antiparkinson's

Question 1

familial PD

Answer 1

10%

gene that codes for synuclein

Question 2

sporadic PD

Answer 2

90%

Question 3

PD risk factors

Answer 3

infections
trauma
endocrine
drugs/toxins:
neuroleptics
metoclopramadine
reserpine
pesticides
MPTP

Question 4

gene mutations

Answer 4

mitochondrial dysfunction
impaired protein/organelle degradation
axonal transport
synaptic homeostasis

Question 5

motor S/S (TRAP)

Answer 5

tremor at rest
rigidity
akinesia
postural reflex impairment

Question 6

nonmotor S/S (early)

Answer 6

sleep abnormalities
autonomic dysfunction
sensory

Question 7

nonmotor S/S (late)

Answer 7

psychiatric disorders

cognitive disorders

Question 8

nigrostriatal pathway

Answer 8

fine motor control

Question 9

medium spiny striatal neuron

Answer 9

ACh
regulate direct/indirect pathways
overactivated in PD

Question 10

mesolimbic/mesocortical pathway

Answer 10

memory, motivation, emotions, reward, desire, addiction

Question 11

tuberoinfundibular pathway

Answer 11

hormonal regulation

Question 12

Rx goals

Answer 12

1 - restore DAergic transmission

2 - inhibit AChergic transmission

Question 13

Levodopa (L-dopa)

Answer 13

precursor to DA
doesn’t cross BBB (1-3% enters brain)
extracerebral metabolism: rapidly converted to DA by DDC

indirect (D2)
direct (D1) - stimulate adenyl cyclase

Question 14

L-dopa loses effectiveness

Answer 14

progressive loss of nigral DA neurons

downregulation of D1/D2 receptors

Question 15

L-dopa SE

Answer 15

dyskinesias
on/off effect (use DA agonists)
nausea
anorexia
hypotension
confusion
insomnia
nightmares
schizophrenia

Question 16

AADH inhibitor (carbidopa)

Answer 16

inhibit decarboxylation of peripheral L-da

doesn’t cross BBB

SE:
increased L-dopa SE
increase COMT degradation of L-dopa

Question 17

COMT inhibitors

Answer 17

diminish peripheral metabolism of L-dopa

reduce on/off fluctuations

Question 18

entacapone

Answer 18

COMT inhibitor

orange urine

Question 19

tolcapone

Answer 19

COMT inhibitor

hepatotoxic

Question 20

DA receptor agonists

Answer 20

early PD: monotherapy
late PD: adjunctive

reduces on/off motor fluctuations

Question 21

pramipexole

Answer 21

DA receptor agonist
binds D2/D3/D4

neuroprotective/antioxidant

SE: sleep attacks

Question 22

ropinirole

Answer 22

DA receptor agonist
D3, then D2/D4

mild disease

neuroprotective/antioxidant

SE: orthostatic hypotension

CYP1A2 metabolism

Question 23

amorphine

Answer 23

DA receptor agonist

short duration: temp relief of akinesia

SE: dyskinesias, drowsiness, sweating, hypotension

Question 24

MAO inhibitors

Answer 24

early PD: monotherapy
late PD: adjunctive

reduce on/off motor fluctuations

irreverisble inhibitors of MAO, inhibit degradation of DA

Question 25

selegiline

Answer 25

MAO inhibitor SE: forms toxic metabolite in elderly

Question 26

rasagiline

Answer 26

MAO inhibitor no toxic metabolite

Question 27

hypertensive crisis

Answer 27

tyramine rich diet causes peripheral accumulation of NE

Question 28

fatal hyperthermia

Answer 28

meperidine, cocaine, fluoxetine + selegine

Question 29

anticholinergics

Answer 29

block central cholinergic receptors mild cases, younger pts, pts on neuroepileptic drugs no improvement of bradykinesia blocks M1 receptors on striatal neurons (presynaptic inhibition of Da release) SE: atropine-like

Question 30

amantadine

Answer 30

NMDA receptor antagonist early PD: monotherapy late PD: adjunct to reduce L-dopa induced dyskinesias interferes w/Glu transmission indirectly modifies DA cycle, binds DA receptors excreted unchanged in urine

Question 31

amantadine SE

Answer 31

elderly - restlessness, depression, instability, insomnia, agitation, excitement, hallucinations, confusion headache, edema postural hypotension, heart failure, GI upset

Question 32

amantadine OD

Answer 32

acute toxic psychosis

Question 33

early-onset PD

Answer 33

1) DA agonists 2) adjunctive L-dopa 3) adjunctive MAO-B inhibitors **lower risk of L-dopa induced dyskinesias

Question 34

late-onset PD

Answer 34

1) L-dopa 2) adjunctive DA agonists, COMT inhibitors, or MAO-B inhibitors **best control of motor S/S