B7-071 Drugs for Parkinsons Disease

Question 1

what dopamine pathway modulates the extrapyrimidal motor system for controlled initiation of purposeful movement

Answer 1

nigrostriatal

Question 2

what dopamine pathway functions in emotion, reward, and memory

Answer 2

mesolimbic

Question 3

what dopamine pathway functions in attention and planning?

Answer 3

mesocortical

Question 4

what dopamine pathway inhibits prolactin release from the anterior pituitary?

Answer 4

tuberoinfundibular (D2)

Question 5

what dopamine pathway functions in emesis?

Answer 5

area postrema (d2)

Question 6

D2 receptors function in the […] pathway of the basal ganglia

Answer 6

indirect

Question 7

D1 receptors function in the […] pathway of the basal ganglia

Answer 7

direct

(D1rect)

Question 8

which dopamine family of receptors is most important to therapeutic strategies in PD?

Answer 8

D2

Question 9

primary strategy for PD therapy

Answer 9

replace or mimic dopamine

Question 10

dopamine cannot cross the BBB, so it’s precursor […] is used to replace dopamine

Answer 10

L-DOPA

Question 11

rate limiting step of dopamine synthesis

Answer 11

tyrosine hydroxylase

(why you can’t just take supplementary tyrosine for PD therapy)

Question 12

reversal of rigidity, tremor, and bradykinesia in patients with PD

Answer 12

levodopa

Question 13

levodopa works well for […] years of treatment

Answer 13

first few

(also only works really well for 1/3 of patients and doesn’t treat balance issues, etc)

Question 14

most common side effects of levodopa [2]

Answer 14

nausea/vomiting via stimulation of D2 in CTZ
orthostatic hypotension

Question 15

long term side effects of levodopa [3]

Answer 15

fluctuations in efficacy

abnormal involuntary movements (different than typical PD movements-80% of people develop this)

psychic side effects

Question 16

fluctuations in efficacy of levodopa can be treated with [2]

Answer 16

opicapone- (COMT antagonist)
istradefylline (adenosine 2A antagonist)

Question 17

levodopa can cause hallucinations, paranoia, mania, anxiety, depression, and impulse control via activation of […] pathways [2]

Answer 17

mesolimbic
mesocortical

Question 18

management of psychic side effects of levodopa includes [3]

Answer 18

anti-psychotics that do not cause PD
lower dose of levodopa
pimavanserin

Question 19

peak levels of levodopa occur […] to […] after administration

Answer 19

.5 - 2 hours

Question 20

absorption of levodopa is dependent on

Answer 20

GI transit time

(less absorption with more time in transit)

anticholinergics decrease transit time

Question 21

GI transit time is decreased by

Answer 21

anticholinergics

(may affect efficacy of levodopa)

Question 22

half life of levodopa

Answer 22

1-3 hrs

Question 23

95% is decarboxylated in the periphery and excreted in urine

Answer 23

levodopa

Question 24

blocks AADC in periphery

Answer 24

carbidopa

Question 25

allows you to use a lower dose of levodopa and decreases side effect profile of levodopa

Answer 25

carbidopa

Question 26

levodopa is now only available in the US in formulation with

Answer 26

carbidopa

Question 27

levodopa + carbidopa =

Answer 27

sinemet

Question 28

other drugs used to increase dopaminergic activity [2] (prevent LDOPA breakdown in either the brain or periphery)

Answer 28

MAO-B inhibitors COMT inhibitors

Question 29

preferentially metabolizes dopamine

Answer 29

MAO-B

Question 30

MAO-B inhibitors [2]

Answer 30

selegeline rassagaline

Question 31

COMT inhibitors [3]

Answer 31

tolcapone entacapone opicapone (helps to protect LDOPA in the periphery)

Question 32

COMT inhibitor that only works in the periphery

Answer 32

entacapone

Question 33

absolute contraindications to drugs increasing dopamine bioavailability

Answer 33

abrupt discontinuation closed-angle gluacoma (stimulate B receptors) melanoma (precursor of melatonin) breast feeding (inhibits prolactin secretion)

Question 34

drugs increasing dopamine bioavailability should be used with caution in patients with [2]

Answer 34

psychoses open angle glaucoma

Question 35

dopamine agonists approved as monotherapy [3]

Answer 35

pramipexole ropinerole rotigotine (**all involve D3**)

Question 36

add-on dopamine agonists with levodopa [2]

Answer 36

bromocriptine apomorphine

Question 37

D2 agonist also used to treat hyperprolactinemia

Answer 37

bromocriptine

Question 38

anticholinergics [3]

Answer 38

benzotropine procyclidine trihexypheidyl (secondary strategy)

Question 39

blocks actions of striatal cholinergic interneurons can be used alone early in PD disease course, but not as effective as LDOPA

Answer 39

anticholinergics

Question 40

the anticholinergics used are all [...] which gives better CNS penetration

Answer 40

tertiary amines (over atropine, which has a lot of peripheral effects)

Question 41

mechanism is unknown may release dopamine and/or have anticholinergic properties

Answer 41

amantadine (secondary strategy)

Question 42

side effect is livedo reticularis skin condition causing engorged capillaries and redness

Answer 42

amantadine

Question 43

antiviral that can be used as monotherapy or adjunct to LDOPA

Answer 43

amantadine

Question 44

late developing side effects of LDOPA [3]

Answer 44

abnormal movements psychic symptoms (hallucinations, paranoia) hypersexuality

Question 45

MOA of entacapone

Answer 45

blocks catabolism of L-DOPA in the periphery (COMT inhibitor)

Question 46

inhibits AADC to block peripheral metabolism of levodopa

Answer 46

carbidopa

Question 47

D2/D3 agonist that can be used as monotherapy for PD [3]

Answer 47

pramipexole ropinerole rotigotine | all are D3

Question 48

is bromocriptine approved as monotherapy or add-on?

Answer 48

add on

Question 49

the psychic side effects that can occur after long-term used of levodopa are due to overactivation of the [...] system

Answer 49

limbic and cortical

Question 50

used to block the catabolism of dopamine in patients treated with L-DOPA

Answer 50

MOA inhibitors

Question 51

[...] inhibitors are used to block the catabolism of dopamine in the brain and periphery in patients treated with LDOPA

Answer 51

COMT

Question 52

hepatotoxicity is a side effect of

Answer 52

tolcapone

Question 53

specifically indicated for treatment of Parkinson's disease psychosis

Answer 53

Pimavanserin