Parkinson Disease

Question 1

Parkinson Disease: features

Answer 1

resting tremor
rigidity
bradykinesia
postural instability

Question 2

Parkinson Disease: pathology

Answer 2

dopamine deficiency

acetylcholine excess

Question 3

Parkinson Disease: non-pharmacologic treatment

Answer 3

education
exercise
nutrition
psychosocial support

Question 4

Parkinson Disease: pharmacologic treatment

Answer 4

dopamine precursor
dopamine agonist
MAOB inhibitor
COMT inhibitor
muscarinic antagonist
amantadine

Question 5

SLUDGE

Answer 5

S: salivation
L: lacrimation
U: urination
D: defecation
G: GI
E: emesis

Question 6

Dopamine and the brain

Answer 6

dopamine cannot cross the blood brain barrier

levodopa is a dopamine precursor that can cross the BBB

BUT levodopa is rapidly metabolized in the periphery - need medications to prevent this

once levodopa is in the brain it is converted to dopamine

Question 7

MAO-B Inhibitor: Rasagiline, Selegiline: MOA

Answer 7

irreversible inhibition of monoamine oxidase type B in the brain
–>
interferes with the degradation of dopamine
–>
prolonged dopaminergic activity

Question 8

MAO-B Inhibitor: Rasagiline, Selegiline: ADEs

Answer 8

nausea
orthostatic hypotension
confusion
insomnia
hallucinations

Question 9

MAO-B Inhibitor: Rasagiline, Selegiline: drug interactions

Answer 9

serotonin syndrome with meperidine, opioids

SSRI’s are not contraindicated

Question 10

Serotonin Syndrome: signs and symptoms

Answer 10

change in BP
rapid HR
N/V
tremor
agitation/restlessness

Question 11

Selegiline

Answer 11

oral or ODT

improves motor function
inc on time

metabolizes down to amphetamines

ADEs:

• agitation
• insomnia
• hallucinations
• orthostatic hypotension
• can make sx worse when given with levodopa

Question 12

MAO-B Inhibitor: Safinamide

Answer 12

selective, reversible adjunct tx with levodopa/carbidpoa

inc on time w/out dyskinesia
improves motor function, clinical status, QOL

ADEs:

• dyskinesia
• nausea
• insomnia
• halls
• HTN
• hallucinations
• impulse control disorder
• serotonin syndrome
• LFT elevation
• very high tyramine containing foods

Question 13

What is the treatment if the main physical exam finding is tremor?

Answer 13

anticholinergic medication

Question 14

Anticholinergic Medication

Answer 14

mild tremor predominant PD

<65 years of age: monotherapy

65+: adjunct

used with caution:

• elderly
• cognitive difficuties

decreases acetylcholine

Question 15

Anticholinergic Medications: medications, ADEs

Answer 15

benztropine
trihexyphenidyl

ADEs:

• inc body temp
• dry mouth, dry eyes, dec sweat
• dilated pupils
• flushing
• delirium

Question 16

Levodopa/Carbidopa

Answer 16

dopamine precursor

65+ years of age

most effective drug for symptomatic treatment of PD

Question 17

Carbidopa

Answer 17

reduces side effects

inhibits peripheral metabolism of levodopa –> inc the fraction that reaches the brain

Question 18

Levodopa/Carbidopa: drug interaction

Answer 18

COMT and MAOB inhibitors

• diminish doses
• prolong action

patient would exhibit excess dopamine

Question 19

Levodopa/Carbidopa: ADEs

Answer 19

drowsiness
dyskinesias
-motor complications

Question 20

COMT Inhibitor: MOA

Answer 20

blocks the conversion of levodopa to 3-OMD
–>
provides greater percentage of levodopa to cross BBB

Question 21

COMT Inhibitor

Answer 21

entacapone
tolcapone

attenuate motor fluctuations in carbidopa/levodopa treated patients

neuroprotective effect

not used as monotherapy

Question 22

COMT Inhibitor: ADEs

Answer 22

dyskinesia
confusion
nausea
diarrhea
liver toxicity (tolcapone)
orthostatic hypotension

Question 23

COMT Inhibitor: drug interaction

Answer 23

reduce dose

• levodopa
• antidiarrheals

Question 24

Dopamine Agonist

Answer 24

pramipexole

stimulates dopamine activity in the substantia nigra and striatum

Question 25

Dopamine Agonist: ADEs

Answer 25

``` postural hypotension pulmonary fibrosis confusion hallucinations sedation vivid dreaming impulsive behavior ```

Question 26

Amantadine

Answer 26

enhances dopamine release blocks glutamatergic NMDA receptors benefits: - tremor - rigidity - bradykinesia add on agent to attenuate dyskinesias

Question 27

Amantadine: ADEs

Answer 27

``` confusion dizziness dry mouth hallucinations livedo reticularis (lacey pattern appearance) ```

Question 28

Apomorphine

Answer 28

derived from morphine - lacks narcotic properties premedicated w/ trimethobenzamide (antiemetic) --> SQ --> on response w/in 20 minutes indication: advanced PD w/ intermittent off episodes ADEs: N/V

Question 29

End of dose "wearing off"

Answer 29

inc frequency add COMT inhibitor or MAOB inhibitor or dopamine agonist

Question 30

"Delayed on" or "no on" response

Answer 30

give on an empty stomach use ODT form avoid CR (long acting) form use apomorphine

Question 31

Start hesitation

Answer 31

inc C/L dose add dopamine agonist or MAOB inhibitor PT w/ assistive walking devices or sensory cues

Question 32

Peak dose dyskinesia

Answer 32

smaller doses of C/L add amantadine

Question 33

Duopa

Answer 33

gel form C/L (enteral suspension) treats motor symptoms tube placed in the intestine - duopa delivered directly to intestine improved absorption reduced off times

Question 34

Deep Brain Stimulation (DBS)

Answer 34

adjunct to pharmacotherapy bilateral, chronic, high frequency electrical stimulation does NOT improve gait or postural instability

Question 35

Thalamic DBS

Answer 35

suppresses tremor (sp arm tremor) ``` does NOT improve bradykinesia rigidity motor fluctuations dyskinesia ```

Question 36

STN and GPi DBS

Answer 36

``` improves tremor rigidity bradykinesia motor fluctuation dyskinesia activities of daily living ``` STN DBS: allows for greater reduction in meds