Parkinson Meds Flashcards
Characteristic features of Parkinson
Tremor
Rigidity
Badykinesia
Postural instability
What happens as a result of complications of Parkinson
Death
What is the pathophys of Parkinson
Loss of dopaminergic neurons in substantia nigra
What percent of pts develop motor complications of Parkinson
50-90% of pts on levodopa >5 years develop motor complications
How to deal with wearing off of levodopa effect
Initially: treat by more frequent dosing
Later: add dopamine agonist
How to deal w/ on-off effect of levodopa
Treat w/ rescue apomorphine or adjust dose/frequency of dosing
Describe the physical disability associated with Parkinson
Progressive
Unavoidable
Highly individualized***
Levoadopa (LD)
Mainstay of tx since the 1960s
DOES cross blood brain barrier (BBB)
Does LD have peripheral effects?
Yes
Ex: dyskinesias, NV, etc.
What do you always administer LD with?
Peripheral dopa decarboxylase (DDC) inhibitor
Ex: Carbidopa
What does LD compete w/ for absorption?
Other amino acids
GI upset with LD?
Yes, but minimized
How is LD best absorbed
W/ low protein meals
Peripheral dopa decarboxylase inhibitor agent
Carbidopa
COMT-Inhibitor Agents
Entacapone
Tolcapone
**good peripherally and centrally
MAO-B Inhibitor Agents
Selegiline
Rasagline
Carbidopa
Available alone or in combo w/ Levodopa
Sinemet
Carbidopa dosing
75-100 mg CD/d usually needed to inhibit peripheral DDC
*Usually start w/ IR product of 25/100 mg Sinemet TID
What dose of Levodopa do most pts respond to?
750-1000 mg of LD
After 8 Tabs/day of 25/100 mg Sinemet -> switch to to 1 tab of 25/250 TID
Carbidopa/Levodopa (SInemet) forms
Immediate release (generic) Sustained release (generic) Orally disintegrating (generic)
Carbidopa form
Brand = Lodosyn
Allows greater individualization for pts w/ advanced Parkinson
Entacapone dosing and cost
Generic
Available as 200 mg tabs or combo w/ Sinemet
Generic is significantly less expensive than brand Tolcapone
What is the combo of Entacapone and Sinemet called?
Stalevo
Tolcapone dosing and AE
Dosed as single drug TID
Associated w/ fatal cases of acute liver failure
So limited clinical use
MAO-B Inhibitors for Parkinson
Prolong dopamine agonist affects Modest effects Adjunct therapy in most cases Minimized tyramine intake Dont use SSRIs at the same time (Serotonin syndrome)
What are selegiline advantages and what is it less effective at?
Early use may delay need for LD by 9 months
May improve wearing off effects
Less effective in improving on off effects
Selegiline dosing
Generic (least expensive): BID
Brand Zelapar: daily-decreased 1st pass effect
Brand Emsam: only FDA approved for depression
Rasagiline inhibition strenght and cost
More potent inhibition of MAO-B than selegiline
Brand and generic are expensive
What is safinamide useful for treating and how is it used?
Use adjunct to levadopa/carbidopa
Useful for treatment of off episodes
Adverse effects off Safinamide
severe HTN
Hypersexual behavior
Retinal degeneration
Dopamine Agonists
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
Dopamine Agonist Agents
Bromocriptine Pramipexole Ropinirole Apomorphine Rotigotine
Bromocriptine
1st generation ergot-derivative (wheat)
Rarely used
Adverse effects: pericardial and cardiac valve fibrosis
Pramipexole
2nd generation
Fewer dyskinesias
Fewer wearing off effects
Fewer motor complications
Ropinirole
Equally efficacious per indirect comparisons
Dosing: generic = TID; brand = daily
Apomorphine
Injectable but expensive
Rescue therapy of hypomoblility or off episodes
What drug is contraindicated for apomorphine
Serotonin RAs (ondasetron-Zofran) Can cause severe hypotension and syncope
Dosing of IV apomorphine
SC 2-6 mg -> Higher than book recommends
IV administration is contraindicated
Rotigotine
Only one available as transdermal patch
very expensive
Anticholinergics
Mainstay of tx until 1960s
Reserved for resting tremor early in disease
Side effects of anticholinergics
Constipation Dry mouth Blurred vision Confusion Urinary retention
Benzotropin
Anticholinergic
May inhibit reuptake of dopamine
Divided BID or single dose at hs
IV/IM injection solution
Trihexyphenidyl
Anticholinergic
Divided 3-4x/day
Oral elixir
Amatadine
Primarily antiviral agent found to have anti-PD activity
Previously used as monotherapy
Now and add-on for levodopa-induced dyskinesias
Pramipexole dosing
Generic TID
Brand TID or daily
How is pramipexole eliminated?
Renally
Its the only dopamine agonist that is!
What is the recommended taper for pramipexole when d/cing it?
None!
Anticholinergic agents
Benzotropin
Trihexyphenidyl
Ropinirole taper
Taper over 7 days if D/Cing
How is ropinirole metabolized and if there is an issue w/ this organ is there a dose adjustment?
Hepatically metabolized
No dose adjustment
Apomorphine SE
Severe emesis
Will need an antiemetic
