Term
| Clinical symptoms of Parkinson's Disease |
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Definition
PD is a neurodegenerative disease characterized by the progressive loss of dopaminergic neurons
primary clinical symptoms:
bradykinesia - slowed movement; decrease of absence of normal automatic movements; difficulting performing ADLs; development on dominant side oaffects handwriting; postural changes (bent forward, festination, freezing); later stages includes falls and injuries
muscular rigidity - cogwheeling; rigidity superimposed on tremor;
demonstrated by: holding arm out with hand supporting elbow, moving arm towards and away from chest, rigidity felt through elbow and seen through movements in arm
resting limb tremor - commonly first obvious symptom; begins unilaterally in the upper extremities; rapid and rhythmic; absent during sleep and slowed by sedation; increased when angry, upset, or tense; more marked with time; can spread to lower extremities, face, jaw, and tongue
gait dysfunction and loss of postural reflexes
nonmotor symptoms can include:
autonomic dysfunction (bladder and bowel dysfunction, sexual dysfunction, orthostatic hypotension)
depression
cognitive difficulties
dementia
sleep disturbances
others:
masked face
less blinking/staring
salivation and drooling
constipation and urinary incontinence
declining intellect - begins early and is progressive, hallucinations common later in course, delusions, dementia, anxiety and confusion |
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Term
| agents that can cause drug induced PD |
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Definition
dopamine antagonists:
antipsychotics
antiemetics
metoclopramide
n-MPTP: by product of synthesis of streat heroin |
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Term
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Definition
bradykinesia AND at least 2 of the following 3:
limb/muscle rigidity
resting tremor abolished by movement
poastural instability
unmistakable in advanced disease
difficult to differentiate in mild disease |
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Term
| physical examination: observation and objective measures |
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Definition
observation:
gait disturbances
reduced arm swing
postural instability
reduced strength
rigidity
lack of manual dexterity
objective measures:
mild orthostatic hypotension
labs generally not useful
CT/MRI normal early, may show cortical atrophy in advanced stages |
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Term
| MOA of levodopa/carbidopa |
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Definition
L-dopa crosses BBB and is converted to dopamine
carbidopa inhibits dopa-decarboxylase to prevent peripheral conversion of dopamine
binds to D1 and D2
overall effect: increased amounts to brain and decreased ADRs |
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Term
| levodopa/carbidopa dosing |
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Definition
need 200-800 mg levodopa and 75-100 mg carbidopa
initiate therapy with 200-300 mg levodopa/day and titrate slowly
WHEN SWITCHING FROM IM TO CR: INCREASE DOSE BY 25-30% |
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Term
| ADRs of levodopa/carbidopa |
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Definition
N/V: can try additional carbidopa in patients who cannot tolerate levodopa due to N/V
orthostasis
hallucinations
dyskinesias: movement problems associated with too much dopamine, jerky movements rather than tremor |
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Term
| response to levodopa and progression of PD |
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Definition
the development of motor fluctuations and dyskinesias appears to reflect a progressive narrowing of the therapeutic window for levodopa as the disease and levodopa treatment progresses
the threshold level of levodopa exposure that is required to achieve a therapeutic response progressively increases
at the same time, the threshold level above which levodopa causes dyskinesias decreases
in patients with advanced PD, it may therefore become impossible to find a levodopa dose which has an antiparkinsonian effect without causing dyskinesias |
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Term
| place in therapy of levodopa/carbidopa |
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Definition
traditionally used first line
?long-term use may lead to degeneration of neurons
"on-off" and "wearing-off" phenomenon occurs with prolonged therapy
increasing dose may lead to increased ADRs with little improvement in mobility
patients with a life expectancy of 20-30 years may not want to start with levodopa b/c it will work for ~6 years
especially patients with mild disease and are young, will start with other options |
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Term
| MOA of dopamine agonists (ergot derivatives - bromocriptine and pergolide, non-ergot - pramipexole and ropinirole) |
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Definition
primarily bind to D2 and D3
may prolong or decrease need for levodopa
do not generate oxidative metabolites
WHEN YOU ADD SOMETHING ELSE TO LEVODOPA/CARBIDOPA HAVE TO BACK OFF ON THE LEVODOPA DOSE |
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Term
| ADRs of dopamine agonists |
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Definition
motor complications less than with levodopa/carbidopa
N/V, postural hypotension, SOMNOLENCE (spontaneously falling asleep is a specific ADR to dopamine agonists), hallucinations, confusions, unsteadiness, dyskinesias
more common with bromocriptine and pergolide (ergot)
ergot derivatives also associated with valvulopathies |
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Term
| initial dosing of dopamine agonist: pramipexole |
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Definition
0.125 mg TID
has to be adjusted for renal function
titrate dose weekly based on patient's symptoms |
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Term
| initial dosing of dopamine agonists: ropinirole |
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Definition
0.25 mg TID
titrate dose weekly based on patient's symptoms |
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Term
| place in therapy of dopamine agonists |
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Definition
first line therapy as monotherapy
adjunctive therapy to levodopa/carbidopa
if the dopamine agonist stops working, you would SWITCH it for levodopa/carbidopa, don't add |
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Term
| indication for apomorphine in PD |
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Definition
treatment of acute, intermittent "off" episodes associted with advanced PD
non-ergot dopamine agonist with high affinity for D4, and moderate affinity for D2, D3, and D5
given subcutanesouly at a starting dose of 2mg |
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Term
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Definition
monoamine oxidase-B inhibitor to decrease breakdown of dopamine
?neuroprotective effects by reducing oxidative metabolism of dopamine |
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Term
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Definition
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Term
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Definition
insomnia
dizziness
nausea
abdominal pain
dry mouth |
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Term
| place in therapy for selegiline |
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Definition
1st line in patients with mild disease to slow progression and delay need for levodopa
as adjunctive therapy to decrease "wearing off" |
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Term
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Definition
MAO-B inhibitor
reduces breakdown of DA
?neuroprotection |
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Term
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Definition
dosed at 1 mg QD as monotherapy
start at 0.5 mg QD as add-on; may increase to 1 mg QD |
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Term
| contraindications for rasagaline |
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Definition
meperidine
tramadol
propoxyphene
sympathomimetic amines (pseudofed)
dextromethorphan
MA
O inhibitors
St. John's wort
mirtazepine
cyclobenazaprine
tyramine "cheese" reaction unlikely, but still listed as strong warning in package insert |
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Term
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Definition
headache
dizziness
N/V
orthostatic hypotension
dyskinesias |
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Term
| MOA of tolcapone and entacapone |
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Definition
inhibit COMT, decreasing breakdown of levodopa and increasing availability to brain
results in smoother levodopa plasma levels
only indicated in patients who are taking levodopa/carbidopa; IS NEVER MONOTHERAPY |
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Term
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Definition
100-200 mg TID
may need to decrease levodopa dose |
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Term
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Definition
200 mg with each levodopa/carbidopa dose (max 8/day)
may need to decrease levodopa dose |
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Term
| ADRs of tolcapone and entacapone |
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Definition
orthostatic hypotension, somnolence, dyskinesia
explosive diarrhea, less frequent with entacapone
urine discoloration
liver failure, less frequent with entacapone
must monitor LFTs with tolcapone |
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Term
| place in therapy of COMT inhibitors (tolcapone and entacapone) |
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Definition
2nd line agents used only in combination with levodopa/carbidopa
may decrease "wearing off", on-off times, and motor fluctuations |
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Term
| appropriate use of stalevo (carbidopa/levodopa/entacapone) |
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Definition
patient has:
total daily levodopa dose less than or equal to 600 mg
no dyskinesias
concurrent IR carbidopa/levodopa + entacapone
IR carbidopa/levodopa and end-of-dose "wearing off" |
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Term
| dosing of stalevo (levodopa/carbidopa/entacapone) |
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Definition
1 tablet/dose
frequency similar to previous carbidopa/levodopa
maximum 8 tablets/d |
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Term
| ADRs of stalevo (levodopa/carbidopa/entacapone) |
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Definition
diarrhea
hallucinations
dyskinesias
nausea
may need to reduce carbidopa/levodopa portion |
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Term
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Definition
stimulates dopamine receptors
increases dopamine release
reduces dopamine uptake
mild anticholinergic activity
?neuroprotective effect (NMDA modulation)
overall effect: useful for akinesia, rigidity, and tremor |
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Term
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Definition
100-300 mg/day divided BID
decreased dose in renal impairment |
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Term
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Definition
**dry mouth
**dizziness
confusion
livedo reticularis (red blotchiness on the skin)
insomnia
nightmares
hallucinations
blurred vision
depression |
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Term
| place in therapy for amantidine |
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Definition
? 1st line agent for younger patients or as adjunctive therapy in those with akinesia, rigidity, and tremor
duration of benefit < 1 year
if effects wane, need to D/C and start levodopa
the correct answer IS NOT start amantidine. benefits are short lived |
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Term
| MOA of anticholinergics (trihexyphenidyl, benztropine, diphenhydramine, diperiden, procyclidine) |
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Definition
reduce relative excess Ach in basal ganglia
useful for tremor |
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Term
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Definition
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Term
| dosing of diphenhydramine |
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Definition
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Term
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Definition
cognitive impairment
urinary retention
constipation
drymouth
blurred vision
flushing
poorly tolerated |
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Term
| place in therapy of anticholinergics |
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Definition
? 1st line agent for younger patients with tremor
adjunctive therapy for tremor
in older patients, it is difficult to use anticholinergics b/c of ADRs making them poorly tolerated |
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Term
| why is there a need for neuroprotective therapies for PD? |
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Definition
prevent disease progression
motor complications of current therapies
non-motor symptoms related to disease progression (depression, dementia, psychosis) |
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Term
| effects of coenzyme Q10 in early PD |
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Definition
coenzyme Q10 was safe and well tolerated by PD patients
worsening of PD was slowed significantly by 1200 mg/day |
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Term
| managing adverse effects: hallucinations/psychiatric symptoms |
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Definition
reduce dopaminergic drug dose:
may not be helpful
likely to worsen PD symptoms
2nd Generation Antipsychotics:
quetiapine - 1st line
clozapine - 2nd line |
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Term
| managing adverse effects: orthostatic hypotension |
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Definition
evaluate antihypertensive meds, if present
increase salt and fluid intake
compression stockings
NSAIDs (hold on to more water), fludrocortisone, midodrine (pure alpha agonist = vasocontriction = increased BP) |
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Term
| managing adverse effects: falls |
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Definition
check for orthostatic hypotension
postural instability
motor fluctuations |
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Term
| managing adverse effects: wearing off/motor fluctuations |
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Definition
increase frequency of levodopa/carbidopa
add COMT inhibitor
add rasagaline/selegiline
add dopamine agonist |
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