Lecture 11 - Parkinson Disease Flashcards by Patryk Lasiuk

Parkinsons Diagnosis

typical age 55-65

men> women

inc as get older

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Parkinson’s Etiology

Degeneration of DA neurons, appearance of Lewy bodies, mostly in substania nigra
causes:
Toxicity/oxidative stress/apoptosis
Genetics
Pesticides, smoking,caffeine,heavy metals

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T.R.A.P

Tremor
Rigidity
Akinesia = slowness of movement, freezing
Postural Instability = inc fall risk

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which class is most effective in pts experiencing only (early) tremor symptoms?

Anticholinergic agents

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Anticholinergic Agents

Trihexyphenidyl (Artane)
Benztropine (Cogentin)

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Anticholinergic side effects

drowsiness, confusion
dry eyes, mouth, blurred vision
constipation

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Amantadine info

MOA unclear

Modest efficacy in control of early PD symptoms
Shown to improve dyskinesias

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Amantadine side effects

generally mild, dose related

CNS
Nausea, dry mouth n skin
Rare, Lived Reticularis but reversible

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Carbidopa/Levodopa info

most effective drug to treat PD

improvements in bradykinesia,rigidity
less effective against speech/gait disturbances

timing of treatment is patient specific

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Carbidopa/Levodopa Side effects

GI, nausea, vomiting, anorexia = most common when starting
motor fluctuations later on

Ortho HTN + neuropsychiatric

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Carbidopa/Levodopa DI

Compazine = prochlorperazine
Reglan = metoclopramide
Droperidol

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Motor complications/fluctuations are….

different from motor symptoms
observed in 20-75% of pts after 3-5yrs with Levodopa

due to prolonged therapy with DA over time

drug wears off, get on/off symptoms
Can get Dyskinesias in face/limbs/posture

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how to manage motor complications of Carb/Levodopa

reduce amount of med
can add another agent

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COMT inhibitor uses….

always used as adjunct therapy for carbidopa/levodopa motor fluctuations

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COMT inhibitors….

Tolcapone = Tasmar
Entacapone = Comtn
Opicapone (ongentys)
Stalevo (Levo/Carb/Entacapone)

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COMT inhibitor info

longer clinical levodopa response
not indicated as monotherapy

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Entacapone info

less side effects, dont have to monitor liver
but give 8 times per day

Opicacope info

significant reduction in OFF time and dyskinesias

some SE = Dyskinesia (20%) constipation, nausea, dry mouth

MAO-B inhibitors

Irreversible substrate of MAO-B

Selegiline = effective monotherapy but not FDA approved….indicated as adjunct

not neuroprotective

Selegiline info n SE

can cause serotonin syndrome with SSRIs, TCA, etc so not used much
metabolized to amphetamine derivative

ODT = nice if pt cant swallow, lower dose

Rasagiline (Azilect) info

irreversible MAO-B inhibitor

can be used as monotherapy or adjunct

significant improvements in time off

SE: dopaminergic, hallucinations but well tolerated
DI = CYP1A2, Cipro

0.5-1mg QD

Rasagiline Contraindicated items

Bupropion
Dextromethorphan
Fentanyl
Mirtazapine
Pseudoephedrine
Tramadol

Safinamide (Xadago)

adjunct but not mono therapy
SE: dyskinesias, AST/ALT elevations,HTN
caution: SSRI, tyramine foods, monitor BP

50-100mg QD

Common CI agents for Safinamide

Opioids
SNRIs
TCAs
Cyclobenzaprine
methylphenidate
St.John Wart

Dopamine Agonist

Pramipexole Ropinirole

Pramipexole dosing info

3-4.5mg day in 3 doses 0.125mg TID, inc every 5-7 days to target dose renal elim, dose adjust

Ropinirole dosing info

5-9mg day in 3 doses 0.25mg TID to start, titrate weekly hepatic formulations also used RLS

Side effect for dopamine agonist

dopaminergic: n/v/orthostatic HTN CNS: "sleep attacks", dizziness, confusion, psychosis Impulse control disorders (ICDs) tend to be younger and underlying history Dopaminergic dysregulation syndrome (DDS) rare

Rotigotine

transdermal Dopamine agonist used as adjunct therapy in advanced disease d/c off times contains metabisulfite** avoid sulfa allergy

Apomorphine (Apokyn)

SubC formulation

Inbrija

inhaled levodopa

Nourianz (istradefylline)

used as adjunct for "off" episodes primarily used as adjunct DI: CYP3A4

Pt diagnosis of Parkinsons disease, no significant impairment treatment?

Consider rasagiline

Pt diagnosis of Parkinsons disease, has symptoms of impairment such as tremor txxm

> 65 yrs = carbidopa/levodopa < 65 yrs = consider anticholinergic, carbidopa/levodopa if needed

Pt diagnosis of Parkinsons disease, has symptoms of impairment such as bradykiniesia/rigidity txm

> 65yrs old = carbidopa/levodopa < 65 yrs old = Dopamine against, carbidopa/levodopa if needed

Pt diagnosis of Parkinsons disease, has symptoms of impairment such as postural instability/gait impairment txm

> 65yrs old = carbidopa/levodopa + PT < 65 yrs old = dopamine agonist + PT

When is Surgery (Deep brains Stim) used for Parkinson

when running out of options

Early disease, younger, minimal symptoms n no cognitive or functional impairment txm

MAO-B (not safinamide as mono), DA agonist, amantadine, anticholinergic

Early Disease, older with cognitive/functional impairment txm

Carbidopa/levodopa

what to do if medication seems to be wearing off?

try to inc frequency, so take smaller dose more frequently try to find sweet spot