Parkinsons Flashcards
dopamine
carbidopa
L-DOPA
selegiline
PD symptoms
tremor
rigidity
akinesia (slow movement)
postural instability
PD is characterized by ___
loss of dopamine neurons in substantia nigra
studies suggest that 50% of ______ or 70-80% of ____ in striatum are lost before patients present with motor symptoms
dopamine neurons
nerve terminals
PD can be characterized by presence of what ?
Lewey bodies
what is a Lewey body
spherical protein deposit that is enriched with protein alpha synuclein
where are Lewey bodies found
substantia nigra, cortex
stages of Braak and what is it
Braak is measure of spreading aloha synuclein
1. brainstem
2. raphe
3. substantia nigra
4.meocortex/thalamus
5. neocortex/prefrontal cortex
6. entire neocortex
basal ganglia includes what
striatum and globus pallidus
striatum includes what
caudate nucleus and putamen
signaling from the substantia nigra to ______ receptors in the striatum favors ____
D1 and D2 receptors
thalamocortical signaling
(this is disrupted in PD)
antimuscarinic used in PD
benztropine
loss of dopamine results in ____ activity the cholinergic pathway
excess
why is there a bioavailability difference in L-DOPA and dopamine
L-DOPA can cross BBB
dopamine positive at pH 7
L-DOPA side effects
nausea, hypertension, psychosis
how can we lower a dose of L-DOPA?
add carbidopa which is peripherally acting DDC inhibitor
carbidopa MOA
inhibits Dopa decarboxylase in periphery, does not penetrate BBB
we can eliminate on/off ausciltations with L-DOPA therapy how
continuous administration of L-DOPA with infusion
if we cant convert L-DOPA to dopamine what can we use?
dopamine agonists - postsynaptic dopamine receptors are still present in striatum
what is apomorphine
D1/D2 dopamine agonist
apomorphine MOA
relieves off state rapidly but causes vomitting
non-ergoline dopamine agonists
ropinirole, pramipexole, rotigotine
non-ergolines are what
D2/D3 agonists with fewer side effects than ergolines
dopamine agonist that is a patch
rotigotine
MAO-B inhibitors irreversible
selegiline
rasagiline
MAO-B inhibitor reversible
safinamide
COMT inhibitors
entacapone
tolcapone
opicapone
COMT inhibitors MOA
inhibit methylation 3-OH group of dopamine
which drugs inhibit COMT to decrease metabolism of L-DOPA in the periphery
entacapone
opicapone
which drugs inhibit COMT in CNS to keep CNS dopamine levels high
tolcapone
L-DOPA, carbidopa, and entacapone combo drug
Stalevo
cardinal sign of parkinsons
bradykinesia (slow movement)
non motor symptoms of parkinsons
anxiety, depression
constipation
dementia
insomnia
orthostatic hypotension
psychosis / delirium
sexual dysfunction
1st line before adding an agent
rule out drug induced PD
drugs that could worsen/cause sx of PD
antipsychotics, metoclopramide, prochlorperazine, promethazine
dopamine precursors hold a higher risk of what?
dyskinisias (abnormal movement)
first line agents
dopamine precursors
dopamine agonists
MOA inhibitors
when to use dopamine agonist as first line
if < 60 years and high risk for dyskinesias
when to avoid dopamine agonists
> 70
history CID, cognitive impairment, daytime sleepiness, hallucinations
therapy should be initiated with ___ dosage form at ____ dose
IR, lowest dose
dopamine precursors and side effects
levodopa and carbidopa
motor fluctuations, dyskinesias, hallucinations
carbidopa/levodopa dosing
25/100 mg PO BID-TID with meals
increase to 5-6 x per day
dopamine agonists drugs and side effects
ropinirole, pramipexole, rotigatone
se: ICD, hallucination, edema
fewer motor fluctuations
MAO B inhibitors and side effects
selegiline, rasagiline, safinamide
se: n/v, insomnia
risk serotonin syndrome
which drugs adjunct for PD depression
MAOis
selegiline
rasagiline
safinamide
dosing
selegiline 5 mg PO BID
rasagiline 0.5 mg PO daily
safinamide 50 mg PO daily
COMT inhibitors place in therapy
manage symptom fluctuation, wearing offen
entacapone side effect
brown urine
tolcapone side effect
hepatotoxicity
entacapone
tolcapone
opicapone dosing
entacapone 200 mg PO with CD/LD dose
tolcapone 100 mg TID
opicapone 50 mg qhs
amantadine use
manages peak dose dyskinesias and motor symptoms
amantadine dosing
100 mg PO BID
when can we use anticholinergics
<65 yo tremor dominant pts
starting dose benztropine
0.5 mg PO qhs
starting dose trihexphenidyl
1 mg PO daily
how to treat psychosis in PD
clozapine or quetiapine
avoid: olanzapine, halloperiodol, paliperidone, risperidone
