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Parkinson disease- Pharmacotherapy 3 (semester 5)

2016

Mampu mengenali gejala motor dan non-motor


pada parkinson disease (PD), membuat therapeutic
plan untuk pasien PD, merekomendasikan
penggantian terapi jika terjadi efek samping,
memberikan edukasi terkait PD dan terapinya.

Parkinson disease
Gangguan sistem ekstrapiramidal pada otak yang
melibatkan ganglia basalis yang berperan menjaga
postur tubuh dan tonus otot, dan meregulasi otot polos
Pada Parkinson disease (PD) , dopamin (neurotransmiter
inhibitorik) secara progresif berkurang pada traktus
nigrostriatal, dan asetilkolin (neurotransmiter eksitasi)
relatif meningkat.
Pada pemeriksaan patologis ganglia basalis postmortem,
terdapat badan Lewy (agregat protein intraneuronal
abnormal, sferik) pada sel-sel dopaminergik yang tersisa
pada substantia nigra.
The presence of Lewy bodies is considered pathognomic
for the disease.

Epidemiology
1. Third most common neurologic disorder, behind
AD and stroke
a. Average age at onset is 60 years.
b. More common in men, approaching a 2:1 ratio

2. Incidence
a. Age-dependent, increased with age
b. Annual incidence of 20/100,000 in adults older than 50
years

3. Prevalence
a. Between 2% and 3% of adults older than 65 years
b. Affects around 1 million people in the United States, 4
million worldwide

Caused by
(Etiology and Risk Factors)
1. Idiopathic disease
a. Genetic factors (several possible genetic links and mutations)
b. Aging-related factors (oxidative stress, mitochondrial dysfunction)
c. Environmental factors (heavy metals, pesticides)
Viral encephalitis
Cerebrovascular disease
Hydrocephalus
2. Drug-induced effects on dopamine
a. Antipsychotics Phenothiazines, butyrophenones, atypical agents
b. Antiemetics Metoclopramide, prochlorperazine
c. Toxic substances Manganese dust, carbon monoxide poisoning,
MPTP (1-methyl-4-phenyl- 1,2,5,6-tetrahydropyridine)

Drug-induced PD
Drugs with strong
antidopaminergic activity
Parkinsonism
Neuroleptics, prochlorperazine,
metoclopramide
Valproate, amiodarone,
phenytoin, lithium
Reversible, may persist for
weeks/ months after
discontinuation

4 characteristics
(no need to be
present all at
once)
Tremor (unilateral,
bilateral)
Rigidity, Ratchet
(catch-release)
Slow movement
(bradykinesia)
Postural disturbance

Clinical Presentation
1. Cardinal features
a. Resting tremor Unilateral or bilateral;
reduced/absent with movement and sleep
b. Rigidity Limb muscles, cogwheeling
c. Bradykinesia Slowed movement

2. Motor symptoms
a. Gait abnormalities, stooped posture, shuffling,
festinations, lack of arm swing
b. Impaired fine movements (buttoning shirt)
c. Micrographia (small handwriting)
d. Masked face, dysarthric hypophonic speech
e. Decreased blinking, dysphagia, drooling

3. Autonomic symptoms
a. Orthostatic hypotension Can be problematic because
both the disease and the drugs used to treat it can
cause orthostatic changes
b. Impaired GI motility, constipation
c. Bladder dysfunction, sexual dysfunction
4. Cognitive and psychiatric symptoms
a. Cognitive decline
b. Hallucinations Can also be disease related or
treatment related (dopaminergic medications)
c. Anxiety, depression, sleep disorders
d. Behavioral symptoms, agitation
5. Similar features in other neurologic diseases
a. Benign essential tremor
b. Wilson disease
c. Huntington disease
d. Lewy body dementia
e. Progressive supranuclear palsy
f. Creutzfeldt-Jacob disease

Clinical Management
1. Treatment goals
a. Minimize motor and nonmotor symptoms.
b. Maximize functional status and quality of
life.
c. Minimize medication-related adverse
effects.
d. Maximize safety (reduce fall risk).

2. Nonpharmacologic Therapy
a. Physical therapy
b. Balance and gait training

Overview of drug therapy


Because the salient pathophysiologic feature of PD is the progressive loss of
dopamine from the nigrostriatal tracts in the brain, drug therapy for the
disease is aimed primarily at replenishing the supply of dopamine (Table1 ).
This is accomplished through one, or a combination, of the following methods:
(a) administering exogenous dopamine in the form of a precursor, levodopa;
(b) stimulating dopamine receptors within the corpus striatum through the
use of dopamine agonists (e.g., pramipexole, ropinirole); or
(c) inhibiting the major metabolic pathways within the brain that are
responsible for the degradation of levodopa and its metabolites.
This latter effect is achieved through the use of
aromatic L-amino acid decarboxylase (AAD) inhibitors (e.g., carbidopa),
Catechol-O-methyltransferase (COMT)-inhibitors (e.g., entacapone), or
monoamine oxidase type B (MAO-B) inhibitor (e.g. selegiline, rasagiline)
Anticholinergic agents may occasionally be used to counterbalance the
negative effects of the relative increase in acetylcholine activity and
improve tremor symptoms.

Pharmacologic Therapy
a. Anticholinergics (benztropine, diphenhydramine)
i. Help correct imbalance between dopamine and acetylcholine
ii. Mainly beneficial for tremors; can be used as initial therapy if
tremors are predominant
iii. Limited utility because of adverse effects, particularly among older
patients (confusion, urinary retention, constipation)
b. Dopamine precursor
i. Levodopa is the most clinically effective therapy for PD symptoms.
ii. Effective for all three cardinal features.
iii. Dopa decarboxylase inhibitor (carbidopa) added to prevent peripheral
conversion of levodopa to dopamine
(a) Reduces levodopa dose requirement
(b) Improves tolerability (nausea, orthostasis, cardiac adverse
effects)
(c) Need 75100 mg of carbidopa daily to saturate dopa
decarboxylase enzyme peripherally
iv. Most patients eventually develop motor complications (wearing off,
dyskinesias, on-off phenomenon, freezing) with this drug after several
years of use; some clinicians advocate delaying use of levodopa until
symptoms become quite bothersome or more severe because of the high

Motor complications (wearing off,


dyskinesias, on-off phenomenon,
freezing) with levodopa
(a) Wearing off describes loss of the clinical effect
toward the end of the dosing interval; as the disease
progresses, the wearing-off effect occurs earlier,
necessitating shorter dosing intervals.
(b) Dyskinesias are involuntary choreiform
movements involving the neck, trunk, and upper
extremities; usually associated with peak drug effects
(c) On-off phenomenon or fluctuations describe rapid
transitions from normal or controlled motor activity to
bradykinetic or uncontrolled motor activity.
(d) Freezing describes a drug-resistant off period or
inability to initiate motor function; start hesitations

Initial therapy
i. Therapy generally initiated when symptoms become
sufficiently bothersome to patient functioning
ii. Dopaminergic agents (levodopa, dopamine agonists) are
generally preferred as initial therapy because of their superior
control of motor symptoms.
iii. MAO-B inhibitors (selegiline, rasagiline) can be considered in
patients with mild symptoms before initiating dopaminergic
treatments.
iv. Motor control: Levodopa > dopamine agonist > MAO-B
v. Risk of dyskinesias or motor complications: Levodopa >
dopamine agonists
vi. Hallucinations: Dopamine agonists > levodopa
vii. No clear evidence that using sustained-release levodopa
provides advantages relative to immediate-release levodopa

Add-on therapy
i. If treatment is initiated with a dopamine agonist
and unable to control motor symptoms, levodopa
should be considered.
ii. If treatment is initiated with levodopa, can
consider adding agents if total daily levodopa dose
is 8001000 mg; choice of agent depends on
patient characteristics.
iii. If adding on therapy, need to watch closely for
complications of excess dopaminergic response
(e.g., dyskinesias, nausea and vomiting,
hallucinations); adding therapy to levodopa may
necessitate a decrease in the levodopa dose

Motor complications (wearing off, on-off phenomenon,


freezing)

i. To reduce off time, a MAO-B inhibitor, COMT


inhibitor, or dopamine agonist can be considered.
ii. End-of-dose wearing off occurs because of
shorter duration of individual doses of levodopa;
can consider increasing frequency of levodopa
dosing; if not helpful, consider adding MAO-B
inhibitor, COMT inhibitor, or dopamine agonist.
iii. Freezing episodes: Add a dopamine agonist or
MAO-B inhibitor; intermittent apomorphine;
physiotherapy and assistive walking devices and
sensory cues.

Selected PD Pharmacotherapy
guidelines

Sialorrhea=excessive drooling,
hypersalivation, obatnya: hiosiamin;
hiosin, scopolamin, oscimin, atropin,
glikopirolat

Simplified treatment algorithm for


PD

Generic
(trade
name)

Unit dosis

Jadwal
titrasi

Dosis lazim

Efek
samping

1-2 mg/hari
ditingkatkan
1-2 mg tiap
3-5 hari

6-15 mg
dibagi 2-3
dosis
(BID/TID)

Konstipasi,
xerostomia
(mulut
kering), kulit
kering,
disfagia,
bingung,
gangguan
ingatan

Titrasi
dengan
bentuk
tunggal
terlebih

Bervariasi

Spt tiap
kandunganny
a

Amantadine
Antikolinegik
Benztropin
Trihexyphenid 2, 5 mg tab;
yl (Arkine,
2mg/5mL
Hexymer)

Kombinasi
Carbidopalevodopa
(immediate
release)/ente
capone

12,5/50/200;
25/100/200;
dan
37,5/150/200
mg tab

Agonis
dopamin
Bromokripti
n (Parlodel)

2,5 mg tab;
5 mg kap

1,25 HS;
titrasi
perlahan
dalam 4-6
minggu

10-40 mg
dibagi dalam
3 dosis (TID)

Pramipexole
(Sifrol)

0,125; 0,25;
0,50; 1; 1.5
mg tab

0,125 dibagi 1,5-4,5 mg


3 dosis
dibagi 3 dosis
(TID), titrasi (TID)
mingguan
0,125-0,25
mg/dosis

Hipotensi
ortostatik,
bingung,
pusing,
halusinasi,
mual,
somnolence
(ngantuk
sekali)

Ropinirole

0,25; 0,5; 1;

Titrasi

sda

3-12 mg

Hipotensi
ortostatik,
bingung,
pusing,
halusinasi,
mual, kram
kaki, fibrosis
perikardiak,
penebalan
katup jantung

COMT (catechol-O-methyltransferase) inhibitor


Entecapone
(Stalevo)

200 mg tab

1 tab setiap
3-8 tab/hari
pemberian
levodopa/car
bidopa,
sampai 8
tab/hari

Diare
diskinesia,
nyeri
abdomen,
pewarnaan
urin

MAO (monoamine oxydase) inhibitor


Selegiline

5 mg
pagi;dapat
ditingkatkan
sampai 5 mg
BID

5-10 mg (5
mg bersama
sarapan; 5
mg bersama
makan
siang)

Insomnia,
pusing,
mual,munta
h,
xerostomia,
diskinesia,
perubahan
mood,
hindari
makanan
mgd tiramin,
hati-hati
peemberian
bersama
simpatimime

Bromocriptine
Ergot dopamine agonists such as bromocriptine have
fallen out of favor in the treatment of PD. Concern for
rare but serious cardiac valve regurgitation has
prompted providers to use safer choices with similar
efficacy (Schade 2007). Other serious adverse effects
include reversible pleural effusions and irreversible
pulmonary and cardiac valvular fibrosis (Sprenger
2013). Although ergot dopamine agonists may be
used at lower dosages in other indications (e.g.,
hyperprolactinemia), the doses needed to treat PD
are more likely to lead to the rare but serious adverse
effects (Medical Letter 2013).

Apomorphine
Apomorphine is a high-potency rescue non-ergot nonselective
dopamine agonist for off periods, including wearing-off episodes
or unpredictable on/off episodes.
The drug must be administered subcutaneously and initiated in an
office setting so that close monitoring of orthostasis can occur.
Onset of effect is rapid and precluded by yawning (Goren 1998).
It is NOT to be used in conjunction with serotonin receptor
antagonists such as the antiemetic ONDANSETRON because the
combination may lead to severe hypotension.
As with other dopamine agonists, a common adverse effect of
apomorphine is nausea. Nausea may respond best to
trimethobenzamide, with pretreatment to start 3 days before
apomorphine initiation. Nausea often subsides within 24
months of apomorphine treatment, allowing for elimination of
antiemetic use (Chen 2011).

For hypomobility/off episodes in PD


Apomorphine: use with antiemetic
trimethobenzamide 3 days before initiating
apomorphine and continued for 2 months
of treatment.
NOT with ondansentron (serotonin
antagonist) may cause severe
hypotension
NOT with prochlorperazine and
metoclopramide (dopamine antagonists)
decrease effectiveness of apomorphine

#1
A 56-year-old man with advanced PD continues to have severe
unpredictable off periods that cause significant impairment.
His home drugs include carbidopa/ levodopa/entacapone
18.75/75/200 mg 1 tablet four times daily, rasagiline 1 mg by
mouth daily, ropinirole 1 mg by mouth three times daily,
ondansetron 4 mg by mouth every 8 hours as needed for
nausea, and atropine eyedrops 2 drops by mouth at bedtime
for drooling. Which one of the following would be best to
discontinue when initiating the rescue medication
apomorphine subcutaneous injection for this patient?
A. Rasagiline.
B. Ropinirole.
C. Atropine.
D. Ondansetron.

Time Course of Response


Treatment for motor symptoms with PD agents
should be initiated at a low dose and titrated to
response according to efficacy and tolerability.
Improvements in motor symptoms usually occur
within the first few days of achieving a
therapeutic dose.
Dyskinesias that result from treatment with
carbidopa/ levodopa may require treatment
modifications.
Progression of disease also requires treatment
modifications.

Assessment of
Response/Scales
Patients should be assessed at least every 3 months
during treatment for motor and nonmotor symptoms as
well as quality of life. However, making assessments at
more frequent intervals (e.g., every 2 weeks) may
be needed in the initial treatment stages for
appropriate dose titration.
Assessments should include symptom severity,
nonmotor symptoms, comorbid mental disorders,
functioning and quality of life, treatment adherence, and
adverse effects.
Despite their limited use in clinical practice, scales may
be used to determine the progression of both motor and
nonmotor symptoms of PD.

Staging of Disability in PD
Sta
ge

Signs/symptoms

Unilateral involvement only; minimal or no functionl


impairment

II

Bilateral involvement, without impairment of balance

III

Evidence of postural imbalance; some restriction in activities;


capable of leading independent life; mild to moderate
disability

IV

Severely disabled, canno twalk and stand unassisted;


significantly incapacitated
I-II : mild;
V
Restricted to bed or wheelchair unless aided
III daily activities are restricted; III-IV: advanced stage levodopa and
combination with COMT inh (carbidopa, Sinemet) or dopamin agonist
(pramipexole, ropinirole) or selegiline or rasagiline or amantadine.
V: do not respond well to drug therapy.

Pharmacologic and
Pharmacokinetics Dopamin Agonists
Bromocrip
tine

Pramipex
ole

Ropinirole

Apomorph
ine

Rasagiline

Type of
compound

Ergot
derivative

Nonergoline

Nonergoline

Nonergoline

Nonergoline

Receptor
specificity

D2, D1,*1,
2, 5-HT

D2,D3,D4,
2

D2, D3, D4

D1,D2,D3,D D1,D2,D3,5
-HT1
4D5, 1,
2, 5HT1;5-HT2

Bioavailabili 8%
ty

>90%

55% (first
<5% orally;
pass
100%subcu
metabolism taneous
)

<1% orally

Tmax (min)

70-100

60-180

90

10-60

15-18 (hr),
no
characterist
ic peak
observed

Protein
binding

90-96%

15%

40%

>99.9%

89.5%

Levodopa Interactions

Pharmacotherapy for Essential


Tremor

#2
A 45-year-old man presents to your outpatient
clinic with bilateral tremor in his hands. The
tremor is of low amplitude and rapid frequency.
This has become impairing to his career as an
electrician. Other neurologic symptoms are
absent. Which one of the following is most helpful
in confirming this patients essential tremor (ET)?
A. Improvement with smoking cigarettes.
B. Worsening with smoking cigarettes.
C. Improvement with alcohol intake.
D. Worsening with alcohol intake.

#3
A 67-year-old man has symptoms of bilateral
upper extremity resting tremor and moderate
rigidity of limbs. His current drugs include
metformin 1000 mg twice daily and
metoclopramide 5 mg with meals. Which one of
the following would most likely indicate PD rather
than ET or pseudoparkinsonism in this patient?
A. Olfactory dysfunction.
B. Metoclopramide treatment.
C. Improvement with primidone.
D. Advanced age of onset.

Patient education
Patients with a diagnosis of PD must be educated about treatment
options and realistic expectations with respect to symptom
management (SIGN 2010).
Possibly the most important issue to convey is the relationship between
symptomatology and medication timing. Small adjustments in time
of dosing throughout the day may allow for fewer movement difficulties.
Understanding how to manage the common adverse effects may
improve adherence. Patients who experience nausea with drug therapy
may benefit from taking the medication with food or adding an
antiemetic. Dizziness and blood pressure changes must be managed by
instructing that patients use care when rising and minimize sudden
movements. If a patient has hypertension, blood pressure drugs may
need to be lowered once the patient is prescribed PD agents.
Participation in support groups often helps patients (and their caregivers)
feel less isolated by their illnesses. In fact, some providers perform group
encounters for both the assessment of symptoms and the opportunity for
encouragement from peers.
For optimization of care, patients should be encouraged to complete
movement diaries, including instances of falling as well as dyskinesias.

Pharmacoeconomics
In 2010, treatment of PD in the United States cost
almost $22,800 per patient (totaling $14 billion), a
daunting number as the older adult population
continues to grow (Kowal 2013).
A review of privately insured patients determined that
patients with newly diagnosed PD incur a lower annual
cost of treatment (about $4000). Cost increases as the
illness progresses (upper range nearing $37,400), with
the highest factors being hospitalization and presence
of motor fluctuations (Johnson 2013, Scheife 2000).
With this information, it seems that delaying motor
fluctuations, which result from carbidopa/levodopa,
may slow the escalation of treatment costs.
The availability of generic formulation of most classes
of PD drugs allows for patient options in treatment

4
A patient presents with an onset of rigidity and
bradykinesia over 48 hours. Her home drugs
include lisinopril 20 mg daily, simvastatin 40
mg every night at bedtime, and risperidone
3 mg twice daily. Which one of the following
is this patient most likely experiencing?
A. PD.
B. ET.
C. Pseudoparkinsonism.
D. Tardive dyskinesia (TD).

5
A patient presents with the following regimen:
carbidopa/levodopa 25/100 mg 2 tablets three
times daily, amantadine 100 mg daily, and
pramipexole 1 mg daily. Which one of this
patients nonmotor symptoms is least likely to
respond to dopaminergic medications?
A. Muscle pain.
B. Micrographia.
C. Constipation.
D. Depression.

6
A 68-year-old woman has PD managed with the following drugs:
carbidopa/levodopa 25/100 mg four times daily, rasagiline 1 mg
daily, atorvastatin 10 mg daily, polyethylene glycol 17 g daily,
and chlorthalidone 50 mg daily. Her most prominent PD
symptoms/complications include wearing off nearing the time of
her next dose of carbidopa/levodopa and bilateral resting tremor
of her upper extremities. She has no edema or hypertensive
blood pressure readings. She is currently experiencing orthostasis
and has fallen a few times in the past week. Which one of the
following would best treat this patients postural instability?
A. Decrease the dose of carbidopa/levodopa.
B. Decrease the dose of rasagiline.
C. Add fludrocortisone.
D. Decrease the dose of chlorthalidone.

6a
A 72-year-old female patient is in the clinic for assessment after a fall
1 week ago. She was seen in the emergency department at that
time, but no significant injuries were noted. She states that she
was dizzy before her fall. She has a history of hypertension, PD,
and osteoarthritis. Her current medications include
hydrochlorothiazide 25 mg/day, metoprolol XL (extended release)
50 mg/day, lisinopril 10 mg/day, tramadol 50 mg three times daily
as needed for pain, levodopa/carbidopa CR (controlled release)
200/50 mg twice daily, and pramipexole 0.125 mg twice daily. She
states that her PD symptoms are much better controlled since
adding pramipexole and decreasing levodopa/carbidopa 1 month
ago. On physical examination, blood pressure is 136/72 mm Hg,
with a heart rate of 60 beats/minute sitting, and 118/60 mm Hg,
with a heart rate of 62 beats/minute standing. Her gait looks good,
and her strength is good. Which is the most appropriate
recommendation to reduce her risk of future falls?
A. Discontinue pramipexole.
B. Decrease metoprolol dose.

7
R.M. is a 55-year-old man who has received a diagnosis
of PD. At this time, his symptoms are mild but slightly
embarrassing, consisting primarily of mild
bradykinesia and impaired dexterity, most notably
with micrographia. Minimal tremor is present. R.M.
asks to be initiated on treatment.
Which one of the following is best to recommend for
R.M.?
A. Carbidopa/levodopa 25/100 mg three times daily.
B. Bromocriptine 1.25 mg daily.
C. Benztropine 1 mg twice daily.
D. Rasagiline 1 mg daily.

8
Four years later, R.M. has continued to receive treatment
by the movement disorder clinic, but his illness has
progressed. He now has worsened bradykinesia and
muscle stiffness. He is currently taking ropinirole 6 mg
three times daily. Which one of the following is best to
recommend for R.M.?
A. Add amantadine 100 mg daily and continue ropinirole.
B. Switch to carbidopa/levodopa 25/100 mg three times
daily.
C. Switch to apomorphine 2 mg daily.
D. Add entacapone 200 mg daily and decrease ropinirole.

9
A 58-year-old man is referred to you after a new
diagnosis of early-onset PD. His symptoms are still
mild and consist of right hand tremor,
bradykinesia, and muscle stiffness. Which one of
the following education points is the best to
provide this patient?
A. He should start carbidopa/levodopa.
B. Long-acting medications prevent adverse effects.
C. Consumption of coffee will delay progression.
D. Delaying the start of carbidopa/levodopa is
prudent.

10
An 86-year-old woman with PD arrives for her yearly checkup. She is
currently treated with carbidopa/levodopa 25/100 mg 2 tablets
three times daily. Her symptoms are well enough controlled that
she can function independently, and she has had no falls.
However, she has postural instability because of her dyskinesias.
Reducing her carbidopa/levodopa dose was previously
unsuccessful because her rigidity and bradykinesia increased. At
this visit, the physician adds pramipexole 0.125 mg three times
daily to optimize symptom improvement. Which one of the
following factors would best optimize this patients treatment
when pramipexole is added?
A. Increase carbidopa/levodopa.
B. Stop carbidopa/levodopa.
C. Decrease carbidopa/levodopa.
D. Add rasagiline.

11
A 56-year-old man with advanced PD continues to have severe
unpredictable off periods that cause significant impairment.
His home drugs include carbidopa/levodopa/entacapone
18.75/75/200 mg 1 tablet four times daily, rasagiline 1 mg by
mouth daily, ropinirole 1 mg by mouth three times daily,
ondansetron 4 mg by mouth every 8 hours as needed for
nausea, and atropine eye drops 2 drops by mouth at bedtime
for drooling. Which one of the following would be best to
discontinue when initiating the rescue medication
apomorphine subcutaneous injection for this patient?
A. Rasagiline.
B. Ropinirole.
C. Atropine.
D. Ondansetron.

12
Q.T. is a 70-year-old man with a 9-year history of Parkinson
disease (PD). He comes to the clinic today with impairing onand-off periods that occur at least once per day, often at
unpredictable times. Q.T.s drug regimen is as follows:
carbidopa/levodopa 25/250 mg CR 1 tablet four times daily (3
years), pramipexole 1 mg three times daily (1 year), and
entacapone 200 mg four times daily (2 years).
Which one of the following would best improve Q.T.s on-and-off
periods?
A. Add apomorphine 2 mg as needed during off period.
B. Increase entacapone to 200 mg five times daily.
C. Increase carbidopa/levodopa to 25/250 mg 4 tablets four
times daily.
D. Change from pramipexole to ropinirole.

13
Two years later, Q.T.s illness has progressed as
expected. He is now experiencing dyskinesias of
the upper extremities and significant postural
instability, which impair his ability to complete
activities of daily living independently. Which one
of the following is most likely to prevent Q.T. from
undergoing deep brain stimulation?
A. Advanced age.
B. Length of carbidopa/levodopa treatment.
C. Apomorphine treatment.
D. Onset of PD dementia.

14, 15

16,18

19,20

21,22

23,24

25,26

27
A 66-year-old man with a diagnosis of PD is being examined today in the clinic.
He has been taking levodopa/ carbidopa for 6 years. His current
levodopa/carbidopa dose is 100/25 mg, 1 tablets in the morning, 1 tablet at
11 a.m., 1 tablet at 2 p.m., 1 tablet at 5 p.m., and tablet at 8 p.m. He has
been experiencing motor complications for about 3 months, including on-off
symptoms and freezing episodes. On physical examination, he has some
weakness, gait and balance abnormalities, and rigidity. His ability to ambulate
and perform self-care activities during the past 3 months has continued to
decline. Which is the most appropriate recommendation for this mans
symptoms?
A. Add benztropine to levodopa/carbidopa.
B. Decrease the levodopa/carbidopa dose to 4 tablets daily.
C. Switch to levodopa/carbidopa CR.
D. Add entacapone to levodopa/carbidopa.

28
The 66-year-old patient in the previous question returns to the clinic 2
weeks after your recommendation above. He states that, overall, he
thinks he is doing better, but that he often feels nauseated and
occasionally feels light-headed or dizzy. He also describes some
abnormal movements, which are identified as dyskinesias on physical
examination. He also states that he has experienced hallucinations
on two occasions, which was rather disturbing to him. Which is the
most appropriate recommendation for this man?
A. Add prochlorperazine for nausea.
B. Decrease the daily dose of levodopa/carbidopa.
C. Initiate rasagiline therapy.
D. Initiate ropinirole therapy.

29
T.B. is a 63-year-old man who received a diagnosis of early PD about 6 months
ago but who is otherwise healthy. He did not receive treatment with any
medications when his PD was first diagnosed, but on the advice of his
physician he started therapy with selegiline 5 mg twice daily about 4 weeks
ago. He is in the clinic today because of difficulty sleeping and difficulty with
his memory. He states that, on most days, he feels tired but just cannot fall
asleep. He states that his wife has a prescription for lorazepam 0.5 mg and
that he has taken one tablet when he has had difficulty sleeping. He is asking
for a prescription for lorazepam to help him sleep. Which is the best
recommendation for this patient?
A. Give him a prescription for lorazepam 0.5 mg at bedtime.
B. Have him take diphenhydramine 50 mg at bedtime.
C. Change the selegiline dosing from twice daily to morning and noon.
D. Add levodopa/carbidopa to selegiline.

30
A 68-year-old woman with PD has been taking levodopa/carbidopa 100/25
mg four times daily for 2 weeks. Previously, she was taking
levodopa/carbidopa 100/25 mg three times daily. She is calling your clinic
to see what she can do about the symptoms she describes, which include
nausea, light-headedness, and involuntary movements, which sound like
dyskinesias. Her PD symptoms were fairly well controlled on the threetimes-daily schedule, but her physician increased the dose to four times
daily to achieve additional benefit. Which is the best recommendation to
address this womans symptoms?
A. Add rasagiline.
B. Decrease the levodopa/carbidopa dose to 100/25 mg three times daily.
C. Add ropinirole.
D. Change the levodopa/carbidopa dose to 100/10 mg four times daily.

Case presentation
L.M., a 55-year-old, right-handed male artist, presents to the neurology clinic complaining of
difficulty painting because of unsteadiness in his right hand. He also complains of increasing
difficulty getting out of chairs and tightness in his arms and legs.
His wife claims that he has become more "forgetful" lately, and L.M. admits that his memory
does not seem to be as sharp.
His medical history is significant for depression for the past year, gout (currently requiring no
treatment), constipation, benign prostatic hypertrophy, and aortic stenosis.
On physical examination, L.M. is noted to be a well-developed, well-nourished man who displays
a notable lack of normal changes in facial expression and speaks in a soft, monotone voice. A
strong body odor is noted. Examination of his extremities was slight "ratchetlike" rigidity in both
arms and legs, and a mild resting tremor is present in his right hand. His gait is slow, but
otherwise normal, with a slightly bent posture. His balance is determined to be normal , with no
retropulsionor loss of righting reflexesafter physical threat. His genitourinary is only remarkable
for enlargement of prostate. The remainder physical examination of LM and laboratory findings
are normal.
What signs and symptomssuggestive of PD present in LM?
Which of symptoms are of classic symptoms for diagnosing PD and which are considered
associatedsymptoms?
How should LM be treated for PD and associated symptoms?
In what stage of the disease is LM?
Should therapy be initited with a dopamine agonist or levodopa?

LM is to be started on dopamine agonist. Which agent


should be selected?
What is the most effective way to dose pramipexole or
ropinirole?
What are the adverse effects of pramipexole and
ropinirole? How can these be managed?
When to begin levodopa?
What are the advantages and disadvantages of
Sinemet over levodopa alone?
How is Sinemet dosed? Before, with or after meals?
When should entacapone (COMT inhibitor) be
initiated? How is it dosed?

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