Parkinson's Disease

Question 1

Features of Parkinson’s Disease

Answer 1

Parkinson's:
resting tremor
rigidity
bradykinesia
postural instability
hypomimia (masked face)
hypophonia (soft speech)
depression

Question 2

Pathology of Parkinson’s Disease

Answer 2

Dopamine deficiency or acetylcholine excess

Question 3

What are the pharmacologic treatment options for PD?

Answer 3

Dopamine precursors
Dopamine agonists
MAOI inhibitors
COMT inhibitors
Muscarininc antagonists
Amantadine

Question 4

What 2 enzymes decrease the metabolism of dopamine in the brain (aka raise the level of dopamine)?

Answer 4

MAOI inhibitors and COMT

Question 5

When should treatment for Parkinson’s be initiated?

Answer 5

when the disease begins to interfere w/activities of daily living, employment, or quality of life

Question 6

MOA of Amantadine

Answer 6

enhances dopamine release

Blocks glutamatergic NMDA receptors

Question 7

Why is Rasagiline (MAOI inhibitor) the 1st line tx?

Answer 7

• over Levodopa bc of Levo’s ADE’s

- pts w/ mild to moderate sxs, <65yo, start early

Question 8

ADE’s of Rasagiline (MAOI inhibitor)

Answer 8

nausea
orthostatic hypotension
confusion
insomnia
hallucinations

Question 9

Rasagiline (MAOI inhibitor) drug interactions

Answer 9

Serotonin syndrome w/ Meperidine (BP changes, tachycardia, N/V, tremor, agitation)

Question 10

When is Amantadine most useful?

Answer 10

in treating younger patients w/early or mild PD and perhaps later when dyskinesia becomes problematic

Question 11

Amantindine works well for which specific sxs?

Answer 11

tremor
rigidity
bradykinesia

Question 12

ADE’s of Amantidine

Answer 12

confusion
dizziness
dry mouth
hallucinations

(similar to anticholinergics)

Question 13

MOA of Dopamine agonists (Pramipexole)

Answer 13

stimulates dopamine activity on the nerves in the substantia nigra and striatum

Question 14

ADE’s of Dopamine agonists

Answer 14

*postural hypotension
*impulsive behaviors
pulmonary fibrosis
confusion, hallucinations, sedation, vivid dreaming

Question 15

Dopamine precursor MOA

Answer 15

replace dopamine once broken down by DOPA-D

Levodopa

Question 16

Why is Carbidopa added to Levodopa?

Answer 16

carbidopa prevents breakdown of L-Dopa into dopamine in the body therefore preserves more for the brain and lessens body ADE’s
(aka incr. fraction of dose that reaches brain)

Question 17

Drug interactions b/t Levodopa/Carbidopa

Answer 17

COMT and MAO type B inhibitors diminish doses and prolongs action

Question 18

ADE’s of Levodopa/carbidopa

Answer 18

drowsiness

dyskinesias (motor complications)

Question 19

Possible initial treatment for end-of-dose “wearing off” (motor fluctuation)

Answer 19

Increase frequency of carbidopa/L-dopa doses

Add either COMT inhibitor or MAO-B inhibitor or dopamine agonist

Question 20

Possible initial treatment for “delayed on” or “no on” response

Answer 20

Give carbidopa/levodopa on empty stomach
Use carbidopa/levodopa orally dissolved tablet (avoid controlled release)
Use apomorphine subcutaneous

Question 21

Possible initial treatment for start hesitation or “freezing”

Answer 21

Increase carbidopa/levodopa dose
Add a dopamine agonist or MAO-B inhibitor
Use PT, assistive walking device, sensory cues

Question 22

Possible initial treatment for Peak-dose dyskinesia

Answer 22

Provide smaller doses of carbidoopa/L-dopa

Add amantadine

Question 23

MOA for COMT inhibitors

Answer 23

• blocks conversion of L-Dopa into 3-OMD & prevents conversion of Dopamine to 3-MT
• provides greater percentage of L-dopa to cross the blood brain barrier

Question 24

What are 2 available COMT inhibitors?

Answer 24

Entacapone

Tolcapone

Question 25

What are the benefits of using COMT inhibitors?

Answer 25

- w/ MAO-B inhibitors --> attenuate motor fluctuations in carbidopa/levodopa treated pts - Modest benefit as monotherapy - benefit may be from neuro-protective effect

Question 26

ADE's of COMT inhibitors

Answer 26

``` related to increased levels of L-dopa dyskinesias confusion Nausea, diarrhea liver toxicity orthostatic hypotension ```

Question 27

drug interactions of COMT inhibitors

Answer 27

L-dopa (reduce dose) | anti-diarrheals

Question 28

What should you monitor if a pt is on a COMT inhibitor?

Answer 28

LFT's

Question 29

Muscarinic antagonists (anticholinergic meds) are best for which pt's?

Answer 29

- (most useful as a monotherapy) for <70 w/ disturbing tremor but NOT significant bradykinesia or gait disturbance - also good for pts w/advanced disease w/ persistent tremor despite other meds

Question 30

Muscarinic antagonists (anticholineric meds) should be used w/caution in...

Answer 30

the elderly and those w/pre-existing cognitive difficulties

Question 31

What are 2 muscarinic antagonists/ anticholinergic medications?

Answer 31

Benztropine (Cogentin) | Trihexyphenidyl (Artane)

Question 32

ADE's of muscarinic antagonists/ anticholinergic medications

Answer 32

``` Hot as a hare Dry as a bone Blind as a bat Red as a beet Mad as a hatter ```

Question 33

MOA of muscarinic antagonists

Answer 33

partially blocks cholinergic activity in basal ganglia, blocks dopamine reuptake and storage (useful for mild tremor-predominant PD)

Question 34

What is another form of carbidopa/levodopa that is delivered in a gel form called enteral suspension?

Answer 34

Duopa

Question 35

What does the patient need before starting Duopa?

Answer 35

surgery - to create a stoma in your stomach wall, a tube is placed in this hole to deliver the Duopa medication (improves absorption)

Question 36

When is immediate-release carbidopa/L-dopa absorbed best?

Answer 36

on an empty stomach, although it is commonly taken w/food to minimize nausea

Question 37

What are the 2 MAO-B inhibitors?

Answer 37

Rasagiline and Selegiline