function of cerebellum- basal ganglia Flashcards
D1 receptors pathway
1) D1 activ by DA and stim cAMP
2) stim GABAergic neurons from striatum (putamen) to incr inhib on globus pallidus internus
3) GPi inhib VL thalamus
4) VL activates cortex (activate direct pathway )
D2 receptors pathway
1) D2 inhib by DA, inhib GPe neurons using GABA
2) GPe project to STN which uses glutamate to stim GPi
3) excite GPi causes inhib of VL thalamus
Subst nigra pars compacta sends DA axons to 2 populations of medium spiny neurons where?
what are the receptors
in striatum
D1 and D2 receptors
how does parkinson’s disease affect D1 vs D2
D1 = GPi not inhib –> unopposed inhib from GPi to VL thalamus (too much inhib)
D2 = striatum not inhib anymore so fire GABA –> unopposed inhib of GPe so STN active –> excite GPi to ihib VL thalamus
inhib thalamus signal to cortex so inhib movement initiation
most effective drug for parkinson’s
Sinemet = L-dopa + carbidopa)
why is L-dopa such a good drug for parkinson
why paired with carbidopa
L-dopa = dopamine precurosr converted to DOPA via dopa decarboxylase
carbidopa = peripheral DDC inhib in liver and gut so more L-dopa to the brain
why are dopamine receptor agonists good treatment for parkinsons’
bind to D2 recpetors and block dopamine effects
used sometimes instead of L-dopa because of longer half life so able to sustain dopaminergic activity and smooth the short half life of L-dopa
also decr risk of dyskinesia
why use monoamine oxidase inhib
MAO important for breaking down Dopamine –> DOPAC
thereby potentiating effects of dopamine and L-DOPA
difference btwn MAO-A and MAO-B
MAO-A = dangerous since breakdown many monoamines (Epi, NE, 5-HT, DA)
MAO-B = more dopamine sleective
why use COMT inhib
prevent breakdown of L-dopa and dopamine by COMT to potentiate effects of L-dopa
why use amantadine
incr availability of endogenous dopamine in caudate and putamine
also NMDA antagonist
L-dopa with carbidopa = sinemet
class
duration of action
ADRs
class = endogenous precursor to DA
duration of action = short = peak 30-60 min, clear by 2 hrs
ADRs=
- acute = nausea, hypotension, depression, psychosis
- chronic = dyskinesia and psychosis
Bromocriptine
class
ADRs
class = D2 agonist
ADRs = nausea, change mentation, sudden onset sleep
pergolide
class
ADRs
class = D2 agonist + D1 + 5-HT
ADRs = nausea, change mentation, sudden onset sleep, cardiac valve thickening
pramipexole and ropinirole
class
ADRs
class = D2 agonist + D3 + D4
ADR = nausea, change mentation, sudden onset sleep
