Parkinson's disease

Question 1

1st line treatment for Parkinson’s

Answer 1

Increasing synaptic concentration of DA

Levodopa, carbidopa

Question 2

2nd line treatment for Parkinson’s

Answer 2

Direct activation of DA receptors via DA agonists

Pramipexole, rotigitine

Question 3

Adjunct therapies for Parkinson’s

Answer 3

MAO-B inhibitors (selegiline, rasagiline)

Altering neurotransmitter efficacy (benztropine)

COMT inhibitors (entacapone)

Amantadine, bromocriptine

Question 4

Levodopa MoA

Answer 4

Metabolic precursor of DA which can cross the BBB - increases synaptic levels of DA

Question 5

Levodopa AE

Answer 5

Dyskinesia (excessive DA receptor activation), nausea, vomiting, end-of-dose deterioration, hypotension, hallucinations, benefits diminish over time

Question 6

Levodopa administration

Answer 6

Co-administered with carbidopa (peripheral DDC inhibitor) - increases availability

Question 7

Pramipexole MoA

Answer 7

Direct DA agonist - activates D2 receptors (high selectivity for D2 and D3 receptors)

Question 8

Advantages of pramipexole

Answer 8

No CNS metabolism, increased reliability in dose-by-dose effects, longer half life than levodopa, less risk of dyskinesia

Question 9

Pramipexole AE

Answer 9

Nausea, vomiting, hypotension, dyskinesia, delusions, mania, anxiety, impulse control disorder, hallucinations, orthostatic hypotension

All can be treated with domperidone (peripheral D2 antagonist, does not cross BBB)

Question 10

Apomorphine MoA

Answer 10

Direct DA agonist - activates D2 receptors

Question 11

Apomorphine AE

Answer 11

Highly emetic

Question 12

Bromocriptine MoA

Answer 12

Direct DA agonist - activates D2 receptors

Question 13

Bromocriptine AE

Answer 13

Can cause impulse control disorders

Question 14

Selegiline MoA

Answer 14

Irreversible inhibitor of MAO-B (responsible for DA metabolism) - prolongs effects of DA

Question 15

Selegiline AE

Answer 15

Nausea, vomiting, dyskinesia, orthostatic hypotension, insomnia, headache, serotonin toxicity with serotonergic drugs

Question 16

Entacapone MoA

Answer 16

Blocks COMT (this breaks down levodopa) - prolongs levodopa half life

Question 17

Entacapone AE

Answer 17

Nausea, vomiting, diarrhoea, dyskinesia, hallucinations, delusions, confusion

Question 18

Amantadine MoA

Answer 18

Poorly understood - increases DA release and blocks reuptake

Question 19

Amantadine AE

Answer 19

Dizziness, falls, hallucinations, delusions, confusion, urinary retention, drowsiness, livedo reticularis, increased risk of compulsive behaviour

Question 20

Benztropine MoA

Answer 20

Centrally acting anti-cholinergic (M antagonist) - this is for symptomatic relief only

Question 21

Benztropine AE

Answer 21

Dry mouth, constipation, urinary retention, blurred vision, mental confusion/hallucinations