Parkinson's and Movement Disorders Flashcards
What are the classical symptoms of parkinson’s disease?
Asymmetrical bradykinesia
Hypokinesia
rigidity (cog-wheel)
tremor (pill rolling)
gait (shuffle)
What are the non-motor sx of parkinsons disease?
Constipation
REM sleep disturbances
PLMS/RLS
hyposmia
Depression/anxiety
What are the non-dopamine related sx of parkinson’s disease?
Posture disturbances
dec autonomic function
speech changes
cognitive changes
Pain
seborrhoea
weight loss
fatigue
What is an essential tremor?
Neurological cause of action tremor different from parkinsons
Describe the pathophysiology of parkinson’s disease?
Dopamine depletion from basal ganglia –> disrupt connection to thalamus and motor cortex –> parkinsonians signs
DA depletion in substantia nigra and nigrostriatal pathway –> inc inhibition of thalamus, reduced excitatory input into motor cortex –> bradykinesia and other parkinsonian signs
What is the role of the nigrostriatal pathway?
Nigrostriatal pathway = coordination of movement
hypokinesia of intentional movement and resting tremor
What is the role of the mesocortic pathway?
attention, cognition
What is the role of the mesolimbic pathway?
pleasure response
What is the role of the tuberoinfundibular pathway?
sexual dysfunction
Does parkinsons disease have more DA or ACH?
Hypokinetic state has more ACH and less dopamine
What are the five cardinal symptoms of parkinson’s disease?
Tremor - pill rolling
Rigidity - almost all patients
Bradykinesia - slowness in performing voluntary movement, reduced facial movement
hypokinesia - reduced ability to initiate movement/freezing
Postural instability/gait disorder - stooped flexed posture
What are the dopamine prodrugs used in parkinsons?
Levodopa (+carbidopa or benserazide)
When is parkinson’s therapy started?
When symptoms/functional disability becomes a problem for the patient
What is the first line therapy for parkinsons disease?
Levodopa (+carbidopa or benserazide) = choice in older people
Can start with dopamine agonist in younger patients w/ significant motor disability
Use anticholinergics if tremor predominates
How is levodopa used in parkinsons disease?
Used as first line - improves bradykinesia and rigidity
Need 75mg/day of benserazide or carbidopa to adequately inhibit peripheral dopamine production
Start low, gradual inc
What is a common ADR of levodopa and how is it treated?
Nausea - treat with domperidone (be mindful of QT prolongation)
What happens in levodopa is dosed too high or too low?
Too high = pt becomes dyskinetic - involuntary, writhing movement
Too low = akinetic - no movement/ can’t move muscles on own
What is the levodopa end dose effect?
When the pattern between the on (w/ dopamine) period becomes unpredictable with the pt experiencing off (when there is no dopamine) when they should be in an on period
How does the action of levodopa differ during advanced PD compared to early PD?
Advanced - inadequate symptom control, short duration of clinical result followed by an ON period where dyskinesia returns
Early - Sx control food, smooth and extended durations of movement, low dyskinesia
List some strategies that can be used to overcome the end of dose effect
Combine levodopa and dopamine agonist
Use modified release levo
Smaller more frequent doses of levodopa
adjust dietary protein
switch to dopamine agonists
Use COMT inhibitors (entacapone)
use rasagiline or selegiline
What is dyskinesia?
Difficulty performing voluntary movement
What is dystonia?
Involuntary muscle contractions - slow repetitive movements or abnormal posture
What are motor fluctuations?
Rapid (sometimes unpredictable) fluctuations of akinetic (off) and on (normal of dyskinetic) state
What is the role of dopamine agonists in parkinsons disease?
Less effective than levodopa as initial therapy - delay onset of dyskinesia and motor fluctations
improve bradykinesia and rigidity
Higher incidence of = confusion, impulse control disorders, hallucinations
What are the ergot derivative dopamine agonists? Why are they worse/better?
Bromocriptine, cabergoline, pergolide
High doses needed –> inc ADRs
- can cause respiratory or cardiac valve fibrosis
What are the non-ergot derivative dopamine agonists? Why are they worse/better?
Pramipexole - MR
Rotigotine - transdermal patch
Apomorphine - highly emetic, subcut
How is entacapone used in parkinsons disease?
Prolongs clinical response to levodopa - used as adjunct to levodopa in patients with motor fluctuations
Pushed dyskinesia a bit more
What are the MAO-B inhibitors used in parkinsons disease and what are their roles?
Inhibit the metabolism - breakdown - of dopamine
Selegiline (adjunct) - reduces off time in advanced disease
Rasagiline (mono or adjunct) - theoretical risk of MOA-food interactions
What is the role of anticholinergics in parkinsons disease? (name some drugs)
Used as adjunctive tx when tremor is troublesome - poor efficacy
anticholinergic ADRs = dry mouth, constipation, urinary retention, hallucinations, cog impair, confusion
Benzhexol, benztropine, biperiden
How is nausea treated in parkinsons?
Worse at initiation and inc dosage
Used = domperidone 10mg tds
AVOID = metoclopramide, prochlorperazine, and other centrally acting dopamine-blocking antiemetics
List the CNS effects of Parkinsons disease
Hallucinations - secondary to meds (reduce dose)
- occasional + retained insight - don’t treat
- Troublesome = tx w/ antipsychotics - clozapine or quetiapine
Sleep disturbances
Depression - SSRI tx - no quetiapine
Cognitive impairment
Dementia
How is orthostatic hypotension treated in parkinsons disease?
Defined by drop of 20 mmHg systolic on postural change
Tx: add salt to diet, fludrocortisone
- may add domperidone - QT interval prolongation
What are the huntington’s disease symptom triad?
Personality changes = impulsive, aggressive
Cognitive decline
chorea = involuntary, irregular movements - dance like
How is huntington’s disease treated? (chorea)
Tetrabenazine - depleted dopamine and MOA
Antidopaminergic drugs - atypical antipsychotics
Riluzole - antiglutaminergic + neuroprotective
Nabilone
Tx depression - SSRI
How is mild restless leg syndrome treated?
Its not
How is troublesome restless less syndrome treated?
Low dose dopamine agonist
Levodopa/ pramipexole/ ropinirole
ADRs = rebound legs, can worsen sx or make it syndrome occur earlier in the day
