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adverse effects of carbidopa/levodopa
- motor fluctuations
- "wearing off, freezing"
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carbidopa/levodopa (sinemet) dosing
- IR & CR - 25/100 QD increase to TID
- IR take on MT stomach
- CR take with food
- max 200/2000mg
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dosing of DA agonists for PD if pt has dementia
start at 50% of usual dose
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pramipexole - Mirapex MOA and AE
- specific to D3 receptor
- dose related peripheral edema (compression and elevation)
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pramipexole - Mirapex dosing
- 0.125 mg TID
- increase Q5-7d prn
- max 4.5mg/day
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which DA agonist would you avoid in severe renal damage
pramipexole - mirapex
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ropinirole - requip dosing
- 0.25 mg TID
- increase weekly
- max 24 mg/day
- 30% reduction of levodopa dose
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ropinirole (requip) MOA and a DI
- high affinity for D2 & D3 receptors
- CYP1A2 substrate
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apomorphine (apokyn) MOA and CI's
- postsynaptic D2 receptors agonist - rescue therapy and effective in decreasing "off" episodes
- CI- 5HT antagonists (ondansetron)
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apomorphine (apokyn) dosing
- pretreatment with antiemetic is necessary
- 2-6 mg (SQ) usually TID - 2 mg challenge doses must be given under medical supervision before routine use
- max 20 mg/day
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bromocriptine (parlodel) MOA and DI
- ergot derived agonist; stimulates D2 and blocks D1
- CYP3A4 substrate
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bromocriptine (parlodel) dosing
- 1.25 mg QD BID
- increase to 20-90 mg/day
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amantadine (symmetrel) dosing
100-400 mg/day
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amantadine (symmetrel) AE and DI & CI
- confusion, nightmares
- DI- anticholinergics increase CNS side effects
- CI - severe renal disease
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what are the tx options when distinguishing between age groups
- use DA agonist in younger pts < 65
- older pts initiate levodopa
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what is the drug of choice if symptoms are severely debilitating
levodopa
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selegiline (eldepryl) MOA
- MAO-B inhibition - offers 1 hour of increased action of levodopa
- decreases "wearing off" effect
- up to 50% reduction of levodopa dose
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selegiline (eldepryl) CI and AE
- CI - meperidine = serotonin syndrome
- AE - hallucinations, jitteriness
- metabolized into L-meth & L-amphetamine
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selegiline (eldepryl) dosing
- 5 mg BID or 10 mg QD
- zelapar (ODT) 1.25 mg QD
- max 2.5 mg QD
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rasagiline (azilect) CI
- cyclobenzaprine
- dextromethorphan
- meperidine
- methadone
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rasagiline (azilect) AE and DI
- AE = postural HoTN, dyspepsia
- DI = 1A2 substrate - MANY!
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rasagiline (azilect) MOA
- MAO-B inhibitor
- slight reduction in levodopa
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tolcapone (tasmar) MOA
- COMT inhibitor - peripherally & centrally
- increases levodopa by up to 100%
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tolcapone (tasmar) AE
hepatotoxicity - can be fatal
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tolcapone (tasmar) dosing
- 100-200 mg TID
- not as monotherapy
- if pt sees no benefit after 3 weeks = discontinue
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entacapone (comtan) MOA and DI
- COMT inhibitor peripherally
- iron
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entacapone (comtan) dosing
- 200 mg with each dose of carbi/levo up to 8 times/day
- not as monotherapy
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benztropine (Cogentin) MOA and dose
- anticholinergic, antihistamine
- 0.5-6 mg/day
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trihexyphenidyl (artane) MOA and dosing
- anticholinergic
- 1-15 mg/day
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stage 1 of PD disability
unilateral involvement only, minimal or no functional impairment
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stage 2 of PD disability
bilateral involvement, w/o impairment of balance
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stage 3 of PD disability
evidence of postural imbalance, some restriction in activities, capable of leading independent life
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stage 4 of PD disability
severely disabled, can't walk and stand unassisted, significantly incapacitated
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stage 5 of PD disability
restricted to bed or wheelchair unless aided
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what are the 5 cardinal clinical characteristics of PD. two of more of these
- tremor - pill rolling
- rigidity - stiffness and pain
- bradykinesia - most common feature
- postural instability - less responsive to pharmacotherapy, not diagnostic
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gold standard of diagnosis of PD
neuropathologic exams
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methods to diagnose PD
- cardinal manifestation
- response to dopaminergic therapy
- unilateral onset
- presence of a rest tremor
- persistent asymmetry with the side of onset most affected
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drugs that may produce or exacerbate PD
- antipsychoticsantiepileptics
- antidepressants
- antihypertensives
- amiodarone
- cholinesterase inhibitors
- disulfiram
- phenothiazines
- metoclopramide
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PD and the relation with cigarette smoking and caffeine
inverse relationship
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