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