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Therapeutics > Parkinson's Disease > Flashcards

Parkinson's Disease Flashcards

1
Q

Is Parkinson’s more common in males or females?

A

males

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2
Q

What are the primary patho features of Parkinson’s?

A

loss of dopaminergic cells in substantial nigra & basal ganglia

formation of Lewy bodies

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3
Q

What are the non-pharm options for Parkinson’s?

A

surgery

physical therapy & exercise

nutrition (fluids & fiber to prevent constipation)

occupational therapy & fall prevention

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4
Q

What 4 mechanisms are used to treat Parkinson’s?

A
  1. decrease cholinergic activity
  2. increase endogenous dopamine
  3. activate dopamine receptors w/ synthetic agonists
  4. block adenosine A2A receptor
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5
Q

Which anticholinergics are used in Parkinson’s

A
  1. benzotropine (Cogentin)
  2. trihexyphenidyl (Artane)
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6
Q

What is the issue with using levodopa alone?

A

very little can cross BBB without a decarboxylase inhibitor

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7
Q

What is the purpose of carbidopa in Parkinson’s

A

decarboxylase inhibitor, combo w/ levodopa -> to get levodopa to the CNS and decreases peripheral ADR

USELESS AS MONOTHERAPY

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8
Q

What are the CI of levodopa?

A

breastfeeding

closed angle glaucoma

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9
Q

What are the CI of carbidopa?

A

pregnancy

lactation

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10
Q

What is the minimum carbidopa dose needed to decrease GI ADR from levodopa?

A

70-100 mg/day

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11
Q

What are the carb/levo brands/formulations?

A
  1. Sinemet IR & CR, PO
  2. Duopa, intestinal gel via wearable pump w/ J-tube
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12
Q

What is Inbrija?

A

levodopa powdered inhalation

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13
Q

What is the indication for Duopa?

A

advanced PD

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14
Q

If a patient is on oral carb/levo before switching to Duopa what is required of the oral regimen?

A

must be put on IR to switch to the pump

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15
Q

How should you adjust the dose when switching from IR to CR carb/levo?

A

decrease the frequency by 50% and consider a dose increase by 25%/day

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16
Q

What are the benefits of using CR carb/levo over IR?

A

decreased time “off”

dec dosing frequency

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17
Q

What are the typical carb/levo ratios?

A

1:4 (IR also has 1:10)

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18
Q

What is the indication for Inbrija?

A

supportive PRN therapy for intermittent “off” periods

NOT a replacement for PO carb/levo

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19
Q

What is a CI for Inbrija?

A

use of a MAOI in last 2 weeks

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20
Q

What Parkinson’s agent can cause black saliva/nasal secretions?

A

Inbrija (levodopa powder inhalation)

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21
Q

What COMT inhibitors are used in Parkinson’s?

A
  1. entacapone (Comtan)
  2. tolcapone (Tasmar)
  3. opicapone (Ongentys)
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22
Q

Which COMT inhibitor has the shortest half life?

A

entacapone (Comtan)

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23
Q

What is the indication for COMT inhibitors in PD?

A

adjunct therapy to extend effect of levodopa (prevents breakdown)

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24
Q

How is entacapone dosed?

A

200mg with EACH DOSE of carb/levo

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25
Q

What is Stalevo?

A

carb/levo, entacapone
1:4, 200 mg

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26
Q

What type of meal decreases levodopa absorption?

A

high protein

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27
Q

How is tolcapone (Tasmar) dosed?

A

100 mg TID

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28
Q

How is opicapone dosed?

A

50 mg QHS (no food 1 hour before/after)

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29
Q

What Parkinson’s agent has an ADR of brown/orange urine?

A

entacapone (Comtan)

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30
Q

Which COMT inhibitor has a risk of induced hepatocellular injury?

A

tolcapone (Tasmar)

31
Q

What COMT inhibitor is contraindicated in hepatic disease?

A

tolcapone (Tasmar)

32
Q

What are the CI for opicapone (Ongentys)

A

MAOI use

catecholamine secreting neoplasms (pheochromocytoma, paraganglioma)

33
Q

What type of MAOI inhibitors can be used for Parkinson’s?

A

MAOI B* inhibitors

34
Q

What MAOI B inhibitors are used in Parkinson’s?

A
  1. selegiline (Eldepryl, Zelapar)
  2. rasagiline (Azilect)
  3. safinamide (Xadago)
35
Q

Which Parkinson’s agent is potentially disease modifying?

A

rasagiline (Azilect)

36
Q

What makes safinamide (Xadago) stand out among PD MAO-B inhibitors?

A

is also a Na & K channel blocker

37
Q

What Parkinson’s agents can be used as mono therapy in healthy patients and potentially delay need for levodopa?

A

selegiline (Eldepryl, Zelapar) & rasagiline (Azilect)

38
Q

What is the purpose of MAO B inhibitors as adjunct to levodopa?

A

decrease the dose of levodopa needed

39
Q

What are common ADR of selegiline (Eldepryl, Zelapar)?

What causes these ADR?

A

insomnia, jitteriness, hypertensive crisis

selegiline has 3 active amphetamine metabolites

40
Q

What is the indication for MAO-B inhibitor safinamide (Xadago)?

A

adjunct therapy to levodopa for wearing “off” symptoms

41
Q

What MAO-B inhibitor is contraindicated in Child-Pugh Class C?

A

safinamide (Xadago)

42
Q

What is the use of amantadine (Symmetrel IR, Gocovri ER) in Parkinson’s?

A

adjunct for patients on high doses of levodopa to REDUCE L-DOPA INDUCED DYSKINESIA

43
Q

What is a unique ADR of amantadine?

A

livedo reticularis
- idiosyncratic skin mottling & lower extremity edema

44
Q

What is a common ADR of amantadine?

A

anticholinergic effects

45
Q

What is the place is therapy for dopamine agonists in Parkinson’s?

A

mono therapy in young, healthy patients

adjunct w/ levodopa for pt with diminished response to levodopa

46
Q

ADR of dopamine agonists compared to levodopa

dec risk of ________

inc risk of ________

A

dec risk of motor ADR

inc risk of non-motor ADR (psych symptoms, N/V, sedation, hypotension)

47
Q

What dopamine agonists used for Parkinson’s?

A
  1. pramipexole (Mirapex)
  2. ropinirole (Requip)
  3. rotigotine (Neupro)
  4. apomorphine (Apokyn)
48
Q

Which dopamine agonist for Parkinson’s is metabolized by CYP1A2?

A

ropinirole (Requip)

49
Q

Which dopamine agonist for Parkinson’s is a transdermal patch?

A

rotigotine (Neupro)

50
Q

What is the minimum effective dose for Parkinson’s of a rotigotine (Neupro) patch?

51
Q

Which dopamine agonist for Parkinson’s is given subQ?

A

apomorphine (Apokyn)

52
Q

What is the indication for apomorphine (Apokyn)?

A

advanced PD as a PRN adjunct for unpredictable “off” episodes

53
Q

What is needed to start using apomorphine (Apokyn) PRN?

A

test dose with blood pressure monitoring

54
Q

What agent is given alongside apomorphine (Apokyn) to manage an ADR?

What are some pearls of the addition of said agent?

A

antiemetic
- no 5HT3 antagonists -> contraindicated!
- typically use antihistamine (trimethobenzamide - Tigan)

55
Q

What is the adenosine A2A receptor antagonist used for Parkinson’s?

A

istradefylline (Nourianz)

56
Q

What is the indication for istradefylline (Nourianz)?

A

combo therapy w/ carb/levo in patients w/ “off” episodes (decreases “off” time)

57
Q

When are dose adjustments needed for istradefylline (Nourianz)? (3 scenarios & the adjustment)

A

smokers (20 cigs/day) -> need max dose (40mg QAM)

moderate hepatic impairment (Class B) -> stay on starting dose (20mg QAM)

concomitant strong CYP3A4 inhib -> MAX dose of 20 mg QAM

58
Q

PD Treatment Complications:

What adjustments can be made to help with wearing off or on-off response?

A

increase levodopa frequency or switch to CR

ADD adjunct dopamine agonist, MAO-B inhib, COMT inhib, amantadine, istradefylline (Nourianz)

59
Q

PD Treatment Complications:

What adjustments can be made to help with off, NO on?

A

increase levodopa dose, frequency, water

switch to ODT

if advanced PD -> subQ apomorphine or Duopa

60
Q

PD Treatment Complications:

What adjustments can be made to help with delayed onset?

A

take on empty stomach, water & avoid protein

if on CR -> switch to IR or ADD IR

61
Q

PD Treatment Complications:

What adjustments can be made to help with peak effect dyskinesia?

A

decrease levodopa dose/increase frequency

ADD amantadine

switch to CR or dopamine agonist

62
Q

PD Treatment Complications:

What adjustments can be made to help with dystonia?

A

use CR levodopa QHS to help w/ AM symptoms

ADD dopamine agonist, baclofen, botox

63
Q

PD Treatment Complications:

What adjustments can be made to help with freezing?

A

increase levodopa dose

ADD dopamine agonist

gait modification & physical therapy

64
Q

PD Treatment Complications:

What agents can be used to treat depression?

A

pramipexole

venlafaxine

TCAs (notriptyline, desipramine)

SSRIs

65
Q

PD Treatment Complications:

What agents can be used to treat dementia/cognitive impairment?

A

AChE inhibitors:
rivastigamine

donepezil

galantamine

66
Q

PD Treatment Complications:

What agents can be used to treat insomnia?

A

eszopiclone

melatonin

67
Q

PD Treatment Complications:

What agents can be used to treat daytime somnolence?

68
Q

PD Treatment Complications:

What agents can be used to treat orthostatic hypotension?

A

droxidopa (SHORT TERM ONLY)

fludrocortisone

midodrine

69
Q

PD Treatment Complications:

What agents can be used to treat sexual dysfunction?

A

sildenafil

70
Q

PD Treatment Complications:

What agents can be used to treat constipation?

A

probiotics & fiber

PEG

lubiprostone

71
Q

PD Treatment Complications:

What agents can be used to treat drooling?

A

botox

glycopyrrolate

72
Q

Steps to address psychosis in PD:

A
  1. rule out other causes -> hypoxemia, infection, electrolyte disturbances
  2. simplify regimen (D/C higher risk agents first)
  3. consider atypical antipsychotic
73
Q

In what order should a Parkinson’s regimen be simplified when a pt has psychosis? (list out drugs from 1st to last removed)

A
  1. anticholinergics
  2. taper & D/C amantadine
  3. selegiline
  4. taper & D/C dopamine agonists
  5. consider decreasing levodopa & D/C COMT inhib

Therapeutics (17 decks)

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