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Neurology > Parkinson's Disease > Flashcards

Parkinson's Disease Flashcards

1
Q

What are the risk factors associated with PD?

A
  • Rural living
  • well water
  • pesticides
  • heavy metal exposure
  • fungus (mushroom alcohol)
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2
Q

What are the protective factors associated with PD?

A
  • Cigarette smoking
  • caffeine consumption
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3
Q

Where is the dopamine depleted in the brain?

A

Substantia nigra
* Striatum
* Globus pallidus
* Thalamus

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4
Q

What is the role of dopamine in the brain?

A
  • Smooth, controlled muscle movement
  • Cognition and frontal cortex function
  • Pleasure and motivation
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5
Q

What is the role of dopamine in the cardiovascular?

A

Vasodilator

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6
Q

What is the role of dopamine in the renal?

A

INCREASE sodium excretion and urine output

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7
Q

What is the role of dopamine in the digestive?

A

DECREASE GI motility and protects intestinal mucosa

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8
Q

What is the role of dopamine in the immune?

A

DECREASE activity of lymphocytes

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9
Q

Symptoms appear when
____ of SN neurons are depleted?

A

70-80%

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10
Q

What are the cardinal signs of Parkinson’s?

A
  • Onset is usually unilateral, asymmetric
  • Tremor
    • Usually occurs at rest
    • May disappear with voluntary movement or sleep
    • Initially affects upper extremities
    • May manifest as “pill-rolling”
  • Rigidity
    • May manifest as “cogwheeling” or hypomania
  • Akinesia/Bradykinesia
    • Slow throughout an intended action
    • Difficulty initiating movement
    • May manifest as micrographia, shuffling, freezing
  • Postural instability
    • Common in advanced stages of PD
    • Increased risk of falls
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11
Q

What are the differential diagnosis of PD?

A
  • Insult (stroke, TBI, pugilism)
  • Infection
  • Intoxication (Carbon monoxide, mercury, Wilson’s)
  • Drug-induced
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12
Q

Which drugs can induce PD?

A
  • Antipsychotics (except clozapine)
  • Antiemetics (DA antagonists)
  • Others
    • Methyldopa
    • Anesthesia
    • Opioid overdose
    • MPTP–> contaminant in some street drugs
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13
Q

L-DOPA

A
  • Drug of choice for symptomatic PD
    • Initial therapy if rigidity or bradykinesia is chief complaint
  • Preferred in older adults (65+)
    • Safest side effect profile
    • Younger patients report LDOPA dyskinesias
  • Only effective for a finite period of time
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14
Q

How do you get CR/ER dose of Cabidopa/L-DOPA?

A

Increase IR dose by 30%

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15
Q

What dose do you need if patient is experiencing nausea/vomiting with Carbidopa/L-DOPA?

A

75 mg/day of cabidopa

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16
Q

What are the adverse effects of L-DOPA?

A
  • DECREASE GI motility and protects intestinal mucosa
  • Vasodilator
  • Smooth, controlled muscle movement
  • Cognition and frontal cortex function
  • Nausea/vomiting
  • Postural hypotension
  • Dyskinesias, psychiatric disturbances
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17
Q

What are some patient counseling of C/L?

A
  • IR onset of action may take up to 1 hour
    • Longer for CR formulation–> may give IR in AM
    • ODT administration technique
  • ER formulation:
    • Do not chew/divide/crush capsules
    • May open capsule and sprinkle on 1-2 tbsp applesauce
  • L-DOPA competes with protein for absorption
  • Must taper when discontinuing
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18
Q

DA Agonist

A
  • May be considered as early monotherapy in initial L-DOPA sparing strategy (LDOPA only works for finite time)
  • Reserved for younger patients
  • Can cause psychiatric disturbance in older patients
  • Initial therapy option if rigidity or bradykinesia is chief complaint
  • Renally cleared–> dose adjustments required
19
Q

Rotigotine (Neupro)

A
  • Daily transdermal patch
  • Useful in advanced PD when swallowing is difficult
  • Must counsel on application/removal/disposal
20
Q

What are some patient counseling of Ropinirole and Pramipexole?

A
  • Sleep attacks - serious problems when driving
  • Must taper when discontinuing
21
Q

What are the adverse effects of dopamine agonist?

A
  • Hallucinations
  • Impulse control disorders
  • Gambling, compulsive shopping
22
Q

Why must we taper?

A

Abrupt cessation can lead to physiological withdrawal (DA agonist) or exacerbating of underlying PD (DA agonist & L-DOPA)

23
Q

What are some physiological withdrawal of DA agonist?

A
  • Anxiety
  • Panic attacks
  • Depression
  • N/V/D
  • Pain
  • Diaphoresis
  • Suicidal ideation
  • Drug cravings
24
Q

What are some exacerbation of underlying PD?

A
  • Diaphragm rigidity–> asphyxiation
  • Immobility–> clots
    Most problematic in advanced PD
25
Q

Motor complications of L-DOPA

A
  • More than half of patients develop complications after 5-10 years
  • More common in younger patients (<60 years)
  • Dyskinesias
    • Chorea: Irregular rapid purposeless movement
    • Dystonia: Sustained contractions
26
Q

What should you do if patient is experiencing a “wearing off” effect?

A

Change L-DOPA administration
* DECREASE dose but INCREASE frequency of C/L
* Give combination of IR and CR formulations

27
Q

COMT Inhibitors

A
  • Selective and reversible inhibition of COMT (catecyl-o-methyl-transferase) inhibits degradation of DA
  • Used to “extend life” of L-DOPA in patients with motor fluctuations
  • Ineffective when given as monotherapy
  • Administer simultaneously with L-DOPA
28
Q

What medications are the COMT inhibitors?

A
  • Entacapone–> peripheral inhibition
  • Tolcapone–> central inhibition (no longer used b/c severe hepatoxicity)
  • Opicapone–> once daily, expensive
29
Q

Entacapone (Comtan)

A
  • DECREASE L-DOPA dose by ~25% when starting COMT
  • Available as combination tablet with carbidopa/L-DOPA (Stalevo®)
    • May DECREASE pill burden and INCREASE adherence, BUT…
    • Not able to titrate component agents
30
Q

What are the adverse effects of Entacapone (Comtan)

A
  • Dopaminergic ADRs
  • Urine discoloration
31
Q

MAO-B inhibitors

A
  • Selective and irreversible inhibition of MAO-B in brain interferes with degradation of DA
  • May take 1-2 months to see a (modest) effect
  • DECREASE L-DOPA dose by ~10% when starting MAOI
32
Q

Which medications are MAO-B inhibitors?

A
  • Selegiline–> tablet (Eldepryl), ODT (Zelapar)
  • Safinamide (Xadago)
  • Rasagiline (Azilect)
33
Q

What are some drug interactions of MAO-B inhibitors?

A
  • Prolonged potential for DDIs even after stopped
  • Contraindicated with opioids/serotonin drugs
  • ?Interaction with foods containing tyramine
    • E.g., wine & beer, aged cheese, overripe foods

Generally well-tolerated

34
Q

Apomorphine (SQ Apokyn and SL film Kynmobi)

A
  • DA agonist used in L-DOPA “off” episodes
  • Intermittent subcutaneous injection
  • Requires test dose under medical supervision due to risk of severe hypotension
  • Start trimethobenzamide 3 days prior
  • If treatment interrupted for > 1 week, must restart at 2 mg and gradually titrate dose
35
Q

What are some new special formulations for “off”?

A
  • CD/LD intestinal gel (Duopa)
  • Levodopa inhalation powder (Inbrija) - NOT recommended for pts with asthma or COPD due to bronchospasm
36
Q

Istradefylline (Nourianz)

A
  • Once daily dosing for “off” periods as add on to CD/LD
  • Special dosing
    • Smokers (> 20 cig/day) – 40 mg/day - Strong CYP3A4 inhibitors – 20 mg/day
    • Strong CYP3A4 inducers – AVOID USE
  • Beneficial effects – increased “on-time” and decreased “off-time”
  • Not causing orthostatic hypotension as other dopaminergic agents
37
Q

What are the ADE of Istradefylline?

A
  • dyskinesia
  • hallucinations
  • insomnia
38
Q

Benztropine (Cogentin®) or trihexyphenidyl (Artane®)

A
  • Anticholinergics
  • Monotherapy in patients < 65 yo if ONLY tremor
  • Adjunct therapy if persistent tremor despite DA therapy
39
Q

Amantadine

A
  • Antiviral with mild, transient antiparkinsonian activity
    • INCREASE DA release, prevent DA reuptake, & directly stimulates DA receptors
    • Exerts central anticholinergic activity
    • Antagonizes NMDA receptor
  • Adjunct therapy to DECREASE intensity of L-DOPA dyskinesias
  • Renally cleared–> requires dose adjustments
40
Q

What are the ADE of amantadine?

A
  • Hallucinations, confusion, dizziness, edema
  • Older adults especially susceptible to CNS effects
41
Q

How to treat psychosis in PD?

A

Discontinue offending agents
* AC–> Amantadine–> MAOBI–> COMT/DA agonists

Consider low-dose atypical antipsychotics
* Efficacy: Clozapine (Level B) ≥ Quetiapine (Level C)
* New FDA approved agent: Pimavanserin $$$$
* Safety: Quetiapine > Clozapine (granulocytopenia)

42
Q

How to treat constipation in PD?

A
  • May consider PEG
  • Avoid psyllium
43
Q

How do you treat sexual dysfunction in PD?

A
  • PDE-5 inhibitors
    • Sildenafil 50 mg
  • PGE-1 analogue
44
Q

What is the treatment of urinary incontinence of PD?

A
  • ? urinary antispasmodic
  • Botulinumtoxin A

Neurology (21 decks)

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