Parkinson's Flashcards
Does the indirect pathway promote or prevent movement?
Prevents
Does the direct pathway promote or prevent movement?
Promotes
Does DA and the indirect pathway promote or prevent movement?
Promote
Does DA and direct pathway promote or prevent movement?
Promote
What are the symptoms of Parkinson’s?
Rigidity (resistance to passive movement)
Bradykinesia (slowness of movement once initiated), Resting tremor
Akinesia (absence or reduction of movement)
What is the normal output of basal ganglia to thalamus? Why?
Inhibitory to suppress unwanted movements
What does DA reinforce in movement?
Initiation
What are the SE of directly acting DA Parkinsonian drugs?
Emetic and psychomimetic
What happens in Parkinson’s to the neurons?
loss of nigro-striatal dopaminergic pathway this leads to excessive inhibition of thalamo-cortical pathway
Overactivity of STN
Lose neurons that made DA
Why type of neurons are basal ganglia full of?
GABA
What are the pathological landmarks of Parkinson’s seen in post-mortem?
No Black patch in parkinsons where nigra is.
Lewy bodies are pathological hallmark of parkinsons disease in neurons.
What treatments are there for Parkinson’s?
Drugs like L-DOPA
Surgery
DBS - inactivates STN neurons
How does DA replacement ameliorate symptoms?
Reduces rigidity and hypokinesia
What enzyme is used to metabolise L-DOPA –> DA
DOPA-decarboxylase
What negative events happen after being on L-DOPA for a while?
Due to progressive nature of disease, neurones still dying, so cant produce dopamine if wasting. Effectiveness diminishes over 2-5 years. Decrease in dopaminergic nerve terminals leads to decrease in capacity to convert L-DOPA to dopamine. Increase in L-DOPA dose frequency and eventual development of: dyskinesia and on-off effect of sudden transitions between symptom relief and hypokinesia.
Apart from L-DOPA what other DA acting agonists are there?
Bromocriptine directly acting DA receptor agonist, non selective.
Pramipexole more D2 receptor selection. Apomorphine which is reserved for advanced stage PD.
Bromocriptine
MoA: direct acting DA receptor agonist, non-selective
Pramipexole
More D2 receptor agonist selectivity
Apomorphine
For advanced stage PD.
Selegiline
Selegiline – MAOi (MAOB breaks down dopamine) inhibitor selectively elevates conc of DA
Amantidine
Dopamine releaser
mAchR antagonists
In striatum produce some symptomatic relief
What is L-DOPA given with?
Carbidopa-inhibits the peripheral conversion of L-DOPA to DA.
DOPA decarboxylase inhibitor. Doesn’t cross BBB
What does the striatum include?
Striatum will encompass: Caudate nucleus, putamen and nucleus accumbens
What are the basal ganglia?
A functional unit, circuit within the brain. Group of associated subcortical nuclei
Integration of sensory and motor information
Cortex -> basal ganglia –> cortex loop
Descending excitatory input from cortex into basal ganglia. Output from basal ganglia through thalamus to cortex.
Not just part of the cortex feeding in, mostly the thinky parts. Pre-frontal cortex sends a lot, sensory less and motor cortex also sending some.
Basal ganglia feed back to Area 6 to the part not necessarily doing the movement but initiating the movement. So motor circuit output to premotor/SMA cortex. Selection and initiation of voluntary movement.