Unit 7: CNS Drugs.Parkinson's Disease Flashcards
cause of Parkinson’s disease
depletion of dopamine-containing neurons in SUBSTANTIA NIGRA –> loss of normal inhibition
symptoms of Parkinson’s
tremor rigidity bradykinesia = slow movement postural instability flexed hips/knees short/shuffle steps
how much dopamine is usually lost by the time a patient presents with symptoms?
70-80%
what is the goal in Parkinson’s treatment?
correct imbalance of cholinergic neurons by REPLACING DOPAMINE
What is the issue with Parkinson’s treatment?
dopamine does NOT cross the blood brain barrier
name the drug classes used to treat Parkinson’s
dopaminergic agents MAO-B inhibitors anticholinergics COMT inhibitors miscellaneous
Why are COMT inhibitors used to treat Parkinson’s?
COMT metabolizes levodopa
What do MAO-B inhibitors do?
slow the breakdown of dopamine
When are dopamine agonists used to treat Parkinson’s?
early: monotherapy
later: adjunct ot Levodopa
MOA for Dopamine Agonists
direct stimulation of dopamine receptors
Name 5 dopamine agonists
Bromocriptine Pramipexole Ripinirole Roigotine Apomorphine
How long must a dopamine agonist be tried in order to see if it works?
4-8 weeks
adverse effects of dopamine agonists
N/V
dizziness
hallucinations
daytime somnolence
Why is Levodopa given?
Levodopa is a precursor to dopamine.
Dopamine does not cross the BBB.
Levodopa does
Why is Carbidopa given with Levodopa?
If given alone, Levodopa would require HIGH doses because it gets decarboxylated (1-3% would make it to the brain).
When given together, Carbidopa decreases the required Levodopa dose by 75%.
Does Carbidopa cross the BBB?
No
Main effect of Carbidopa
increases the amount of Levodopa that makes it to the brain
Expected effects of Carbidopa-Levodopa
improvement in bradykinesia
decreased mortality
Carbidopa-Levodopa does NOT improve:
speech
postural instability
motor freezing
cognitive dysfunction
When a patient is taking Carbidopa-Levodopa, when are the best results expected?
in the 1st few years of treatment
adverse effects of Carbidopa-Levodopa
N/V Depression Anxiety tachycardia agitation confusion postural hypotension
What metabolizes dopamine (hint: parkinson’s drug classes)
MAO-A
MAO-B
COMT
COMT Inhibitors are used for ____
adjunct treatment for Parkinson’s
MOA for COMT inhibitors
inhibit COMT, which metabolizes Levodopa –> Levodopa around longer
name 2 COMT inhibitors
entacapone
tolcapone
adverse effects of COMT inhibitors
N/D
somnolence
hallucinations
How do the MAO-B inhibitors work?
metabolize dopamine selectively
Name 2 MAO-B inhibitiors
selegiline
rasagiline
Adverse effects of MAO-B Inhibitors
Nausea
dizziness
sleep disorders impaired gobnition
MAO-B inhibitors interact with…
tramadol
dextromethorphan
cyclobenzaprine
antidepressants
Dietary advice for people taking MAO-B inhibitors
avoid tyramine containing foods
Why should tyramine be avoided when taking MAO-B inhibitors?
MAO breaks down tyramine in the body; tyramine affects BP; too much tyramine can spike BP (medical emergency)
What increases tyramine in foods?
tyramine occurs naturally in some foods and increases with age
cooking does not decrease it
Anticholinergics are used to treat what with Parkinson’s?
drooling or tremors in early disease stages
Name 2 anticholinergics used in Parkinson’s treatment
benztropine
trihexyphenidyl
What is important to remember about anticholinergic dosing with Parkinson’s?
avoid abrupt discontinuation
adverse effects of the anticholinergics used to treat Parkinson’s
dry mouth constipation delirium confusion sedation urinary retention
What is Amantadine used to treat?
dystonias in Parkinson’s disease
uncontrollable muscle contraction that leads to repetitive movement or abnormal postures
What effect are we hoping for with Amantadine treatment?
improvement in bradykinesia, rigidity, tremors
What is the downside of Amantadine treatment?
drug loses effectiveness in 4-8 weeks –> TAPER off
adverse effects of Amantadine
restlessness agitation GI disturbances urinary retention hypotension insomnia
