Card Set Information
Parkinson\'s Disease PHPR521
When does Parkinson's usually set in?
45-70 years of age
What are the causes of Parkinson's?
toxins, oxidative stress
environmental factors (pesticides, rural living, well water)
medications (antipshychotics, antiemetics)
What behaviors have an inverse relationship to PD?
Why doesn't glutathione protect against Parkinson's?
We don't produce enough of it
What are the effects of PD on the cortex?
decreased direct pathway stimulation = decreased facilitation of movement
increased indirect pathway stimulation = increased inhibition of movement
When symptoms occur how much damage is already done to the DA neurons?
70-80% loss of neurons
2 of what symptoms present in a patient are probable for Parkinson's diagnosis?
resting tremor (usually unilateral)
What are the motor symptoms of PD?
difficulty rising from sitting
diminished arm swing
What are the autonomic and sensory symptoms of PD?
What are the mental status changes of PD?
slow thought process
What is not always present at PD diagnosis?
What is often found on an autopsy of a person with PD?
What are the comorbidities of PD?
dementia ~ 40%
psychosis ~ 25%
mild psychotic symptoms ~ 50%
depression ~ 40%
What are the goals of PD therapy?
minimize side effects of medication
What are the nonpharmacological treatments for PD?
exercise (tango is best)
deep brain stimulation (implanted stimulator)
implantation of DA secreting tissue in the brain
glial-derived neurotrophic factor (GDNF)
What causes PD?
How do we treat PD?
Mimic DA (stimulate the receptors)
Stop the breakdown of DA
in brain and periphery)
entacapone (stops breakdown of L-Dopa by
carbidopa (stops breakdown of L-Dopa by
What causes depletion of DA?
What factors increase risk of motor disturbances in PD?
duration of disease
dose of medication
severity of disease
What drug is used in PD as a precursor to DA that can cross the BBB?
What is used to increase the amount of L-Dopa that crosses the BBB?
Carbidopa - inhibits the breakdown of L-Dopa in the periphery by Dopa Decarboxylase
What is the half-life of L-Dopa?
1-3 hrs (duration may exceed half-life during early treatment because the neurons can still absorb and use it)
What are the advantages of L-Dopa?
It works fast (peak in 1-2 hrs)
What are the disadvantages of L-Dopa?
waning effect results in "off" periods (motor fluctuations) = even shorter half-life
may be converted in periphery = increased SE and decreased levels in brain
NAUSEA if broken down in periphery
competes with proteins for absorption in the gut and for transport across BBB
absorption affected by GI conditions
How can you combat the waning effect of L-Dopa?
increase dosing frequency
add a DA agonist (apomorphine - only helps for 100 min)
What are the SE of L-Dopa?
; use antacids)
dyskinesias (as soon as 6 mo;
no use in pts with psychosis
How do you combat delayed "on" or "no on" with L-Dopa?
use oral disintegrating tablets
separate from protein
How do you combat "freezing" with L-Dopa?
add a DA agonist or MAO-B inhibitor
How do you combat dyskinesias with L-Dopa?
What DI does L-Dopa have?
pyridoxine (vitamin B6)
What are the CI of L-Dopa?
Why not start L-Dopa in everyone right away?
other classes of drugs are effective
What type of drug are selegiline and rasagiline?
What is the MOA of selegiline and rasagiline?
irreversible inhibition of MAO-B
What are the advantages of selegiline and rasagiline?
May use as monotherapy in early PD (delays need for L-Dopa)
modest improvements in motor function
evidence that rasagiline delays functional decline
oral disintegrating tablet available
What are the disadvantages of selegiline and rasagiline?
side effects from active metabolites....methamphetamine, amphetamine (selegiline only)
may augment motor and cognitive side effects of L-dopa therapy
interactions with tyramine containing foods (cheddar, tap beer, salami, wine, soy)
What else can selegiline and rasagiline be used for besides PD?
major depressive disorder
What are the SE of selegiline and rasagiline?
worsens existing psychosis and dyskinesia SE of L-Dopa (
What are the DI of selegiline and rasagiline?
may increase risk of serotonin syndrome
pseudoephedrine and pheynylephrine cause HTN
What are the CI of selegiline and rasagiline?
dextromethorphan, methadone, propoxyphene, tramadol - with the ODT
Do selegiline and rasagiline modify the disease in PD?
Yes, the slowed breakdown of DA may result in less free radicals
When should selegiline and rasagiline be administered?
last dose should be early in day due to SE
What are the COMT inhibitors used in PD?
tolcapone and entacapone
What is the MOA of tolcapone and entacapone?
prevent peripheral conversion of L-Dopa by COMT
What are the advantages of tolcapone and entacapone?
reduce off time
combination available with carbidopa/levodopa (
extend duration of activity for L-Dopa
first line adjunct for motor fluctuations (
What are the disadvantages of tolcapone and entacapone?
cannot be used as monotherapy
administered up to 8 times daily (
What are the SE of tolcapone and entacapone?
delayed onset diarrhea (tolcapone)
brownish-orange colored urine (tolcapone)
How are tolcapone and entacapone administered for PD?
co-adminster with carbidopa/levodopa
do not stop abruptly
What are the advantages to using DA agonists in PD?
fewer motor fluctuations; reduced risk
well tolerated in younger patients
longer DOA than L-Dopa
do not rely on neuronal functional capacity
monotherapy in mild disease
What are the disadvantages of DA agonists in PD?
worsening of L-Dopa induced dyskinesias
class SE (
nausea, neurologic, postural hypotension, compulsive behaviors, hallucinations
What are the advantages of pramipexole and ropinirole in PD?
can titrate faster than ergot derivatives
safer than ergot derivatives
well tolerated in
duration of action longer than L-Dopa
potentially less generation of free radicals (d/t less catabolism of DA)
may be used as initial therapy (monotherapy in mild PD)
do not rely on neuronal function
may be taken with food to decrease nausea SE
What are the disadvantages of pramipexole and ropinirole in PD?
worsening of dyskinesias
What are the SE of pramipexole and ropinirole?
What are the DI of pramipexole and ropinirole?
Do pramipexole and ropinirole modify the disease in PD?
potentially (decreased free radicals)
How are pramipexole and ropinirole administered for PD?
with or without food (may help with nausea)
What are the advantages of apomorphine in PD?
rapidly triggers "on" response
What are the disadvantages of apomorphine in PD?
; premedicate with trimethobenzamide
What are the SE of apomorphine?
postural hypotension (test dose)
What are the CI for apomorphine?
concomittant administration with 5-HT
agents (ondansetron, dolasetron, granisetron, palonosetron)
What is the duration of action of apomorphine?
Why are anticholinergics used in PD?
because decreased levels of DA results in extra ACh (causes EPS - tremor, rigidity; drooling
What are the disadvantages to anticholinergics?
(trihexylphenidyl and benztropine)
minimal improvement of bradykinesia
elderly are more susceptible to SE of anticholinergics
no more effective than DA agents
What are the side effects of anticholinergics?
(tryhexyphenidyl and benztropine)
mad as a hatter
hot as a hen
red as a beet
dry as a bone
blind as a bat
What is the MOA of trihexyphenidyl and benztropine in PD?
inhibition of PNS
What are the DI of trihexyphenidyl and benztropine?
may increase levels and/or effect of potassium
What are the CI of trihexyphenidyl and benztropine?
narrow angle glaucoma
use with caution in males with BPH
What PD drugs are CI in glaucoma?
Why is amantadine used in PD?
it supresses L-Dopa induced dyskinesias
What is the MOA of amantadine in PD?
What are the disadvantages of amantadine?
benefit is short lived
What are the SE of amantadine?
What are the DI of amantadine?
may increase levels and/or effect of potassium
What are the risks for PD psychosis?
disease duration and severity
medication use -
dose and duration DO NOT MATTER
When removing PD agents to improve PD psychosis, in what order do you do so?
What drugs are used for PD psychosis?
What should be the initial treatment for PD?
What should you consider when choosing a PD agent?
delay initiation of L-Dopa if possible
MAO-B inhibitors for most patients
DA-agonists for younger patients
amantadine for dyskinesias
What drugs should be used as adjuntive tx for "wearing off" in PD?