Parkinson's Disease: Pathology + Pharmacology

Question 1

What are the symptoms?

Answer 1

Tremor
Rigidity
Bradykinesia
Depression
REM sleep behaviour disorder
Pain
Gait instability

Question 2

What are the 3 main symptoms?

Answer 2

Tremor
Bradykinesia
Rigidity

Question 3

When does the tremor appear + disappear?

Answer 3

Tremor at rest
Disappears with voluntary movement

Question 4

What is an example of a tremor?

Answer 4

Pill rolling

Question 5

What is bradykinesia?

Answer 5

Slowness in planning, initiating + executing movement

Question 6

What is rigidity?

Answer 6

Stiffness + resistance to limb movement caused by increased muscle tone
= excessive + continuous contraction
= joint pain

Question 7

Describe the pathology of PD

Answer 7

Degeneration of dopaminergic neurones
= diminished substantia nigra
= less pigment

Question 8

What happens in normal dopamine levels?

Answer 8

Dopamine is released from substantia nigra
Acts on putamen
Acts on thalamus
Which controls inhibitor neurones (GABA)
+ excitatory neurones on thalamus promotes movement

Question 9

What is present in PD?

Answer 9

Impairment + loss of myelinated dopaminergic neurons
Accumulation of Lewy bodies

Question 10

What are the affected dopamine pathways?

Answer 10

Nigrostriatal
Mesocortical
Mesolimbic
Tubero-infundibular

Question 11

What is the main dopamine pathway affected?

Answer 11

Nigrostriatal

Question 12

Is there a cure for PD?

Answer 12

NO

Question 13

What is the aim of PD treatment?

Answer 13

To increase dopamine neurotransmission in striatum

Question 14

Why does Levodopa have to be given with Carbidopa?

Answer 14

Because L-DOPA can cross BBB
BUT only 1-3% reaches brain as rest being decarboxylated

Question 15

What is Carbidopa?

Answer 15

DOPA decarboxylase inhibitor

Question 16

What is Benserazide?

Answer 16

DOPA decarboxylase inhibitor unable to cross BBB
= reduce peripheral effect of dopamine

Question 17

What can happen with the chronic use of of Levodopa?

Answer 17

Dyskinesia
End of dose deterioration function

Question 18

What is dyskinesia?

Answer 18

Uncontrolled movement

Question 19

What is the end of dose deterioration?

Answer 19

1st 5 years fine
BUT afterwards body can show resistance = symptoms show before next dose

Question 20

What is the 2nd line treatment?

Answer 20

Monoamine oxidase inhibitors

Question 21

Describe monoamine oxidase

Answer 21

Responsible for metabolism of dopamine
2 forms = MAOa + MAOb

Question 22

What is an example of a MAOb inhibitor?

Answer 22

Selegiline

Question 23

What does Selegiline do?

Answer 23

Blocks metabolism of DA
Increases DA content of synaptic vesicles

Question 24

What is COMT?

Answer 24

Catecholamine-o-methyl transferase

Question 25

What does COMT do?

Answer 25

Breaks down catecholamines, including dopamine + L-DOPA

Question 26

What does COMT inhibitors do?

Answer 26

Increase amount of dopamine

Question 27

What is an example of COMT inhibitors?

Answer 27

Entacapone Tolcapone

Question 28

What is COMT inhibitors given with?

Answer 28

L-DOPA