parkinsons disease Flashcards
Epidemiology
- Typical age of onset: 65yr
- Prevalence:
- 6-64yr: 0.6%
- 85-89: 3.5%
Pathophysiology
- Destruction of dopaminergic neurones in pars compacta of substantia nigra.
↓ striatal dopamine levels
Clinical features
- TRAPPS PD
- Asymmetric onset: side of onset remains worst
- Tremor: at rest (hand, chin, tongue and legs), ↑ by stress, disappears in sleep
- Rigidity: lead-pipe, cog-wheel, made worse by asking patient to voluntarily move the opposite limb (synkinesis)
- Akinesia: 3 main movements:
- Hypokinesia: poverty of movement – micrographia (handwriting ↓ in size/spidery), monotonous voice, mask-like face
- Bradykinaesia: slowness of movement
- Difficulty w/ repetitive movement,
- Postural changes: stooped gait w/ festination, slow initiation, freezing (poor simultaneous motor and cognitive function)
- Postural hypotension: + other autonomic dysfunction
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Autonomic Dysfunction
- Combined effects of drugs and neurodegeneration
- Postural hypotension
- Constipation
- Hypersalivation → dribbling (↓ ability to swallow saliva)
- Urgency, frequency, Nocturia
- ED
- Hyperhidrosis
- Sleep disorders: insomnia, EDS, OSA, RBD
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Sleep Disorder
- Affects ~90% of PD pts.
- Insomnia + frequent waking → EDS
· Inability to turn
· Restless legs
· Early morning dystonia (drugs wearing off)
· Nocturia
· OSA
- REM Behavioural sleep Disorder
· Loss of muscle atonia during REM sleep
· Violent enactment of dreams
- Da SEs: insomnia, drowsiness, EDS
- Psychosis: esp. visual hallucinations
Depression / Dementia / Drug SEs
Investigation
- DaTSCAN: dopamine transporter (DaT) single-photon emission computed tomography (SPECT) – shows ↓ dopamine transporters
- CT/MRI: to exclude other causes
Prognosis
- ↑ mortality
- Loss of response to L-DOPA w/i 2-5yrs
Differential diagnosis
- Parkinson plus syndromes
- Multiple infarcts
- Drugs: neuroleptics, metoclopramide, prochlorperazine
- Inherited: Wilson’s
- Infection: HIV
- Trauma/boxing
- restless leg syndrome:
- Association: associated with iron deficiency, anaemia, pregnancy, peripheral neuropathy or uraemia
PC: unpleasant sensation in legs
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For first-line treatment:
if the motor symptoms are affecting the patient’s quality of life: levodopa
if the motor symptoms are not affecting the patient’s quality of life: dopamine agonist (non-ergot derived), levodopa MAO‑B inhibitor
If a patient continues to have symptoms despite optimal levodopa treatment or has developed dyskinesia: then NICE add a dopamine agonist, MAO‑B inhibitor or catechol‑O‑methyl transferase (COMT) inhibitor as an adjunct.
Again, NICE summarise the main points in terms of decision making
Dopamine agonists
MAO‑B inhibitors
COMT inhibitors
Amantadine
Motor symptoms
Improvement in motor symptoms
Improvement in motor symptoms
Improvement in motor symptoms
No evidence of improvement in motor symptoms
Activities of daily living
Improvement in activities of daily living
Improvement in activities of daily living
Improvement in activities of daily living
No evidence of improvement in activities of daily living
Off time
More off‑time reduction
Off‑time reduction
Off‑time reduction
No studies reporting this outcome
Adverse events
Intermediate risk of adverse events
Fewer adverse events
More adverse events
No studies reporting this outcome
Hallucinations
More risk of hallucinations
Lower risk of hallucinations
Lower risk of hallucinations
No studies reporting this outcome
specific points regarding parkinson’s meds
NICE reminds us of the risk of acute akinesia or neuroleptic malignant syndrome if medication is not taken/absorbed (for example due to gastroenteritis) and advise against giving patients a ‘drug holiday’ for the same reason.
Impulse control disorders have become a significant issue in recent years. These can occur with any dopaminergic therapy but are more common with:
- dopamine agonist therapy
- a history of previous impulsive behaviours
- a history of alcohol consumption and/or smoking
If excessive daytime sleepiness develops then patients should not drive. Medication should be adjusted to control symptoms. Modafinil can be considered if alternative strategies fail.
If orthostatic hypotension develops then a medication review looking at potential causes should be done. If symptoms persist then midodrine (acts on peripheral alpha-adrenergic receptors to increase arterial resistance) can be considered.
Levodopa
- usually combined with a decarboxylase inhibitor (e.g. carbidopa or benserazide) to prevent peripheral metabolism of levodopa to dopamine
- reduced effectiveness with time (usually by 2 years)
- unwanted effects: dyskinesia (involuntary writhing movements), ‘on-off’ effect, dry mouth, anorexia, palpitations, postural hypotension, psychosis, drowsiness
- no use in neuroleptic induced parkinsonism
Dopamine receptor agonists
- e.g. Bromocriptine, ropinirole, cabergoline, apomorphine
- ergot-derived dopamine receptor agonists (bromocriptine, cabergoline) have been associated with pulmonary, retroperitoneal and cardiac fibrosis. The Committee on Safety of Medicines advice that an echocardiogram, ESR, creatinine and chest x-ray should be obtained prior to treatment and patients should be closely monitored
- patients should be warned about the potential for dopamine receptor agonists to cause impulse control disorders and excessive daytime somnolence
- more likely than levodopa to cause hallucinations in older patients. Nasal congestion and postural hypotension are also seen in some patients
MAO-B (Monoamine Oxidase-B) inhibitors
e.g. Selegiline
inhibits the breakdown of dopamine secreted by the dopaminergic neurons
Amantadine
mechanism is not fully understood, probably increases dopamine release and inhibits its uptake at dopaminergic synapses
side-effects include ataxia, slurred speech, confusion, dizziness and livedo reticularis
COMT (Catechol-O-Methyl Transferase) inhibitors
e.g. Entacapone, tolcapone
COMT is an enzyme involved in the breakdown of dopamine, and hence may be used as an adjunct to levodopa therapy
used in conjunction with levodopa in patients with established PD
Antimuscarinics
- block cholinergic receptors
- now used more to treat drug-induced parkinsonism rather than idiopathic Parkinson’s disease
- help tremor and rigidity
- e.g. procyclidine, benzotropine, trihexyphenidyl (benzhexol)
summary of all parkinsons drugs
