Parkinson's

Question 1

What causes Parkinson’s?

Answer 1

loss of nigrostriatal dopamine neurons

Question 2

What is key in providing clinical improvement?

Answer 2

activation of D2 dopamine receptor

Question 3

How is PD diagnosed?

Answer 3

bradykinesia plus 2 or more of following:

• limb muscle rigidity
• resting tremor
• posutral instability
• micrographia

also responsiveness to L-dopa

Question 4

Modified Hoehn and Yahr Staging

Answer 4

• staging from 0 to 5 where 0 is no sign of dz and 5 is w/c bound and bedridden
• PD is progressive and sxs worsen over time

Question 5

Tx Goals

Answer 5

• maintain independence, ADLs, QOL
• alleviate sxs
• minimize development of response fluctuations
• limit medication-related adverse effects

Question 6

Possible Tx Approaches

Answer 6

• lifestyle changes, nutrition, exercise
• pharmacologic intervention
• surgical treatment

Question 7

What is the most effective tx for PD?

Answer 7

levodopa/carbidopa

Question 8

Levodopa/Carbidopa MOA

Answer 8

increases DA in CNS

Question 9

Why is levodopa used instead of straight dopamine?

Answer 9

-levodopa crosses BBB but DA does not

Question 10

Amantadine

Answer 10

-antiviral w/ mild therapeutic effects in PD

Question 11

Amantadine MOA

Answer 11

• NMDA receptor antagonist
• blocks glutamate (excitatory NT) transmission
• promotes DA release

Question 12

What can happen if amantadine is abruptly discontinued?

Answer 12

rebound PD

Question 13

Name 2 MAO-B inhibitors.

Answer 13

selegiline and rasagiline

Question 14

MAO-B Inhibitor MOA

Answer 14

• prevent breakdown of DA

- rasagiline may be neuroprotective and neurorestorative

Question 15

Drug Interactions of MAO-B Inhibitors

Answer 15

• TCA, SSRI, SNRI, meperidine: CNS toxicity, HTN, increased temp, death
• MAOI: HTN crisis
• tyramine containing foods: risk of HTN crisis

Question 16

Name 2 catechol-o-methyltransferase (COMT) inhibitors.

Answer 16

entacapone and tolcapone

Question 17

COMT MOA

Answer 17

inhibit breakdown of levodopa –> increase DA

Question 18

What is the benefit of COMT meds?

Answer 18

increase half life of levodopa by 50% –> more continuous stimulation of DA receptors

Question 19

Levo/carbidopa, amantadine, MAO-B inhibitors and COMT inhibitors all increase the amount of DA in CNS. What are their adverse effects?

Answer 19

• agitation, confusion
• insomnia, psychosis
• HA, dizziness
• orthostasis, dyskinesias
• N/V

Question 20

Which COMT med is preferred and why?

Answer 20

entacapone is preferred b/c tolcapone can cause liver toxicity

Question 21

Why might dopamine agonists be used?

Answer 21

may delay need for use of levodopa in early dz or decrease levodopa dose in advanced dz

Question 22

Give a couple examples of dopamine agonists.

Answer 22

bromocriptine
pramiprexole (Mirapex)
ropinirole
rotigotine

Question 23

What are adverse effects of DA agonists?

Answer 23

• confusion, dizziness
• hallucinations, orthostasis
• nausea, asthenia
• syncope, peripheral edema

Question 24

What is a side effect that can happen with pramiprexole or ropinirole?

Answer 24

episodes of suddenly falling asleep (sleep attack)

Question 25

If a pt is having CNS effects like confusion and hallucinations, how should their carbidopa be adjusted?

Answer 25

decrease carbidopa

Question 26

If a pt is having systemic effects like GI complaints and orthostatic HoTN, how should their carbidopa be adjusted?

Answer 26

increase carbidopa

Question 27

What can develop in some patients who are on dopamine therapy like dopamine enhancement or dopamine agonists?

Answer 27

-impulse control disorders/addictive behaviors

Question 28

Anticholinergics MOA

Answer 28

- increased striatal cholinergic activity causes tremor | - anticholinergics decrease that cholinergic activity and improve tremor

Question 29

Give an example of an anticholinergic med used in PD.

Answer 29

-benztropine (Cogentin)

Question 30

AEs of Anticholinergics

Answer 30

- anti-SLUD - confusion, memory loss - sedation, depression - drowsiness, orthostasis

Question 31

Why would you use a combinatino drug with carbidopa/L-dopa/entacapone?

Answer 31

-more steady levels of DA in CN b/c entacapone increases the levodopa half life

Question 32

If a patient experiences end of dose "wearing off," what are possible tx options?

Answer 32

- decrease levodopa dosing interval - add COMT inhibitor if on levodopa - add DA agonist to levodopa or vice versa - add MAO-B inhibitor to levodopa

Question 33

If a patient experiences a delayed on or no on response, what can be done?

Answer 33

- give levodopa on empty stomach - avoid levodopa controlled release, use levo ODT - use apomorphine subQ

Question 34

If a pt experiences start hesitation/freezing, what can be done?

Answer 34

- increase levodopa dose - add DA agonist or MAO-B inhibitor - PT and assistive walking devices or sensory cues

Question 35

If a pt experiences peak dose dyskinesia, what can be done?

Answer 35

- decrease levodopa dose and add/increase DA agonist - add amantadine - if COMT inhibitor recently added, consider decreasing levodopa dose

Question 36

What is used to treat hypomobility in PD?

Answer 36

- apomorphine (DA agonist w/ strong emetic properties) | - give with an anti-emetic (not 5-HT3 antagonist)

Question 37

Efficacy of Selegiline

Answer 37

mild, symptomatic benefit

Question 38

Efficacy of Dopaminergic Therapy

Answer 38

- effective in ameliorating motor and ADL disability - levodopa more effective than DA agonists - DA agonists have fewer motor complications, but more frequent adverse effects

Question 39

What can be used to treat PD psychosis and dementia?

Answer 39

- quetiapine (seroquel) is recommended - clozapine considered, but required frequent lab monitoring - typical antipsychotics are contraindicated

Question 40

Pt Education for PD

Answer 40

- educate about PD - community support - tx: adverse effects and optimizing care

Question 41

Why should anticholinergics not be used in PD pts over 65?

Answer 41

-due to higher risk of cognitive adverse effects