Parkinson's Disease Flashcards by Jessica Weaver

PD average age of onset

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PD possible causes

mutations in alpha-synuclein gene
inverse relationship with cig smoking and caffeine consumption
DA deficiency
TWO MAIN CAUSES: loss of dopaminergic cells in substantia nigra and basal ganglia; formation of lewy bodies in remaining SN neurons and other parts of the brain

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PD patho

inc DA breakdown via MAO-B –> inc hydrogen peroxide + iron ions in substantia nigra –> inc free radicals

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PD Dx

bradykinesia (slowness and difficulty initiating voluntary movement) and at least 1 of the following
1. limb muscle rigidity
2. resting tremor
3. postural instability

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bradykinesia

slowness and difficulty with motor acts
mycografia
cardinal sx
freezing can occur

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PD motor sx

dec dexterity
dysarithria
freezing of initiating movement
slow turning

bladder and anal sphincter disturbances
constipation
diaphoresis

confusion
dementia
psychosis

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on vs off

on = good movement (sx of tremor, rigidity, slowness are well controlled by medication)
off = poor movement (return of tremor, rigidity or slowness or complete immobility)

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DA normally _________ ACh in the striatum
why is this an issue in PD?

inhibits
in PD there is decreased DA so there is less inhibition of ACh –> leads to increased cholinergic activity

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anticholinergic options in PD

benztropine
trihexyphenidyl

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carbidopa/levodopa/entacapone MOA

levodopa is DA metabolite
carbidopa inhibits peripheral metab by dopa decarboxylase
entacapone is a COMT-i

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levodopa AE

dyskinesia
on-off, dec effectiveness w time
psychiatric disturbances, vivid dreams
nausea
orthostatic hypotension
saliva, sweat, urine discoloration
NMS w abrupt D/C

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levodopa DDI

DA-antagonists (metoclopramide, APs)
non-selective MAOis
high protein intake (pyridoxine)
iron salts

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levodopa dosing starting and max

200-300mg/d in divided doses to start
titrate up by no more than 100mg/week
MDD: 800-1000mg/d

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carbidopa/levodopa ratio availabilities

1:10 OR 1:4

10mg/100mg
25mg/100mg
25mg/250mg

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Sinemet CR
onset
IR –> CR ?

peak at 2 hours, can supplement with IR in am until onset
can also take at bedtime

IR –> dec freq 50% –> CR

ex) if taking IR QID change to CR BID

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what dose does carbidopa need to be at when used in combination with levodopa

at least 70-100mg/day

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Inbrija
use
AE
CI

levodopa powder inhaler for intermittent tx of episodes
not to replace Sinemet
AE: cough (60%)
CI: MAOi non-sel, asthma, COPD etc.

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COMT-is, MOA, caveat

entacapone, tolcapone
inhibit L-dopa breakdown which increases its AUC by 35% and inc “on: by 1-2 hours

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entacapone dosing
AE
DDI

200mg w each dose of Sinemet p to 8x a day
AE: brown/orange urine
DDI: drugs metab by COMT, MAOi (ns)

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what is Stalero

Carbidopa/levodopa/entacapone
1:4:200 mg

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why is tolcapone not used anymore

high risk of hepatocellular injury

MAOi-s
MOA

selegiline, rasagiline
inhibit MAO-B to dec DA breakdown, sx control, dec free radical production

rasagline pearl

ay be disease modifying!!!

selegiline pearl

metabolites includes amphetamines which linger for WEEKS

selegiline CI SE DI (rasagiline too)

CI (no absolute): dementia, severe psychosis, concominant use of meperidine, tramadol, methadone, propoxyphene SE: GI, CNS, HTN crisis, serotonin syndrome, INSOMNIA, JITTERINESS, HA, irritation of buccal mucosa DI: MAOIs (ns), TCAs, SSRIs, DXM, tyramine foods, sympathomimetics

how long is the washout period for MAOIs

2 week washout

Safinamida (Xadago) MOA use dose

selective MAOB-i; Na and K channel blocker, dec glutamate release use in the wearing off sx 50 and 100mg tabs available (hepatic impairment do not exceed 50mg)

DA ags options and whether they are ergot or non ergot

pramipexole, ropinorole, rotigotine (Neupro) - non ergot bromocriptine, cabergoline, pergoline - ergot

pramipexole dosing DDI

renal dosing for <60mL/min *start low, go slow* IR: 1.25mg TID --> MDD 1.5mgTID ER: 0.375mg qd --> 4.5mg qd DDI: cimetidine

ropinorole dosing DDI

0.25mg TID --> 24mg/d 2mg qd --> 24mg/d DDI: R is substrate of 1A2 --| 1A2: cipro, clarithro, erythro, cimetidine, diltiazem, fluvoxamine, norflox, omeprazole, ritonavir

bromocriptine moa CI AE DDI

MOA: antag at D1, ag at D2, suppresses prolactin secretion CI: breastfeeding, eclampsia, ergot hypersensitivity, uncontrolled HTN AE: CNS, GI, pulmonary fibrosis DDI: BP meds, erythro

cabergoline FDA approved? AE

only FDA approved for prolactinemia AE: heart valve damage

apomorphine use dose pearl AE

used in advanced PD for off periods 2mg SQ under medical supervision (can increase by 1mg every few days, rotate sites) AE: NV, dizziness, angina, somnolence, dyskinesia, falls, yawning, rhinorrhea pearl: PRE-tx w antiemetic 3 days before ; trimethobenzamide

rotigotine dose caution AE

2mg/24h, inc qwk 2mg/d up to 6mg caution: heat, MRI AE: site reaction, CNS, GI, peripheral edema

pt experiencing off or on-off response with medication what can be done

increase frequency before increasing dose change to CR adjunctive DA ag/MAOi/COMT/amantadine

pt is experiencing off, no on (always in the bottom of graph) what can be done

delayed stomach emptying/dec absorb- inc dose/freq/water, use ODT, APO SQ, EMPTY STOMACH

peak-effect (peak on) dyskinesia what can be done to help

dec dose, use CR Sinemet instead of IR dec freq., add amantadine, DA ag

pt experiencing dystonia (painful cramping), what can be done

CR at bedtime, DA ag, baclofen, botox

pt experiencing freezing while on PD med, what can be done

inc dose, add DA ag, gait modification, PT

pt taking Levodopa but having delayed onset what can be done

empty stomach, water, avoid protein if CR, add IR or switch to IR

PD depression tx

pramipexole, venlafaxine

PD dementia and cognitive impairment tx

rivastigmine

PD insomnia tx

eszopiclone, melatonin

PD excessive daytime somnolence tx

modafanil

orthostatic hypotensoin in PD tx

fludrocortisone midodrine droxidopa - best

sexual dysfunction in PD tx

sildenafil

constipation in PD tx

PEG, probiotics and fiber, lubiprostone

urinary frequency in PD tx

solifenacin

drooling in PD tx

glycopyrrolate, botox

pt admitted for psychosis in dementia stepwise approach

1. eval hypoxemia, infection, electrolyte disturbances 2. simplify regimen (anticholinergics dc and switch, taper d/c amantadine, selegiline, taper d/c da ags, consider dec ldopa, dc COMT) 3. consider atypical APs: quetiapine, clozapine-monitor, pimvanserin tartrate)

pimvanserin tartrate MOA, use, AE

5HT2A/2C inverse agonist for hallucinations and delusions in PD BBW: inc death in elderly w dementia treated w APs AE: QT p, peripheral edema, nausea, confusion