Parkinson's Flashcards
What is Parkinson’s?
Chronic, progressive neurodegeneration
Describe the pathology of Parkinson’s.
Degeneration of dopaminergic neurones in the nigro-striatal pathway
Presence of Lewy bodies in neurones
Changes in GABA-glutamate pathway
Describe the epidemiology of Parkinson’s.
Average age at onset is 60 years
Affects 1 in 500 in UK
Men more commonly affected
What are the motor symptoms of Parkinson’s?
Tremor
Rigidity
Bradykinesia
What are the non-motor symptoms of Parkinson’s?
Micrographia Monotone voice Swallowing problems Drooling Loss of smell Excessive sweating Depression Memory problems Constipation Urinary problems Dementia Dizziness
When is drug treatment indicated in Parkinson’s? What is the aim?
Should only be started when motor symptoms are affecting daily life
Aim to increase levels of dopamine in the brain, treats symptoms only
What is Levodopa? How is it used in Parkinson’s?
Precursor to dopamine
Used in combination with peripheral dopa-decarboxylase inhibitor to relieve motor symptoms
Give examples of levodopa
medication for Parkinson’s.
Madopar (co-beneldopa)
Sinimet (co-careldopa)
Why is levodopa given in combination with a peripheral dopa-decarboxylase inhibitor?
To prevent breakdown of levodopa into dopamine before it crosses the BBB
Why is the dose of levodopa formulations low initially?
Titrated up to reduce side effects such as postural hypotension, nausea and psychiatric effects
What is duodopa?
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
What are monoamine oxidase B inhibitors? Give examples.
Prevent dopamine metabolism, increasing availability at receptors, useful in early PD
Selegiline, rasagiline
What are the disadvantages of selegiline compared to rasagiline?
Can cause hallucinations and insomnia
Given no later than 1pm to avoid insomnia
What are the two classes of Parkinson’s dopamine agonists? Give examples.
Non-ergot- ropinirole, pramipexole, rotigotine
Ergot- pergolide, lisuride, bromocriptine, cabergoline
When are dopamine agonists used in Parkinson’s?
Initial mono therapy due to having fewer long term problems than levodopa
Used with levodopa in advanced disease
Which dopamine agonist is available as a 24 hour patch?
Rotigotine
What is apomorphine? When is it used?
Dopamine agonist used in Parkinson’s
Given as a bolus or 12 hour infusion SC injection to allow steady state plasma levels
What are the disadvantages of apomorphine?
Requires specialist supervision
Pre-treat with domperidone PR for 3 days
Can cause abscess/nodule formation and insertion site
Yawning and drowsiness
What are the side effects of dopamine agonists?
Lung and cardiac valve fibrosis (ergot) N+V Psychiatric Postural hypotension Sudden sleep onset Dopamine dysregulation syndrome
What are the signs of dopamine dysregulation syndrome?
Gambling
Hypersexuality
Binge eating
What should be considered in later stage Parkinson’s?
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
What are catechol-o-methyl transferase (COMT) inhibitors? Give an example.
Used in combination with levodopa
Prevent metabolism of levodopa to 3-o-methyldopa
Entacapone
What is stavelo?
Contaisn entacapone, levodopa and carbidopa
What are the side effects of catechol-o-methyl transferase (COMT) inhibitors?
Dyskinesia
Nausea
Diarrhoea
What is amantadine? What is it used for?
Glutamate antagonist at NMDA receptors
Treat dyskinesia in late Parkinson’s disease
Only used for 12 months as efficacy decreases
What are the side effects of amantadine?
Psychiatric
GI
Oedema
Skin rash (lived reticularis)
When are anticholinergics used in Parkinson’s? When are they contraindicated?
Used in tremor
Avoid in elderly due to psychiatric effects, constipation, urinary retention and hypotension
How can early morning bradykinesia be managed in Parkinson’s?
Dispersible levodopa taken on wakening
Night time dose of dopamine agonist or MR levodopa
How can dyskinesias be managed in Parkinson’s?
Reduce levodopa dose
Add dopamine agonist of COMT inhibitor
Add amantadine
Duodopa infusion via PEG
How can on-off fluctuation symptoms be managed in Parkinson’s?
Add dopamine agonist or apomorphine
Reduce protein intake to increase levodopa absorption
How may sialorrhoea be managed?
Hyoscine patches
Sublingual 1% atropine eye drops BD
How may restless legs syndrome be managed?
Ropinirole or pramipexole
How may REM sleep behaviour disorder be managed?
Clonazepam 500mcg at night
Describe the use of antidepressants in Parkinson’s.
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
