Antiparkinsons Flashcards
What are the 3 cardinal features of PD?
Rest tremors, bradykinesia and rigidity
When is the average age of onset of PD? Young-onset? Juvenile?
Average: early to mid 60s
Young-onset: 21-40s
Juvenile: before 20, higher freq of genetically inherited PD amongst this group
Describe the pathophysiology of PD.
There is impaired cleaning of abnormal/damaged intracellular proteins by ubiquitin-proteasomal system. The failure to clear these toxic proteins leads to accumulation of aggresomes (Lewy bodies) and apoptosis.
Degeneration of dopaminergic neurons with Lewy body inclusions in the substantia nigra (which has dopaminergic projections to basal ganglia) ➝ decreased dopamine to basal ganglia, which facilitates and modulates motor movements in the motor cortex
How is PD diagnosed?
No reliable diagnostic marker. Diagnosed based on presentation of clinical features + exclusion of alternative diagnoses.
*10-25% of pts with parkinsonism syndromes don’t have PD; may have atypical parkinsonian disorders
What are the non-motor manifestations of PD and how do they affect the pt?
Autonomic, neuropsychiatric, olfactory and sensory
- e.g. falls, postural hypotension, confusion, dementia, suboptimal nutrition, speech and sleep disorders).
- Common in PD and more prominent in later stages.
- Relatively resistant and may be worsened by dopaminergic agents
- Cause significant disability
- Often neglected in PD management :/
What is the course of PD like?
- Progressive disorder, causes significant disability 10-15 year after onset.
- Rate of disability progression highest in early years, plateaus at later stages.
- At later stages, PD pt becomes increasingly dependent in activities of daily living
- Motor fluctuations, dyskinesias, non-motor symptoms are common at later stages.
Once PD is diagnosed, all pts should be started on meds. True or false?
False. Early symptomatic disease may not even need meds if coping well. - Physio and exercise regime - Healthy, balanced diet - Knowledge on disease - Social support
What is the gold standard for PD treatment?
Levodopa (an L-dopa analogue) ➝ converted to dopamine by dopa decarboxylase. Most efficacious for symptomatic management of both early and late Parkinson’s.
Side effects of Levodopa
Short term: N/V, postural hypotension
Long term: Motor fluctuations, tardive dyskinesia*
*dyskinesia is chronic once developed!!!
hence should keep levodopa to minimum effective dose necessary to achieve good motor function
Why are anticholinergics used to treat PD?
Trihexyphenidyl (Artane)
- May be effective in controlling tremors
- Peripherally acting agents may be useful in treating sialorrhoea
Which drugs can be used as monotherapy or adjunct to levodopa for PD?
- Levodopa
- Trihexyphenidyl (Artane)
- MAO-B inhibitors (Seligiline)
- Dopamine agonists
- Amantadine
Which drug class is only effective when used with levodopa?
COMT inhibitors ➝ inhibit enzyme that inactivates levodopa. Increases duration of action of each dose of levodopa, beneficial in treating wearing off response
Why might it be useful to use combination therapy for PD?
Can reduce dose of levodopa needed and prevent dyskinesia.
What are the side effects of MAO-B inhibitors?
Heartburn, loss of appetite, nausea, constipation, dizziness, anxiety, headache, palpitation, insomnia, confusion, nightmares, visual hallucination
What are some examples of levodopa formulations?
Comes in 2-in-1 prep containing levodopa + a peripheral decarboxylase inhibitor
- levodopa + benserazide: madopar
- levodopa + carbidopa: sinemet
- available as regular form or long acting form
