Flashcards in Dopamine Regulation Deck (36)
CNS what does ACh and dopamine do respectively?
ACh - excitatory input
Dopamine - Tonic inhibition
Parkinson's is an imbalance between ACh and Dopamine in what two regions?
MOtor signs and symptoms of Parkinson's?
Facial and speech changes with Parkinson's?
speech - monotonous
Non-motor signs and symptoms of Parkinson's?
Bowel and Bladder
which nerves degenerate in Parkinson's?
dopaminergic nerves in substantia nigra (presence of Lewy bodies)
how much substantia nigra do you need to lose to get symptoms?
Main Management of Parkinson's is?
Drugs: symptomatic relief
what Drugs to restore striatum balance?
cholinergic antagonists to allow increase in Dopamine
4 way to restore dopamine deficiency:
Reduce metabolism of D
if you ingest pure dopamine:
dopamine crosses BBB?
L-DOPA in the body, what happens?
90% of it metabolised in periphery
How to prevent L-DOPA metabolism in periphery?
combine with inhibitor of peripheral DOPA decarboxylase
what do you need in order for L-DOPA to work?
need some functional dopaminergic neurons
what happens once you start L-DOPA? why?
increase degen of the neurons possibly due to increased oxidative stress
Levodopa ingestion you get what phenomenon?
Levodopa absorption/half-life? continued usage?
1. rapid absorption
2. 1-2hr half-life
3. effectiveness declines with time
Levodopa drug interactions? 4 big ones
1. vitamin B6
2. MAOa inhibitors
3. inhaled anaesthetics
adverse effects of Levodopa?
what kind of drug preferred in younger patients?
What to use to decrease dopamine metabolism? 2 of them.
1. MAO(B) inhibitors (Selegiline)
-may reduce free radicals, use early
2. COMT inhibitors
What is Amantadine?
type of flu antiviral that enhances dopamine release, less efficacious than L-DOPA
When to take muscarinic receptor antagonists to restore dopa-ACh imblance?
adjunct to Levodopa only
what are the classic anti-muscarinic side effects?
1. reduced SLUD
2. dry mouth
3. memory impairment
Next 5 years for Parkinson's include 3 things
1. adenosine R antagonists
2. glutamate reduction
next 5-10 years for parkinson's. 2 things:
1. deep brain stim
2. Optogenetics (modulating genes with light pulses)
10-20 years for parkinson's: 2 things.
2. stem cell replacement
what fibril is found in Lewy bodies in Parkinson's?