Parkinson's disease

Question 1

Parkinson’s is a neurodegenerative disease, but not a …

Answer 1

Dementia

Question 2

What is the cause of Parkinson’s?

Answer 2

Loss of dopaminergic neurons in the substantia nigra
Area controls movement

Question 3

Symptoms of Parkinson’s

Answer 3

Changes in movement and posture
Lose regulation of movement
Resting tremor
Difficulty in starting movement

Question 4

Movement that is controlled by the motor cortex is modulated by…

Answer 4

The balance of facilitatory and inhibitory inputs from the striatum

Question 5

Parkinson’s inhibitory vs facilitatory pathways

Answer 5

Dopamine from substantia nigra enhances facilitatory via D1-type receptors.
Inhibits the inhibitory pathway via D2-type receptors
In Parkinson’s inhibitory pathway dominates

Question 6

Causal genes for rare familial forms of PD

Answer 6

• Alpha synuclein – rare single point mutations lead to PD in affected families
• Parkin, DJ-1 and PINK – A role in oxidative stress, mitochondria and protein degradation
• LRRK2

Question 7

How can we fix low dopamine?

Answer 7

Provide more dopamine (L-Dopa)
Decrease dopamine reuptake
Inhibit dopamine breakdown (COMT and MAO-B inhibitors)
Dopamine agonists

Question 8

What is the main approach to Parkinson’s treatment?

Answer 8

Levodopa

Question 9

Levodopa

Answer 9

Usually administered at the early onset of disorder.
Drug is well tolerated within first 5 years
Does result in symptoms that become intolerable later
Converted to dopamine by dopa decarboxylase

Question 10

L-Dopa issues

Answer 10

Dopamine cannot cross the blood-brain barrier, so given with carbidopa which inhibits dopa decarboxylase to prevent premature metabolism

Question 11

Side effects of L-Dopa

Answer 11

Major side effect is dyskinesia (involuntary movement)
Almost all other treatments are about managing this or reducing L-dopa taken
Means that these other treatments are “late-stage” PD treatments

Question 12

Monoamine Oxidase B (MAOB) inhibitors

Answer 12

Delays or reduces breakdown of dopamine by MAO-B.
Used as monotherapy or in conjunction with L-DOPA to reduce it’s dosage by 15%.

Question 13

Side effects of MAOB inhibitors

Answer 13

Side effects of L-DOPA may be enhanced by selegeline (nausea and dizziness).

Question 14

Catechol O-Methyl Transferase (COMT) Inhibitors

Answer 14

Inactivates enzyme that degrades neurotransmitters, such as dopamine.
Mainly used in combination with L-DOPA, it increases the half-life.
Delays “wearing-off” effect of L-DOPA and other motor complications such as dyskinesia

Question 15

Side effects of COMT inhibitors

Answer 15

Diarrhea and sleep disturbances
Some toxicity to liver cells

Question 16

Dopamine Agonists as a Treatment for Parkinson’s

Answer 16

Acts directly on the dopamine receptors, so has to be specific to D1 or D2.
Initially was used with L-DOPA.
Sometimes prescribed before L-DOPA, to delay complications brought on by prolonged use of L-DOPA.

Question 17

Side effects of dopamine agonists

Answer 17

Nausea, dizziness, hallucinations
Sleep attacks, hypotension

Question 18

Surgery for PD

Answer 18

Deep brain stimulation
Brain pacemaker, sends electrical impulses to brain to stimulate the subthalamic nucleus.
Improves motor functions and reduces motor complications.

Question 19

Complications of deep brain stimulation

Answer 19

Brain haemorrhage, seizures, death