PARKINSONS

Brian Gates, Pharm.D., CGP

brian.gates@wsu.edu
Objectives
After this lecture the student should be
able to:
Identify medications that potentially could
worsen PD
Suggest appropriate interventions for a
person with PD experiencing nausea
Suggest an anti-psychotic that is
appropriate for a person with PD
Objectives
Give suggestions for a person with PD who
is experiencing wearing off of
levodopa/carbidopa
Provide suggestions for a person with PD
who is experiencing swallowing difficulties
Provide recommendations to help with low
blood pressure and/or orthostatic
hypotension in a person with PD
The main issue in
Parkinsons is:
A. Lack of Dopamine
B. Excess acetylcholine

Answer: Lack of Dopamine

There is not too much acetylcholine in

Parkinsons, but the imbalance can
contribute to tremors. Note that since
lack of dopamine is the main issue,
replacing dopamine is the main goal of
A Patient Case
You are on rotations at the IMR clinic
A patient there has been diagnosed with
Parkinsons
The patient has been holding off on
treatment
The patient now wants to start treatment
The medical resident asks which
Parkinsons treatment you would
recommend
Which would you
recommend?
A. Carbidopa/levodopa
B. Amantadine
C. Pramipexole
D. Trihexyphenidyl
Which Treatment is First
Line?
Note the importance of non-
pharmacologic
Exercise can help tremendously
Physical therapy can make tremendous
difference as Parkinsons progresses
May be more beneficial than meds
Fewer side effects
Speech therapy can be very important
Swallowing
Singing-Tremble Clefs
Which Treatment is First
Line?
No question that carbidopa/levodopa is
the most effective
Major challenge with this is dyskinesia
Greater likelihood with longer treatment
Greater likelihood with higher dose
Individual patient sensitivity
Levodopa in older patients
Note that the older someone is at
diagnosis, the less likely that dyskinesia
is to occur
Reason that levodopa appears earlier in
treatment algorithm in older patients
Dyskinesia
https://
www.youtube.com/watch?v=koL0PWCJ4lo

This is a video of the actor Michael J Fox.

If you watch the first part after he begins
his interview with Oprah, you will see his
movements.
These are dyskinesia movements from
levodopa, not symptoms of Parkinsons
With the levodopa he would potentially be
very stiff.
A Case
ZA is a 76 year old person with
Parkinsons. He has had long-standing
hypertension and mild heart failure. He
was just started on carbidopa/levodopa
10/100 TID. He states he is going to
stop taking it because it causes too
much nausea. What do you suggest?
Suggestion
A. Take it with food
B. Give additional carbidopa
C. Give metoclopramide PRN
D. All of the above
Take with food
This helps the patients nausea a bit but
he still finds this to be troublesome

Back to the case

Add carbidopa
This helps his nausea quite a bit. His MD
then switches him to a 25/100 mg
product

Back to the case

Add metoclopramide
His nausea gets much better, but his
Parkinsons symptoms become even
worse than before he started the
carbidopa/levodopa

Back to the case

Nausea
Why is carbidopa used with levodopa?
Nausea: peripheral breakdown issue
Increased benefit: getting into the brain
Early in PD will usually have no problem
with benefit
Nausea may be an issue if carbidopa
insufficient
Generally need 75-100 mg per day
Can add this separately instead of combo
Food and
carbidopa/levodopa
Food may help with nausea
High protein meals may decrease
absorption
Generally not a problem early on
May be more important later with PD
progression
Nausea medications
Dopamine blockers are a problem
Metoclopramide
Prochlorperazine
Several others
Non-dopamine blockers acceptable
Ondansetron/other 5HT-3 antagonists
Anti-cholinergics
What could these help in Parkinsons?
What problems could they cause?
ZA
Over time, ZA begins to have difficulty
with low blood pressure, reading 90-100
systolic and 40-50 diastolic. He is no
longer on any anti-hypertensives. His
physician cut back on his pramipexole
and increased carbidopa/levodopa, but
this is still a problem. You are asked to
recommend a medication. What would
you suggest?
Decisions.
Midodrine
Fludrocortisone
Both A and B
Other
Midodrine
ZA has some improvement in his overall
blood pressure, and he has less dizziness
when he is first standing up

Back to the case

Fludrocortisone
His blood pressure improves, but he
notices some increased edema in his
legs with some shortness of breath

Back to the case

Both midodrine and
fludrocortisone
His blood pressure improves, but he
notices some increased edema in his
legs with some shortness of breath

Back to the case

Raise Blood Pressure
What non-pharmacologic suggestions
could help?
What pharmacolgic measures?
Midodrine: alpha 1agonist
Fludrocortisone: mineralcorticoid
Psychosis
ZA begins to develop severe
hallucinations and tries to swing at his
caregivers. You are asked for a
suggestion.

Why do Parkinsons patients get

hallucinations/psychosis?
Decisions, decisions.
Risperidone
Quetiapine
Clozapine
Haloperidol
Risperidone
This helps with the symptoms, but his
Parkinsons symptoms seem somewhat worse

Back to the case

Quetipine
The hallucinations improve. They still
occur some but are tolerable enough
that ZA is no longer so aggressive
toward family.

Back to the case

clozapine
The patients symptoms improve, but
the family finds it very difficult to get
him to all the appointments required for
the monitoring he needs for this
medication and ask if he can be
switched to something else.

Back to the case

haloperidol
The patients hallucinations and behaviors
improve, but he seems somewhat sedated,
and his Parkinsons is noticeably worse.

Back to the case

Wearing Off
ZA begins to have severe wearing off
episodes. He even has periods of
freezing. He is taking 8 tablets of
Sinemet CR 50/200 daily and ropinirole
ER 16 mg daily.

What would you suggest?

Wearing Off
A. Add entacapone
B. Add Sinemet IR
C. Increase
ropinirole
D. All of the above
Add entacapone
The patients symptoms improve. He
notices less off time, though he still
sometimes experiences some freezing
episodes

Back to the case

Add Sinemet IR
This helps at times. The caregivers
report giving it at times when he usually
starts to have difficulty and the mid
afternoon when he has had some
freezing episodes.
Do you think this is an OK way to dose?

Back to the case

Increase ropinirole
This does provide some help with the
symptoms, both reducing off time and
fewer freezing episodes. However, his
hallucinations become more of a
problem again.

Back to the case

All of the above
The symptoms noticeably improve, but
ZA also experiences more hallucinations
and has some dizziness.

Back to the case

 As the Disease Progresses,
the Therapeutic Window Narrows

Plasma Levodopa Concentrations

Smooth, extended response Diminished duration Shorter, unpredictable

response
Absent or infrequent dyskinesia Increased incidence On time with increased
dyskinesia
of dyskinesia
Stocchi F, et al. Eur Neurol, 1996.
Dyskinesia
Note that since disease progression is an
issue people who have PD longer will
have greater likelihood of dyskinesia
Patients with diagnosis at a later age will
be less likely to have an issue with
dyskinesia
Older patients also may not tolerate the
dopamine agonists as well, changing
which therapy may be preferable (hence
the age 60 in flow chart)
Dyskinesia
Dyskinesia vs freezing/rigidity
Freezing more likely as PD progresses
Patients may prefer dyskinesia to freezing
Have greater function with dyskinesia
Providers sometimes focus more on
dyskinesia
 On with Dyskinsea

Therapeuti
c Window
In
Early
Disease

o se
D

se s e
o se Do
Off Do
o se e D
D os
D
 On with Dyskinsea

Therapeuti
c Window
In
Moderate
Disease

Off
 On with Dyskinsea

Therapeuti
c Window
Advanced
Disease

Off
Swallowing Difficulty
ZA begins to have significant difficulty
swallowing. He has a speech evaluation
and the speech and language
pathologist notes that ZA should be on
honey thick liquids. Which of the
following would be the best option?
What to do?
A. Give liquid version
of medications
when possible
B. Crush medications
when possible and
put in pudding
C. Other
liquid
ZA coughs with some of his medications and
even has some trouble with aspiration. He
has to get treatment for aspiration-related
pneumonia

Back to the case

Crush and use pudding
This works well for many of his
medications and he is able to swallow
the pudding effectively

Back to the case

Other
Note that a thickening agent can be helpful
the cornstarch based products do not interefere
with medications
We may also need to change some medications
might need to change Sinemet CR to IR
potentially could use the new Duodopa gel

Back to the case

Deep Brain Stimulation
May have substantial benefit for some
patients
Some research into whether this can be
helpful earlier in PD
Patients can turn on or off
Thanks!
Dr. Stephen Setter
Dr. Joshua Neumiller
Dr. Jeff Clark