Parkinson's Disease

Question 1

What are symptoms of parkinson’s disease?

Answer 1

Bradykinesia

With either:

• rigidity
• tremor

And +/- postural instability

Question 2

What are other motor features of PD?

Answer 2

Masked fascies
Decreased blinking

Shuffling gait
Decreased arm swing

Stooped posture
Difficulty turning

Small handwriting

Question 3

What are non-motor features of PD?

Answer 3

Neuropsychiatric
(Depression, anxiety)

Sleep abnormalities

Cognitive changes

Autonomic dysfunction
(Constipation common; also orthostasis)

Question 4

What are medications/treatments for motor symptoms of PD?

Answer 4

Anticholinergic
Amantadine

Levodopa
Dopamine agonists

MAO-B inhibitors
COMT inhibitors

Deep brain stimulation

Question 5

How is dopamine metabolized?

Answer 5

By two enzymes:

MAO-B and COMT

Question 6

What anticholinergic medications are used for PD?

What do they treat?

Answer 6

Trihexyphenidyl

Benztropine

Tremor

Question 7

Describe MOA of anticholinergics for treatment of PD

Answer 7

Reduces cholinergic input to striatum and blocks muscarinic ACh receptors

Question 8

What are AEs of anticholinergic agents for PD?

Answer 8

Sedation

Confusion/hallucinations
(Patients 65+)

Dry mouth
Glaucoma
Urinary retention
Constipation

Hyperthermia, flushing
Acute anticholinergic toxicity

Question 9

What does Amantadine treat?

What is its MOA?

Answer 9

Early Tremor + later dyskinesia

MOA:
NMDA antagonist + anticholinergic and dopamine agonist properties to block overstimulation

Question 10

What are AEs associated with Amantadine?

Answer 10

May inc. dementia, confusion in elderly

Insomnia

Livedo reticularis and ankle edema

Question 11

What is a PEARL associated with Amantadine?

Answer 11

Dose earlier than NOON to avoid insomnia

For use with fatigue

Question 12

What are 3 dopamine strategies for increasing dopamine levels, and the drug classes that achieve them?

Answer 12

• prevent dopamine breakdown (MAO-B inhibitors)
• stimulate body’s own dopamine pathways (dopamine agonists)
• direct replacement (levodopa)

Question 13

What are MAO-B inhibitors and what do they treat?

Answer 13

Selegiline
Rasagiline

Some benefit to all motor symptoms:
Tremor > rigidity > bradykinesia

Question 14

What are AEs associated with MAO-B inhibitors?

Answer 14

Interactions with MAO-A
+tyramine (wine and cheese)
+hypertensive crisis

Question 15

What are CIs associated with MAO-B inhibitors?

Answer 15

Serotonin syndrome:
+cognitive = confusion, agitation, hyperactivity
+autonomic = CV, GI
+neurological = tremors, myoclonus, hyperreflexia, hypertonia

Question 16

What are dopamine agonists?

Answer 16

Ropinirole

Pramipexole

Rotigotine

Bromocryptine

Apomorphine

Question 17

What do dopamine agonists treat?

What is their MOA?

Answer 17

All motor features:
Tremor > rigidity > bradykinesia

MOA:
Potentiates action of existing dopamine neurons

Question 18

What is the difference in half-lives of dopamine agonists?

Answer 18

Ropinirole = 6 hours

Pramipexole = 8 hours

Question 19

What are AEs associated with dopamine agonists?

Answer 19

Sedation
Sudden sleep onset

Worsen hallucinations/ dyskinesia

Leg swelling

Impulse control disorder in some **

Question 20

What is Carbidopa?

Answer 20

Enzyme inhibitor that prevents breakdown of levodopa

Avoids peripheral side effects of nausea and orthostasis

Does not pass BBB

Question 21

What does carbidopa/levodopa treat?

Answer 21

All motor features!
Tremor > rigidity > dyskinesia

(Not gait)

Question 22

What are motor complications associated with cabidopa/levodopa?

Answer 22

As disease progresses, less dopamine neurons exist to process dopamine

Freezing
Dyskinesia (“extra” movements”)
Shorter time windows of efficacy

Question 23

What are AEs associated with carbidopa/levodopa?

Answer 23

Early: nausea, dizziness

Late

• fluctuations
• dyskinesia
• hallucinations
• orthostatic hypotension
• incomplete/ unreliable absorption

Question 24

What should patients be advised for carbidopa/levodopa?

Answer 24

Tell patients to take it away from food in order to improve absorption and limit dosing

Question 25

When should anticholinergic meds be used for PD?

Answer 25

Young + tremor predominant disease

Question 26

When should Amantadine be used to treat PD?

Answer 26

Younger patients with mild symptoms

+ fatigue

Question 27

When should MAO-B inhibitors be used for PD?

Answer 27

Mild symptoms

Question 28

When should dopamine agonists be used for PD?

Answer 28

Younger patients with moderate symptoms

Sleep difficulties

Question 29

When should CD/LD be used to treat PD?

Answer 29

Severe symptoms
Older patients (>80 yo)
- do not tolerate other meds
Unclear diagnosis

Question 30

What are COMT inhibitors?

Answer 30

Entacapone

Tolcapone

Combination Sinemet/entacapone

Question 31

What do COMT inhibitors do?

Answer 31

Only useful with exogenous levodopa

Prevent breakdown of dopamine

Question 32

What are side effects of COMT inhibitors ?

Answer 32

Dopamine side effects

Question 33

What black box warning is associated with tolcapone?

Answer 33

Liver failure

Question 34

What is duodopa?

Answer 34

Levodopa with carbidopa pumped into stomach, small doses at a time

Question 35

What is deep brain stimulation?

Answer 35

Implant for patients with:
+significant dyskinesia
+fluctuations
+“off” time despite medication

Patients not tolerating medication