WHH's Primer on

SINEMET

--THINGS I DISCOVERED OVER THE YEARS (ONLY SOME OF WHICH WERE TOLD ME BY
DOCTORS)

     Disclaimer:  this represents most of what I know or think I know about
the drug Sinemet.  It may not work this way for you.
     In 1999, the chances are that when it comes time to do so, a doctor will
start Sinemet with 25/100 tablets.  Regular Sinemet also comes in 10/100 and
25/250.  Two strengths (25 /100 and 50/200) of time release are also
available.  In both types, the first number is the mg of Carbidopa, the
second, that of L-dopa.
     The object is to get dopamine into the brain.

LEVODOPA (L-DOPA)

    Normal brains convert certain amino acids into dopamine in a series of
enzymatic steps.
     L-dopa readily crosses the blood -brain barrier (dopamine does not),
bypassing the brain's dopamine producing step controlled by tyrosine
hydroxylase--the rate-limiting enzyme in normal and Parkinson's diseased
brains.  L-dopa is converted into dopamine by the enzyme dopa-decarboxylase
(an enzyme little effected in the Parkinson's diseased brain).
     Oral L-dopa is not absorbed from the stomach.
     It is rapidly absorbed (Like giving I.V.) when it reaches the small
bowel.

CARBIDOPA

Sinemet also contains Carbidopa, a drug that binds to peripheral (outside the
brain) dopa decarboxylase to prevent L-dopa to dopamine conversion outside
the brain.  A PWP needs roughly 150-mg of Carbidopa a day.  More than 300 mg
of the drug daily is not recommended.  This is not a totally benign drug to
take in large amounts.

Carbidopa does two things:
     Prevents side effects of dopamine on blood pressure, heart function,
stomach, etc.
    Allows the use of less L-dopa while delivering a similar amount of that
drug to the brain.

SINEMET USE:

SHORT TERM EFFECTS:

    Within a week, new users notice the disappearance of symptoms about an
hour after taking a dose.
     The patient (PWP) soon notices the difference between "OFF"(medicine not
working acutely) and "ON" (medicine working acutely).

LONG TERM EFFECTS:
     When initially started, this medicine tends to build long term
improvement in the "Off" state--often for a period of about six months.
More frequent doses initially lead to better symptom control.  However, more
frequent dosing also seems to speed the onset of side effects.
     Morning "off" improves most The PWP notices the "sleep effect,"
awakening "on," (prior to taking the first dose of the day), and maintaining
good early morning function for about a half-hour.
     However, within a couple of years it usually controls symptoms for a
progressively shorter time.
     One tablet every one and a half hours within six years is neither
uncommon nor desirable.  This usually happens when the PWP attempts to always
be in the "on "state during waking hours

SIDE EFFECTS:

Dyskinesias (uncommanded movements) are the most common, usually most
troublesome side effect.  These are initially mild, but they typically grow
over the course of years from a localized curiosity to a major, uncomfortable
generalized flailing of the limbs and torso
     Dystonia- (uncommanded straining of a muscle or group of muscles) often
responds temporarily to another person shaking the affected limb.  This
resembles a cramp.

MENTAL CHANGES:

     Dopamine addiction: It feels good to transition from off to on.  In
addition, ones mental outlook is chemically transformed from depressed and
uncomfortable to feeling good (often approaching mania after a few years).
     Elevated dopamine levels in one's brain often stimulates heightened
sexuality in many patients.
     Many patients report hallucinating while on Sinemet,

PROTEIN INTAKE--A FURTHER COMPLICATION:

Many report an increase in the time to onset and a reduction in the power of
Sinemet when taken with dietary protein.  This is thought to be due to
competitive inhibition of L-dopa uptake into the brain. The net effect is to
delay and lower the uptake and effect of L-dopa.

The same active uptake mechanism is thought to take in both Sinemet's L-dopa
and certain other amino acids (like those contained in dietary protein).
This mechanism can be overwhelmed or maxed out when the blood contains both.

I believe most expert's agree that it is a good idea to take as little
Sinemet (L-dopa) as possible, while still doing the job.  To do so, various
strategies are employed.
    Take your symptoms to your local friendly movement disorder specialist
for occasional tune-ups

Regards,
WHH 55/38/37