Pharmacology of Movement

Question 1

What are present in neurones in Parkinson’s disease?

Answer 1

Lewy bodies

Question 2

What are Lewy bodies?

Answer 2

Intracellular aggregations of protein such as Alpha-synuclein (also found in dementia)

Question 3

How to diagnose Parkinson’s disease?

Answer 3

Gradual dopaminergic nigra cell loss possible via dopamine transporter imaging

Question 4

Where does dopamine transporter imaging occur?

Answer 4

Striatum

Question 5

What is highly oxidisable and produces free radicals?

Answer 5

Dopamine
and oxidation products such as H2O2
MAO – monoamine oxidase (B isoform) is critically involved in oxidation
processes

Question 6

What are the oxidation products of dopamine?

Answer 6

H2O2

Question 7

What enzyme is involved in oxidation of dopamine?

Answer 7

MAO - monoamine oxidase (B isoform)

Question 8

What occurs in Parkinson’s disease with dopamine?

Answer 8

Increased oxidative stress

Question 9

Which complex would there be a dysfunction in in mitochondria which would lead to increased oxidative stress?

Answer 9

Complex I

Question 10

What are the main types of dopamine receptors?

Answer 10

D1-like

D2-like

Question 11

What type of receptor are dopamine receptors?

Answer 11

GPCR

Question 12

What type of receptors does D1-like include?

Answer 12

D1 and D5 subtypes

Question 13

What time of receptors does D2-like include?

Answer 13

D2, D3 and D4 subtypes

Question 14

What do dopaminergic compounds do?

Answer 14

Compensate directly for dopaminergic deficit

Question 15

What type of drug is L-DOPA?

Answer 15

Levodopa

Question 16

What is L-dopa?

Answer 16

biosynthetic precursor of dopamine

Question 17

What can LDOPA be combined with?

Answer 17

DOPA decarboxylase inhibitors (carbidopa)

Question 18

Give an example of a dopaminergic agonist

Answer 18

Ropinirole

Question 19

What do MAOb inhibitors do?

Answer 19

Protect residual dopamine against oxidation

Question 20

Give examples of two MAOb inhibitors

Answer 20

Rasagiline

Selegiline

Question 21

What does Catechol-O-methyl transferase (COMT) do?

Answer 21

Break down dopamine and other NTs

Question 22

Give 2 examples of COMT inhibitors

Answer 22

Entacapone

Tolcapone

Question 23

Why would you give anticholinergic compounds in Parkinson’s?

Answer 23

Loss of dopamine leads to hyperactivity of cholinergic cells

Question 24

Give an example of an anticholinergic compounds

Answer 24

Orphenadrine

Question 25

What does Amantadine do?

Answer 25

Inhibits dopamine reuptake and increases dopamine release

Question 26

What are side effects of L-DOPA?

Answer 26

Nausea/vomiting
Postural hypotension
Psychosis
Impulse-control disorders

Question 27

What can you do surgically to help with Parkinson’s disease?

Answer 27

DBS in the subthalamic nucleus or GPi
Pallidotomy
Thalamotomy

Question 28

What chromosome is Huntington’s disease associated with?

Answer 28

4

Question 29

Huntington’s gene presents with an abnormal number of which codon?

Answer 29

CAG

Question 30

What pathological changes occur in Huntington’s disease?

Answer 30

Cortical atrophy
Prominent striatal degradation
Loss of medium sized spiny neurones

Question 31

Give some neurodegeneration mechanisms in Huntington’s disease

Answer 31

Excitotoxicity
Loss of neurotrophic factors
Accumulation of aggregates of mutant huntington protein

Question 32

Treatment of Huntington’s disease?

Answer 32

Synaptic vesicular amine transporter inhibitor
Antidopaminergic
Antidepressant drugs
Striatal fetal grafts

Question 33

Give an example of a synaptic vesicular amine transporter inhibitor

Answer 33

Tetrabenazine

Question 34

Give 2 exampleso f antidopaminergics

Answer 34

Olanzapine

Haloperidol

Question 35

Give an example of an antidepressant

Answer 35

Amitriptyline