Parkinson's disease / Parkinsonism Flashcards
What is Parkinson’s disease?
What is the underlying pathology of Parkinson’s disease?
Parkinson’s is a sporadic movement disorder.
- Presence of lewy bodies and loss of dopaminergic neurones from pars compacta of the substantia nigra that project to the striatum of the basal ganglia.
=> The degree of nigrostriatal dopaminergic cell loss correlates with degree of akinesia.
- Lewy bodies contain tangles of alpha-synuclein and ubiquitin
- Distribution becomes widespread from lower brainstem to midbrain and then cortex
- Degeneration of basal ganglia nuclei
Who does parkinson’s affect?
Prevalence of PD increases with age esp. >70yrs
Mean age of onset = 60yrs
What are the symptoms of parkinsonian triad?
Parkinsonian triad:
- Tremor
=> worse at rest
=> pill rolling of thumb over fingers - Hypertonia:
=> rigidity + tremor “cogwheel rigidity” - felt during rapid pronation and supination
3. Bradykinesia: => slow to initiate movement => actions slow & decrease in amplitude on repetition e.g. reduced blink rate, micrograpgia, shuffling gait, reduced arm swing, freezing at obstacles, expressionless face
- Postural & gait changes = late stage features
- Signs are worse on one side
What are the non-motor symptoms in Parkinson’s disease?
Non-motor symptoms
Autonomic dysfunction: => postural hypotension => constipation => urinary frequency/urgency => saliva dribbling
Sleep disturbance
Anosmia
What are the neuropsychiatric complications of Parkinson’s disease?
Neuropsychiatric complications:
=> Depression
=> Anxiety
=> Dementia
=> Psychosis
What are the prodrome pre-motor symptoms of Parkinson’s disease?
Non-specific, non motor symptoms which precede motor symptoms ~7 years
=> anosmia (70%) => depression / anxiety (50%) => aches / pains => REM sleep behaviour disorder => autonomic features i.e. urinary urgency, hypotension, constipation => restless leg syndrome
How do you diagnose Parkinson’s disease?
Clinical diagnosis based on:
=> Core features of bradykinesia
=> Resting tremor and/or hypertonia
=> Cerebellar disease & front-temporal dementia should be excluded
=> Clinical response to dopaminergic therapy is supportive of diagnosis
Education about Parkinson’s and physical activity is beneficial.
Treatment for Parkinson’s disease focuses on symptom control and does not slow down disease progression.
What are the treatments available for motor symptoms of Parkinson’s disease?
- Levodopa i.e. co-beneldopa, co-careldopa
- Dopamine agonists i.e. roniperole, pramipexole
- Apomorphine
- Anti-cholinergic
- Monoamine oxidase B inhibitor i.e. rasaligine, selegiline
- COMT inhibitor i.e. entacapone, tolcapone
Levodopa is the most effective form of treatment in parkinson’s disease.
What is the mechanism of action of Levodopa?
What are the indication of use?
What are the side effects?
- Levodopa = dopamine precursor combined with a dopa-decarboxylase inhibitor in co-beneldopa or co-careldopa to reduce peripheral side effects i.e. nausea and hypotension.
- Efficacy of Levodopa reduces over time and requires larger and more frequent dosage with worsening side effects and response
=> starting Levodopa therapy later might give better response
=> Modified release of Levodopa may be given in late disease
- Side effects: dyskinesia, painful dystonia.
Non-motor side effects: postural hypotension, psychosis, visual hallucination, nausea and vomiting (give domperidone)
What is the mechanism of action of Dopamine agonists?
What are the indication of use?
What are the side effects?
- Dopamine agonists bind to dopamine receptors e.g. pramipexole, ropinirole
- DA can be used as mono-therapy in mild/moderate parkinson’s in younger patients.
=> It can delay the use of Levodopa and start small doses as disease progresses
- Side effects: drowsiness, nausea, hallucinations, compulsive behaviour e.g. gambling, hyper-sexuality
What is the mechanism of action of Monoamine oxidase B inhibitor?
What are the indication of use?
What are the side effects?
- MAO-B inhibitor blocks dopamine breakdown
- Alternative to dopamine agonists in early parkinson’s disease
- Side effects: postural hypotension, atrial fibrillation
What is the mechanism of action of COMT inhibitor?
What are the indication of use?
- COMT inhibitor prolongs dopamine activity by blocking its breakdown .
- COMT inhibitor may help motor complications in late disease
=> Lessen the off time in those with end-of-dose wearing off
What is the mechanism of action of Apomorphine?
What are the indication of use?
What are the side effects?
- Apomorphine is a short acting dopamine agonist administered subcutaneously
- Used to even out end-of-dose effects by continuous infusion or used as a rescue pen for sudden ‘off’ freezing
- Side effects: injection site ulcers
What is the mechanism of action of Anti-cholinergic/muscurinic?
What are the indication of use?
What are the side effects?
- Anti-cholinergic/muscurinic may help reduce tremors
- May be used in young patient with early Parkinson’s
- Side effects: confusion and cognitive impairment especially in elderly + multiple side effects
Treatment of non-motor symptoms i.e. depression, constipation, pain and sleep disorders is also important in improving patient quality of life.
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