Therapeutics - Parkinsons Flashcards
define parkinsons and name some symptoms
progressive neurologic disorder
tremors, rigidity, postural instability, bradykinesia (slow movement)
what are dopamine levels like in parkinsons patients
where? what about acetylcholine levels?
low
in substantia nigra
high acetylcholine (so excess cholinergic activity)
true or false
most parkinsons is idiopathic
true - no known cause
some things that can induce parkinsons
heavy metals
pesticides
MPTP
CO
drugs (1st gen antipsychotics, metoclopramide, phenothiazides)
true or false
parkinsons can occur after encephalitis
true
early and late MOTOR parkinsons symptoms
early - cogwheel rigidity, soft voice, shuffling gair, bradykinesia, pill-rolling tremors
late - freezing, postural imbalance, hard to swallow and talk - get some cognitive deficits
name some autonomic symptoms of parkinsons
orthostatic hypotension
constipation
hard to pee
extreme sweating
seborrhea
effect of parkinsons on blood pressure
can cause orthostatic hypotension - even when just sitting down
hyposmia
nonmotor parkinsons symptom - loss of smell
2 symptoms of parkinsons that may actually occur before the patient is even diagnosed
hyposmia (hard to smell)
REM sleep disorder
when a patient is “on” in parkinsons, is the medication working or not working
working - symptoms are controlled
short term and long term goals for parkinsons treatment
short term - control symptoms, increase functionality
long term - limit complications, maintain effective treatment
trueor false
there are several disease-modifying treatments for parkinsons
FALSE- none
only symptomatic relief
a patient has some parkinsons symptoms with early PD (less than 5 years)… but not causing disability
what is the approach??
ie - a tremor in nondominant hand
wait and see approach – hold off for now
bc once we start levodopa, limited amount of time that the patient will respond
but if pt has significant issues — start LEVODOPA
in general, initial treatment with ____ provides more benefit to dopamine agonists
levodopa
what is considered “early” parkinsons
less than 5 years
a patient is initially started on a MAO-B inhibitor for parkinsons
what will they need in the future
will need additional treatment within 2-3 years — diff from patients who are started on levodopa or dopamine agonist
3 potential initial options for early PD
levodopa
dopamine agonist
MAO B inhibitor
true or false
dopamine agonists are more likely to cause dyskinesias than levodopa
FALSE - levodopa is more likely to cause dyskinesia
for early PD:
levodopa vs levodopa + entacapone vs IR levodopa
which is most effective
all equally effective
which has a higher risk of impulse control disorders — dopamine agonists or levodopa?
dopamine agonists have higher risk
if a patient is less than 60 years old with PD, explain the thought process behind what treatment to start
may start with a dopamine agonist over levodopa
younger people can tolerate the CNS SE of dopamine agonists more….. and also the patient is gonna be living with PD for a long time - want to try to wait to use levodopa
patient has a history of cognitive impairment and PD
what should we start with
start with levodopa
patient has a history of MOOD DISORDERS and PD
what should we start with
levodopa
if patient’s PD disease is SEVERE, what should we start with
levodopa
initial therapy if the patient has TREMOR ONLY (no bradykinesia)
anticholinergics – but only if the patient is younger!!!! dont like the anticholinergic side effects in older people
when may MAO-B inhibitors be used as initial therapy
really only for milder cases
which med is PRIMARILY for dyskinesia as an add on therapy
amantadine
true or false
for PD, nonpharm treatment is just as important as pharmacologic
true
exercise, PT, OT, speech therapy
3 potential add on therapies for PD
istradefylline
amantadine (dyskinesia)
COMT inhibitors
advanced therapy PD
surgical
2 MAO-B inhibitors that may be considered at diagnosis of PD if it is mild
rasagiline
selegiline
true or false
a dopamine agonist should only be started if the patient is under 60
what if over 60?
true
if over 60 - start carbidopa/levodopa
after initial PD therapy, doses should be adjusted as needed and tolerated
as the patient’s symptoms get worse, what should be done
add another agent, then add COMT inhibitor
2 general concerns of PD/PD drugs
melanoma - should be checked by derm
impulse control disorders (anthing that increases dopamine in the brain - includes BOTH dopamine agonists and levodopa) - urges to gamble, sexual urges, etc
MOA of MAO-B inhibitors
binds MAO-B enzyme - the enzyme that metabolizes (oxidizes) dopamine
blocks breakdown of dopamine in the brain
name 3 MAO-B inhibitors
selegiline
rasagiliine
safinamide
4 drugs that should be used with caution with MAO-B inhibitors
tramadol
meperidine
DM
SSRIS
which MAO-B inhibitor was originally thought to be neuroprotective but it was debunked
selegiline
it was just symptomatic relief
only indication for ODT selegiline
in combo with levodopa later in the disease
important note when dosing all the MAO-B inhibitors
-DO NOT GO ABOVE THE MAX DOSE. will not be selective for B anymore. can go into hypertensive crisis
selegiline ADRs
hallucinations, confusion
nausea
INSOMNIA!!!!! - from the amphetamine-like metabolite
how can insomnia from selegiline be avoided
if PO version - dont give the 2nd dose after 2pm
ODT formulation has less CNS stimulation
true or false
transdermal selegiline can be used for parkinsons
FALSE - the transdermal form is only for depression
PO max dose selegiline
ODT max dose selegiline
why is it important not to go above these?
PO - 10mg
ODT - 2.5mg
loses specificity for MAO-B inhibition - can go into hypertensive crisis
use for rasagiline
monotherapy in early PD
carbidopa/levodopa adjunct in moderate-advanced PD
max doses of rasagiline:
-monotherapy
-adjunct to levodopa
monotherapy - 1mg QD
adjunt - 0.5mg but may increase to 1mg
advantages of rasagiline over selegiline
no amphetamine-like side effects (no insomnia)
tyramine reaction unlikely (less CV side effects)
overall - less CV and less CNS side effects
use of safinamide
as an adjunct to carbidopa-levidopa in patients with “off” episodes
NOT USED AS MONOTHERAPY
true or false
safinamide can be effective as monotherapy for PD
FALSE - not effective as monotherapy. only as adjunct to carb/lev in patients experiencing off episodes
what foods should be avoided with safinamide
very high tyramine concentration
dose of safinamide
50mg QD for 2 weeks
increase to 100mg daily after that (100mg is MAX)
in what patients must safinamide be avoided
patients with severe hepatic impairment
safinamide ADRs
CNS depression
dyskinesia
impulse control disorder
serotonin syndrome
HTN
3 anticholinergics that may potentially be used for PD tremors in YOUNGER PATIENTS
diphenhydramine
benztropine
trihexyphenidyl
effect of anticholinergics on the heart
tachycardia
effect of anticholinergics on the eyes
dry eyes
any dose adjustments for amantadine?
in renal impairment (CrCl less than 60mL/min)
place in PD therapy for amantadine
in early disease or late, in combo with other agents
monotherapy effect is short lived – only 6 months
ADRs amantadine
CNS changes
and similar anticholinergic effects
levido reticularis (skin condition)
amantadine administration considerations
dont give after 2pm to avoid insomnia!!!
also, older patients may not tolerate CNS side effects - not preferred
2 names of amantadine ER
state what they’re approved for
gocovri (capsule) - for dyskinesias and off episodes
osmolex ER (tablet) - for PD and drug-induced EPS
differentiate between the dosing time of Gocovri vs Osmolex
QHS - gocovri
qam - osmolex
dose adjustments for gocovri and osmolex
both - dose adjustment in CrCl less than 60, DO NOT USE in CrCl less than 15
true or false
gocovri and osmolex are NOT interchangeable
true
____ is considered the mainstay of therapy for PD
levodopa
why is carbidopa given with levodopa
if we just give levodopa, it will get converted to dopamine in the periphery which we DONT WANT
carbidopa prevents the peripheral conversion (breakdown) of levodopa into dopamine
___mg of carbidopa/day is needed to block the peripheral conversion of levodopa into dopamine
50-100mg
true or false
carbidopa does not cross the BBB
true - this is good
lveodopa does tho - which is good
2 formulations of carbidopa/levodopa for late stage PD to treat the motor fluctuations
enteral suspension for jejunal infusion
SQ continuous infusion
