Applied neuro-pharmacology

Question 1

What is the limited range if neuro transmitters in the body

Answer 1

Acetylcholine

Monoamines

- Noradrenaline
- Dopamine
- Serotonin (5-HT)

Amino acids

- Glutamate
- GABA
- Glycine

Purines

- ATP
- Adenosine

Neuropeptides

- Endorphins
- CCK
- Substance P

NO

Question 2

How is Acetylcholine an exception of a neurotransmitter

Answer 2

Is inactivated by enzymatic breakdown in the synaptic cleft while most other transmitters are inactivated by high affinity uptake into neurones and glia

Question 3

What three things does each neurotransmitter have

Answer 3

its own anatomical distribution

Its own range of receptors it acts on

Its own range of functions in different regions (some separated by the blood brain barrier)

Question 4

What is the anatomical distribution of dopamine

Answer 4

Brain stem
Brain ganglia
Limbic system
Frontal cortex

Question 5

What are the physical function affected by dopamine

Answer 5

Vomiting
Voluntary movements
Emotions/reward

Question 6

What is the synthesis process of dopamine

Answer 6

Glycine –> alanine –> phenylalanine –> Tyrosine –> Levodopa–> Dopamine

Question 7

What enzyme catalyses tyrosine to levodopa

Answer 7

tyrosine hydroxylase

Question 8

What enzyme catalyses levodopa to dopamine

Answer 8

Aromatic aa decarboxylase

Question 9

How in the periphery can dopamine production be stopped

Answer 9

Via pharmacologically

affecting the Aromatic aa decarboxylase enzyme

Question 10

How in the brain can dopamine be stopped

Answer 10

Lost through degeneration affecting the tyrosine hydroxylase enzyme

Question 11

What kind of receptors are dopamine receptors

Answer 11

Metabotropic (G protein coupled) receptors

Question 12

What is the name of the the 5 subtype dopamine receptors

Answer 12

D1 - active adenylate cyclase

D2- inhibit adenylate cyclase

D3 - Inhibit adenylate cyclase

D4 - Inhibit adenylate cyclase

D5 - active adenylate cyclase

Question 13

What are the key enzymes in dopamine metabolic breakdown

Answer 13

Monoamine oxidase B (MAO-B)

Catechol-O-methyltransferase (COMT)

Question 14

What does dopamine metabolic breakdown to form

Answer 14

Homovanillic acid

Question 15

What is the two cause of Parkinson’s

Answer 15

Degeneration of dopamine-secreting cells in substantia nigra

Dopamine secreting cell deficiency in basal ganglia

Question 16

What is the presentation go Parkinson’s

Answer 16

Stiffness
Slow movements
Change in posture
Tremor

Question 17

What are two categories of dopaminergic drugs

Answer 17

DA precursor

DA agonist

Question 18

What is the DA precursor drug

Answer 18

Levodopa

Question 19

What is different types of Dopamine agonists

Answer 19

Ergots:

• Bromocriptine
• Pergolide
• Cabergoline

Non-ergots

• Ropinirole
• Pramipexole
• Rotigotine

Apomorphine

Question 20

What are enzyme inhibitor drugs used in the treatment of parkinson

Answer 20

Peripheral AAAD inhibitors

• Carbridopa
• Benserazide

COMT inhibitors

• Entacapone
• Tolocapone

MAO-B inhibitors

• Selegiline
• Rasagiline
• Safinamide

Question 21

How does peripheral AAD inhibitors work in the treatment of parkinson

Answer 21

Decreases peripheral side effects of levodopa and allows greater proportion of the oral dose to reach the CNS

Question 22

How does COMT and MAO-B inhibitors work in the treatment of Parkinsons

Answer 22

Decrease the metabolism of dopamine and so increase the effectiveness of levodopa

Question 23

What features of Parkinson’s does dopaminergic drugs improve

Answer 23

Limb rigidity

Bradykinesia,

Tremor

Question 24

What is the side effects of dopaminergic drugs (due to worsening or causing)

Answer 24

Nausea

Vomiting

Psychosis

Impulsivity / abnormal behaviours

Dyskinesias - abnormal involuntary movements (to much movement)

Question 25

Dopaminergic drugs fail to help what features of Parkinson’s

Answer 25

Midline features:
Dysarthria
Balance
Cognition

Question 26

What is the benefical affect of dopamine antagonist

Answer 26

Improve symptoms of nausea, vomiting, psychosis

Question 27

Why cant most Dopamine antagonist be used as an antiemetics

Answer 27

As even though area postrema (vomiting centres) in the medulla is functionally outside the blood brain barrier, DA antagonist will still cross blood brain barrier and worsen or cause parkinsons disease

Question 28

What dopamine antagonist doesn’t cross the blood brain barrier therefore can be used an an antiemetic

Answer 28

Domperidone

• relatively safe to use in parkinson
• no antipsychotic properties

Question 29

What does domperidone permit therapeutic use of

Answer 29

Apomorphine

Question 30

What is the affect of long term antagonist use

Answer 30

Antipsychotics / anti-dizziness

Often cause parkinsonism

Sometimes cause tardive dyskinesias (abnormal involuntary movements)

Question 31

How does DA antagonist cause parkisonism

Answer 31

Receptor blockade in basal ganglia

Question 32

Define tardive dyskinesias

Answer 32

A disorder that results in involuntary, repetitive body movements.
This may include grimacing, sticking out the tongue or smacking of the lips. Additionally there may be rapid jerking movements or slow writhing movements

Question 33

How can long term DA antagonist sometimes cause dyskinesias

Answer 33

upregulation or increased sensitivity of certain DA receptor D2

Question 34

How do tricyclic drugs and MAO inhibitors work as antidepressants.

Answer 34

By acting as a noradrenaline Reuptake inhibitors so noradrenaline remains longer in the system

Question 35

What examples of drugs that affect serotonin 5-HT neurotransmitter

Answer 35

-Selective serotonin reuptake inhibitors (SSRIs) work as antidepressants.

Triptans selective 5HT agonists used for the treatment of migraine

Question 36

What is the function of GABA neurotransmitters drugs

Answer 36

GABA agonists are anti-epilepsy drugs and they also have anti-anxiety properties.