Dopamine Regulation Flashcards
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?
Corpus striatum
substantia nigra
MOtor signs and symptoms of Parkinson’s?
tremor
regidity
bradykinesia
festinating gait
Facial and speech changes with Parkinson’s?
face-impassive/no blinking
speech - monotonous
Non-motor signs and symptoms of Parkinson’s?
cognition depression/anxiety olfactory deficiencies Bowel and Bladder fatigue/sleep pain
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?
~80%
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:
increase synthesis
increase release
Receptor agonist
Reduce metabolism of D
if you ingest pure dopamine:
vomit
dopamine crosses BBB?
Nope.
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?
on-off
Levodopa absorption/half-life? continued usage?
- rapid absorption
- 1-2hr half-life
- effectiveness declines with time
Levodopa drug interactions? 4 big ones
- vitamin B6
- MAOa inhibitors
- inhaled anaesthetics
- anticonvulsants/neuroleptics
adverse effects of Levodopa?
Anorexia/nausea/vomiting
depression/anxiety
visual/auditory hallucinations
what kind of drug preferred in younger patients?
dopamine agonists
What to use to decrease dopamine metabolism? 2 of them.
- MAO(B) inhibitors (Selegiline)
- may reduce free radicals, use early - 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?
- reduced SLUD
- dry mouth
- memory impairment
Next 5 years for Parkinson’s include 3 things
- adenosine R antagonists
2. glutamate reduction
next 5-10 years for parkinson’s. 2 things:
- deep brain stim
2. Optogenetics (modulating genes with light pulses)
10-20 years for parkinson’s: 2 things.
- genetics
2. stem cell replacement
what fibril is found in Lewy bodies in Parkinson’s?
a-synuclein
what organelle is implicated in Parkinson’s?
Mitochondria damage
what two things are protective for Parkinson’s?
nicotine and caffeine
higher incidence of Parkinson’s with exposure to?
pesticides
what area is first to be affected by Parkinson’s
olfactory
GI
largest risk factor for Parkinson’s?
age
what is MPTP?
inducer of Parkinson’s
what does MPTP do?
kills dopaminergic cells by killing mitochondria
