PED1003/L15 Anti-Parkinson's Drugs

Question 1

What is the difference between Parkinson’s Disease and Parkinsonism?

Answer 1

PD - idiopathic disease
Parkinsonism - drug-, stroke-, infection-induced symptoms

Question 2

Give 3 symptoms of Parkinson’s Disease.

Answer 2

Motor symptoms
Resting tremor
Muscle rigidity
Suppression of voluntary movements

Question 3

Describe the post-mortem neuropathology of Parkinson’s Disease.

Answer 3

Loss of DA cell bodies in substantia nigra

Question 4

Describe the presentation of PET images in a patient with Parkinson’s

Answer 4

Loss of DA terminals (tail) in striatum

Question 5

Describe the pathology of Parkinson’s Disease. (2)

Answer 5

Degeneration of DAergic neurones of nigrostriatal tract
Loss of DA neurotransmission in striatum

Question 6

Describe the pathology of Parkinsonism. (2)

Answer 6

Loss of DA transmission in striatum
Pharmacological blockade, brain lesion etc

Question 7

Give 3 of the 4 dopaminergic pathways.

Answer 7

Nigrostriatal
Mesolimbic
Mesocortical
Tuberoinfundibular

Question 8

Describe the healthy nigrostitial system. (3)

Answer 8

Cell bodies in SN fire AP to striatum
Dopamine released into SC
In striatal output neurones, D2 receptor binding inhibits AP

Question 9

Describe the nigrostitial system in Parkinson’s Disease. (3)

Answer 9

Cell bodies in SN fire AP to striatum
Decreased DA release
Less inhibition of AP in striatum

Question 10

Describe dopamine synthesis. (2)

Answer 10

Tyrosine -> L-DOPA via tyrosine hydroxylase
L-DOPA -> Dopamine via DOPA decarboxylase

Question 11

How is dopamine transported and stored?

Answer 11

VMAT transports DA into vesicles

Question 12

How is dopamine metabolised?

Answer 12

By monoamine oxidase (MAO) outside the vesicles

Question 13

Describe the metabolic pathway of dopamine. (3)

Answer 13

DA -> DOPAL via monoamine oxidase
DOPAL -> DOPAC via aldehyde dehydrogenase
DOPAC -> HVA via catechol-O-methyl transferase

Question 14

Where are the 2 isoforms of monoamine oxidase found?

Answer 14

Both on X chromosome

Question 15

DA is mainly metabolised by which isoform of MAO?

Answer 15

MAO(B)

Question 16

What kind of receptor are all dopamine receptors?

Answer 16

G-protein coupled receptors

Question 17

Give the 2 types of dopamine receptor and their action.

Answer 17

D1-like: excitatory
D2-like: inhibitory

Question 18

How is dopamine reuptaken?

Answer 18

By transporter (DAT)
12-span transmembrane protein

Question 19

Why is L-DOPA given to treat Parkinson’s? (3)

Answer 19

Intermediate in DA synthesis
Bypasses rate-limiting step
Increases DA synthesis

Question 20

Why is L-DOPA given with carbidopa? (2)

Answer 20

Carbidopa is a peripherally acting decarboxylase inhibitor
Stops dopamine synthesis in periphery

Question 21

Why can’t dopamine be given to treat Parkinson’s? (3)

Answer 21

Polar so can’t cross membranes
Metabolised by MAO in gut
Can give sympathomimetic effects (NA-like)

Question 22

How does selegiline help treat Parkinson’s? (3)

Answer 22

MAO(B) inhibitor
Blocks intraneuronal metabolism of DA
Increases DA content of vesicles

Question 23

How do D2 receptor agonists help to treat Parkinson’s?

Answer 23

Inhibit striatal output neurones directly

Question 24

Give an example of a D2 agonist.

Answer 24

Bromocriptine

Question 25

Give 2 side effects of D2 agonist drugs.

Answer 25

Psychosis
Cognitive dysfunction
Addictions

Question 26

Describe how antipsychotic drugs can cause Parkinsonism. (2)

Answer 26

Block D2 receptor in all 4 pathways
Decreased neurotransmission and increased AP firing in striatum