Parkinsons Flashcards
MOA of levodopa
converted in the CNS to dopamine
What converts levodopa to dopamine?
AA decarboxylase
AADC
What is the DOC for primary PD?
Levodopa
What agents decreased enzymatic metabolism of levodopa?
AADC inhibitors
COMT inhibitors
How many times per day is levodopa given? why?
3-5
short 1/2 life
Levodopa has the fastest onset to treat_____________
bradykinesias
What is a con of treating with levodopa?
Duration of action becomes shorter, and risk of dyskinesias increased w/increasing dosage
Levodopa may activate _________________
malignant melanoma
What medications should you give with levodopa?
entacapone
tolcapone
carbidopa
MOA of entacapone
Inhibits COMT which INCREASES levodopa uptake
-enhances bioavailability
MOA of carbidopa
Inhibits AADC so levodopa is not broken down before it can pass the BBB
MOA of tolcapone
Inhibits COMT which INCREASES levodopa uptake
-enhances bioavailability
Carbidopa is only given with _____________
levodopa
You can ____________ levodopa dosage when combined with carbidopa
decrease
Carbidopa + levodopa
sinemet
What is AACD?
responsible for converting levodopa to dopamine in periphery and CNS
-which is why we want to inhibit it-prevents the breakdown
AE of tolcapone
diarrhea, liver issues
LFTs q2wks x 1 year
AE of entacapone
Confusion, dizziness, sedation, hallucinations
What is something unique about tolcapone?
Crosses the BBB so it also inhibits CNS metabolism of dopamine by COMT (in addition to its action on levodopa)
MOA of carbidopa
inhibits AADC
The following are what type of drug: bromocriptine pramiprexole ropinirole apomorphine
Dopamine receptor agonists
-Directly stimulates postsynaptic DOPAMINE receptors
Apomorphine is contraindicated in pt w/___________________
orthostatic hypotension
What is something unique about apomorphine?
Need an antiemetic to avoid severe nausea and vomiting
Apomorphine can be given with _____________ to reduce the risk of nausea and vomiting
trimethobenzamide
What is a uncommon but unique AE of dopamine receptor agonists?
gambling
-especially ropinirole
In what situation would dopamine receptor agonists may be used as first line?
to treat early onset PD to delay the use of levodopa
-avoid dyskinesias
Bromocriptine is a dopamine ____________
agonist
What kind of drug is pramirexole?
dopamine receptor agonist
Which of the dopamine receptor agonists are given in subQ form?
apomorphine
Dopamine receptor agonists are also used in the treatment of __________
RLS
-i have no idea what this is but it was in his slides
In what situation is apomorphine useful?
acute
Dopamine is ____________
inhibitory
Acetlycholine is _________
excitatory
What regulates voluntary movement?
substantia nigra in basal ganglia of midbrain
What two drugs are inhibitors of dopamine metabolism?
selegiline
rasagiline
Where is selegiline active?
CNS-not periphery
MOA of rasagiline
inhibits breakdown of dopamine
Selegiline and rasagiline are ___________ inhibitors
MAO-B
MAO-A vs MAO-B
MAO-A: tyramine, NE, epi, serotonin
MAO-B: dopamine
What is the difference between selegiline/rasagiline and COMT inhibitors?
COMT acts in periphery
selegiline/rasagiline act in CNS
Selegiline may last for _____________
months
Is rasagiline selective for MAO-B?
nope
Which is more potent, selegiline or rasagiline?
rasagiline is x5 more potent
What kind of drug inhibits the metabolism of dopamine?
selegiline/rasagiline
-inhibitors of dopamine metabolism
In advanced disease you can give selegiline/rasagiline with _____________ to enhance effect
levodopa
What kind of drug is amantadine?
dopamine reuptake inhibitor
MOA of amantadine
stimulates presynaptic release of dopamine
inhibits presynaptic reuptake of dopamine
What is a unique con about amantadine?
starts working in a few weeks and stops after a few months
-given in 1-2 week periods during exacerbations
Amantadine vs. levodopa
not as effective but fewer AE
Amantadine is ___________ effective than anticholinergics
less
What kind of drug is benztropine?
anticholinergic
What kind of drug is trihexyphenidyl?
anticholinergic
What kind of drug is diphenhydramine?
anticholinergic
MOA of benztropine
reduces the relative excess of ACh vs dopamine
What are could you give to treat tremors, salivation and spasticity associated with PD?
anticholinergics
- benztropine
- trihexyphenidyl
- diphenhydramine
What drug essentially “replaces” dopamine?
levodopa
What drugs stimulate dopamine receptors?
bromocriptine
ropinirole
pramiprexole
rotigotine
What drugs inhibit the breakdown of CNS dopamine?
selegiline
rasagiline
What drug increases the levels of CNS dopamine?
amatadine
What kind of drugs may exacerbate PD?
antipsychotics antiemetics -promethasize, metoclopramide, prochlorperizine DA depleting Rx -reserpine, methyldopa
What agents decreased the metabolism of levodopa?
AADC inhibitors
COMT inhibitors