24 - Neurological Disorders Flashcards
What are some clinical features of Parkinsonism?
Motor: resting/pill rolling tremor, bradykinesia, rigidity, postural instability, shuffling gait
Non-motor: mood changes (depression), cognitive change, urinary symptoms, sleep disorders, sweating, pain
After 15 years, what clinical features will patients with PD have during follow up?
- Dyskinesia (94%) (secondary to LDopa treatment)
- Falls (81%)
- Cognitive decline (84%)
- Somnolence (80%)
- Swallowing difficulties (50%)
- Severe speech problems (27%)
How do you make a diagnosis of idiopathic Parkinson’s Disease?
- Clinical features
- Exclude other causes of Parkinsonism
- Response to treatment
- Normal structural neuro-imaging e.g PET
What are some non-idiopathic causes of Parkinsonism?
- Drug induced
- Vascular
- Progressive supranuclear
- Corticobasal degeneration
What is the pathology of idiopathic parkinson’s disease?
- When over 50% loss of pigment this is when symptoms occur
- Lewy body deposition in pars compacta of substantia nigra causes neurodegeneration
How is the basal ganglia circuit affected in Parkinson’s disease?
How is dopamine synthesised and degraded?
What are the six different classes of drugs used to treat IPD?
- Levodopa (L-DOPA)
- Dopamine receptor agonists
- MAOI type B inhibitors
- COMT inhibitors
- Anticholinergics
- Amantidine
Why is L-DOPA used to treat IPD instead of Dopamine?
- Dopamine receptor agonists
- It is given orally and must be taken up by dopaminergic cells in the substantia nigra to be converted to dopamine
- Given up to 5 times a day as short half life of 2 hours
How is L-Dopa absorbed when taken orally?
Don’t eat big protein meals with Levodopa as there will be more competition for absorption
What is L-Dopa administered with?
- Peripheral DOPA decarboxylase inhibitor (co-careldopa/co-beneldopa)
- Reduces the dose required, reduces side effects and increases amount of L-Dopa reaching the brain
What are the advantages and disadvantages of using L-Dopa in IPD?
+ Highly efficacious
+ Low side effects (e.g nausea, vomiting, hypotension, tachycardia, psychosis)
- Needs enzyme conversion
- Involunrary movements
- Loses efficacy as disease progresses as loss of neurones
- Motor complications e.g freezing, dystonia
What DDIs does L-Dopa have?
- Pyridoxine (Vit B6): increases peripheral breakdown of L-DOPA
- MAOIs: risk hypertensive crisis
- Antipsychotic drugs: lead to parkinsonism (block dopamine receptors)
What are some different subtypes of dopamine receptor agonists and give some examples in each subtype?
What are the advantages and disadvantages of using dopamine receptor agonists as treatment for IPD?
+ direct acting
+ less motor complications/dyskinesias
+ possible neuroprotection
- less efficacy than L-Dopa
- impulse control disorders
- more psychiatric side effects
- expensive