Parkinson's

Question 1

What is Parkinson’s?

Answer 1

Chronic, progressive neurodegeneration

Question 2

Describe the pathology of Parkinson’s.

Answer 2

Degeneration of dopaminergic neurones in the nigro-striatal pathway
Presence of Lewy bodies in neurones
Changes in GABA-glutamate pathway

Question 3

Describe the epidemiology of Parkinson’s.

Answer 3

Average age at onset is 60 years
Affects 1 in 500 in UK
Men more commonly affected

Question 4

What are the motor symptoms of Parkinson’s?

Answer 4

Tremor
Rigidity
Bradykinesia

Question 5

What are the non-motor symptoms of Parkinson’s?

Answer 5

Micrographia
Monotone voice
Swallowing problems
Drooling
Loss of smell
Excessive sweating
Depression
Memory problems
Constipation
Urinary problems
Dementia
Dizziness

Question 6

When is drug treatment indicated in Parkinson’s? What is the aim?

Answer 6

Should only be started when motor symptoms are affecting daily life
Aim to increase levels of dopamine in the brain, treats symptoms only

Question 7

What is Levodopa? How is it used in Parkinson’s?

Answer 7

Precursor to dopamine

Used in combination with peripheral dopa-decarboxylase inhibitor to relieve motor symptoms

Question 8

Give examples of levodopa

medication for Parkinson’s.

Answer 8

Madopar (co-beneldopa)

Sinimet (co-careldopa)

Question 9

Why is levodopa given in combination with a peripheral dopa-decarboxylase inhibitor?

Answer 9

To prevent breakdown of levodopa into dopamine before it crosses the BBB

Question 10

Why is the dose of levodopa formulations low initially?

Answer 10

Titrated up to reduce side effects such as postural hypotension, nausea and psychiatric effects

Question 11

What is duodopa?

Answer 11

Used for Parkinson’s patients with severe motor fluctuations and dyskinesia
Available as intestinal gel given via PEG tube, can be given as a constant infusion for up to 16 hours per day

Question 12

What are monoamine oxidase B inhibitors? Give examples.

Answer 12

Prevent dopamine metabolism, increasing availability at receptors, useful in early PD
Selegiline, rasagiline

Question 13

What are the disadvantages of selegiline compared to rasagiline?

Answer 13

Can cause hallucinations and insomnia

Given no later than 1pm to avoid insomnia

Question 14

What are the two classes of Parkinson’s dopamine agonists? Give examples.

Answer 14

Non-ergot- ropinirole, pramipexole, rotigotine

Ergot- pergolide, lisuride, bromocriptine, cabergoline

Question 15

When are dopamine agonists used in Parkinson’s?

Answer 15

Initial mono therapy due to having fewer long term problems than levodopa
Used with levodopa in advanced disease

Question 16

Which dopamine agonist is available as a 24 hour patch?

Answer 16

Rotigotine

Question 17

What is apomorphine? When is it used?

Answer 17

Dopamine agonist used in Parkinson’s

Given as a bolus or 12 hour infusion SC injection to allow steady state plasma levels

Question 18

What are the disadvantages of apomorphine?

Answer 18

Requires specialist supervision
Pre-treat with domperidone PR for 3 days
Can cause abscess/nodule formation and insertion site
Yawning and drowsiness

Question 19

What are the side effects of dopamine agonists?

Answer 19

Lung and cardiac valve fibrosis (ergot)
N+V
Psychiatric
Postural hypotension
Sudden sleep onset
Dopamine dysregulation syndrome

Question 20

What are the signs of dopamine dysregulation syndrome?

Answer 20

Gambling
Hypersexuality
Binge eating

Question 21

What should be considered in later stage Parkinson’s?

Answer 21

Response to treatment declines
Plasma drug concentrations trough and cause akinesia and rigidity
When concentrations peak patients can experience motor complications
Shortening interval between doses can reduce fluctuation

Question 22

What are catechol-o-methyl transferase (COMT) inhibitors? Give an example.

Answer 22

Used in combination with levodopa
Prevent metabolism of levodopa to 3-o-methyldopa
Entacapone

Question 23

What is stavelo?

Answer 23

Contaisn entacapone, levodopa and carbidopa

Question 24

What are the side effects of catechol-o-methyl transferase (COMT) inhibitors?

Answer 24

Dyskinesia
Nausea
Diarrhoea

Question 25

What is amantadine? What is it used for?

Answer 25

Glutamate antagonist at NMDA receptors
Treat dyskinesia in late Parkinson’s disease
Only used for 12 months as efficacy decreases

Question 26

What are the side effects of amantadine?

Answer 26

Psychiatric
GI
Oedema
Skin rash (lived reticularis)

Question 27

When are anticholinergics used in Parkinson’s? When are they contraindicated?

Answer 27

Used in tremor

Avoid in elderly due to psychiatric effects, constipation, urinary retention and hypotension

Question 28

How can early morning bradykinesia be managed in Parkinson’s?

Answer 28

Dispersible levodopa taken on wakening

Night time dose of dopamine agonist or MR levodopa

Question 29

How can dyskinesias be managed in Parkinson’s?

Answer 29

Reduce levodopa dose
Add dopamine agonist of COMT inhibitor
Add amantadine
Duodopa infusion via PEG

Question 30

How can on-off fluctuation symptoms be managed in Parkinson’s?

Answer 30

Add dopamine agonist or apomorphine

Reduce protein intake to increase levodopa absorption

Question 31

How may sialorrhoea be managed?

Answer 31

Hyoscine patches

Sublingual 1% atropine eye drops BD

Question 32

How may restless legs syndrome be managed?

Answer 32

Ropinirole or pramipexole

Question 33

How may REM sleep behaviour disorder be managed?

Answer 33

Clonazepam 500mcg at night

Question 34

Describe the use of antidepressants in Parkinson’s.

Answer 34

SSRIs are safest, sertraline consider most ideal due to short half life and lack of insomnia, fluoxetine half life too long
TCAs highest risk
MAOIs rarely used
If also on anti platelet with limited bleeding risk, consider PPI to reduce bleeding risk in stomach