Parkinson's Disease (General)

Question 1

How do neurodegenerative diseases develop

Answer 1

A protein misfolds from mutational external factors

Misfolded proteins aggregate forming insoluble aggregates

Forms deposits –> Neurotoxicity

Question 2

Amyloid / Amyloidosis

Answer 2

Proteins Aggregate

Question 3

How are misfolded proteins repaired

Answer 3

Molecular Chaperones

Question 4

What Protein Misfolds in Parkinson’s

Answer 4

alpha-synuclein

Question 5

What Amyloid Deposit forms in Parkinson’s

Answer 5

Lewy Bodies

Question 6

What is Parkinson’s Disease

Answer 6

Degenerative disease of basal ganglia
(Substantia Nigra and Corpus Striatum)

• Suppresses Voluntary Movement
• Tremors at Rest
• Muscle Rigidity

Question 7

As PD progresses what symptoms can develop

Answer 7

Disorder of movement, can also develop cognitive decline

Question 8

What drugs cause Parkinson?

Answer 8

Antipsychotics

Question 9

How does Parkinson’s Develop

Answer 9

Alpha-Synuclein proteins misfold and aggregate into intracellular Lewy Bodies
–> Causes loss of dopaminergic neurons in substantia nigra and corpus striatum

Question 10

What kinds of signals does Parkinson effect

Answer 10

Damages Neurons that control Dopaminergic, 5-HT, NA, and Cholinergic
–> Leads to overactivation of GABAergic signalling to thalamus
–> Reduces excitatory signalling to motor cortex that is supposed to initiate movement

Question 11

Levodopa (L-DOPA)

Answer 11

Acts as a dopamine precursor and enters brain
Replaces deficient neurotransmitter

Question 12

Carbidopa

Answer 12

Given in combination Levodopa
–> Prevents L-DOPA being converted into dopamine in the periphery

Peripheral DOPA Decarboxylase Inhibitors that does not cross BBB

Question 13

Entacapone

Answer 13

Given in combination Levodopa
–> Slows metabolism of L-DOPA
Catechol-O-methyl transferase Inhibitor
(COMT)

Question 14

Levodopa Unwanted Effects

Answer 14

Involuntary Movements
Effects are On and OFF (With Off effects causing sudden worsening of bradykinesia & rigidity)
Hypotension
Psychological Effects

Question 15

Pramipexole Mechanism of Action

Answer 15

Dopamine Receptor Agonist

Controls Parkinson’s by activation of dopamine receptors in the neuronal circuitry responsible for motor control

Question 16

Pramipexole Unwanted Effects (D2)

Answer 16

Pramipexole is selective for D2 receptors and thus, causes less nausea and vomiting

Question 17

Pramipexole Unwanted Effects

Answer 17

Nausea and Vomiting
Somnolence (Sleepiness)
Hallucinations
Compulsive Behaviours

Question 18

Selegiline Mechanism of Action

Answer 18

Monoamine Oxidase B Inhibitor
(MAO-B Inhibitor)

Protects dopamine from extraneuronal degradation
–> Selective for MAO-B
–> Lacks periphery side effects

Question 19

MAO-A (Mostly Found In)

Answer 19

Found in brain and outside of CNS

Question 20

MAO-B (Mostly Found In)

Answer 20

Mostly found in the brain

Thus, MAO-B Inhibitors lack unwanted peripheral effects

Question 21

Amantadine

Answer 21

Increases Dopamine Release
Inhibits Amine Uptake
Acts on Dopamine Receptors

Question 22

Orphenadrine Mechanism of Action

Answer 22

Muscarinic Receptor Antagonist

Inhibits M4 (mAchR) on dopaminergic nerve terminals
- M4 usually inhibits the release of dopamine
- Inhibiting M4 leads to enhancement of dopamine release

Question 23

Orphenadrine is used to treat?

Answer 23

Parkinsonian Symptoms caused by antipsychotics
–> Antipsychotics are usually dopamine receptor antagonists