Lec 17: Pharmacologic Management of Movement Disorders

Question 1

What is the mean age of onset for Parkinson’s Disease?

Answer 1

55

Question 2

What are the pathological hallmarks of Parkinson’s Disease?

Answer 2

• loss of pigmentation in the substantia nigra

* appearance of abnormal cytoplasmic inclusions (Lewy Bodies)

Question 3

What is the main dopamine subtype in basal ganglia neurons?

Answer 3

D2 receptor

Question 4

Which dopamine receptor subtypes are important for movement?

Answer 4

D1, D2, D3

Question 5

What drugs can contribute to the development of Parkinson’s Disease?

Answer 5

older antipsychotics (ex. chlorpromazine, haloperidol)

Question 6

What is the rate-limiting step in the process of dopamine production?

Answer 6

conversion of tyrosine to L-dopa through tyrosine hydroxylase

Question 7

What substances metabolize dopamine?

Answer 7

COMT and monoamine oxidase - B (MAO-B)

Question 8

What neurotransmitter and receptor changes are observed in PD?

Answer 8

• loss of dopamine-producing cells in the substantia nigra
• loss of norepinephrine-containing cells in the locus ceruleus
• increased acetylcholine turnover
• striatal GABA increased
• depleted serotonin levels

Question 9

What effect does the lowering of dopamine levels have on the direct and indirect pathways?

Answer 9

The indirect pathway predominates resulting in the inhibition of the thalamus and VL-VA nuclei. This results in the inhibition of motor function (ex. akinesia, rigor, tremor).

Question 10

How are akinesia and rigors/tremors controlled?

Answer 10

akinesia - dopaminergic agonists

rigidity/tremors - anticholinergics

Question 11

What is the precursor of dopamine?

Answer 11

levodopa

Question 12

What dopamine agonists are used?

Answer 12

bromocriptine, pergolide, pramipexole, ropirinole, rotigotine, apomorphine

Question 13

What drugs are used to inhibit the breakdown of levodopa?

Answer 13

MAO-B - inhibitors: selegeline, rasagiline

COMT - inhibitors: entacapone, tolcapone

Question 14

What drugs are used to inhibit the cholinergic and glutaminergic transmitter system?

Answer 14

amantadine, anticholinergics

Question 15

(T/F) levodopa penetrates the blood-brain barrier

Answer 15

T

Question 16

What vitamin enhances the extracerebral metabolism of levodopa?

Answer 16

pyridoxine (B6)

Question 17

What are the contraindications for levodopa?

Answer 17

psychosis, acute angle-closure glaucoma, active peptic ulcer, melanoma or undiagnosed skin lesions, hallucinations

Question 18

What drugs are selective inhibitors of peripheral L-dopa conversion?

Answer 18

carbidopa, benzerazide

Question 19

Which dopamine agonists are eliminated exclusively renally?

Answer 19

pramipexole, ropinirole

Question 20

Which dopamine agonist has the longest half-life?

Answer 20

cabergoline (65 hrs)

Question 21

Which dopamine agonist has the shortest half-life?

Answer 21

lisuride (2-3 hours)

Question 22

Which dopamine agonist is associated with the development of valvular heart disease?

Answer 22

pergolide

Question 23

Which dopamine agonist was pulled out of the market in the US due to crystalline formation in the patch?

Answer 23

rotigotine

Question 24

Which dopamine agonist is used for temporary relief of akinesia in patients on dopaminergic therapy?

Answer 24

apomorphine

Question 25

Which dopamine agonist scavenges hydrogen peroxide?

Answer 25

pramipexole

Question 26

Which COMT-inhibitor acts centrally AND peripherally?

Answer 26

tolcapone

Question 27

Which COMT-inhibitor can cause acute fulminant liver failure?

Answer 27

tolcapone