Transcript Treatment of Parkinson Disease

Treatment of Parkinson
Disease
David Tran, 2013 Mercer University
PharmD Candidate
Epidemiology
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Second to Alzheimer disease as the most common
neurodegenerative disorder
Men affected more than women
Peak onset between 55 and 65 years
Occurs in 1% to 2% of individuals older than 60
years
Estimated prevalence is 1 million individuals in the
U.S. and 5 million individuals worldwide
Positive risk factors- advanced age, family history of
Parkinson disease, early-life rural living, early
exposure to pesticides and heavy metals
Protective risk factors- cigarette smoking and
caffeine use
Clinical Presentation
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4 cardinal manifestations- resting tremor,
bradykinesia, rigidity, and gait disturbance
Non-motor symptoms- dementia, depression,
anxiety, sleep disturbance, and autonomic
dysfunction
Typically presents with unilateral or
asymmetric motor signs
Medical Treatment
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Levodopa (grade A)
Peripheral decarboxylase inhibitors
Dopamine agonists (grade B)
Catechol-o-methyl transferase inhibitors (grade
B)
Monoamine oxidase B inhibitors (grade C)
Anticholinergics (grade C)
Amantadine (grade B and C)
Deep brain stimulation
Medical Treatment of Advanced
Parkinson Disease
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30-50% of patients develop motor
complications within 5 years of treatment with
Levodopa
Duration of response to each dose shortens
Dyskinesia as a result of excessive Levodopa
Dystonia due to wearing-off effects of
Levodopa
Management of Motor Fluctuations
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Levodopa adjustments
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Enzyme inhibitors
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Dystonia and wearing-off effects  reduce Levodopa
dose intervals
Dyskinesia  reduce Levodopa dose
No response to Levodopa  increase dose or reduce
dose interval
COMT and MAO-B inhibitors
Prolong and potentiate Levodopa effects
Dopamine agonists
Deep Brain Stimulation (DBS)
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Implantation of a stimulating electrode with 4 electrical
contacts into a brain target connected to a pulse generator
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Improves bradykinesia, rigidity, and tremor while producing
reversible effects without destroying significant amounts of
brain tissue
Provides continuous relief from motor fluctuations
5% of patients with Parkinson disease severe enough to
warrant DBS use
60,000 DBS implants placed worldwide for Parkinson
disease
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Effectiveness of Subthalamic DBS
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3 prospective, randomized controlled trials
were conducted
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showed improvements in motor scores, daily living
scores while off medication, and quality of life
scores
Levodopa dyskinesias improved, off-time was
reduced, and on-time was increased
Level AIIa recommendation
Potential Complications of DBS
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Procedure-related
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Hardware-related
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Foreign body reaction, surgical site infection, surgical
site pain, cerebral hemorrhage
Paresthesias, dyskinesias, and muscle contractions
during programming, infection
Adverse effects
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Impaired verbal fluency, declines in working memory,
processing speed, and delayed recall, acute
depression, mania, aggressive behavior, increased
suicide risk
Indications and Contraindications for
DBS for Parkinson Disease
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Indications
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Idiopathic Parkinson disease
Disturbing motor fluctuations and/or dyskinesias unresponsive to
medical management
Motor symptoms must be responsive to Levodopa
Medication resistant tremor
Contraindications
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Atypical parkinsonism
No response to Levodopa
Main disability is gait freezing and postural instability
Significant cognitive deficits
Significant psychiatric disturbance
Poor medical health
Advanced age
Case Study
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ML is a 64 y/o AAM with a past history of stroke who has advanced
Parkinson disease. He was diagnosed with PD in 1999. He initially
presented with left-sided clumsiness, loss of dexterity, and
depression. Over the years, his symptoms progressed and has had
increasing difficulty with fluctuating on/off symptoms. His current
medication regimen is Carbidopa-Levodopa-Entacapone 31.25-125200 mg q4h and Pramipexole 1 mg q4h. On this regimen, he has
difficulty with fine and gross motor skills. Walking has slowed
considerably with frequent episodes of gait freezing. His tremor is
minor and intermittent. His voice has become softer and harder to
understand. He reports feeling depressed and anxious due to his
public perception. Pmh include left thalamic infarct in 1991 without
residual symptoms and BPH. Other medications include
Clonazepam 0.5 prn, Lansoprazole 30 mg daily, and Aspirin 81 mg
daily.
Case Study
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ML is experiencing moderate rigidity and severe bradykinesia of the
upper extremities four hours after his last Levodopa dose. He walks
with a stooped posture with decreased stride length and foot
elevation. Forty-five minutes after his Levodopa dose, he developed
dyskinesia of the head and upper extremities.
What treatment options are available to improve ML’s Parkinson
disease management?
References
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Jann, Michael. Neurodegenerative Disorders: Parkinson Disease.
12/12/2010
Tarsy, Daniel. Treatment of Parkinson Disease: A 64-Year-Old Man
with Motor Complications of Advanced Parkinson Disease. JAMA.
June 6, 2012:307(21);2305-2314.