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701 > Exam 2: Parkinson's > Flashcards

Exam 2: Parkinson's Flashcards

1
Q

Parkisonism vs. Parkinson’s

A

Parkinsonism: disorder presenting with classic s/s, usually secondary to some other factor

Parkinson’s disease: no known secondary cause

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2
Q

Istradefylline (Nourianz) AE

A

dyskinesia
insomnia
hallucinationss
dizziness

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3
Q

Istradefylline (Nourianz) DDI

A
  • strong cyp3A4 inhibitors → take 20mg
  • avoid if using strong CYP3A4 inducers
  • also CYP1a1
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4
Q

Istradefylline (Nourianz) MOA

A

adenosine A2A recceptor antag

use in combo with carb/levo for off episodes

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5
Q

Istradefylline (Nourianz) dosing

A

20mg QAM to MDD of 40

  • higher dose needed if pt smokes 20+ cigarettes a day
  • 20mg QD if Child-Pugh Class B
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6
Q

Amantadine AE

A

orthostatic hypotension, dizziness, falls

hallucinations

sedation

anticholinergic AE

Livedo reticularis - mottling of skin with LE edema

NMS with abrupt d/c

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7
Q

Amantadine DDI

A
  • LIVE flu vaccine (less effective)
  • quinine/quinidine
  • HCTZ/triamterene
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8
Q

Amantadine agents and dosing

A

Symmetrel IR
- 300mg/day in divided doses

Gocovri ER
- start 137 mg, increase to 274mg after 1W

Osmolex ER
- start 129mg, increase to 322 after 1W

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9
Q

Apomorphine (Apokyn) AE

A
  • N/V
  • dizziness, sommnolence, yawning
  • chest pain, pressure
  • dyskinesia
  • falls
  • rhinorrhea
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10
Q

Rotigotine (Neupro) AE

A
  • CNS
  • GI
  • peripheral edema
  • application site
  • Sodium metabisulfite allergy
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11
Q

Apomorphine (Apokyn) DDI

A
  • 5HT3 antags increase hypotensive effects CI
  • QTc prolonging agents may have additive effects
  • Dopamine antags may decrease effectivenes
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12
Q

Pramipexole DDI

A

inhibitors of renal tubular secretion (cimetidine)

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13
Q

Ropinirole DDI

A

Ropinirole is a CYP1A2 substrate

  • Inhibitors of CYP1A2
    • cimetidine
    • cipro
    • macrolide abx
    • omeprazole
  • Inducers of CYP1A2
    • CBZ
    • phenobarbital
    • phenytoin
    • rifampin
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14
Q

Rotigotine (Neupro) DDI

A

dopamine antags
- APS
- metoclopramide

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15
Q

Ropinirole CI

A
  • abrupt d/c
  • hepatic disease
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16
Q

Apomorphine (Apokyn) dosing and admin

A
  • 2mg SC under medical supervision
  • Monitor bp pre-dose, and Q20min for an hour post dose
  • Can increase by 1mg every few days to max of 6mg
    • do NOT exceed TID dosing
  • rotate injection sites
  • can pre-treat with antiemetic (Tigan- trimethobenzamide hydrochloride)
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17
Q

Pramipexole dosing

A
  • IR: 0.125 mg TID; MDD of 1.5 mg TID
  • ER: 0.375 mg QD; MDD of 4.5 mg QD
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18
Q

Ropinirole dosing

A
  • IR: 0.25 mg TID; MDD of 24 mg
  • XL: 2 mg QD; MDD of 24 mg
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19
Q

Rotigotine (Neupro) dosing

A

patch - start 2mg/24 hours, increase QW by 2 mg up to 6 mg

4 mg = minimum effective dose.

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20
Q

Selegiline AE

A
  • CNS
  • GI
  • HTN crisis
  • Serotonin syndrome
  • insomnia, jitteriness
  • HA
  • Irritation of buccal mucosa (zelapar)
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21
Q

Rasagiline (Azilect) AE

A

Monotherapy
- HA
- Arthralgia
- GI upset
- Falls

WIth levodopa
- dyskinesia
- weight loss
- orthostasis

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22
Q

Safinamide (Xadago) AE

A

dopaminergic
- Dyskinesia
- hallucinations/psychosis
- Impulse control
- Daytime somnolence
- NMS with abrupt withdrawal
- retinal pathology

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23
Q

Selegiline DDI

A
  • non-selective MAOI
  • TCAs, SSRI, SNRI, DXM - serotonin syndrome
  • tyramine containing foods at doses >10mg
  • sympathomimetics
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24
Q

Rasagiline (Azilect) DDI

A
  • non-selective MAOI, needs a 2 week washout
  • metabolized CYP1A2 (cipro)
  • TCAs, fluoxetine, needs a 5 week washout
  • sympathomimetics
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25
Q

Safinamide (Xadago) DDI

A
  • serotonergic drugs: opioids, SSRI, SNRI, TCA, cyclobenzaprine, methylphenidate, amphetamines, St. John’s wort
  • DXM (bizzare behavior)
  • BCRP substrates
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26
Q

Selegline CI

A

not absolute contraindications

  • dementia, severe psychosis
  • meperidine, tramadol, methadone, propoxyphene
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27
Q

Rasagiline (Azilect) CI

A

meperidine, tramadol, methadone, propoxyphene, mirtazapine, cyclobenzaprine, DXM, St. John wort

vasoconstrictors (d/t potential for HTN crisis)

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28
Q

Safinamide (Xadago) CI

A

Child-Pugh class C

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29
Q

Selegeline MOA

A
  • Non-competitive, selective antag of MAO-B → decrases breakdown of DA
  • Decerase free radical production
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30
Q

Rasagiline (Azilect) MOA

A
  • Non-competitive, selective antag of MAO-B → decrases breakdown of DA
  • Decerase free radical production
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31
Q

Safinamide (Xadago) MOA

A

Na and K blocker → decrease glutamate release

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32
Q

Selegiline dosing

A
  • 5mg QD or BID
  • Zelepar - ODT 1.25mg (2.5mg after 2 weeks)
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33
Q

Rasagiline (Azilect) dosing

A
  • 0.5 mg with levodopa
  • 1.0 mg monotherapy
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34
Q

Safinamide (Xadago) dosing

A
  • start 50mg QD, increase to 100mg Q2W
  • If some hepatic impairment, MDD 50mg
35
Q

Tolcapone dosing

A

100mg TID

36
Q

Tolcapone AE

A

hepatocellular injury (incrase in LFTs, monitor)

CI in pts with exiting hepatocellular disease

37
Q

Opicapoine (Ongentys) AE

A

similar to levodopa and other COMT inhibitors

38
Q

Entacapone AE

A

similar to levodopa + urine discoloration (brown/orange)

39
Q

COMT inhibitor (class) DDI

A

Drugs metabolized by COMT

non-selective MAOIs

40
Q

Opicapone (Ongentys) CI

A

catecholamine secreting neoplasm

non-selective MAOIs

41
Q

COMT inhibitor (class) MOA

A

Reversible, selective inhibitor of COMT, prevent breakdown of L-dopa and extend L-dopa’s effects

NO EFFECT IN ABSENCE OF L-DOPA

42
Q

Levodopa AE

A

dyskinesia (choreiform and dystonic reacion)

on-off phenomenon; decrased effectiveness over time

psychatric disturbances/vivid dreams

GI effects

orthostatic hypotension

saliva, sweat, or urine discolration

neuroleptic malignant syndrome w abrupt d/c

43
Q

Levodopa DDI

A
  • DA antags (metoclopramide, antipsychotics)
  • non-selective MAOIs → toxic effects
  • pyridoxine (if dose >200mg) redcues efficacy of levo → moitor
  • high protein intake → separate admin by 2hrs
  • iron salts → separate admin by 2hrs
44
Q

Levodopa CI

A
  • brastfeeding
  • closed angle glaucoma
  • preggers (d/t carbidopa)
  • non-selective MAOI (within 2 weeks of Inbrija only)
45
Q

Levodopa PKPD

A

Large amino acid transporter in GI and BBB

95% metabolized by LAAD into DA

<1% reaches CNS without a decarboxylase inhibitor (carbidopa - inhibits peripheral L-dopa metabolism)

Renally eliminated

46
Q

Levodopa PO dosing

A

Carb
- carbidopa dose usually 70-100mg/day

Levo
- start 200-300mg/day in divided doses
- increase by no more than 100 mg/week
- avoid >1000mg/day d/t AE

47
Q

Levodopa MOA

A

Precursor to DA

Crosses BBB when DA does not

48
Q

Available agents containing levodopa

A

PO IR

PO ER

Carb/Levo/Entacapone (Comtan)

intestenal gel (Duopa)

powder inhalation I(nbrija)

49
Q

Levodopa IR vs ER

A

IR: 30 min onset, ER is 2 hrs

if switching from IR to ER half the dosing frequency

ER has a lower F

ER decrease the off time

50
Q

Duopa

A

intestinal gel levodopa

infused by wearable pump through PEG-J to bypass GI absorption → more consistent L-dopa levels

must be switched from IR tabs

MDD 2000mg

risk of bleeding and infection

51
Q

Inbrija

A

powder inhalation levodopa

does NOT replace PO meds

inhale 2mg PRN for off symptoms

respiratory AE (don’t use in pts with lung diseases)

52
Q

Anticholinergic AE

A

blind as a bat (mydraisis)

dry as a bone (dry mouth, constipation)

hot as a hare (fever)

mad as a hatter (depressioin, agitation)

red as a beat (flushed)

53
Q

Parkinson’s anticholinergic agents and dosing

A

Benztropine
- start 0.5-1 mg/day; MDD 6mg/day

Trihexyphenidyl
- start 1-2mg/day; MDD 15mg/day

54
Q

Which Parkinson’s med MAY slow down progression of the disease and not just provide symptom treatment?

A

Rasagiline

55
Q

Parkinson’s primary s/s

A
  • Bradykinesia
  • Postural instability
  • Resting tremor
  • Rigidity
56
Q

Parkinson’s motor s/s

A
  • Decreased dexterit
  • Dysarthria
  • Freezing at initiation of movement
  • Slow turning
57
Q

Parkinson’s autonomic s/s

A
  • Bladder and anal sphincter disturbances
  • Constipation
  • Diaphoresis
58
Q

Parkinson’s mental status changes

A
  • Confusion
  • Dementia
  • Psychosis
59
Q

Parkinson’s dx

A

bradykinesia + one of the following

  • Limb muscle rigidity
  • Resting tremor
  • Postural instability
60
Q

bradykinesia

A

slowness and difficulty iniating voluntary movement

Initially distal muscles, eventually all

facial masking - lack of facial expression

motor acts become difficult, especially with repetitive motions

“freezing”

61
Q

Things that could cause parkinsonism (not parkinson’s disease)

A
  • First gen antipsychotics
  • Prochlorperazine and metoclopramide
  • Neurogenerative conditions
  • Strokes
  • Toxins
62
Q

Parkinson’s patho

A

state of DA deficiency

functional imbalance between DA and ACh

loss of dopaminergic cells in substantia nigra

formation of lewy bodies in remaining SNc neurons

potentially: overactivation of adenosine A2A receptor can cause inhibition of motor function

63
Q

Stages of levodopa on/off and management

A

On/Off : d/t DA neurons dying off → lose ability to store DA → response time gets shorter and shorter

- Stage I: not aware of variation in effect
- Stage II: midafternoon loss of benefit, needs second dose
- Stage III: sleep benefit is lost, early morning akinesia appears
- Stage IV: regular “wearing off” Q4H, then response gradually shortens
- Stage V: “wearing off” from each dose and abrupt “off periods”
    - May require dosing Q2H
64
Q

Parkinson’s motor complications

A

On-off response
off, no on
delayed onset
peak-effect dyskinesia
dystonia (muscle cramps)
freezing

65
Q

Parkinson’s non-motor complications

A

depression
dementia and cognitive impairment
insomnia
excessive daytime somnolence
orthostatic hypotension
sexual dysfunction
constipation
urinary frequency
drooling
psycosis

66
Q

Managing on-off response options

A

switch to CR (decresed frequency)

add DA agonist, MAOI-B, COMT or amantadine

67
Q

Managing off, no on response options

A

increase dose frequency and water intake

use ODT formuations

in advanced disease, APO SQ

68
Q

managing delayed onset options (Parkinson’s)

A

take on empty stomach, with water, avoid protein

if on CR, add or switch to IR

69
Q

managing peak-effect dyskinesia options

A

decrease dose, increase frequency

add amantadine

use CR or a DA agonist

70
Q

managing dystonia options

A

take IR in early morning, use CR at nigh

consider switch to DA agonist, or adding baclofen, or botox

71
Q

managing freezing options (Parkinson’s)

A

increase dose

add DA agonist

try non-pharm

72
Q

managing depression (Parkinson’s)

A

pramipexole
SSRI
venlafaxine
TCAs

73
Q

managing dementia and cognitive impairment

A

Ach inhibitors (rivastigie donepezil, galantamine)

74
Q

Managing insomnia

A

eszopiclone
melatonin

75
Q

managing excessive daytime somnolence

A

modafanil

76
Q

managing orthostatic hypotension

A

fludrocortisone
midodrine
droxidopa (short term)

77
Q

managing sexual dysfunction

A

sildenafil

78
Q

managing constipation

A

PEG
probiotics
fiber
lubiprostone

79
Q

managing urinary frequency

A

solifenacin

80
Q

managing drooling

A

glycopyrrolate
botox

81
Q

managing psychosis in Parkinson’s

A
  1. Evaluate hypoxemia, infection, electrolyte distrubnace, esp if abrupt chnge in mental status
  2. Simply regimen: d/c meds withh highest risk:benefit ratio
    • Anticholinergics
    • Taper and d/c amantadine (abrupt withdrawal can cause delirium)
    • Selegiline
    • Taper and d/c DA agonists
    • consdier decreaseing L-Dopa and d/c’ing COMT
  3. Consider atypical antipsychotic drugs
    • Seroquel: 23.5-50mg QHS, increase QW
    • Clozapine: 12.5-50mg QHS, increase QW (monitor neutrophils)
    • Pimavanserin tartrate (Nuplazid) 17mg G2T QD
82
Q

Pimvavanserin tartrate (Nuplazid) MOA

A

5HT2A/2C inverse agonist (no action at DA recceptor)

83
Q

Pimvavanserin tartrate (Nuplazid) BBW

A

increased death in elderly pts with dementia

84
Q

Pimvavanserin tartrate (Nuplazid) AE

A

QTc prolongation, peripheral edema, nausea, confusion

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