Parkinson Meds

Question 1

Characteristic features of Parkinson

Answer 1

Tremor
Rigidity
Badykinesia
Postural instability

Question 2

What happens as a result of complications of Parkinson

Answer 2

Death

Question 3

What is the pathophys of Parkinson

Answer 3

Loss of dopaminergic neurons in substantia nigra

Question 4

What percent of pts develop motor complications of Parkinson

Answer 4

50-90% of pts on levodopa >5 years develop motor complications

Question 5

How to deal with wearing off of levodopa effect

Answer 5

Initially: treat by more frequent dosing
Later: add dopamine agonist

Question 6

How to deal w/ on-off effect of levodopa

Answer 6

Treat w/ rescue apomorphine or adjust dose/frequency of dosing

Question 7

Describe the physical disability associated with Parkinson

Answer 7

Progressive
Unavoidable
Highly individualized***

Question 8

Levoadopa (LD)

Answer 8

Mainstay of tx since the 1960s

DOES cross blood brain barrier (BBB)

Question 9

Does LD have peripheral effects?

Answer 9

Yes

Ex: dyskinesias, NV, etc.

Question 10

What do you always administer LD with?

Answer 10

Peripheral dopa decarboxylase (DDC) inhibitor

Ex: Carbidopa

Question 11

What does LD compete w/ for absorption?

Answer 11

Other amino acids

Question 12

GI upset with LD?

Answer 12

Yes, but minimized

Question 13

How is LD best absorbed

Answer 13

W/ low protein meals

Question 14

Peripheral dopa decarboxylase inhibitor agent

Answer 14

Carbidopa

Question 15

COMT-Inhibitor Agents

Answer 15

Entacapone
Tolcapone
**good peripherally and centrally

Question 16

MAO-B Inhibitor Agents

Answer 16

Selegiline

Rasagline

Question 17

Carbidopa

Answer 17

Available alone or in combo w/ Levodopa

Sinemet

Question 18

Carbidopa dosing

Answer 18

75-100 mg CD/d usually needed to inhibit peripheral DDC

*Usually start w/ IR product of 25/100 mg Sinemet TID

Question 19

What dose of Levodopa do most pts respond to?

Answer 19

750-1000 mg of LD

After 8 Tabs/day of 25/100 mg Sinemet -> switch to to 1 tab of 25/250 TID

Question 20

Carbidopa/Levodopa (SInemet) forms

Answer 20

Immediate release (generic)
Sustained release (generic)
Orally disintegrating (generic)

Question 21

Carbidopa form

Answer 21

Brand = Lodosyn

Allows greater individualization for pts w/ advanced Parkinson

Question 22

Entacapone dosing and cost

Answer 22

Generic
Available as 200 mg tabs or combo w/ Sinemet
Generic is significantly less expensive than brand Tolcapone

Question 23

What is the combo of Entacapone and Sinemet called?

Answer 23

Stalevo

Question 24

Tolcapone dosing and AE

Answer 24

Dosed as single drug TID
Associated w/ fatal cases of acute liver failure
So limited clinical use

Question 25

MAO-B Inhibitors for Parkinson

Answer 25

``` Prolong dopamine agonist affects Modest effects Adjunct therapy in most cases Minimized tyramine intake Dont use SSRIs at the same time (Serotonin syndrome) ```

Question 26

What are selegiline advantages and what is it less effective at?

Answer 26

Early use may delay need for LD by 9 months May improve wearing off effects Less effective in improving on off effects

Question 27

Selegiline dosing

Answer 27

Generic (least expensive): BID Brand Zelapar: daily-decreased 1st pass effect Brand Emsam: only FDA approved for depression

Question 28

Rasagiline inhibition strenght and cost

Answer 28

More potent inhibition of MAO-B than selegiline | Brand and generic are expensive

Question 29

What is safinamide useful for treating and how is it used?

Answer 29

Use adjunct to levadopa/carbidopa | Useful for treatment of off episodes

Question 30

Adverse effects off Safinamide

Answer 30

severe HTN Hypersexual behavior Retinal degeneration

Question 31

Dopamine Agonists

Answer 31

Cross BBB and stimulate the dopamine receptors Can be use as monotherapy early in disease, or adjunct later on ADLs improve on these 30% Monotherapy more effective with younger pts Early use my postpone use of levodopa

Question 32

Dopamine Agonist Agents

Answer 32

``` Bromocriptine Pramipexole Ropinirole Apomorphine Rotigotine ```

Question 33

Bromocriptine

Answer 33

1st generation ergot-derivative (wheat) Rarely used Adverse effects: pericardial and cardiac valve fibrosis

Question 34

Pramipexole

Answer 34

2nd generation Fewer dyskinesias Fewer wearing off effects Fewer motor complications

Question 35

Ropinirole

Answer 35

Equally efficacious per indirect comparisons | Dosing: generic = TID; brand = daily

Question 36

Apomorphine

Answer 36

Injectable but expensive | Rescue therapy of hypomoblility or off episodes

Question 37

What drug is contraindicated for apomorphine

Answer 37

``` Serotonin RAs (ondasetron-Zofran) Can cause severe hypotension and syncope ```

Question 38

Dosing of IV apomorphine

Answer 38

SC 2-6 mg -> Higher than book recommends | IV administration is contraindicated

Question 39

Rotigotine

Answer 39

Only one available as transdermal patch | very expensive

Question 40

Anticholinergics

Answer 40

Mainstay of tx until 1960s | Reserved for resting tremor early in disease

Question 41

Side effects of anticholinergics

Answer 41

``` Constipation Dry mouth Blurred vision Confusion Urinary retention ```

Question 42

Benzotropin

Answer 42

Anticholinergic May inhibit reuptake of dopamine Divided BID or single dose at hs IV/IM injection solution

Question 43

Trihexyphenidyl

Answer 43

Anticholinergic Divided 3-4x/day Oral elixir

Question 44

Amatadine

Answer 44

Primarily antiviral agent found to have anti-PD activity Previously used as monotherapy Now and add-on for levodopa-induced dyskinesias

Question 45

Pramipexole dosing

Answer 45

Generic TID | Brand TID or daily

Question 46

How is pramipexole eliminated?

Answer 46

Renally | Its the only dopamine agonist that is!

Question 47

What is the recommended taper for pramipexole when d/cing it?

Answer 47

None!

Question 48

Anticholinergic agents

Answer 48

Benzotropin | Trihexyphenidyl

Question 49

Ropinirole taper

Answer 49

Taper over 7 days if D/Cing

Question 50

How is ropinirole metabolized and if there is an issue w/ this organ is there a dose adjustment?

Answer 50

Hepatically metabolized | No dose adjustment

Question 51

Apomorphine SE

Answer 51

Severe emesis | Will need an antiemetic