P6: Parkinson's Disease Flashcards
what type of disease is Parkinson Disease
neurodegenerative
what % of the population over 60 has Parkinson Disease
1%
what are the classic symptoms of Parkinson Disease (4)
- rigidity
- resting tremor of hands
- bradykinesia
- postural instability
what is bradykinesia
slow movement
what is the primary cause of Parkinson Disease and what part of the brain is affected
degeneration of dopaminergic neurons in substantia nigra
in the basal ganglia, what two neurotransmitters are in balance with one another
dopamine and acetlycholine
what happens in Parkinson’s when dopamine is decreased (directly)
Ach increases
what other NTs are affected by the depletion of dopamine (4)
- GABA
- glutamate
- 5-HT (serotonin)
- norepinephrine
what is the process of creation of dopamine (3 step process)
- tyrosine
–>
- dopa
–>
- dopamine
what enzyme transforms tyrosine into dopa
tyrosine hydroxylase
what enzyme transforms dopa into dopamine
dopa decarboxylase
will dopa cross the blood brain barrier
yes
will dopamine cross the blood brain barrier
no
what part of dopa can cross the BBB
L-hand isomer (levodopa)
what is the rationale for levopoa therapy (3)
- attempt to increase dopamine content in the basal ganglia
- direct administration of dopamine ineffective because dopamine can’t cross the BBB
- must provide precursor to dopamine (levodopa (L-DOPA))
what does the BBB divide
cerebral capillary and cerebral tissue
what is the role of the BBB
be selective on what can and can’t reach the brain
once L-DOPA crosses the BBB, what enzyme converts it to dopamine
DOPA decarboxylase
what is the problem with DOPA decarboxylase
it’s found in the blood stream and brain.. L-DOPA needs to be converted to dopamine in the brain, not the blood.. means we need another drug to protect it until it can reach the brain (carbidopa)
what drug is a protective drug that is often given with L-DOPA
carbidopa
brain or blood stream:
90% of L-DOPA is converted to dopamine here
the blood stream
mechanism of carbidopa
inhibits dopa decarboxylase (prevents premature conversion)
what two things are often included in the same pill
l-dopa and carbidopa
side effects of L-Dopa therapy (5)
- GI irritation
- hypotension
- psychotropic, behavioral effects
- dyskinesias
- “freezing” of gait
in l-dopa therapy, there are fluctuations in response to l-dopa.. what are the two types
- end-of-dose akinesia
2. on-off phenomenon
what is the end-of-dose akinesia
decreased response toward end of cycle
what is the on-off phenomenon
response fluctuates within dose cycle
for l-dopa therapy, what type of response may be present with long-term use
diminished response
benefits may be lost after ____-____ of l-dopa therapy
4-5 years
what are the two ideas for why a diminished response is present for l-dopa therapy
- tolerance builds
2. disease is progressing and getting worse, the drug can’t be supplied enough to give them what they need
if a tolerance to the drug is present, what should we do
delay the administration
if the disease is too progressed that the drugs won’t help, what should we do
use as needed (when symptoms are the worst)
do dopamine agonists cross the BBB
yes
what do dopamine agonists do after they cross the BBB
stimulate dopamine receptors
what is noted regarding half-life for dopamine agonists
longer half-life
what does the longer half-life do for dopamine agonists
cause more stable responses
what can dopamine agonists be used for
initial treatment in early Parkinson Disease
dopamine agonists may be ____
neuroprotective
what stage of parkinson disease are dopamine agonists generally used in
early
problems with dopamine agonists (4)
- nausea/vomiting
- confusion, hallucinations
- postural hypotension
- increased dyskinesia
what are the problems with dopamine agonists similar to
parkinson disease
what does catechol-O-methyltransferase (COMT) do
enzyme that breaks down l-dopa in peripheral tissue
what do COMT inhibitors do
allow more l-dopa to reach the brain
benefits of COMT inhibitors (2)
- decrease fluctuations
2. increase “on-time” in on-off phenomenon
what does COMT break l-dopa into
3-O-methyldopa (useless)
what can be combined with L-DOPA and carbidopa
COMT inhibitors
what are are problems with COMT inhibitors (3)
- GI distress (diarrhea)
- orthostatic hypotension
- increased dyskinesia
what do anticholinergic drugs do
decrease acetlycholine
what does anticholinergic drugs decreasing acetlycholine do
help decrease rigidity and tremor
anticholinergic agents are limited somewhat by side effects known as
anticholinergic package
mechanism of MAO-B inhibitors
inhibit monamine oxidase type B (MAO-B)
what do MAO-B inhibitors do
prolong dopamine effects in brain
what do MAO-B inhibitors combine with to increase and prolong effects
l-dopa
what are the major problems with MAO-B
no major concerns
MAO-B inhibitors have possible ____ effects
neuroprotective
amantadine was initially created to treat…
the flu
amantadine is a ____ agent
antiviral
mechanism of amantadine
blocks NMDA receptor in brain
by blocking the NMDA receptor in the brain, what does amantadine do
decreases influence of excitatory amino acids (glutamate)
amantadine decreases chance of
dyskinesias
problems with amantadine (3)
- orthostatic hypotension
- psychotropic effect
- skin discoloration
when is the optimal treatment time for antiparkinson drugs
30 to 60 minutes after meds
what are three future considerations of parkinson disease
- tissue transplant
- surgery
- role of toxins
