A 63-year-old woman presents with a 6-month history of a mild right hand tremor, stiffness, slowness, and sleep problems affecting her job performance. She also reports constipation, depressed mood, loss of smell, and acid reflux. On examination, she has signs consistent with early Parkinson's disease. Treatment goals include controlling her motor symptoms to improve function, as well as treating non-motor symptoms like depression, insomnia, and constipation. Non-drug therapies like exercise and sleep hygiene may help. Initial pharmacotherapy options for her Parkinson's include levodopa, dopamine agonists, MAO-B inhibitors, or COMT inhibitors.

1. Parkinson Disease
Case study
Pharma D/Atef Al Saman

2. PAKINSON DISEAS
PD is a chronic progressive movement disorder first described in 1817 by Dr James Parkinson. Since that time, the term
parkinsonism has come to refer to any disorder associated with two or more features of tremor, rigidity, bradykinesia, or
postural instability.
The salient features of PD result from a loss of dopaminergic neurons in the nigrostriatal tracts of the brain and development
of abnormal intraneuronal protein aggregates called Lewy bodies that interfere with neuronal function. The nigrostriatal
tracts are neuronal tracts between the substantia nigra and the striatum. They are part of the extrapyramidal system of the
brain involving the basal ganglia. This area is involved with maintaining posture and muscle tone
by regulating voluntary smooth muscle activity.
❖ It is essential to rule out drug induced pseudo parkinsonism due to
dopamine antagonists such as antipsychotics, metoclopramide, and
antiemetics (prochlorperazine) before diagnosis. Removing the
offending agent generally resolves symptoms.

5. Diagnosis:
1. Diagnosis is made after ruling out other neurologic disorders with overlapping clinical features and assessing motor
signs and symptoms.
A. Presence of bradykinesia with at least one of the following cardinal features: resting tremor, rigidity,
postural instability
B. Other types of parkinsonism or tremor disorders excluded (e.g., essential tremor, drug-induced tremor, stroke,
infections)
C. Presence of at least three of the following supportive positive criteria:
i. Asymmetry of motor signs/symptoms
ii. Unilateral onset
iii. Progressive disorder
iv. Resting tremor
v. Response to levodopa
2. United Parkinson’s Disease Rating Scale
A. Mainly used for evaluating symptom severity in PD studies
B. Assesses mood and behavior, daily function, and motor symptoms and complications

9. Case:
A 55-year-old, right-handed male artist, presents to the neurology clinic complaining of difficulty painting because of
unsteadiness in his right hand. On questioning, he notes that it is becoming increasingly difficult to get out of chairs after
sitting for a long period because of tightness in his arms and legs. He also reports having a loss in sense of smell. His
medical history is significant for gout (currently requiring no treatment), constipation, benign prostatic hypertrophy, and
aortic stenosis. He does not smoke, but usually drinks one alcoholic beverage in the evenings.
His only prescription medication is citalopram 10 mg by mouth once daily. On physical examination Ali 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.
Examination of his extremities reveals a 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 retropulsion or loss of righting reflexes after physical threat. His genitourinary examination is remarkable only for prostatic
enlargement. The remainder of his physical examination is within normal limits.

10. . Laboratory values and vital signs obtained at this visit include the following:
A. Blood pressure, 119/66 mm Hg Heart rate, 71 beats/minute Sodium, 132 mEq/L Potassium, 4.4 mEq/L Blood urea
nitrogen, 19 mg/dL
Creatinine, 1.1 mg/dL Thyroid stimulating hormone, 3.65 microunits/L Vitamin B12, 612 pg/mL Folate, 5.2 ng/mL
White blood cells, 4,400 cells/μL Red blood cells, 5.9 × 106/μL Hemoglobin, 13.8 g/dL Hematocrit, 41% Uric acid, 6.3
mg/dL
B. How is PD diagnosed?
- The neurologic examination to assess motor function, along with a positive response to levodopa, is highly diagnostic.
- Other associated premotor symptoms, such as hyposmia (a reduced ability to smell and detect odors), rapid eye movement
(REM) sleep disorder, and softening and tonal changes of the voice are among the earliest symptoms to appear.
- A noticeable unilateral resting tremor is present along with evidenced by his difficulty handling a paintbrush.
- a symptom of bradykinesia.
- Rigidity(ratcheting of the arms) and a mask-like facial expression also are present.
- B. Is neuroimaging or any other testing helpful in establishing the diagnosis of PD?
With further scientific advancements, the diagnosis of PD may rely on clinical, imaging, genetic, and a panel of laboratory
biomarker data. However, by the time patients such as Ali present the a diagnosis can be made clinically, without the need for
further laboratory or radiologic testing

11. What signs and symptoms suggestive of PD are present in Ali and which of these symptoms are among the classic
symptoms for diagnosing PD?
A. A noticeable unilateral resting tremor is present .
B. a symptom of bradykinesia.
C. Rigidity(ratcheting of the arms) and a mask-like facial expression also are present.
What are the stages of PD? In what stage of the disease is Ali?
A. Ali appears to be in late stage 2, early stage 3 of the disease .
B. In general patients in Hoehn and Yahr stage 1 or 2 of PD have mild disease that does not interfere with activities of daily
living (ADLs) or work and usually requires minimal or no treatment.
C. In stage 3 disease, daily activities are restricted and employment may be significantly affected unless effective treatment is
initiated.
D. With advanced-stage disease (3, 4), most patients require a double or triple drug therapy strategy.
E. Patients with end-stage disease (stage 5) are severely incapacitated and, because of advanced disease progression, often do
not respond well to drug therapy.

12. When should Ali begin treatment for his PD?
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14. What are the adverse effects of pramipexole and ropinirole? How can these be managed?
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Case:
A 68-year-old woman with PD has taken levodopa/carbidopa 100/25 mg four times daily for 2 weeks. Previously she took
levodopa/carbidopa 100/25 mg three times daily. She calls your clinic to ask about her symptoms, which include nausea,
light-headedness, and involuntary movements that she describes similarly to dyskinesias. Her PD symptoms were fairly
well controlled on her dose schedule of three times daily, but her physician increased the dose to four times daily for
additional benefit.
Which is the best recommendation to address this patient’s symptoms?
A. Continue levodopa/carbidopa; add rasagiline.
B. Decrease levodopa/carbidopa dose to 100/25 mg three times daily.
C. Continue levodopa/carbidopa; add ropinirole.
D. Change levodopa/carbidopa dose to 100/10 mg four times daily

15. Case: A 63-year-old man received a diagnosis of early PD about 6 months ago but is otherwise healthy. He did not
receive treatment with any medications when his PD was first diagnosed; however, on his physician’s advice, 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; on most days he feels tired but cannot fall asleep. He notes that his wife has a prescription for
lorazepam 0.5 mg and that he has taken 1 tablet when he has had difficulty sleeping. He asks for a prescription for
lorazepam to help him sleep.
Which is the best recommendation for this patient?
A. Continue selegiline; add lorazepam 0.5 mg at bedtime.
B. Continue selegiline; add diphenhydramine 50 mg at bedtime.
C. Continue selegiline, but change the twice-daily dose timing to morning and noon.
D. Continue selegiline; add levodopa/carbidopa

16. Case:
A 52-year-old man, was admitted to the neurology clinic because of a mild, intermittent resting tremor in his right hand that
had worsened over the past 2 months and had recently progressed to the contralateral hand. He admitted that it took a more
effort to get movement started and that his muscles felt a little stiff. The patient also noticed a loss in the sense of smell and
excessive sweating, especially during the night.
Ahmed’s medical history was significant for hypercholesterolemia, partially controlled with lovastatin. The patient never
smoked and denied the use of alcohol or illicit drugs. His family history was unremarkable.
Physical examination showed a well-nourished man with a notable lack of normal changes in facial expression. He spoke slowly
with a monotone voice. A right-sided resting tremor of the pill-rolling type was noted. An impairment with fine coordination
was made apparent by the rapid alternating movements and finger taps. Ahmed’s gait was slow but otherwise normal, with
slightly bent posture, and he had no problem with his balance. A handwriting sample was progressively smaller in size,
indicating micrographia.

17. A diagnosis of early, mild Parkinson’s disease was made, and the patient was dismissed from the clinic with a prescription of
rasagiline. His symptoms did not improve after 2 months of therapy, and the neurologist discontinued rasagiline and
prescribed pramipexole. Four months later, Ahmed returned to the neurology clinic for a routine follow-up visit. He stated that
his slowness and stiffness had improved but the tremor was minimally changed, and he still suffered occasionally from
insomnia. He also noted that he sometimes had the urge to walk a great distance, with no purpose or destination.
The neurologist explained that Ahmed’s symptoms were most likely related to pramipexole. The daily dose of the drug was
decreased, and benztropine was added to the therapy. One year later Ahmed was admitted to the neurology clinic because of
worsening of his disease, in spite of the ongoing therapy with pramipexole and benztropine. Ahmed reported that he no longer
had trouble with compulsive behavior, but he felt an increased rigidity, stiffness and tremor. He was slower in all activities and
was tired throughout much of the day.

18. Physical examination confirmed the patient’s report and revealed a loss of balance resulting in gait abnormalities. The
neurologist decided to add to the ongoing therapy a levodopa/carbidopa combination and entacapone.
After 2 years of levodopa/carbidopa therapy, Ahmed started experiencing periods of substantial immobility lasting for a few
minutes that occurred 2 to 4 hours after the last levodopa intake. but often by a period of dyskinetic activity. The neurologist
added amantadine to the current therapy and tried to change the dose and time of administration of levodopa, with little
success. Eventually he decided to prescribe subcutaneous injections of apomorphine. He also prescribed another drug to
counteract a disturbing adverse effect of apomorphine.
Ahmed showed several symptoms and signs typical of Parkinson’s disease. Which of the following symptoms and signs could
also most likely affect this patient?
A. Dry mouth
B. Choreiform movements
C. Symmetric leg weakness
D. Aphasia
E. Insomnia

19. Rasagiline was prescribed to Ahmed The inhibition of which of the following enzymes most likely mediated the therapeutic
effect of the drug in the patient’s disease?
A. DOPA decarboxylase
B. Monoamine oxidase B
C. Dopamine β-hydroxylase
D. Tyrosine hydroxylase
E. Catechol O-methyltransferase
Which of the following adverse effects would most likely occur during the first days of pramipexole treatment?
A. Diplopia
B. Visual impairment
C. Peripheral edema
D. Nausea
E. Diarrhea
F. Muscle cramps
Benztropine was most likely given to improve which of the following of Ahmed's signs?
A. Gait disturbances
B. Tremor
C. Bradykinesia
D. Insomnia
E. Pramipexole-related symptoms

20. Case4: Chief Complaint
“My work performance has declined because my tremor makes it difficult to type on the computer, and I am slower with most
tasks.”
Amal is a 63-year-old, right-handed woman who presents to the neurology clinic because of a mild tremor in her right hand
that has worsened over the past 6 months. It takes her longer to do things because it takes a little more effort to get
movement started, and her muscles feel a little stiff. She also admits to difficulty falling asleep but has no issues staying asleep.
The stiffness, slowness, tremor and sleep problems have affected her job performance as a graphic designer, resulting in her
contemplating early retirement. She also complains of constipation, depressed mood, lack of pleasure in her usual activities,
and loss of sense of smell for about 2 years. Due to complaints of acid reflux, she is currently receiving treatment for it.
PMH GERD × 1 month
Broken left wrist after fall 1 year ago
■FH
Mother died at age 89 of complications associated with a hip fracture, osteoporosis, and Alzheimer disease (clinical diagnosis )
father died from an ischemic stroke at age 58; two daughters are in good health
VS
BP 118/74 mm Hg sitting, 116/70 mm Hg standing, P 70 bpm,RR 13; T 36.8°C; Wt 53 kg.

21. Na 136 mEq/L Hgb 13.5 g/dL AST 20 IU/L
K 4.3 mEq/L Hct 40.5% ALT 24 IU/L
Cl 101 mEq/L RBC 4.42 × 106 Alk phos 80 IU/L
CO
2 23 mEq/L
WBC 5.0 × 103/mm3 GGT 18 IU/L
BUN 12 mg/dL Plt 395 × 103/mm3 Ferritin 100 ng/mL
SCr 0.73 mg/dL Homocysteine 6 μmol/L TSH 2.0 mIU/L
Glu 83 mg/dL
Vitamin D, 25-hydroxy
18 ng/mL
T
4 total 7.5 mcg
Labs
Assessment
1. PD, untreated and uncontrolled, with mild depression
2. Insomnia, untreated and uncontrolled
3. Constipation, untreated and uncontrolled
4. Vitamin D deficiency, untreated
5. GERD

22. Develop a Care Plan
What are the goals of pharmacotherapy in this case?
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What nondrug therapies for PD might be useful for this patient?
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What feasible pharmacotherapeutic alternatives are available to treat this patient’s PD?
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