neurodegeneration

Question 1

main Parkinson’s disease treatment

Answer 1

dopamine replacement levodopa (L-DOPA; account for loss of dopamine in CNS due to neurodegeneration of nigrostriatal tract, but not post-synaptic neurones)

Question 2

why is L-DOPA given as treatment, and not L-tyrosine or dopamine

Answer 2

tyrosine hydroxylase is rate-limiting step, and dopamine causes effects in periphery

Question 3

how does levodopa treat Parkinson’s disease

Answer 3

is rapidly converted to dopamine by DOPA decarboxylase (DOPA-D), which can cross BBB into CNS

Question 4

2 short term side side effects of levodopa due to peripheral breakdown by DOPA-D

Answer 4

nausea and vomiting

Question 5

2 long term side effects of levodopa, and 1 disadvantage

Answer 5

dyskinesias (too much dopamine to treat bradykinesia, so sudden motor movements which are not voluntary), “on-off” effects (large doses in one go, not gradual release, so given as slow-release intestinal gels), not disease modifying (doesn’t prolong life, just improves quality as targets symptoms)

Question 6

adjuncts of Parkinson’s disease treatment

Answer 6

DOPA decarboxylase inhibitors (reduces conversion of L-DOPA to dopamine in periphery)

Question 7

2 examples of DOPA decarboxylase inhibitors

Answer 7

carbidopa, benserazide (both cannot cross BBB, so carry L-DOPA to CNS where it is converted to dopamine)

Question 8

describe what happens to peripheral breakdown of levodopa with co-administration with DOPA decarboxylase inhibitors, and consequence on levodopa dosage

Answer 8

prevent peripheral breakdown of levodopa, so reduces required levodopa dosage

Question 9

2 examples of COMT inhibitors used as adjuncts of levodopa in treatment of Parkinson’s disease

Answer 9

entacapone, tolcapone

Question 10

what do COMT inhibitors do to levodopa

Answer 10

increase amount of levodopa in brain (less likely to see “on-off” effects)

Question 11

what receptors can dopamine act on

Answer 11

D1,5 (Gs linked) or D2-4 (Gi linked)

Question 12

what uptakes and metabolises dopamine

Answer 12

uptaken by DAT and metabolised by MAO enzymes

Question 13

2 classes of dopamine receptor agonists for treatment of Parkinson’s disease (don’t require pre-synaptic neurones, so if pre-synaptic neurone is damaged so cannot produce dopamine from levodopa)

Answer 13

ergot derivatives, non-ergot derivatives

Question 14

2 examples of ergot derivative dopamine receptor agonists

Answer 14

bromocriptine, pergolide

Question 15

what do ergot derivative dopamine receptor agonists act as, but what problem is this associated with

Answer 15

act as potent agonists of D2 receptors, but is associated with cardiac fibrosis (causes valve problems)

Question 16

2 examples of non-ergot derivative dopamine receptor agonists (not associated with cardiac fibrosis)

Answer 16

ropinirole, rotigotine

Question 17

how is ropinirole available as

Answer 17

extended-release formulation

Question 18

how is rotigotine available as

Answer 18

patch

Question 19

side effects associated with all dopamine agonists due to affecting all dopaminergic pathways

Answer 19

hallucinations, compulsive gambling disorders etc.

Question 20

2 examples of MAO-B inhibitors used as treatment for Parkinson’s disease

Answer 20

selegiline, rasagiline

Question 21

effect of MAO-B inhibitors on levodopa as treatment for Parkinson’s disease

Answer 21

reduce dosage of L-DOPA required, and can increase amount of time before levodopa treatment is required

Question 22

what reaction do MAO-B inhibitors cause

Answer 22

cheese reaction