B7-071 Drugs for Parkinsons Disease Flashcards
what dopamine pathway modulates the extrapyrimidal motor system for controlled initiation of purposeful movement
nigrostriatal
what dopamine pathway functions in emotion, reward, and memory
mesolimbic
what dopamine pathway functions in attention and planning?
mesocortical
what dopamine pathway inhibits prolactin release from the anterior pituitary?
tuberoinfundibular (D2)
what dopamine pathway functions in emesis?
area postrema (d2)
D2 receptors function in the […] pathway of the basal ganglia
indirect
D1 receptors function in the […] pathway of the basal ganglia
direct
(D1rect)
which dopamine family of receptors is most important to therapeutic strategies in PD?
D2
primary strategy for PD therapy
replace or mimic dopamine
dopamine cannot cross the BBB, so it’s precursor […] is used to replace dopamine
L-DOPA
rate limiting step of dopamine synthesis
tyrosine hydroxylase
(why you can’t just take supplementary tyrosine for PD therapy)
reversal of rigidity, tremor, and bradykinesia in patients with PD
levodopa
levodopa works well for […] years of treatment
first few
(also only works really well for 1/3 of patients and doesn’t treat balance issues, etc)
most common side effects of levodopa [2]
nausea/vomiting via stimulation of D2 in CTZ
orthostatic hypotension
long term side effects of levodopa [3]
fluctuations in efficacy
abnormal involuntary movements (different than typical PD movements-80% of people develop this)
psychic side effects
fluctuations in efficacy of levodopa can be treated with [2]
opicapone- (COMT antagonist)
istradefylline (adenosine 2A antagonist)
levodopa can cause hallucinations, paranoia, mania, anxiety, depression, and impulse control via activation of […] pathways [2]
mesolimbic
mesocortical
management of psychic side effects of levodopa includes [3]
anti-psychotics that do not cause PD
lower dose of levodopa
pimavanserin
peak levels of levodopa occur […] to […] after administration
.5 - 2 hours
absorption of levodopa is dependent on
GI transit time
(less absorption with more time in transit)
anticholinergics decrease transit time
GI transit time is decreased by
anticholinergics
(may affect efficacy of levodopa)
half life of levodopa
1-3 hrs
95% is decarboxylated in the periphery and excreted in urine
levodopa
blocks AADC in periphery
carbidopa
allows you to use a lower dose of levodopa and decreases side effect profile of levodopa
carbidopa
levodopa is now only available in the US in formulation with
carbidopa
levodopa + carbidopa =
sinemet
other drugs used to increase dopaminergic activity [2]
(prevent LDOPA breakdown in either the brain or periphery)
MAO-B inhibitors
COMT inhibitors
preferentially metabolizes dopamine
MAO-B
MAO-B inhibitors [2]
selegeline
rassagaline
COMT inhibitors [3]
tolcapone
entacapone
opicapone
(helps to protect LDOPA in the periphery)
COMT inhibitor that only works in the periphery
entacapone
absolute contraindications to drugs increasing dopamine bioavailability
abrupt discontinuation
closed-angle gluacoma (stimulate B receptors)
melanoma (precursor of melatonin)
breast feeding (inhibits prolactin secretion)
drugs increasing dopamine bioavailability should be used with caution in patients with [2]
psychoses
open angle glaucoma
dopamine agonists approved as monotherapy [3]
pramipexole
ropinerole
rotigotine
(all involve D3)
add-on dopamine agonists with levodopa [2]
bromocriptine
apomorphine
D2 agonist also used to treat hyperprolactinemia
bromocriptine
anticholinergics [3]
benzotropine
procyclidine
trihexypheidyl
(secondary strategy)
blocks actions of striatal cholinergic interneurons
can be used alone early in PD disease course, but not as effective as LDOPA
anticholinergics
the anticholinergics used are all […] which gives better CNS penetration
tertiary amines
(over atropine, which has a lot of peripheral effects)
mechanism is unknown
may release dopamine and/or have anticholinergic properties
amantadine
(secondary strategy)
side effect is livedo reticularis
skin condition causing engorged capillaries and redness
amantadine
antiviral that can be used as monotherapy or adjunct to LDOPA
amantadine
late developing side effects of LDOPA [3]
abnormal movements
psychic symptoms (hallucinations, paranoia)
hypersexuality
MOA of entacapone
blocks catabolism of L-DOPA in the periphery
(COMT inhibitor)
inhibits AADC to block peripheral metabolism of levodopa
carbidopa
D2/D3 agonist that can be used as monotherapy for PD [3]
pramipexole
ropinerole
rotigotine
all are D3
is bromocriptine approved as monotherapy or add-on?
add on
the psychic side effects that can occur after long-term used of levodopa are due to overactivation of the […] system
limbic and cortical
used to block the catabolism of dopamine in patients treated with L-DOPA
MOA inhibitors
[…] inhibitors are used to block the catabolism of dopamine in the brain and periphery in patients treated with LDOPA
COMT
hepatotoxicity is a side effect of
tolcapone
specifically indicated for treatment of Parkinson’s disease psychosis
Pimavanserin
