Pharm - Movement Disorders Flashcards
(40 cards)
MOA levodopa
agonist at dopamine receptors
benefits of coadministration of levodopa with carbidopa
- doesn’t cross BBB
- reduced metabolism
- increased plasma levels
- increased half life
- increased levodopa available for entry into the brain
describe the wearing-off phenomenon
occurs with long-term treatment with levodopa
each dose of levodopa effectively improves mobility for a period of time but rigidity and akinesia returns rapidly at the end of the dosing interval
side effects levodopa
GI: anorexia, nausea, vomiting
CV: postural hypotnesion, HTN with large doses
Dyskinesia: choreoathetosis (movement of intermediate speed, between quick, flitting movements of chorea and the slower, writing movements of athetosis)
Behavioral: depression, anxiety, agitation, insomnia, somnolence, confusion, delusions, hallucinations, nightmares, euphoria
describe the on-off phenomenon
off-periods of marked akinesia alternate over the course of a few hours with on-periods of improved mobility but often marked dyskinesia
what can provide temporary benefit to patients with severe off-periods in off-on syndrome when taking levodopa
subcutaneous injections of apomorphine
drug interactions with levodopa
MAOIs
levodopa is contraindicated in what patients
- psychotic pts
- pts w/ angle-closure glaucoma
- pts w/ history of melanoma or suspicious undiagnosed skin lesions
- pts with active peptic ulcer
MOA and metabolism of bromocriptine
ergot alkaloid derivate that is a D2 agonist
28% bioavailability - peak plasma concentration at 13 hours
extensive first pass metabolism with CYP3A4
MOA and metabolism of pramipexole
affinity for D3 receptors
90% excreted unchanged in urine - peak plasma concentration at 2 hours
MOA and metabolism of ropinirole
affinity for D2 receptors
CYP450 metabolism - peak plasma concentration 1-2 hours
side effects for dopamine agonists
GI: anorexia, nausea, vomiting, constipation, dyspepsia, reflux
CV: postural hypotension, digital vasospasm, peripheral edema, cardiac arrhythmias
Dyskinesias: similar to levodopa
Mental Disturbances: confusion, hallucinations, delusions
dopamine agonists are contraindicated in those with _____
- pts with psychotic illness
- recent MI
- active peptic ulceration
- peripheral vascular dz
compare MAO-A and MOA-B
what is significant about MAO
A: preferentially metabolizes NE and 5-HT
B: preferentially metabolizes phenylethylamine and benzylamine
(dopamine and tryptamine are metabolized equally by MAO-A and MAO-B)
MOA and metabolism of selegiline
selectively irreversible MAO-B inhibitor
slows breakdown of dopamine and prolongs antiparkinsonian effects of levodopa
10% bioavailability
selegiline should not be taken in patients who are also taking _____
meperidine, TCAs, or SSRIs
what are the other two drugs that are MAO-B inhibitors like selegiline?
rasagiline and safinamide
MOA tolcapone
catechol-O-methyltransferase (COMT) inhibitors
prolongs activity of levodopa by inhibiting its peripheral metabolism –> decreases clearance and increases bioavailability
compare tolcapone and entacapone
both COMT inhibitors
tolcapone: central and peripheral acting
entacapone: peripher only
side effects COMT inhibitors (tolcapone and entacapone)
- orange discoloration to urine
- diarrhea
- abd pain
- sleep disturbances
MOA and administration of apomorphine
agonist at dopamine D2 receptors
injected subcutaneously
adverse effects apomorphine
- nausea
- dyskinesias
- drowsiness
- sweating
- hypotension
- injection site bruising
MOA amantadine
antiviral agent whose MOA in parkinsonism is unknown
adverse effects amantadine
- livedo reticlaris (purplish mottling of skin)
- restlessness
- depression, irritability
- insomnia
- agitation, excitement
- hallucinations
