Parkinson's Disease Flashcards
What causes Parkinson’s disease? (pathophysiology)
Presence of Lewy Body (protein aggregates) and degeneration of dopaminergic neurons. Risk factors include age, genetics and environmental factors (eg. pesticides).
Clinical presentation of Parkinson’s disease?
Presence of bradykinesia (slow movement) and one of 3:
-muscle rigidity
-tremor
-postural instability (usually occurs in later stages)
Usually sx begin unilaterally and progress to bilatera;
Many non-motor sx can also be associated eg. cognitive impairment, depression, anxiety, OAB, psychosis etc.
Drug Induced causes for Parkinson’s Disease
Drugs that block D2 receptors like antipsychotics (eg. haloperidol), metoclopramide, phenothiazine antiemetics (prochlorperazine).
Why and why not are anticholinergic drugs useful in Parkinson’s disease
Dopamine provides negative feedback to acetylcholine, high cholinergic activity contributes to tremor. Thus anticholinergic drugs (benztropine & trihexyphenidyl) were historically used for tremor but use is no longer recommended due to side effects (blurred vision, confusion, constipation, dy mouth, memory difficulty, drowsiness, urinary retension.)
Why and how is levodopa useful in treating Parkinson’s disease?
L-dopa is a dopamine precursor. It’s useful because Parkinson’s is characterized by reduced dopaminergic activity. Ultimately all PD patients will require levodopa.
What is levodopa used in combination with and why?
A peripherally acting L-amino acid decarboxylase inhibitor (carbidopa or beserazide) which reduces unwanted peripheral conversion of levodopa to dopamine in the rest of the body besides the brain.
What are some complications in Parkinson’s disease treatment with levodopa?
end-of-dose “wearing off” - use longer acting formulations or add-on tx (entacapone)
peak-dose dyskinesias - involuntary twitching/jerking develops after 5y- lower the dose and use add-on therapies
“delayed-on” - maybe due to delayed gastric emptying - use ODT or chew/crush tablet
How do MAO-B Inhibitors work in Parkinson’s disease? What’s their place in therapy?
Selegiline, rasagline, safinamide
Used as monotx or adjunct (selegiline is one of 1st line adjunct)
MAO-B is what degrades dopamine so inhibiting it will increase dopamine activity.
Note some meds are CI to use with this due to serotonin syndrome risk (meperidine, opioids).
How do COMT Inhibitors work in Parkinson’s disease? What’s their place in therapy?
Entacapone and tolcapone
Reduce peripheral conversion of levodopa to dopamine, useless without levodopa so can’t be used as monotherapy but entacapone is 1st line adjunct esp for wearing off
AE of MAO-B inhibitors
Selegiline - minimal AE but can include: agitation, insomnia (avoid dosing in pm), hallucinations, ortho hypo
Rasagiline - minimal GI and neuropsych effects
AE of COMT inhibitors
-brownish orange urine discoloration
-delayed onset diarrhea (in wks to mths)
-confusion, hallucinations, dyskinesias, sleep disorders, anorexia
How do dopamine agonists work in Parkinson’s disease? What’s their place in therapy?
Subcategories: Ergot (bromocriptine) Non-ergot (apomorphine sc, pramiprexole, ropinarole, rotigotine) better tolerated.
Useful as monotx in mild-mod and as adjunct but less effective vs levodopa and more s/e.
May be preferred in younger pts as these don’t cause motor complications like levodopa.
Avoided in older pts and pts w cognitive problems.
Dopamine agonist AE
Common: nausea, confusion, drowsiness, hallucinations, leg edema, ortho hypo
Rare: impulsive/compulsive behaviours, delusions/psychosis, sleep attacks
What is Amantadine’s place in therapy in Parkinson’s disease?
Insufficient evidence to recommend but may be used to manage dyskinesias (twitching/jerking) caused by levodopa, has antiglutamate properties.
Amantadine AE
confusion, dizziness, dry mouth, hallucinations
