Parkinson's Disease

Question 1

True or False: Parkinson’s Disease is characterized as a syndrome of motor and non-motor symptoms

Answer 1

True

Question 2

What does diagnosis of PD rely on?

Answer 2

Signs/symptoms and ruling out other causes

-no lab testing available for diagnosis

Question 3

What are the risk factors of PD?

Answer 3

• Age (60 or older)
• heredity (close relative)
• Sex (M>F)
• Toxin exposure

Question 4

Describe the Dopamine imbalance in PD

Answer 4

Progressive loss of Dopamine in nigrostriatal tracts of brain; acetylcholine increased–> imbalance

Question 5

Clinical presentation (symptoms) can be separated into what 3 categories?

Answer 5

• Motor symptoms
• autonomic symptoms
• cognitive and psychiatric symptoms

Question 6

What are the motor symptoms of PD?

Answer 6

• abnormal gait, posture, impaired fine movements (buttoning shirt), masked facies, micrograph
• dysphagia, drooling, less blinking

Question 7

What are the autonomic symptoms of PD?

Answer 7

• Orthostatic hypotension
• impaired GI motility and constipation
• bladder dysfunction and sexual dysfunction

Question 8

What are the cognitive and psychiatric symptoms of PD?

Answer 8

• Cognitive decline
• hallucinations
• anxiety, depression, sleep disorders
• behavioral symptoms and agitation

Question 9

What are the cardinal features of PD?

Answer 9

Resting tremor (pill rolling), rigidity, bradykinesia

Question 10

What resources are used to diagnose a patient with PD?

Answer 10

• medical history and physical exam
• Neurologic Exam (cardinal features): one cardinal feature (possible), at least two (probable), at least two and positive response to levodopa (Definite)
• Neuroimaging to rule out other causes

Question 11

What drug classes may be used in the treatment of PD?

Answer 11

• carbidopa/levodopa
• dopamine agonists
• anticholinergics
• MAO-B inhibitors
• COMT inhibitors

Question 12

Which drug class is best for treatment of tremors? What if the patient is over the age of 65 with CC of tremors?

Answer 12

• anticholinergics

- use carbidopa/levodopa because anticholinergics increase fall risk

Question 13

Which dopamine agonists are used in the treatment of PD?

Answer 13

Bromocriptine, Rotigotine, Ropinirole, Pramipexole, apomorphine

Question 14

What are the benefits/downsides of Dopamine agonist use?

Answer 14

• Not as effective as levodopa
• fewer motor complications than levodopa
• longer half-life than levodopa (less daily dosing needed)
• non-ergot derivatives (pramipexole and ropinirole) preferred over ergot derivatives (bromocriptine) b/c of cardiac fibrosis and valve disease

Question 15

Which dopamine agonist has renal dosing? What is its dosage form?

Answer 15

pramipexole (mirapex); IR or ER tablet

Question 16

how is apomorphine administered

Answer 16

subcutaneous injection for intermittent freezing episodes

Question 17

Ropinirole dosage form

Answer 17

IR tablet, XL tablet

Question 18

Rotigotine Dosage form

Answer 18

transdermal patch; rotate app sites daily

Question 19

Bromocriptine dosage form

Answer 19

Tablet or capsule; give with food; give within 2 hours of waking in the morning

Question 20

What are the benefits and drawbacks of Levodopa for PD?

Answer 20

• most clinically effective therapy for PD symptoms
• 1st line in elderly
• long term use–> dyskinesia and motor complications
• effective for all cardinal symptoms

Question 21

Why is carbidopa administered with levodopa?

Answer 21

carbidopa reduces levodopa dose requirements and improves tolerability

Question 22

What is the difference between IR and CR carbidopa/levodopa (sinemet)

Answer 22

CR formulation is 30% less bioavailable compared to IR; must increase dose by 10% and titrate if switching from IR to CR

Question 23

What are the motor complications caused by Levodopa?

Answer 23

Freezing, on/off effect, wearing off, drug holiday

Question 24

Levodopa: Freezing

Answer 24

immobility in the morning b/c of short half life of levodopa
-take am dose upon waking, intermittent apomorphine, add DA or MAO-B, physiotherapy, assistive walking device, and sensory cues

Question 25

Levodopa: on/off effect

Answer 25

random mobility fluctuations

-add MAO-B, COMT inhibitor or DA

Question 26

Levodopa: Wearing off

Answer 26

dose ends at latter part of dosing interval

-CR levodopa, shorten dosing interval, add MAO-B, DA, or COMT inhibitor

Question 27

Levodopa: Drug holiday

Answer 27

brief period of drug withdrawal (at least one week) to improve response and minimize side effects of long term therapy

Question 28

What are some reasons why Levodopa treatment may fail?

Answer 28

misdiagnosis, inadequate dosage, drug interactions

Question 29

Why are COMT inhibitors used in PD?

Answer 29

inhibits metabolism of levodopa, only useful in combo with levodopa
-may cause brown-orange urine

Question 30

What are the adverse effects of COMT inhibitors?

Answer 30

• Entacapone is preferred tx; may cause severe diarrhea

- tolcapone has BBW for fatal hepatotoxicity

Question 31

Why are MAO-B inhibitor used in treatment of PD?

Answer 31

• blocks oxidative degradation of dopamine thru MAO-B inhibition
• can be used as initial therapy or adjunct with levodopa
• not as good as DA and levodopa for motor symptom control

Question 32

what should be avoided when taking MAO-B inhibitors?

Answer 32

tyramine-containing foods

Question 33

Why are Anticholinergics used in treatment of PD?

Answer 33

• blocks excitatory Ach, minimizing the effect of increase in cholinergic sensitivity
• corrects balance b/t Ach and dopamine
• best for tremors
• less effective than DA and levodopa/carbidopa for bradykinesia and rigidity

Question 34

Why is amantadine used in treatment of PD?

Answer 34

• used as adjunct to levodopa
• treats dyskinesia
• not generally considered as appropriate monotherapy option
• may improve tremor, rigidity, and bradykinesia
• improvement in days
• renal adjustments needed
• tachyphylaxis