Applied neuropharmacology Flashcards
summarise the sequence of events in synaptic transmission
- synthesise/packaging of NT in presynaptic terminal
- Na+ AP invades terminal
- VGCa2+ channels activated
- triggers Ca2+ dependent exocytosis of NT vesicles
- transmitter diffuses across cleft - binds to iono/metabotropic receptors to evoke presynaptic response
- presynaptic autoreceptors inhibit further NT release
- transmitter inactivated by uptake into glia/neurons or extracellular breakdown
- NT metabolised by cells
by what mechanisms can you reduce synaptic transmission
- block VGNa+ channels
- inhibit synthesis/packaging of NT
- activate presynaptic inhibitory receptors
- block postsynaptic receptors
- block VGCa2+ channels
- increase breakdown of NT
- block release machinery
- increase uptake of NT
by what mechanisms can you increase synaptic transmission
- block uptake of NT
- increase synthesis/packaging of NT
- activate postsynaptic receptors
- potentiate effects of NT on receptor
- block breakdown of transmitter
list some neurotransmitters
acetylcholine
monoamines
- noradrenaline
- dopamine
- seratonin
amino acids
- glutamate
- GABA
- glycine
purines
- ATP
- adenosine
Neuropeptides
- endorphins
- CCK
- substance P
Nitrous oxide
what characteristics do each individual neurotransmitter have
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)
what is the anatomical distribution of dopamine in the brain
brainstem
basal ganglia
limbic system+frontal cortex
what physiological functions are affected by dopamine
increases vomiting
voluntary movement
emotions/reward
what causes parkinsons
degeneration of dopamine cells in the substantial nigra
dopamine deficiency in the basal ganglia
can be because it it pharmacologically blocked as well
what type of receptor are dopamine receptors
metabotropic - g-protein coupled
5 subtypes - D1-D5
what determines the effect dopamine has in the body
depends what receptor (D1-D5) is expressed
means a selective agonist/antagonist can produce a specific therapeutic effect
what are the key enzymes in dopamine breakdown
MAO-B - monoamine oxidase B
COMT- catechol-O-methyltransferase
how does parkinsons present
stiffness
slow movements
change in posture
tremor - “pill-rolling”
what dopaminergic drugs can improve the symptoms of parkinsons
DA precursor - levodopa
DA agonists
- ergots - cabergoline
- non-ergots - ropinirole
- apomorphine
what enzyme inhibitors are usually taken with levodopa
peripheral AAAD inhibitors
- carbidopa
MAOB inhibitors - safinamide
COMT inhibitors - entacapone
what do peripheral AAAD inhibitors do
decreases peripheral side effects of levodopa
allows greater proportion of oral dose to reach the CNS
