Parkinson's Disease

Question 1

What region of the brain is affected in Parkinson’s

Answer 1

Substantia Nigra

Question 2

What are the mechanisms?

Answer 2

alpha synuclein accumulaton and mitochondria dysfunction in dopamine producing neurons

Question 3

What are the typical Motyor presentations in Parkinson’s

Answer 3

Tremor (pin-rolling)
Bradykinesia/Hypokineasia
Hypertonia typically cogwheel

Question 4

Alpha synuclein accumulations are known as

Answer 4

Lewy bodies

Question 5

Proteins causing mitochondrial dysfunctionn

Answer 5

DJ-1 and PINK-1

Question 6

Classes of Drugs and drugs themeselves

Answer 6

Increase Dopamine (L-DOPA)
– Increase DA release (amantidine)
– DA2 receptor agonists (Bromocriptin and cabergoline)
- DA3 receptor agonists - Ropinirole and Pramipexole
– Reduce DA metabolism (Selegiline via MAOb and entacapone via COMT)
- Reduce L-DOPA metabolism (Carbidopa to inhibit carboxylases)
- Combinations
Levadopa and carbidopa to give Sinemet

Question 7

Why L-DOPA?

Answer 7

Dopamine can’t cross blood brain barrier

Question 8

Disadvantage from making Dopamine

Answer 8

Lots of ROS production through mitochondria leading to neuronal injury

Question 9

Describe Sinemet

Answer 9

L-DOPA and carbidopa

Question 10

Why muscarinic antagonists?

Answer 10

To balance out the ACh to Dopamine ratio

Question 11

Describe the basic Loop that stops working in Parkinson’s Disease

Answer 11

Corpus Striatum signals to the Substantia Nigra via GABA, This will then link back to Corpus Striatum via Dopamine and acts as a Tonic inhibitor. However GABA (inhibitory NT) will release this, allowing the Corpus striatum to signal via ACh and then GABA to the Cortex/spinal cord for motor output.

Question 12

What are the typical non-motor presentations of Parkinsons

Answer 12

SCIDD
Smell reduced
Constipation
vIsual hallucinations
Dribbling
Depression and Dementia