Applied Neuropharmacology Flashcards
how could you use pharmacological intervention to reduce synaptic transmission?
> block Na channels > increase transmitter uptake > block release of machinery > increase breakdown of the transmitter > block voltage gated Ca channels > inhibit synthesis and packaging of neurotransmitter > activate presynaptic inhibitory receptors > block postsynaptic receptors > block voltage gated Ca channels
what pharmacological intervention could increase synaptic transmission?
> block uptake of transmitter
block breakdown of transmitter
potentiate the effects of the transmitter on the receptor
activate postsynaptic receptors with an antagonist
increase synthesis and packaging of neurotransmitter
name 6 types of neurotransmitters
> acetylcholine > monoamines > amino acids > purines > neuropeptides > NO
name three monoamines
> noradrenaline
dopamine
serotonin
name some neuropeptides
> endorphins
CCK
substance P
what is the anatomical distribution of dopamine in the brain?
> brainstem
basal ganglia
limbic system and frontal cortex
what are the physiological functions affected by dopamine?
> vomiting
voluntary movement
emotions and reward
what is the pathophysiology of parkinsons?
> degeneration of the dopamine in the substantia nigra
> dopamine deficiency in the basal ganglia
describe dopamine synthesis
glycine alanine phenylalanine tyrosine DOPA dopamine
how is dopamine synthesis modulated in vivo
> dopamine does not cross the blood brain barrier so cannot just be given
the enzyme that converts DOPA into dopamine is blocked outside the BBB
DOPA crosses the BBB and is converted into dopamine
why can dopamine produce many and different effects in different brain regions?
as there are 5 subtypes of metabotropic receptors that do different things and are expressed in different parts of the brain
what is dopamine broken down into?
homovanillic acid
what are the key enzymes in dopamine breakdown?
> MAO-B
> COMT
what are the two intermediate substances in dopamine breakdown?
> dihydroxyphenylacetic acid
> 3-methoxytryptamine
name a dopamine precursor drug
levodopa
what are the two types of dopamine agonists?
> ergots
non-ergots
apomorphine
what drugs improve the symptoms of parkinsons?
> levodopa
> dopamine agonists
why are ergots no longer used to treat parkinsons?
they stimulate the receptors of fibroblasts so there is fibrosis of lungs and peritoneum
what enzyme inhibitors are there that affect dopamine?
> peripheral AAAD inhibitors
MAOB inhibitors
COMT inhibitors
what are the advantages of peripheral AAAD inhibitors?
> decrease peripheral side effects of levodopa
> allows a greater proportion of the oral dose to reach the CNS
what are the effects of MAOB and COMT inhibitors?
> decrease metabolism of dopamine
> increases the effectiveness of levodopa
what can dopaminergic drugs worsen or cause?
> nausea
vomiting
psychosis
impulsivity/abnormal behaviours
what do dopaminergic drugs not help?
> dysarthria
balance
cognition
what can dopamine antagonists improve?
> nausea
vomiting
psychosis
what can dopamine antagonists cause or worsen?
parkinsons
is the area postrema (vomiting centre) functionally inside or outside the BBB?
outside
can domperidone, a dopamine antagonist be used to treat nausea in a patient with parkinsons?
yes as it does not cross the blood brain barrier
domperidone is an anti-emeic. what has this drug permitted the use of in parkinsons?
apomorphine which is a powerful emetic
what is dyskinesias?
abnormal involuntary movements
what can cause dyskinesias?
dopaminergic drugs
what are the effects of long term dopamine antagonists?
> parkinsonism
> tardive dyskinesias (by continually blocking the dopamine centre it could be sensitised)
what are selective serotonin reuptake inhibitors used as?
antidepressants
what are triptans used to treat?
migraine
what are GABA agonists?
anti-epilepsy drugs
what are noradrenaline reuptake blockers used as?
antidepressants
what are MAO inhibitors used as?
antidepressants
