Management of Parkinson's Disease Flashcards
What causes the motor symptoms of PD
A result of the loss of dopaminergic projections from the substantia nigra pars compacta to the striatum
Levodopa
Prodrug of DA
Converted to DA by dopa-decarboxylase (present in CNS and PNS)
Most potent symptomatic treatment for PD motor symptoms
Administered with a dopa decarboxylase inhibitor to minimize peripheral side effects
DA agonists
Directly stimulate post-synaptic DA receptors
Provide moderate symptomatic benefit, can be used alone or as adjunctive
Risk of impulse control disorders (D3 receptor)
Ex: Pramipexole, ropinirole, rotigotine
MAO-B inhibitors
Inhibit the metabolism of endogenous and exogenous DA by MAO-B
Provide weak symptomatic benefit, extend duration of action of levadopa (need DA to work)
Monotherapy in early disease, then adjunctive
Ex: selegiline, rasagiline, safinamide
Amantadine
Mild symptomatic benefit for the motor symptoms of PD, especially tremor
Also effective for dyskinesias
Monotherapy (early) or adjunct
Anticholinergics
Useful for the treatment of tremor in PD
Use is limited by its side effects, and possible increased risk of dementia with long term use
Only useful for cognitively intact patients with young onset
COMT inhibitors
Block the metabolism of DA by COMT
Must be done in conjunction with levodopa
Important side effect is orange urine
Ex: entacapone
What is the problem with abrupt withdrawal of levodopa/DA agonists fro patients with advanced PD?
Can precipitate a neuroleptic-malignant syndrome-like condition that is life threatening
What intervention is neuroprotective?
Physical activity (cardio, strength, balance)
4 examples of motor fluctuations
Wearing off
Delayed kicking in
Freezing of gait
Off dystonia
Wearing off
Generally begins as end-of-dose failure
< 4 hour duration of an adequate dose of levadopa
Offs become deeper and more severe with disease progression
Delayed kicking in
Taking > 30 mins for a dose of levodopa to start working
Especially common for the first AM dose
Due to delayed gastric emptying, constipation, or poor constipation from competition with aas
Off-period dystonia
Commonly occurs in the early morning when plasma levodopa is low
Usually manifests as leg cramps +/- toe curling
Can be treated with any of the meds
Dyskinesias
Abnormal, involuntary movements related to dopaminergic therapy
May be ballistic, choreiform, or dystonic
Can be at peak dose, or diphasic (D-I-D)
Use lowest effective dose
Amantadine is best treatment
How do you treat
- Peak dose dyskinesia
- Diphasic dyskinesia
- Smaller, more frequent doses
2. Like wearing off (increase dose)
Freezing of gait
Occurs more commonly when off (treat as per wearing off)
Droxidopa shows modest improvement, also levo/carbi intestinal gel
Physio and sensory tricks can help
Pallidotomy
Mainly historical significance
Involves lesioning the GP to improve motor symptoms
Mechanism not well understood - disruption of disordered pathways
Mostly replaced by DBS
Levodopa/carbidopa intestinal gel
Continuous infusion via PEG-J
Results in less fluctuations, improvement in dyskinesias and possible improvement in freezing of gait
Deep brain stimulation
DBS of GPi and STN
Mimics the best “on” state of the patient and does not treat levodopa unresponsive symptoms
STN is most favored (can reduce medication dose)
Generally reserved for younger, cognitively intact patients
Non-motor symptoms
Occur almost universally and tend to have a greater impact on QoL than motor
May fluctuate independently of motor
Non-motor fluctuations an be managed with the same strategies as motor fluctuations
Non-fluctuating non motor symptoms are managed in the same way as someone without PD
