Parkinson's Disease Flashcards
What are symptoms of parkinson’s disease?
Bradykinesia
With either:
- rigidity
- tremor
And +/- postural instability
What are other motor features of PD?
Masked fascies
Decreased blinking
Shuffling gait
Decreased arm swing
Stooped posture
Difficulty turning
Small handwriting
What are non-motor features of PD?
Neuropsychiatric
(Depression, anxiety)
Sleep abnormalities
Cognitive changes
Autonomic dysfunction (Constipation common; also orthostasis)
What are medications/treatments for motor symptoms of PD?
Anticholinergic
Amantadine
Levodopa
Dopamine agonists
MAO-B inhibitors
COMT inhibitors
Deep brain stimulation
How is dopamine metabolized?
By two enzymes:
MAO-B and COMT
What anticholinergic medications are used for PD?
What do they treat?
Trihexyphenidyl
Benztropine
Tremor
Describe MOA of anticholinergics for treatment of PD
Reduces cholinergic input to striatum and blocks muscarinic ACh receptors
What are AEs of anticholinergic agents for PD?
Sedation
Confusion/hallucinations
(Patients 65+)
Dry mouth
Glaucoma
Urinary retention
Constipation
Hyperthermia, flushing
Acute anticholinergic toxicity
What does Amantadine treat?
What is its MOA?
Early Tremor + later dyskinesia
MOA:
NMDA antagonist + anticholinergic and dopamine agonist properties to block overstimulation
What are AEs associated with Amantadine?
May inc. dementia, confusion in elderly
Insomnia
Livedo reticularis and ankle edema
What is a PEARL associated with Amantadine?
Dose earlier than NOON to avoid insomnia
For use with fatigue
What are 3 dopamine strategies for increasing dopamine levels, and the drug classes that achieve them?
- prevent dopamine breakdown (MAO-B inhibitors)
- stimulate body’s own dopamine pathways (dopamine agonists)
- direct replacement (levodopa)
What are MAO-B inhibitors and what do they treat?
Selegiline
Rasagiline
Some benefit to all motor symptoms:
Tremor > rigidity > bradykinesia
What are AEs associated with MAO-B inhibitors?
Interactions with MAO-A
+tyramine (wine and cheese)
+hypertensive crisis
What are CIs associated with MAO-B inhibitors?
Serotonin syndrome:
+cognitive = confusion, agitation, hyperactivity
+autonomic = CV, GI
+neurological = tremors, myoclonus, hyperreflexia, hypertonia
What are dopamine agonists?
Ropinirole
Pramipexole
Rotigotine
Bromocryptine
Apomorphine
What do dopamine agonists treat?
What is their MOA?
All motor features:
Tremor > rigidity > bradykinesia
MOA:
Potentiates action of existing dopamine neurons
What is the difference in half-lives of dopamine agonists?
Ropinirole = 6 hours
Pramipexole = 8 hours
What are AEs associated with dopamine agonists?
Sedation
Sudden sleep onset
Worsen hallucinations/ dyskinesia
Leg swelling
Impulse control disorder in some **
What is Carbidopa?
Enzyme inhibitor that prevents breakdown of levodopa
Avoids peripheral side effects of nausea and orthostasis
Does not pass BBB
What does carbidopa/levodopa treat?
All motor features!
Tremor > rigidity > dyskinesia
(Not gait)
What are motor complications associated with cabidopa/levodopa?
As disease progresses, less dopamine neurons exist to process dopamine
Freezing
Dyskinesia (“extra” movements”)
Shorter time windows of efficacy
What are AEs associated with carbidopa/levodopa?
Early: nausea, dizziness
Late
- fluctuations
- dyskinesia
- hallucinations
- orthostatic hypotension
- incomplete/ unreliable absorption
What should patients be advised for carbidopa/levodopa?
Tell patients to take it away from food in order to improve absorption and limit dosing
When should anticholinergic meds be used for PD?
Young + tremor predominant disease
When should Amantadine be used to treat PD?
Younger patients with mild symptoms
+ fatigue
When should MAO-B inhibitors be used for PD?
Mild symptoms
When should dopamine agonists be used for PD?
Younger patients with moderate symptoms
Sleep difficulties
When should CD/LD be used to treat PD?
Severe symptoms
Older patients (>80 yo)
- do not tolerate other meds
Unclear diagnosis
What are COMT inhibitors?
Entacapone
Tolcapone
Combination Sinemet/entacapone
What do COMT inhibitors do?
Only useful with exogenous levodopa
Prevent breakdown of dopamine
What are side effects of COMT inhibitors ?
Dopamine side effects
What black box warning is associated with tolcapone?
Liver failure
What is duodopa?
Levodopa with carbidopa pumped into stomach, small doses at a time
What is deep brain stimulation?
Implant for patients with:
+significant dyskinesia
+fluctuations
+“off” time despite medication
Patients not tolerating medication
