Applied Neuropharmacology

Question 1

how is ACh removed from the synaptic cleft ?

Answer 1

the anti-cholesterase enzyme breaks down ACh

Question 2

how are most neurotransmitters removed from the synaptic cleft ?

Answer 2

inactivated neurotransmitters are uptake back into the glial or neurones

Question 3

describe how an APs stimulate the release of neurotransmitters

Answer 3

1. Na channels open as AP propagates down the neuron
2. the Na triggers the voltage gated Ca channels to open
3. this triggers the exocytosis of pre packaged vesicles of transmitter
4. transmitter diffuses across the cleft to evoke a post synaptic response
5. neurotransmitters are removed from the synaptic cleft

Question 4

state the names of some neurotransmitters

Answer 4

acetylcholine
amino acids 
purines 
neuropeptides 
NO 
monoamines

Question 5

do all neurotransmitters act on the same area of the brain ?

Answer 5

no

Question 6

do all neurotransmitters act on the same receptors in the brain ?

Answer 6

no

Question 7

what are the three main areas which dopamine neurones are distributed around the brain ?

Answer 7

• brain stem
• basal ganglia
• limbic system and frontal cortex

Question 8

what physiological functions are controlled by dopamine neurones ?

Answer 8

vomiting
voluntary movements
emotions

Question 9

what causes parkinsons disease?

Answer 9

degeneration of the DA cells in the nigrostriatal pathway

Question 10

what is the nigrostriatal pathway ?

Answer 10

the pathway between the substantia nigra and the striatum (caudate and putamen)

Question 11

when there is degeneration of DA neurones what does this result with?

Answer 11

there is less dopamine releases at the synapses as the neurones have been destroyed
- therefore there is loss in voluntary movements

Question 12

what is the precursor of dopamine in its synthesis ?

Answer 12

glycine

Question 13

is dopamine converted into other neurotransmitters ?

Answer 13

yes

- noradrenaline

Question 14

state the three stages of dopamine synthesis ?

Answer 14

tyrosine -> DOPA - > dopamine

Question 15

can tyrosine cross the BBB?

Answer 15

yes

Question 16

can tyrosine in the brain be converted to dopamine ?

Answer 16

yes

Question 17

giving patients more amino acid tyrosine, what effect would this have on parkinsons ?

Answer 17

would decrease the symptoms as they would be able to produce more dopamine

Question 18

giving patients more DOPA, what effect would this have on parkinsons ?

Answer 18

would decrease the symptoms as they would be able to produce more dopamine

Question 19

can dopamine cross the BBB?

Answer 19

no

Question 20

what enzyme can be given to prevent dopamine being produced in the periphery to increase the dopamine in the brain?

Answer 20

aromatic amino acid decarboxylase

Question 21

what effect does increasing the dopamine concentration in the brain have on the symptoms of parkinsons ?

Answer 21

decrease the symptoms of parkinsons

Question 22

does dopamine have one effect on the brain ?

Answer 22

no
- there are 5 different receptors which cause different effects in different areas of the brain depending on which receptors are expressed

Question 23

what two enzymes break down dopamine ?

Answer 23

MAO-B

COMT

Question 24

what is the clinical significance of dopamine breakdown?

Answer 24

the enzymes which breakdown dopamine can be targeted for pharmacological purpose to increase the conc of dopamine in the body

Question 25

is there a cure for parkinsons ?

Answer 25

no

Question 26

what are the clinical signs of parkinsons ?

Answer 26

stiffness slow movements change in posture tremor

Question 27

what dopaminergic drugs can be used to treat parkinsons ?

Answer 27

DA precursor | DA agonists

Question 28

state the name of the DA precursor?

Answer 28

levodopa

Question 29

how do DA agonists work ?

Answer 29

they mimic the dopamine and act on the dopaminergic receptors in the synaptic cleft

Question 30

state the three enzymes which can be inhibited to increase dopamine in the body?

Answer 30

peripheral AAAD inhibitors MAOB inhibitors COMT inhibitors

Question 31

what symptoms do dopaminergic drugs worsen ?

Answer 31

Brain stem effects - nausea - vomiting Limbic system effects - psychosis

Question 32

do dopaminergic drugs improve balance and cognition ?

Answer 32

no they only effect the rigidity and bradykinesia

Question 33

what type of drugs improve nausea, vomiting and psychosis?

Answer 33

dopamine antagonists

Question 34

do dopamine antagonists improve or worsen parkinsonism symptoms ?

Answer 34

Worsen

Question 35

what drug can be used for parkinsons patients to treat nausea and vomiting ?

Answer 35

domperidone

Question 36

why can domperidone be used in parkinsons patients ?

Answer 36

the drug doesn't cross the BBB so doesn't prevent dopamine transmission within the brain

Question 37

is domperidone an anti-emetic ?

Answer 37

yes

Question 38

can domperidone cross the BBB?

Answer 38

no

Question 39

what is dyskinesias ?

Answer 39

abnormal involuntary movements

Question 40

can DA antagonists cause parkinsonism symptoms ?

Answer 40

yes

Question 41

what disease can noradrenaline be used for?

Answer 41

depression

Question 42

what disease can serotonin be used for?

Answer 42

depression | migraine

Question 43

what disease can GABA be used for?

Answer 43

epilepsy | anxiety