Pharmacotherapy for Movement Disroders

Question 1

PD drug for dopa replacement

Answer 1

Levo-Dopa,

L dopa/carbidopa

Question 2

Dopa receptor agonist for PD

Answer 2

Bromocriptine
Pramipexole
Ropinirole
Apomorphine

Question 3

PD drugs that ENHACE dopa release from endogenous stores

Answer 3

Amantidine

flu drug

Question 4

PD drugs that inhibit dopa metabolism

Answer 4

MAO-B inhibitor: Selegiline, rasagiline

COMT inhibitor: Entacapone, Tolocapone

Question 5

Antimuscarinic agents for PD

Answer 5

Benztropine, Trihexyphenidine, Diphenhydramine

*first generating H1 antagonsit that have antisholinergic activity in the CNS and antimuscarinic activity as well

Question 6

Agents used for tx of HD that inihibit VMAT-these are DOPA depleting agents

Answer 6

resperine, tetrabenazine

Question 7

HD treatment, Dopa D2 receptor antagonist

Answer 7

chlorpromazine, heloperidol

Question 8

hallmark of PD pathophysiologically is

Answer 8

selective loss of pigmented (neuromelanin) neurons in substantia nigra pars compacta

Question 9

most symptoms of parkinsonism do not manifest until

Answer 9

striatal DA neuron levels decline by 70%-80%

Question 10

DOPAMINERGIC TONE ON STRIATUM MAINTAINED BY

Answer 10

SUBSTANTIA NIGRA PARS COMPACTA

Question 11

DIRECT PATHWAY

Answer 11

CEREBRAL CORTEX TO STRIATAL NEURONS

DOPA INHIBITION TONICALLY

SN MAINTAINED BY SNpc

Question 12

PRIMARY INPUT IS FROM

Answer 12

CEREBRAL CORTEX

Question 13

OUTPUT IS DIRECTED THROUGH THE

Answer 13

THALAMUS

Question 14

FROM THE THALMUS INFORMATION GOES TO

Answer 14

PREFRONTAL, PREMOTOR, AND MOTOR CORTEX

Question 15

NET EFFECT OF DIRECT PATHWAY

Answer 15

increased thalamic output

Question 16

net effect of indirect pathway

Answer 16

inhibition of thalamic output

Question 17

in parkinsons disease which pathway is favored

Answer 17

indirect pathway

Question 18

goal od PD therapy is to

Answer 18

reactivate the direct pathway to increase thalamic output while inhibiting the direct pathway to disinhibit thalamic output

Question 19

most important receptor agonism in tx of PD

Answer 19

L dopa agonist which inhibits the inhibitory indirect pathway

Question 20

cholinergic neurons within straitum enhance

Answer 20

GABAergic (inhibitory output)

Question 21

can dopa cross the BBB into the CNS

Answer 21

no

Question 22

can L dopa cross the BBB

Answer 22

yes-single most effective treatment for PD

Question 23

99% of adminstered L DOPA is

Answer 23

converted in periphery to DOPA by L aromatic amino acid decarboxylase (L-AAD), and principally excreted in the urine as HVA DOPAC

Question 24

dosing for L-DOPA

Answer 24

due to the fact that 99% of its gets converted toa product that cannot pass BB thus reaching its target, L dopa must be given in extremely high doses when uses as MONOTHERAPY

Question 25

L dopa-coadministered with

Answer 25

Carbidopa

• L-AAD inhibitor, cannot cross the BBB
• prolongs L-DOPA half life , 75% reduction in the amount needed to administer

Question 26

SIde effects of CA replacement due to L DOPA

Answer 26

GI-anorexia, N/V,

2, CV-arrhythmiasm tachycardia, ventricular extrasytoles, a fib, orthostatic hypotension

Question 27

DA replacement side efffects due to the co-administration with Carbidopa

Answer 27

1. behavioral depression-depression, axiety, delusion, agitation, insomia, hallucination, nightmares euphoira altered mood.
2. Dyskeniesias-chorea, myoclonus, tics tremoers (non-resting, intentional_

Question 28

L-DOPA/Carbidopa must be coadministered with

Answer 28

antipsychotics

Question 29

activation of D2 reeptors will

Answer 29

reduce activation of the indirect pathway

Question 30

L DOPA withheld until

Answer 30

functional symptoms begin

*only useful for 3-5 years

Question 31

Preferred strategy for early PD

Answer 31

DA agonists

may be used in combo with L-DOPA in advanced early PD, reduce on off

Question 32

D2 selective agonist

Answer 32

Pramipexole and Ropinorole

Question 33

D1/d2 agonist

Answer 33

apomorphine

Question 34

D2 agonist with partial D1 activity

Answer 34

bromocriptine

Question 35

antivirial that boost Da synhtesis, release and inhibits uptake

Answer 35

amantidine, effects modest and sort lived

Question 36

sideeffects of amantidine

Answer 36

those of L dopa, restlessnessm agitiation, irritability, insomnia, confusioin, hallucinations

Question 37

selective MAO-B inibitor

Answer 37

selegeline-retards breakdown of DA

Question 38

metabolites of selegeline that increase DA release and may be neuroprotective

Answer 38

amphetamine and methamphetamine

Question 39

do not take with meperidine, TCA’s or SSRis

Answer 39

selegeline (MAO-B inhibitor)

Question 40

useful when response to L-DOPA declines

Answer 40

selegeline-little effect when given alone

Question 41

more potent MAO-Bi-useful for late stage PD with l dopa or alone in early PD

Answer 41

Rasagaline

Question 42

selective COMT inhibitors

Answer 42

entecapone, tolcapone

Question 43

MOA for COMT inhibition in tolcapone, entacapone

Answer 43

increases bioavailability of L dopa, prolong action of L DOPA, reduced production of 3OMD-competes with L dopa for tranny carriers in GI and BBB

Question 44

COMTi with central AND peripheral effects

Answer 44

tolcapone

Question 45

COMTi with only peripheral effects

Answer 45

entecapone

Question 46

prefferred COMTi

Answer 46

entacapone

tolcapone causes increased liver enzyme and hepatic failure

Question 47

muscarinic antagonists used to treat DP

Answer 47

trihexyphenidyl
diphenhydramine
benztropine

Question 48

pathophysiology of HD

Answer 48

loss of cholinergic neurons in the striatum

but a greater and earlier loss observed in the striatal medium spiny gabergic neurons–> loss of indirect pathway

Question 49

pathway lost in huntingtons disease

Answer 49

indirect pathwa