Dopamine Regulation

Question 1

CNS what does ACh and dopamine do respectively?

Answer 1

ACh - excitatory input

Dopamine - Tonic inhibition

Question 2

Parkinson’s is an imbalance between ACh and Dopamine in what two regions?

Answer 2

Corpus striatum

substantia nigra

Question 3

MOtor signs and symptoms of Parkinson’s?

Answer 3

tremor
regidity
bradykinesia
festinating gait

Question 4

Facial and speech changes with Parkinson’s?

Answer 4

face-impassive/no blinking

speech - monotonous

Question 5

Non-motor signs and symptoms of Parkinson’s?

Answer 5

cognition
depression/anxiety
olfactory deficiencies
Bowel and Bladder
fatigue/sleep
pain

Question 6

which nerves degenerate in Parkinson’s?

Answer 6

dopaminergic nerves in substantia nigra (presence of Lewy bodies)

Question 7

how much substantia nigra do you need to lose to get symptoms?

Answer 7

~80%

Question 8

Main Management of Parkinson’s is?

Answer 8

Drugs: symptomatic relief

Question 9

what Drugs to restore striatum balance?

Answer 9

cholinergic antagonists to allow increase in Dopamine

Question 10

4 way to restore dopamine deficiency:

Answer 10

increase synthesis
increase release
Receptor agonist
Reduce metabolism of D

Question 11

if you ingest pure dopamine:

Answer 11

vomit

Question 12

dopamine crosses BBB?

Answer 12

Nope.

Question 13

L-DOPA in the body, what happens?

Answer 13

90% of it metabolised in periphery

Question 14

How to prevent L-DOPA metabolism in periphery?

Answer 14

combine with inhibitor of peripheral DOPA decarboxylase

Question 15

what do you need in order for L-DOPA to work?

Answer 15

need some functional dopaminergic neurons

Question 16

what happens once you start L-DOPA? why?

Answer 16

increase degen of the neurons possibly due to increased oxidative stress

Question 17

Levodopa ingestion you get what phenomenon?

Answer 17

on-off

Question 18

Levodopa absorption/half-life? continued usage?

Answer 18

1. rapid absorption
2. 1-2hr half-life
3. effectiveness declines with time

Question 19

Levodopa drug interactions? 4 big ones

Answer 19

1. vitamin B6
2. MAOa inhibitors
3. inhaled anaesthetics
4. anticonvulsants/neuroleptics

Question 20

adverse effects of Levodopa?

Answer 20

Anorexia/nausea/vomiting
depression/anxiety
visual/auditory hallucinations

Question 21

what kind of drug preferred in younger patients?

Answer 21

dopamine agonists

Question 22

What to use to decrease dopamine metabolism? 2 of them.

Answer 22

1. MAO(B) inhibitors (Selegiline)
   - may reduce free radicals, use early
2. COMT inhibitors

Question 23

What is Amantadine?

Answer 23

type of flu antiviral that enhances dopamine release, less efficacious than L-DOPA

Question 24

When to take muscarinic receptor antagonists to restore dopa-ACh imblance?

Answer 24

adjunct to Levodopa only

Question 25

what are the classic anti-muscarinic side effects?

Answer 25

1. reduced SLUD
2. dry mouth
3. memory impairment

Question 26

Next 5 years for Parkinson’s include 3 things

Answer 26

1. adenosine R antagonists

2. glutamate reduction

Question 27

next 5-10 years for parkinson’s. 2 things:

Answer 27

1. deep brain stim

2. Optogenetics (modulating genes with light pulses)

Question 28

10-20 years for parkinson’s: 2 things.

Answer 28

1. genetics

2. stem cell replacement

Question 29

what fibril is found in Lewy bodies in Parkinson’s?

Answer 29

a-synuclein

Question 30

what organelle is implicated in Parkinson’s?

Answer 30

Mitochondria damage

Question 31

what two things are protective for Parkinson’s?

Answer 31

nicotine and caffeine

Question 32

higher incidence of Parkinson’s with exposure to?

Answer 32

pesticides

Question 33

what area is first to be affected by Parkinson’s

Answer 33

olfactory

GI

Question 34

largest risk factor for Parkinson’s?

Answer 34

age

Question 35

what is MPTP?

Answer 35

inducer of Parkinson’s

Question 36

what does MPTP do?

Answer 36

kills dopaminergic cells by killing mitochondria