Block 3 Lecture 3 -- Parkinson's

Question 1

What proteins are misfolded in Parkinsons?

Answer 1

alpha-synuclein,
parkin

in the basal ganglia

Question 2

What are the physiological signs of Parkinsons?

Answer 2

1) alpha-synuclein dysregulation – cortical and nigral Lewy Bodies
2) depigmentation of pars compacta in SN

Question 3

Describe the prevalence of PD.

Answer 3

2nd most common neurodegenerative disease

• • prevalence increases with age
• • mean age = 57
• • twice as common in males

Question 4

What are environmental risk factors of PD?

Answer 4

neurotoxins
pesticides during development
TBI

Question 5

What is the genetic/idiopathic breakdown of PD?

Answer 5

90 percent idiopathic

10 percent genetic

Question 6

What are the actions of MPP+?

Answer 6

1) free radicle introduction into vesicles after DAT uptake
- - increased cytoplasmic catecholamines – ROS – DA neuron death
2) inhibit Complex I in ETC
- - ROS, death

Question 7

What PD symptoms start 5-10 years before diagnosis?

Answer 7

1) hyposmia
2) constipation
3) REM-sleep behavior

Question 8

What are motor sxs of PD?

Answer 8

1) resting tremor
2) cogwheel rigidity
3) bradykinesia
4) postural instability
5) reduced arm swinging, forward tilt, head trembling
6) small handwriting
7) potentially diagnostic
- - hypophonia, dysarthria

Question 9

What are ANS and sensory sxs of PD?

Answer 9

1) fatigue
2) anosmia
3) hyperalgesia/paresthesia
4) seborrhea
5) sexual dysfunction
6) mixed SNS/PNS effects
- - sialorrhea, diaphoresis, orthostasis

Question 10

What are CNS sxs of PD?

Answer 10

1) late-onset cognitive impairment in frontal cortex and subcortical regions
- - visuospatial, executive fx
2) depression
3) anxiety

Question 11

What are goals of PD pharmacotherapy?

Answer 11

1) preserve fx and independence
2) improve mobility
3) improve non-motor sxs
4) delay progression (no drugs for this yet)

Question 12

What is nonpharm tx for PD?

Answer 12

1) subthalamic nucleus deep brain stimulation
2) surgery
- - pallidotomy, thalamotomy, subthalamotomy

Question 13

What is the MoA of amantadine?

Answer 13

1) enhances presynaptic DA release
2) DAT blocker
3) anti-cholinergic properties
4) NMDAr antagonist

Question 14

What is the MoA of benztropine?

Answer 14

M1r antagonist

• • b/c DA inhibits ACh release in striatum (ACh = tremor)
• • adjunct therapy

Question 15

What are the ergot-based D2r agonists?

Answer 15

1) bromocriptine
2) cabergoline
3) pergolide

Question 16

What are the non-ergot-based D2r agonists?

Answer 16

1) pramipexole

2) ropinirole

Question 17

What are the ADRs of non-ergot D2r agonists?

Answer 17

1) nausea
2) edema
3) orthostasis
4) sedation
5) confusion, vivid dreams, hallucination
6) risky behavior (gambling)

NO CERS (no cares)

Question 18

What are the direct-acting DAr agonists?

Answer 18

1) non-ergot D2r agonists

2) ergot D2r agonists

Question 19

What M1r antagonists are used in PD?

Answer 19

1) benztropine

2) trihyexyphenidyl

Question 20

What are the ADRs of DA replacement?

Answer 20

1) nausea
2) hallucination, dreams
3) insomnia
4) syncope

Question 21

What are the COMT inhibitors?

Answer 21

entacapone

tolcapone

Question 22

What are the MAOB inhibitors?

Answer 22

selegiline

rasagiline

Question 23

What is in stalevo?

Answer 23

L-dopa
carbidopa
entacapone

Question 24

What’s in Sinemet?

Answer 24

L-dopa + carbidopa

25/100mg TID

Question 25

What are the goals of physical/speech therapy in PD?

Answer 25

1) regular exercise to maintain mobility, improve strength
2) avoid falls
3) late-stage swallowing therapy

Question 26

What are symptoms of dyskinesias?

Answer 26

1) faciolingual tics
2) choreiform
3) oscillatory rocking

Question 27

What are the shortcomings of DA replacement therapy?

Answer 27

1) tolerance to movement improvements
2) free radicals
3) peak-effect dyskinesias

Question 28

What is the advantage of pramipexole?

Answer 28

less risk of motor complications as monotherapy

– preferred in younger patients

Question 29

What are the bad parts of ergot-based D2r agonist use?

Answer 29

1) more severe ADRs than non-ergot

2) special monitoring required for cardiac valvular fibrosis

Question 30

Where are ergot-based D2r agonists derived from?

Answer 30

fungus Claviceps purpurea

Question 31

What patients suffer from peak-effect dyskinesias?

Answer 31

too much Da

• • 50% of patients in year 5
• • more likely in younger patients

Question 32

When is L-dopa therapy preferred?

Answer 32

cognitive problems/hallucination present

older patients

Question 33

Does DA cross BBB? What about L-dopa?

Answer 33

0% DA; 5% L-dopa

Question 34

When is amantadine preferred?

Answer 34

new patients with mild symptoms