Anti-parkinsons drugs

Question 1

dopamine synthesis originates from which amino acid

Answer 1

tyrosine

Question 2

which transporter is used for tyrosine transport across BBB

Answer 2

SYSTEM L

Na+ independent

Question 3

RLS in dopamine synthesis

Answer 3

tyrosine hydroxylase

Question 4

DOPA decarboxylase

Answer 4

converts DOPA –> dopamine

Question 5

D1 2nd messenger system

Answer 5

G(s) = increased adenylyl cyclase

Question 6

D2 2nd messenger system

Answer 6

G(i) = decreased adenylyl cyclase - inc K+ conductance, dec Ca2+ conductance

Question 7

parkinson’s tx goals

Answer 7

1) restore dopamine actions

2) antagonize acetylcholine

Question 8

dopamine precursor

Answer 8

levodopa

Question 9

levodopa

Answer 9

stereoisomer of dopa
dopamine/norepinephrine precursor

good for pt with early disease = requires presence of residual dopaminergic neurons for conversion of levodopa–> dopamine

Question 10

carbidopa

Answer 10

dopa decarboxylase inhibitor

doesn’t cross BBB

given with levodopa to dec peripheral metabolism to dopamine

Question 11

levodopa use

Answer 11

symptomatic use - only lasts while drug is in body

Question 12

levodopa MOA

Answer 12

transported into CNS, there is converted to dopamine

a lot of it is decarboxylated to dopamine in periphery –> AE: n/v arrhythmias, hypotension

Question 13

sinemet

Answer 13

carbidopa + levodopa prep

Question 14

levodopa PK

Answer 14

food delays appearance in plasma == certain amino acids can compete for absorption from gut and for transport through BBB

Question 15

levodopa metabolites

Answer 15

via COMT = 3-o-methyl dopa, 3-methoxytyramine

–> HVA

Question 16

levodopa fluctuations in response

Answer 16

1) wearing off rxn = related to time of intake

2) on-off phenomenon = unrelated to timing - may benefit from apomorphine

Question 17

levodopa contraindicatiosn

Answer 17

B6 - cofactor for dopa decarboxylase = inc peripheral metabolism

MAOI = HTN crisis

not used in psychotic pt

angle closure glaucoma

arrhythmias

Question 18

which class doesn’t depend on capacity of nigrostriatal neurons

Answer 18

dopamine receptor agonist

Question 19

classes of dopamine receptor agonists

Answer 19

1) ergot dopamine agonists

2) nonergot dopamine agonists

Question 20

bromocriptine

Answer 20

D2 agonist
(ergot dopamine)

Question 21

pramipexole

Answer 21

nonergot dopamine agonists

Question 22

ropinirole

Answer 22

nonergot dopamine agonists

Question 23

nonergot dopamine agonists

Answer 23

better for younger pt

older pt more vulnerable to AE of dopamine agonists

Question 24

rotigotine

Answer 24

nonergot dopamine agonists

available as transdermal

Question 25

which nonergot dopamine agonists is used as a transdermal

Answer 25

rotigotine

Question 26

AE of dopamine agonists

Answer 26

GI: anorexia, n/v, constipation, peptic ulcer bleeding CV: postural hypotension, arrhythmias, periph edema dyskinesias: abnormal movements mental disturbances: confusion, hallucinations misc: ergot - pulmonary infiltrates, pleural fibrosis, erythromelalgia nonergot - uncontrollable somnolence

Question 27

dopamine agonists contraindications

Answer 27

pt with psych hx or recent mi peripheral vascular dz peptic ulceration

Question 28

rescue therapy for nonergot dopamine agonist

Answer 28

apomorphine

Question 29

apomorphine

Answer 29

nonergot dopa agonists rescue used in "off" epsidoes of akinesia emetogenic (given with antiemetic trimethobenzamide) AE: QT prolonged, dyskinesias, drowsiness, sweating

Question 30

MAOI

Answer 30

*deprenyl/selegiline* selectively irreversibly inhibits MAO-B retards breakdown of DA enhances levodopa effects - and can dec its dose levodopa adjunct* metabolized to amphetamine --> insomnia

Question 31

deprenyl

Answer 31

MAOI

Question 32

rasagiline

Answer 32

MAOI | MAO-B inhibitor selective

Question 33

use of carbidopa and levodopa, increases what substance peripherally?

Answer 33

3-o-methyl dopa also competes with levodopa for an active transporter across intestinal mucosa and BBB

Question 34

tolcapone

Answer 34

COMT inhib

Question 35

entacapone

Answer 35

COMT inhib

Question 36

COMT inhib function

Answer 36

dec levodopa metabolism dec plasma 3-o-methyldopa inc levodopa uptake -- higher DA levels in brain

Question 37

COMT AE

Answer 37

hepatic necrosis **tolcapone entacapone = not hepatotoxic - preferred

Question 38

amantadine PD application

Answer 38

increases synthesis, release/re-uptake of dopamine from surviving neurons

Question 39

amantadine AE

Answer 39

restlessness hallucination aucte toxic psychosis peripheral edema (give diuretics) **livedo reticularis** - redness to skin

Question 40

anti-muscarinics for PD

Answer 40

adjuvant improve tremor, rigidty little effect on bradykinesia AE: mood changes, xerostomia, pupillary dilation, hallucination contraindic: glaucoma, BPH, pyloric stenosis

Question 41

DOC for PD

Answer 41

levodopa + carbidopa

Question 42

2nd most effective drugs for PD

Answer 42

dopamine agonists

Question 43

addition of which drug in addition to levodopa to reduce motor fluctuations in adv PD pt

Answer 43

COMT-inhib or MAO-B inhib