Parkinson's Disease

Question 1

PD average age of onset

Answer 1

62

Question 2

PD possible causes

Answer 2

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

Question 3

PD patho

Answer 3

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

Question 4

PD Dx

Answer 4

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

Question 5

bradykinesia

Answer 5

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

Question 6

PD motor sx

Answer 6

dec dexterity
dysarithria
freezing of initiating movement
slow turning

bladder and anal sphincter disturbances
constipation
diaphoresis

confusion
dementia
psychosis

Question 7

on vs off

Answer 7

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)

Question 8

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

Answer 8

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

Question 9

anticholinergic options in PD

Answer 9

benztropine
trihexyphenidyl

Question 10

carbidopa/levodopa/entacapone MOA

Answer 10

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

Question 11

levodopa AE

Answer 11

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

Question 12

levodopa DDI

Answer 12

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

Question 13

levodopa dosing starting and max

Answer 13

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

Question 14

carbidopa/levodopa ratio availabilities

Answer 14

1:10 OR 1:4

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

Question 15

Sinemet CR
onset
IR –> CR ?

Answer 15

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

Question 16

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

Answer 16

at least 70-100mg/day

Question 17

Inbrija
use
AE
CI

Answer 17

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

Question 18

COMT-is, MOA, caveat

Answer 18

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

Question 19

entacapone dosing
AE
DDI

Answer 19

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

Question 20

what is Stalero

Answer 20

Carbidopa/levodopa/entacapone
1:4:200 mg

Question 21

why is tolcapone not used anymore

Answer 21

high risk of hepatocellular injury

Question 22

MAOi-s
MOA

Answer 22

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

Question 23

rasagline pearl

Answer 23

ay be disease modifying!!!

Question 24

selegiline pearl

Answer 24

metabolites includes amphetamines which linger for WEEKS

Question 25

selegiline CI
SE
DI (rasagiline too)

Answer 25

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

Question 26

how long is the washout period for MAOIs

Answer 26

2 week washout

Question 27

Safinamida (Xadago)
MOA
use
dose

Answer 27

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)

Question 28

DA ags options and whether they are ergot or non ergot

Answer 28

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

Question 29

pramipexole
dosing
DDI

Answer 29

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

Question 30

ropinorole
dosing
DDI

Answer 30

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

Question 31

bromocriptine
moa
CI
AE
DDI

Answer 31

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

Question 32

cabergoline
FDA approved?
AE

Answer 32

only FDA approved for prolactinemia
AE: heart valve damage

Question 33

apomorphine
use
dose
pearl
AE

Answer 33

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

Question 34

rotigotine
dose
caution
AE

Answer 34

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

Question 35

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

Answer 35

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

Question 36

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

Answer 36

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

Question 37

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

Answer 37

dec dose, use CR Sinemet instead of IR

dec freq., add amantadine, DA ag

Question 38

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

Answer 38

CR at bedtime, DA ag, baclofen, botox

Question 39

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

Answer 39

inc dose, add DA ag, gait modification, PT

Question 40

pt taking Levodopa but having delayed onset
what can be done

Answer 40

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

Question 41

PD depression tx

Answer 41

pramipexole, venlafaxine

Question 42

PD dementia and cognitive impairment tx

Answer 42

rivastigmine

Question 43

PD insomnia tx

Answer 43

eszopiclone, melatonin

Question 44

PD excessive daytime somnolence tx

Answer 44

modafanil

Question 45

orthostatic hypotensoin in PD tx

Answer 45

fludrocortisone
midodrine
droxidopa - best

Question 46

sexual dysfunction in PD tx

Answer 46

sildenafil

Question 47

constipation in PD tx

Answer 47

PEG, probiotics and fiber, lubiprostone

Question 48

urinary frequency in PD tx

Answer 48

solifenacin

Question 49

drooling in PD tx

Answer 49

glycopyrrolate, botox

Question 50

pt admitted for psychosis in dementia
stepwise approach

Answer 50

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)

Question 51

pimvanserin tartrate
MOA, use, AE

Answer 51

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