Parkinsons Flashcards
common age and gender in parkinsons
male
diagnosed age 66 usually
the four motor features
bradykinesia tremor at rest rigidity postural instability *must have bradykinesia
describe the tremor at rest
rhythmic
asymmetric - doesnt affect both sides equally
pill rolling
feet, lip, jaw
may disappear with voluntary movement and sleep
worsens with mental stress
describe the rigidity
lead pipe, cogwheel
neck, trunk, limbs
resistance to passive movement of the limbs
describe bradykinesia
slowness of all movements
difficulty initiating movement
describe postural instability
later presentation
shuffling gait
narrow base
freezing and falls
main difference in symptoms between motor cortex disorders
no muscle weakness
just a communication issue
other clinical features
depression dementia sleep disturbance difficultly smelling micrographia dysphagia lack of expression -hypomimia
what happens in the substantia nigra
low dopamine causes parkinsons
high dopamine causes dyskinesia
cells start to die in parkinsons
what is the substantion nigra responsible for
controls movements and connects to the motor cortex
how does the nigrostriatal pathway achieve smooth muscle movement
ach (inhibitory) and dopamine(excitatory) are in balance
what happens when there is much more ach than dopamine
movement becomes jerky and stiff
drugs that can cause parkinson like motor symptoms
typical antipsychotics - block all 4 pathways
atypical antipsycotics - selectively block dopamine in mesolimbic pathway
Gi agents - metoclopramide
SSRI
valproic acid
old antihypertensives
4 types of extrapyramidal symptoms
dystonia
akathisia
pseudoparkinsonism
tardive dyskinesia
risk factors for drug induced parkinsonism
old
femal
high dose of offending drug
history of movement disorder
signs its drug induce parkinsonism
symmetric presentation***
onset within a few weeks of starting drug
may take 2-6months to resolve after
what is drug induced neuroleptic malignant syndrome
life threatening
due to sudden decrease in dopaminergic transmission
dopamine blocker»_space;»decrease in dopamine transmission or sudden withdrawal from dopamine enhancer
FARM symptoms of neuroleptic malignant syndrome
fever
autonomic instability - sweat, HR, BP
rigidity
mental status changes
when do symptoms appear in parkinsons
once there is loss of 60-80% of pigmented neurons in the substantia nigra
5 ways to treat parkinsons
dopamine precursor dopamine agonist NMDA receptor antagonist COMT or MOAB inhibitor block acetylcholine
goals of therapy
preserve ability to perform activities of daily living
min AE and treatment complications
improve non motor features
what warrants therapu
when diability interferes with social emotional or work life
why dont we treat early mild symptoms
ldopa is the best drug but loses effect over time so want to save it
anticholinergic MOA
block acetylcholine, relative increase in dopamine
amantadine MOA
NMDA antagonist
increases dopamine release
MAO-B inhibtor MOA
reduce dopamine breakdown in the cns
COMT inhibitor MOA
reduce levodopa breakdown in GI
prolongs half life and increase bioavailability
dopamine agonist MOA
directly stimulates dopamine receptors
levodopa MOA
converted to dopamine by dopa decarboxylase
why cant dopamine just be directly gicen
cant cross the BBB
when to use anticholinergics (benztropine)
generally people <60 due to the AE and modest efficacy
anticholinergic AE
constipation dry mouth eye infections urinary retention blurred vision cognitive impairment headache increased HR overheating
do you have to taper benztropine
yes over 1 week
indication for amantadine
modest effect
used early for tremor
used alter to reduce ldopa dyskinesia
better tolerated in yount patients due to stimulatory effects (normally used for MS fatigue)
AE of amantadine
confusion, insomnia, nervous anticholinergic GI hypotension livedo reticularis *take in AM
what is livedo reticularis
reversible diffuse purple red skin
in the extremeties
not an issue just cosmetic
role of MAOBi
early for monotherapy
add on to levodopa to extend on time
is tyramine intake a concern wtih selegiline and rasagiline
no
AE of selegiline
insomnia hallucination confusion orthostatic hypotension take in AM *bc converted to methamphetamine
AE of rasagiline
GI - take with food
which drugs prevent dopamine degradation in the peripheray
comt inhibitors
DDC inhibitors
why do comt inhibitors have no effect wihtout levodopa
only role is to prevent dopamine from being broken dow
comt inhibitor role
mild improvement
prevode 1-2 hr on time longer for levodopa
later used as an add on
entacapone is a
COMT inhibitor
not covered *
AE of COMT inhibitors
NV brown orange urine/sweat sweating diarrhea dyskinesia hypotension
ergot derived dopamine agonist and why its not used
bromocriptine
cardiac valve disease
examples of non ergot agonists
pramipexole
ropinirole
rotigotine
rold of dopamine agonists
alone in mild
adjunct to levodopa in patients with motor fluctuations
adv and dis of dopamine agonist
less motor complications than levodopa but more AE
rotigotine form
patch
not covered*
dopamine agonist AE
nausea cognitive impairment lower extremity edema impulsivity sleep attacks - caution driving increase levodopa induced dyskinesias
dose initiation and taper with dopamine agonist
initiate low dose and increase over 4-6 weeks to prevent AE
abrupt withdrawal causes NMS
benefits of levodopa
improves disability
prolongs ability to work
reduced mortality rate
primary concern with dopamine
dyskinesias
dopamine decarboixylase inhibitors MOA
allows ldopa to cross BBB
prevents conversion in periphery
also minimizes peripheral AE
examples of dopamine decarboxylase inhibitors
carbidopa
benserazide
