parkinson's Flashcards
what is the pathophysiology of parkinson’s
- impaired clearing of abnormal or damaged intracellular proteins by ubiquitin-proteasomal system (failure to clear toxic proteins can lead to accumulation of aggresomes like lewy bodies and apoptosis)
- degeneration of DA neurons with lewy body inclusions in the susbtantia nigra leads to dysfunction of nigrostriatal pathway (clinical symptoms at ~80% loss of DA)
what are the major components of the basal ganglia
- caudate nucleus
- putamen
(caudate nucleus and putamen forms striatum) - globus pallidus
- subthalamic nucleus
- substantia nigra
what is a key function of the basal ganglia implicated in parkinson’s
involvement in action selection through release of inhibition
- the loss of substantia nigra in parkinson’s = no release of inhibition = hypokinetic state
- direct and indirect pathways involving excitatory D1 and inhibitory D2 receptors
what are the characteristic features of parkinson’s disease
- idiopathic, degenerative, CNS disorder
- T remors (resting)
- R igidity (cogwheel)
- A kinesia (poverty and slowness of movement: loss of dexterity, subjective sense of weakness, difficulty turning when walking, reduced blinking, loss of facial expression, difficulty using tools, difficulty getting out of bed or chair)
- P ostural instability
*TRA are cardinal symptoms of parkinsons and 2/3 must be present for confirmatory diagnosis
compare the initial presentation to progression of parkinsons
initial presentation
- asymmetric
- positive response to levodopa or APO-morphine
- postural instability and falls not present
- less rapid progression
- autonomic dysfunction not present
progression of idiopathic PD
- unable to perform basic ADLs (grooming, dressing, feeding self, toileting, showering, continence)
- choking
- pneumonia
- fall
what are some other non-motor symptoms of parkinsons
- cognitive impairment (dementia)
- psychiatric symptoms (depression, psychosis)
- sleep disorders (REM sleep behavior disorder)
- autonomic (constipation, GI motility, OH, sialorrhea)
- others (fatigue)
how to measure disease progression of parkinsons
- hoehn and yahr staging
I: unilateral
II: bilateral without impairment of balance
III: mild to moderate bilateral disease, some postural instability, physically independent
IV: severe disability, still able to walk or stand unassisted
V: wheelchair bound or bedridden unless aided - MDS-UPDRS
- non-motor experiences of daily living
- motor experiences of daily living
- motor examination
- motor complications
what are the features of early or young onset parkinsons
- slower disease progression
- features include (i) lesser cognitive decline (ii) earlier motor complications (iii) dystonia ie. spasm common initial presentation (compared to falls and freezing in late onset)
what are the goals of therapy for parkinson’s
- manage symptoms
- maintain function and autonomy
what is the non-pharmacological management of parkinson’s
- physiotherapy (stretching, transfers, posture)
- occupational therapy (home and workplace safety, mobility aids)
- speech and swallowing
- surgery
identify the two main categories of pharmacological management for parkinson’s in terms of their endgoal from their mechanism of action
- increase central DA (increase dopaminergic transmission)
- levodopa + DCI
- DA agonists (ergot and non-ergot derivatives)
- MAO-B inhibitor
- COMT inhibitor - correct imbalances in other pathways
- anticholinergics
- NMDA receptor antagonists
what is the moa, pk, s/e and ddi of levodopa
moa
- precursor of DA, converted by striatal enzymes into DA
s/e
- N/V (esp if newly initiated)
- orthostatic hypotension
- drowsiness, sudden sleep onset
- hallucinations, psychosis
- dyskinesia
ddi
- pyridoxine (vitB) (of concern for high dose B6 for hematological problems or high potency vitB complex)
- Fe
- protein
- FGA
- risperidone
- DA antagonists (metoclopramide, prochlorperazine)
what is the motor complications of levodopa
- on-off
- unpredictable and not dose related
- unclear mechanism
- hard to control with medications - wearing off
- effect of levodopa wanes off before next dosing interval
- shortened ON
- associated with disease progression
- manage by changing administration times or changing relevant dose to modified release preparation - dyskinesia
- refers to involuntary uncontrollable jerking or twitching
- related to peak dose
- manage by giving smaller dose but more frequent, add amantadine or change relevant dose to modified release
list the types of DA agonists
ergot derivatives
- bromocriptine
- cabergoline
- pergolide
non-ergot derivatives
- ropinirole
- pramipexole
- rotigotine (transdermal)*
- apo-morphine (subcut)*
*not in sg
what is the moa, pk, s/e and ddi for DA agonists
moa
- act on D2 receptors in basal ganglia to mimic action of DA
pk
- ergot derivatives have lower F due to more extensive first pass
- ropinirole is hepatically metabolised thus caution in H impairment
- pramipexole is renally excreted largely unchanged thus caution in R impairment
- longer half life and duration of action than levodopa
s/e
peripheral
- N/V
- OH
- leg edema
central dopaminergic
- hallucination (visual > auditory)
- somnolence, day time sleepiness
- compulsive behaviors
non-dopaminergic
- fibrosis (lower risk with non-ergot)
valvular heart disease (> with ergot)
