra dissapear not only the ability
> to produce dopamine is diminished, but too the possability to store
> dopamine. When the PD is at the point that no longer enough dopamine can be
> produced he has to take L-dopa. He can take three times a day the same
> amount. The L-dopa arrives in the brain in waves and not in a constant
> flow. This causes no symptoms because next to the possibility to produce
> l-dopa, cells to store it and to let it go the moment one needs it are
> still existing. When the disease proceeds both functions can do their job
> to a lesser extent. The PWP now does not only has to take l-dopa, but  to
> space it too. Taking to much in one time causes symptoms, because the
> dopamine can't be deactivated any more. At the same time a shortage can't
> be compensated for any more.
> So the quantities of l-dopa need more and more fine tuning. The dopamine
> should no longer enter the brain in waves but the variability of the amount
> has to diminish.  This is the narrowing of the therapeutic window.
> You are right saying that you are just a starting PWP. I don't even dare to
> think how I would feel with the same med's schedule, you use.
> So flatten the waves of your med's intake.
>
> Now the first question.
> The story so far is simple.  One can have to much which causes dyskinesia.
> One can have not enough which causes Park. symptoms.
> But how can end of the med's dyskinesia fits into this. I have never found
> an explication about the "mechanism" of this very tormenting symptom.
> A few times people have told me that after heavy drinking and 2 or 3 hours
> sleep they suffer a tormenting sort of restlessness. Wanting to sleep,
> they are very awake and "have to" move. Although they feel tired they can't
> stay in their bed. They walk up and down in their room. The resemblance
> this end of alcohol symptom has to my end of med's symptom is striking.
> Being in my end of med's I have many times been asked: are you cold(I was
> not at all), do you want the window closed or things like that. That is why
> I called it sometimes my cold turkey. The symptoms of the end of med's have
> resemblances with symptoms of junk's who are in need for their next shot.
> Neurofysiologists say (so I read lately) that all those things that cause
> addiction  activate dopamine synapses in different ways. That apply's to
> such different things as amfitamine, morfine and nicotine.
> Maybe there is a common mechanism. Does anybody know more about this?
>
                                                  Ida Kamphuis
                                                       Holland