Parkinson’s disease Flashcards
(29 cards)
Pathology of Parkinson’s disease
Dopaminergic neurones in the substantia nigra degenerate.
Progressive, adult onset movement disorder.
What are the two parts of the substantia nigra and which is affected in Parkinson’s disease?
Pars reticulata
Pars compacta - affected area
Which neuro pathway is affected in Parkinson’s disease and what is its function?
Nigrostriatal pathway - helps to stimulate the cerebral cortex and initiate movement
What are the cardinal motor signs of Parkinson’s disease?
- Bradykinesia
- Resting tremor
- Rigidity
- Postural instability
What does bradykinesia look like in a patient?
- Slow to initiate movement
- Actions slow and decrease in amplitude with repetition
- Festinant gait, pitched forward, turning en bloc
- Decreased arm swing and freezing at obstacles or doors (due to poor simultaneous motor and cognitive function)
- Hypomimia (expressionless face)
Is Parkinson’s disease unilateral or bilateral?
Symptoms often begin on one side of the body or even in one limb on one side of the body. As the disease progresses, it eventually affects both sides. However, the symptoms may still be more severe on one side than on the other.
Non motor symptoms of Parkinson’s disease
- Reduced sense of smell (can lose sense of smell years before motor symptoms)
- Sleep disturbances
- Autonomic dysfunction
- postural hypotension
- constipation
- urinary symptoms
- dribbling of saliva
- Neuropsychiatric complications
- depression
- dementia
- psychosis
Does Parkinson’s disease have a treatment that will stop the progressive neurodegeneration?
No - treatments only aim to control symptoms and will not affect the underlying disease
What are the pharmacological treatments for Parkinson’s disease?
- Levodopa
- Dopamine agonists
- MAO-B inhibitors
- COMT inhibitors
- Anticholinergics
Why is levodopa (precursor to dopamine) given instead of dopamine?
Levodopa can cross the blood brain barrier while dopamine cannot.
What is levodopa combined with and why?
Levodopa is administered with carbidopa - a dopa decarboxylase inhibitor that isn’t able to cross the blood brain barrier
- Levodopa is converted to dopamine by dopa decarboxylase (within nigrostriatal neurones and by peripheral dopa decarboxylase)
- Periperal dopa decarboxylase can metabolise levodopa into dopamine before it gets to the blood brain barrier. Dopamine can be further metabolised into other catecholamines such as epinephrine which can have side effects such as arrhythmias
Risk factors for Parkinson’s disease
- Age: prevalence of 1% in those aged 60-70 and 1-3% in those aged over 80
- Gender: males 1.5x more likely to develop than females
- Family history
Side effects of levodopa
- Compulsive gambling, hypersexuality, binge eating, or obsessive shopping (can develop in patient on any dopaminergic therapy)
- Dyskinesia - involuntary movements
- Wearing off - the effects of the drug wear off before the next dose
Why should levodopa not be withdrawn suddenly?
It risks acute akinesia and neuroleptic malignant syndrome
How do anticholinergics work? Who should they be used for?
They balance acetylcholine with dopamine
They cause confusion in the elderly and have multiple side effects - limit use to younger patients
How do COMT inhibitors and MAO-B inhibitors work?
They inhibit enzymes which metabolise dopamine which increases the dopamine concentration in the brain
MAO-B inhibitor examples, use and side effects
Rasagiline, selegiline
An alternative to dopamine agonists in early Parkinson’s disease
Side effects include postural hypotension and atrial fibrillation
Other causes of Parkinsonism
- Lewy body dementia
- Wilson disease
- Pick disease
- Encephalitis
- Neurosyphilis
- Side effects of:
- antipsychotics (haloperidol) - blocks dopamine receptors
- metclopramide - dopamine antagonist used to treat vomiting
Parkinson’s disease is a clinical diagnosis.
Which investigations might be considered in Parkinson’s disease?
- DaT scan: single-photon emission computed tomography (SPECT) will show reduced dopamine uptake in the basal ganglia
- MRI brain: to exclude other causes of neurological disease but should not be used to diagnose PD
- Ceruloplasmin and urinary copper: if suspecting Wilson’s disease, ceruloplasmin is reduced and urinary copper is raised
What is the first line treatment given to patients with motor symptoms affecting quality of life?
- Levodopa and decarboxylase inhibitor (Co-beneldopa)
What is the first line treatment given to patients with motor symptoms not affecting quality of life?
- Dopamine agonist (pramipexole or ropinirole)
- MAO-B inhibitor (selegilline, rasagilline)
- Levadopa and decaboxylase inhibitor (Co-benyldopa)
Adjuvant treatments suitable for patients with dyskinesia
- COMT inhibitors (entaxapone)
- indicated in those with motor fluctuations or dyskinesia
- reduces breakdown of levodopa peripherally
- Amantadine
- increases dopamine release and reduces reuptake
Which adjuvant treatment may be suitable in advanced disease with significant motor symptoms?
Deep brain stimulation
Which part of the brain is the target for deep brain stimulation?
Subthalamic nucleus and globus pallidus internus are the main targets.
