Applied Neuropharmacology Flashcards
how is ACh removed from the synaptic cleft ?
the anti-cholesterase enzyme breaks down ACh
how are most neurotransmitters removed from the synaptic cleft ?
inactivated neurotransmitters are uptake back into the glial or neurones
describe how an APs stimulate the release of neurotransmitters
- Na channels open as AP propagates down the neuron
- the Na triggers the voltage gated Ca channels to open
- this triggers the exocytosis of pre packaged vesicles of transmitter
- transmitter diffuses across the cleft to evoke a post synaptic response
- neurotransmitters are removed from the synaptic cleft
state the names of some neurotransmitters
acetylcholine amino acids purines neuropeptides NO monoamines
do all neurotransmitters act on the same area of the brain ?
no
do all neurotransmitters act on the same receptors in the brain ?
no
what are the three main areas which dopamine neurones are distributed around the brain ?
- brain stem
- basal ganglia
- limbic system and frontal cortex
what physiological functions are controlled by dopamine neurones ?
vomiting
voluntary movements
emotions
what causes parkinsons disease?
degeneration of the DA cells in the nigrostriatal pathway
what is the nigrostriatal pathway ?
the pathway between the substantia nigra and the striatum (caudate and putamen)
when there is degeneration of DA neurones what does this result with?
there is less dopamine releases at the synapses as the neurones have been destroyed
- therefore there is loss in voluntary movements
what is the precursor of dopamine in its synthesis ?
glycine
is dopamine converted into other neurotransmitters ?
yes
- noradrenaline
state the three stages of dopamine synthesis ?
tyrosine -> DOPA - > dopamine
can tyrosine cross the BBB?
yes
can tyrosine in the brain be converted to dopamine ?
yes
giving patients more amino acid tyrosine, what effect would this have on parkinsons ?
would decrease the symptoms as they would be able to produce more dopamine
giving patients more DOPA, what effect would this have on parkinsons ?
would decrease the symptoms as they would be able to produce more dopamine
can dopamine cross the BBB?
no
what enzyme can be given to prevent dopamine being produced in the periphery to increase the dopamine in the brain?
aromatic amino acid decarboxylase
what effect does increasing the dopamine concentration in the brain have on the symptoms of parkinsons ?
decrease the symptoms of parkinsons
does dopamine have one effect on the brain ?
no
- there are 5 different receptors which cause different effects in different areas of the brain depending on which receptors are expressed
what two enzymes break down dopamine ?
MAO-B
COMT
what is the clinical significance of dopamine breakdown?
the enzymes which breakdown dopamine can be targeted for pharmacological purpose to increase the conc of dopamine in the body
is there a cure for parkinsons ?
no
what are the clinical signs of parkinsons ?
stiffness
slow movements
change in posture
tremor
what dopaminergic drugs can be used to treat parkinsons ?
DA precursor
DA agonists
state the name of the DA precursor?
levodopa
how do DA agonists work ?
they mimic the dopamine and act on the dopaminergic receptors in the synaptic cleft
state the three enzymes which can be inhibited to increase dopamine in the body?
peripheral AAAD inhibitors
MAOB inhibitors
COMT inhibitors
what symptoms do dopaminergic drugs worsen ?
Brain stem effects
- nausea
- vomiting
Limbic system effects
- psychosis
do dopaminergic drugs improve balance and cognition ?
no they only effect the rigidity and bradykinesia
what type of drugs improve nausea, vomiting and psychosis?
dopamine antagonists
do dopamine antagonists improve or worsen parkinsonism symptoms ?
Worsen
what drug can be used for parkinsons patients to treat nausea and vomiting ?
domperidone
why can domperidone be used in parkinsons patients ?
the drug doesn’t cross the BBB so doesn’t prevent dopamine transmission within the brain
is domperidone an anti-emetic ?
yes
can domperidone cross the BBB?
no
what is dyskinesias ?
abnormal involuntary movements
can DA antagonists cause parkinsonism symptoms ?
yes
what disease can noradrenaline be used for?
depression
what disease can serotonin be used for?
depression
migraine
what disease can GABA be used for?
epilepsy
anxiety
