Gilbert Doroff wrote:

>I was diagnosed PD in November '65 (age 70)and prescribed Eldepryl and
>Symmetrel (amantadine).  Everything worked very well until a few weeks
>ago I encountered a pronounced swelling of both ankles and feet.  My
>neurologist says that this is not unusual, that the amantadine
>frequently has such an effect.  So he cut back on the dosage of that.
>
>In reading back messages, I cannot find any previous comments on this
>condition and wonder  if others have encountered it.

Dear Group,
I thought it might be helpful to post Alan Bonander's November 24, 1995
comprehensive summary of PD medications. I hope you don't mind, Alan?  I am
posting it in two sections, they are quite long!
AN EXAMINATION OF MEDICATIONS BOTH COMMONLY AND OCCASIONALLY USED IN
TREATING
PARKINSON'S DISEASE

Neal Slatkin, MD

NOTE: This paper is a reprint of most of the City of Hope Parkinson's Center
Newsletter, Moving Forward, Summer 1995. This reprint is with the authors
approval.  The author would like to acknowledge and thank those who reviewed
the paper for content.  The reviewers were John S. Kovach, MD; Matt Kurth,
MD, PhD; Jeff Chapman, PharmD; and Beatrice Decone, PharmD; with editing by
Stephanie Unger and production by Robin Moore.

INTRODUCTION

In this special issue of Moving Forward we are providing an extended
examination of the various medications that have been used by persons with
Parkinson's disease. The purpose is to provide patients and caregivers with
information on these medications as a clarification of the many approved and
non-approved medications which have entered the array of medical treatments
for Parkinson's disease and associated symptoms. The information contained in
this newsletter is not intended as either medical advice to patients on the
use of their medications or as a replacement for information received from
the patient's physician. Patients having questions about their medications
should discuss them with their physicians. Like all medications, those used
in Parkinson's treatment require the regular guidance and monitoring of the
prescribing physician.

Two categories of medications are included in this discussion, as follows:
+ Those drugs intended to treat the primary motor symptoms of Parkinson's
disease, such as rigidity, rest tremor and bradykinesia and
+ Those that are used in treating symptoms frequently associated with
Parkinson's, such as depression, problems with sleep, action tremor,
light-headedness, etc.

For each class of medication three basic pieces of information are provided:
+ A description of its established or possible value in Parkinson's treatment
and its basic mechanisms of action (if known).
+ Some of the possible side effects which might occur when these medications
are taken
+ A description of situations in which the medications should be used with
caution or avoided altogether, situations that are called contraindications
by physicians and pharmacists.

Since this information is intended to serve as a quick-reference resource,
rather than as a comprehensive guide to each medication, only the most common
or serious side effects and contraindications of each medication are
provided. Moreover, although each medication approved for treatment within
the United States undergoes extensive evaluation, new side effects are often
recognized only after a medication has been in use for many years. Any list
of potential medication-associated problems can therefore become quickly
dated as new side effects and warnings are reported.

This review is intended only as a means of enhancing your basic understanding
of medication effects and facilitating communication with your physician.

GENERAL APPROACH TO MEDICATIONS AND PRECAUTIONS

Before leaving your doctor's office be sure that you thoroughly understand
the following:
+ why a medication has been prescribed
+ how and when to take it
+ its possible side effects and contraindications.

Always bring a list of all of your current medications with you to your
appointments. It is also wise to keep an updated list in your purse or
wallet.

Some patients use several different pharmacies in an attempt to minimize the
cost of their medications. In general, it is best to avoid using more than
two pharmacies, including mail-order pharmacies. Some pharmacists can be very
helpful in advising you about your medications by providing information on
medication side effects and potential drug interactions. However, a
pharmacist can only give you good advice if he or she knows the names of all
of the medications you are taking.

APPROVED MEDICATIONS

Before a medication can be sold or distributed within the United States, it
must be approved by the Food and Drug Administration (FDA) as safe and
effective. Not all substances, however, which are promoted or used for
medical purposes are classified as medications, or are subject to FDA
regulations. For example, most substances sold in health food stores have
neither been proven safe nor effective for their various promoted uses.
Further complicating matters, it is common practice in medicine for even
approved medications to be utilized for "unapproved" purposes, that is in
conditions for which they have not been specifically proven safe or
effective.

With the exception of Motilium (domperidone) all of the medications
discussed
in this newsletter are FDA approved. You should understand, however, that
some of these medications have not been specifically approved for the exact
purposes discussed. A number of other substances which are not medications
are also discussed. You are again reminded that these have generally not
been
rigorously tested or shown as safe or effective in the treatment of any
condition.

PREGNANCY AND BREAST FEEDING

Most medications are contraindicated when a woman is pregnant or breast
feeding. Women who are actively pursuing conception, or who are pregnant or
breast feeding must consult with their physician before taking any
medication.

PREVENTING DRUG INTERACTIONS

Whenever you have a new medication prescribed, make sure your physician
knows
the names of all other medications you are taking (including eye drops,
non-prescription medications, special "health" and nutritional preparations,
birth control pills, hormones, etc.). Combinations of medications can cause
problems different from or more severe than side effects of individual
medications. Alcohol use is contraindicated with a number of medications.
Before taking alcohol and any medication, check with your doctor or
pharmacist.

SLEEPINESS

Many medications can cause sleepiness, especially for the first several
doses. Don't plan to operate potentially dangerous machinery or do much
driving within the first several days of taking a new medication.

STOPPING MEDICATIONS

It is usually unwise to suddenly discontinue a medication that you have been
taking for more than a month or two. Suddenly stopping stimulant
medications,
anti-seizure drugs, certain pain relievers, antidepressants, tranquilizers
and various heart medications can lead to potentially severe withdrawal
symptoms. Consult with your physician whenever possible before you stop
taking a medication. If a new medication causes severe side effects, it may
be acceptable to delay the next scheduled dose until you have had an
opportunity to speak with your doctor. Finally, remember that each person is
unique and that your reaction to a medication may be quite different from
that of a friend or relative. If you expect side effects to occur, you are
bound to experience them. Even placebos--inactive sugar pills--can have a
high incidence of side effects, when patients expect or are fearful of bad
reactions.

IMPORTANT INFORMATION
AND DISCLAIMER

The information in this newsletter is provided solely for the purpose of the
general information of the reader. It is not in any respect intended as
medical advice for patients, nor does it imply treatment recommendations of
City of Hope National Medical Center or the National Parkinson's Foundation.
Some of the medications listed are not approved by the United States Food
and
Drug Administration (FDA) for the treatment of Parkinson's disease; and/or
may not be approved for the purposes discussed; and/or may not be approved
for use within the United States. You are strongly encouraged to consult
your
doctor should you have questions regarding these or other medications.


MEDICATIONS USED TO TREAT PRIMARY MOTOR SYMPTOMS

DOPAMINE REPLACEMENT MEDICATIONS

SINEMET (CARBIDOPA/LEVODOPA)
USUAL TABLET SIZES: 10/100 (OFTEN BLUE), 25/100 (OFTEN YELLOW), 25/250
(OFTEN
BLUE)

This is the most commonly used medication in the treatment of Parkinson's
disease and, generally, the most effective. Levodopa is the active
medication
and must be converted by the brain into dopamine in order to have a
beneficial effect. Carbidopa has no direct anti-Parkinson's effect, but
instead facilitates entry of levodopa into the brain by preventing its
metabolism into dopamine outside of the brain. In doing so, carbidopa also
helps prevent some levodopa-related side effects such as nausea, vomiting
and
palpitations.

Sinemet is the brand name of the original carbidopa-levodopa combination
tablet. Many generic carbidopa-levodopa combinations are now available. For
some patients, generic medications work as well as brand name Sinemet; for
other patients, particularly those with troublesome on-off fluctuations or
dyskinesias, treatment with brand name Sinemet may be preferred.

When taking Sinemet for the first time, take it along with food to decrease
the chance of nausea and vomiting. After Sinemet has been used for more than
four to six months, most patients can begin to take it 30 to 45 minutes
before meals. Taking Sinemet before meals ensures better and more
predictable
drug absorption.

SIDE EFFECTS OF SINEMET (LEVODOPA)

+ Nausea and vomiting, as well as vague symptoms of gastrointestinal
discomfort, which usually subside after weeks or months of treatment
+ Constipation that can cause discomfort and may require a change in diet or
a special bowel program
+ A drop in blood pressure, the primary symptoms being those of
light-headedness, dizziness, neck pain and/or increased imbalance
+ Increased sleepiness, particularly following the morning and afternoon
dose
of medication
+ Increased nightmares, hallucinations and confusion during the later part
of
the day or at night

POTENTIAL DELAYED SIDE EFFECTS OF SINEMET (LEVODOPA)

After five years of levodopa treatment, approximately 50 percent of patients
develop delayed side effects. These can vary greatly in severity from
patient
to patient and some patients fail to develop significant long-term effects
even after 10 to 15 years of therapy. Potential delayed side effects
include:

+ Abnormal and involuntary movements: Twisting and dancing movements of the
arms, legs and trunk (dyskinesias) and unusual muscle contractures or
cramps,
especially in the foot (dystonia)
+ Wearing off: A tendency for the benefits of each individual dose of
medication to wear off in a predictable manner before the next is scheduled
to be taken
+ On-off episodes: Unpredictable fluctuations in motor function, not clearly
associated with the taking of medications
+ The potential for long-term complications of carbidopa/levodopa has led to
controversy about when in the course of Parkinson's to start levodopa
treatment. It is appropriate to discuss concerns about such matters with
your
doctor.

CONTRAINDICATIONS

+ Certain forms of glaucoma
Patients should have eye pressures checked at the beginning of treatment and
at frequent intervals after starting treatment.
+ Malignant melanoma
Controversial, but if a patient has a history of melanoma, this should be
brought to the attention of his or her physician.
+ Peptic ulcer disease
Having this disease may also be a relative contraindication.
+ Stopping levodopa
In general, levodopa should be slowly tapered off over the course of several
days. Abruptly stopping Levodopa can lead to a severe syndrome of increased
muscular rigidity, elevated body temperature and increased confusion
(malignant hyperthermia). If these problems develop, they require immediate
medical attention.

SINEMET CR (CONTINUOUS RELEASE CARBIDOPA/LEVODOPA)
25/100 PINK TABLET, 50/200 TAN TABLET

Sinemet CR is a long-acting carbidopa /levodopa preparation that releases
levodopa more slowly into the intestines. This results in more sustained
levodopa absorption, with a longer duration of action and, in general, lower
peak-dose effects. Due to lower peak-dose levels, some patients may not
"turn-on" with Sinemet CR and may need to take regular Sinemet with it,
especially at the time of the first morning dose. Sinemet CR may be broken
in
half, in which case its effects are intermediate between regular Sinemet and
unbroken Sinemet CR. Crushing this medication is not advised, as it
eliminates its slow-release properties.

The four situations in which Sinemet CR is generally used are as follows:
+ Early in the course of treatment, as the initial form of levodopa therapy
+ When "wearing off" problems begin to appear (Sinemet CR can help by
prolonging the duration of levodopa action)
+ When there are predictable peak dose dyskinesias (Sinemet CR can help by
decreasing peak levodopa levels)
+ When there are parkinsonian mobility problems at night. (Sinemet CR can
help by producing a more sustained level of levodopa through the night and
improve sleep. This may also help to decrease early morning dystonia.)

SIDE EFFECTS OF SINEMET CR (CONTINUOUS RELEASE LEVODOPA)

The side effects for Sinemet CR are the same as for regular release Sinemet
discussed earlier. Some older patients may show increased confusion with
Sinemet CR, whereas others will have fewer problems on this preparation.
Those patients who do not "turn on" with Sinemet CR, may need to couple this
medication with a small dose of regular Sinemet. Sinemet CR may precipitate
the appearance of dyskinesias in some patients, or cause an aggravation of
pre-existing dyskinesias.

DOPAMINE AGONISTS

PERMAX (PERGOLIDE), PARLODEL (BROMOCRIPTINE), APOMORPHINE

INVESTIGATIONAL AGENTS: CABERGOLINE, ROPINEROLE, PRAMIPEXOLE

Dopamine agonists are commonly used as adjuncts to Sinemet in treating the
motor symptoms of Parkinson's disease. Drugs in this class stimulate the
brain directly by mimicking dopamine and do not have to be converted into
other compounds. Although generally not as effective as Sinemet in
decreasing
symptoms, these agents may offer the Parkinson's patient other treatment
advantages including: (a) a longer duration of action, (b) absorption which
is generally not limited by the presence of food or protein; and, (c)
effectiveness even when levodopa ceases to be effective (controversial).

SIDE EFFECTS OF DOPAMINE AGONISTS

+ Low blood pressure upon standing, causing symptoms of light-headedness,
dizziness, neck pain and imbalance
+ Hallucinations, confusion, or bad dreams
+ Nausea, stomach upset, constipation and occasional vomiting
+ Ankle swelling, or edema
+ New or worse dyskinesias, though these generally subside with lowering of
the levodopa dose
+ Note: A rare side effect of treatment with some of these drugs is
increased
shortness of breath, caused by scarring around the heart or within the lung.
This complication requires that the patient be promptly tapered off this
medication.

APOMORPHINE

This dopamine agonist medication is no longer being manufactured in the
United States and has not been approved by the Food and Drug Administration
(FDA) as an anti-parkinsonian medication. It is being utilized in many other
countries throughout the world as a dopamine agonist (see description
above).
Unlike other dopamine agonists available in the United States (pergolide,
bromocriptine), Apomorphine can be injected. When administered in this
manner, it has a rapid onset of action. It can be very useful for reversing
off periods and may also be useful for the treatment of various parkinsonian
dystonias. The major side effects of treatment are severe problems with
nausea and vomiting and a fall in blood pressure upon standing. To a great
extent, these side effects can be prevented by taking domperidone. Skin
nodules can form, at frequent injection sites if apomorphine is injected
subcutaneously.

SYMMETREL (AMANTADINE)
100 MG CAPSULES (RED, YELLOW), SUSPENSION (50 MG / 5 CC = TEASPOON)

Symmetrel (amantadine) is most frequently used as an adjunctive agent in the
treatment of motor symptoms. It was initially introduced to prevent
infection
with influenza A virus. After its introduction, however, it was
serendipitously found to have anti-Parkinson's effects. The mechanism of
anti-parkinsonian action of this medication is still unclear, though it may
increase dopamine release or block certain excitatory brain receptors (the
NMDA receptors) and thereby improve movement.

SIDE EFFECTS OF SYMMETREL (AMANTADINE)

+ Nausea, light-headedness, difficulty with sleep, ankle swelling or edema,
hallucinations
+ Anxiety, bad dreams, dry mouth, difficulty with urination and increased
problems of constipation
+ Occasional mottling of the skin (livedo reticularis), which may require
discontinuation of this medication
+ Symmetrel should be slowly discontinued or malignant hyperthermia could
result. (See earlier discussion on stopping carbidopa/levodopa.)

ELDEPRYL (SELEGILINE)
5 MG WHITE TABLETS, MAXIMUM DOSE _ 10 MG/DAY

Eldepryl (selegiline) is a monoamine oxidase type B inhibitor (MAO-B
Inhibitor). Monoamine oxidase is an enzyme used by the brain to metabolize,
or break down, dopamine. Eldepryl often prolongs the effects of levodopa
therapy by prolonging dopamine action in the brain. The metabolism of
dopamine can also cause potentially harmful substances (called free
radicals)
to accumulate in the brain. By inhibiting dopamine metabolism, Eldepryl may
inhibit the production of these substances and thereby have a protective
action.
Eldepryl has been reported to be of value in three situations, as follows:
+ In the early symptomatic treatment of Parkinson's before levodopa is begun
+ For "wearing off" problems, by prolonging levodopa action
+ As a "neuro-protective" agent or "free-radical scavenger" to slow
Parkinson's disease progression (controversial)

SIDE EFFECTS OF ELDEPRYL

+ Nausea, stomach upset, light-headedness
+ Insomnia, especially if taken after 1 or 2 pm
+ Confusion, hallucinations and nightmares (more commonly encountered in
older patients, or those who have had Parkinson's for many years)
+ Occasionally Eldepryl may worsen dyskinesias or cause other side effects
similar to those of levodopa excess

CONTRAINDICATIONS

When combined with anti-depressant medications, Eldepryl can uncommonly
cause
a severe syndrome characterized by increased rigidity, jerking movements of
the arms and legs, agitation, confusion, restlessness, fever, shivering and
sweating ("serotonin syndrome"). The simultaneous use of anti-depressant
medications and Demerol-a pain reliever _ should be avoided in patients
taking Eldepryl. Patients taking Eldepryl may be advised to wear a
Medic-Alert -type bracelet to decrease the likelihood of receiving a
medication that may interact with Eldepryl.


ANTI-CHOLINERGIC MEDICATIONS


ARTANE (TRIHEXYPHENIDYL), COGENTIN (BENZTROPINE MESYLATE) AND OTHERS

Anti-cholinergic medications are historically the first type of medications
to be successfully used in the treatment of Parkinson's disease and may
still
be of adjunctive value in reducing tremor and rigidity. Many medications
with
strong anti-histamine properties such as Benadryl (diphenhydramine) and
Periactin (cyproheptadine) also have anti-cholinergic effects and may also
be
useful.

SIDE EFFECTS OF ANTI-CHOLINERGIC MEDICATIONS

+ Dry mouth, blurring of near vision, constipation, urinary hesitancy and
retention (especially in men)
+ Mental confusion, decreased memory and hallucinations (especially in older
patients or those who are already having problems with mental clarity)
+ Patients with hiatal hernia and gastroesophageal reflux may experience
increased symptoms of "heart burn"

CONTRAINDICATIONS

Patients who have certain types of glaucoma, who have severe problems with
urination, or who have unusually severe problems with confusion or
forgetfulness, should not take anti-cholinergic medications.


End Part I


"It's better to be healthy, wise, rich and beautiful then to be sick,
dumb, poor and ugly"

Lily Tomlin monologue about life and love.
And she says, "remember--we're all in this alone."
.