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Subject: When to start PD Medicines Hello all: Continuing the debate with Will A Kuipers, Re email dated 6 Oct. Hello Will, A couple of points are worth making: On and Off symptoms are generally only really noticeable in the later years of PD. In the early years the story is more like a slow progression from a condition where the tablets are coping effectively, to one where they are not. The other characteristic which is linked with later years is diskinesias (Or random uncontrolled movements). These are caused by an excess dose of Levadopa. It is, as far as I can tell, the only negative side-effect associated with levodopa (Apart from slight nausea which affects some people.) An interesting point is that if you gave a normal person a large dose of levodopa, the effect would be: Nothing !! Yet if you gave the same dose to a person with PD, they would get these wild diskinesias. The reason is that a normal person's brain has a dopamine production system which can regulate itself so that only the precise quantity required by the brain is produced. Faced with an infusion of levodopa from outside, the brain mechanism just shuts down enough production capacity to cancel out the tablet. The brain of a PWP has insufficient capacity for producing dopamine (You only get the first symptoms when more than 80% of the normal brain's dopamine production capacity has died off.) As time passes, and more brain cells die, so we become more and more reliant on the externally- provided levodopa. For the same reason, the amount of levodopa required to cause diskinesias becomes less and less. So eventually we arrive at a point where we cannot tolerate the amount of levodopa required to relieve the tremor and muscular stiffness, because it produces diskinesias. ( This is where other drugs can help, but that is another story). If you have managed to follow my ramblings, you will see why I say that the point at which the levodopa becomes a liability rather than a help has nothing to do with the levodopa itself; it is due to the continued decay of the area of the brain called the Substantia Nigra, which is precisely what Parkinson's Disease is. I agree with you that too many doctors have their own favourite drugs, and I believe that the same goes for neurologists (not all of them of course. In the 17 years that I have been attnding the Neurology Clinic at my local hospital, I have seen a variety of neurologists come and go. Generally we reach an agreement that they recommend a course of action, but I decide whether to accept their recommendation. one thing that gets me really steaming is the patient who passively accepts everything that the doctor says, in the belief that he is some sort of infallible genius who must not be annoyed. Remember: Neurologists are just people!! Re your comment that you are generally the same throughout the day, does that mean you feel good all day, or bad all day ? If you feel good all day then fine: don't knock it. You could try reducing the drugs ( Always worth a try), but I think you will rapidly find out why you are taking the drugs. If on the other hand you feel bad all day, the answer is simple: You are not taking enough levodopa. It does not work in a linear fashion. What I mean is that you can take say 50 mg per hour of levodopa (This is in my view the best way to describe dosages) and get no noticeable effect, and then raise it to say 60 mg/hr and suddenly feel absolutely great. As I wrote at the start of what was to be a short note, this is another aspcect of PD which gets more sensitive as the disease progresses. I hope that has been of some use. Regards, Brian Collins