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Year 3 - Clinical (Winter) > 12 - Parkinson's > Flashcards

Flashcards in 12 - Parkinson's Deck (45)
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1
Q

What are the cardinal motor features of Parkinson’s?

A
  1. Bradykinesia
  2. Tremor at rest
  3. Rigidity
  4. Postural instability
    - Diagnosis = 1 + 2 or 3; 4 comes later
    * Slow, progressive, degenerative CNS disorder
    - Often presents asymmetrically
2
Q

Describe the “tremor at rest” of Parkinson’s

A
  • 70% of px
  • Rhythmic, asymmetric
  • Hands (pill rolling), feet, lip, jaw (not usually head or neck)
  • May disappear w/ voluntary movement & sleep
3
Q

Describe the rigidity of Parkinson’s

A
  • 90% of px
  • Lead pipe, cogwheel
  • Neck, trunk, limbs
  • Resistance to passive movement of limbs/ joints
4
Q

Describe the bradykinesia of Parkinson’s

A
  • 70% of px
  • Slowness of all movements including walking
  • Difficulty initiating movement
5
Q

Describe the postural instability of Parkinson’s

A
  • Often later presentation
  • Shuffling gait
  • Narrow base, festination
  • Freezing and falls
6
Q

4 dopaminergic pathways in the brain

A
  • Mesolimbic – high DA = positive sx of schizophrenia
  • Mesocortical – low DA = negative sx of schizophrenia
  • Tuberinfundibular – low DA = hyperprolactinemia
  • Substantia nigra – extrapyramidal system; low DA = parkinson’s; high DA = dyskinesia
7
Q

Substantia nigra

A
  • Nigrostriatal pathway achieves smooth movement when acetylcholine (the “no go” or inhibitory NT) & dopamine (the “go” or excitatory NT) are in balance
  • When dopamine is blocked, acetylcholine > dopamine => movement becomes jerky & stiff b/c there is a relative excess of “no go” NT
8
Q

Which drugs cause drug-induced parkinsonism and how?

A
  • Typical antipsychotics (ex: haloperidol) block all 4 pathways
  • Atypical antipsychotics selectively block dopamine in the mesolimbic pathway (less frequent EPS)
  • GI agents (prochlorperazine, promethazine, metoclopramide)
9
Q

What are the types and sx of drug-induced EPS

A
  • Dystonia = sustained contraction (onset = hours to days)
  • Akathisia = restlessness (onset = hours to days)
  • Pseudo-parkinsonism = bradykinesia, cogwheel-like tone/ rigidity, tremor (onset < 30 days of starting medications)
  • Tardive dyskinesia = irregular/ twisting movements (ex: cheek puffing, facial grimacing, lip smacking); onset months to years, often irreversible
10
Q

Which drugs cause drug-induced Parkinson-like motor sx

A
  • Antipsychotics (FGA > SGA; risperidone > olanzapine > quetiapine/ clozapine)
  • Anti-emetics (metoclopramide, prochlorperazine)
  • Older antihypertensives (methyldopa)
  • SSRI (serotonin may inhibit dopamine activity)
  • Valproic acid (GABA – bradykinesia, tremors)
  • Resting tremors –> lithium, valproic acid, SSRIs, TCAs, amiodarone, EtOH
11
Q

Drug-induced Parkinson-like motor sx – onset and resolution

A
  • Onset w/in weeks of starting drug

- May take 2-6 months for sx to resolve after d/c

12
Q

Risk factor for drug-induced parkinsonism

A
  • Older age
  • Female
  • High doses of offending drug
  • Hx of movement disorder
13
Q

Drug-induced neuroleptic malignant syndrome (NMS)

A
  • Life-threatening
  • Thought to be a result of sudden decrease in dopaminergic transmission
  • Antipsychotics (dopamine blocker) & sudden withdrawal of dopamine enhancers (ex: levodopa) has resulted in NMS
  • Sx:
    • FARM (fever, autonomic instability (unstable HR, BP, sweating, drooling), rigidity, mental status changes
    • Delirium, severe immobility
    • Leukocytosis, rhabdomyolysis, high sCr
14
Q

Parkinson’s disease

A
  • Loss of pigmented cells in substantia nigra

- Sx appear when 60-80% of these neurons have been lost

15
Q

Main goal of Parkinson’s disease, what does each drug do to achieve this?

A
  • *Enhance/increase dopamine or block acetylcholine
  • Dopamine precursor – L-dopa converts to dopamine
  • Dopamine agonist – activates dopamine receptors
  • NMDA receptor antagonist – increases dopamine release
  • COMT or MAO-B inhibitor – decreases dopamine metabolism
  • Anticholinergics – block acetylcholine in striatum
16
Q

Goals of therapy

A
  • *Improve motor & non-motor sx to maintain best possible QOL
  • Preserve ability to perform activities of daily living
  • Minimize adverse effects and tx complications
  • Improve non-motor features (ex: cognitive impairment, depression, fatigue, sleep disorders)
17
Q

When should Parkinson’s tx be initiated? How long is it continued?

A
  • Early, mild sx causing no disability (clumsiness of hands, fatigue, sensory discomfort) don’t warrant therapy
  • When disability interferes w/ px social, emotional, or work life, therapy is warranted
  • Duration of therapy is usually lifelong (w/ monitoring)
18
Q

Pharmacotherapy options for Parkinson’s

A
  • Anticholinergic (block acetylcholine, relative increase in DA)
  • Amantadine (NMDA antagonist increases DA release)
  • MAO-B inhibitor (reduce DA breakdown)
  • COMT inhibitor (reduce levodopa breakdown)
  • Dopamine agonist (directly stimulates DA receptors)
  • Levodopa (converted to DA by dopa decarboxylase)
19
Q

Anticholinergics for Parkinson’s – agents, MOA, SE

A
  • Benztropine, trihexyphenidyl, procyclidine, ethopropazine
  • Block acetylcholine in the striatum
  • SE = blurred vision, confusion, constipation, dry mouth, cognitive impairment, urinary retention
    • Need to taper over 1 week when stopping to prevent Parkinson’s exacerbation (even if no perceived benefit was realized)
20
Q

When should anticholinergics be used for Parkinson’s?

A
  • Can be used alone or in combination
  • Tremor is predominant
  • Drooling
  • Drug-induced EPS
  • Modest antiparkinson effect – not as effective for more disabling features of PD
  • SE limit use (younger may tolerate)
21
Q

Amantadine for Parkinson’s – MOA, role, SE

A
  • Inhibits NMDA receptors and increases dopamine release from presynaptic terminals
  • Role:
    • Modest antiparkinson effect
    • Used early to help w/ tremor
    • Used later to reduce L-dopa dyskinesia (antiglutamate)
    • Better tolerated in young px
  • SE = CNS (confusion, insomnia), anticholinergic (dry mouth), GI upset, hypotension, tachyphylaxis (pt initially has good response but then all of a sudden stops working)
  • Abrupt withdrawal can worsen PD/ cause NMS
22
Q

Livedo reticularis

A
  • Cosmetic, not life threatening
  • Not dose-dependent
  • Reversible diffuse purplish-red mottling of the skin
  • Affects upper or lower extremities +/- low extremity edema
23
Q

Drugs that prevent DA breakdown

A
  • COMT inhibitors prevent breakdown of levodopa

- MAO-B inhibitors prevent breakdown of dopamine into active metabolites

24
Q

Monoamine oxidase B inhibitors – dosing, role, SE, drug interaction

A
  • Selegiline, rasagiline
    • Selegiline taken AM or at lunch to decrease insomnia; tyramine intake shouldn’t be a concern at typical doses
    • Rasagiline – high fat meals decrease levels; theoretical tyramine hypertensive crisis (but no diet restrictions)
  • Selective & irreversible MAO-B inhibitor in the brain – interferes w/ DA breakdown
  • Role
    • Mild-moderate symptomatic benefit
    • Early Parkinson’s disease monotherapy
    • Add-on to levodopa (1h extended “on” time)
    • Lab models suggest neuroprotection, but no definitive evidence in px
  • Selegiline SE = insomnia, hallucinations, confusion, orthostatic hypotension
  • Rasagiline SE = minimal GI, neuropsychiatric
  • Drug interaction w/ serotonergic agents (ex: meperidine contraindicated, some antidepressants used w/ caution)
25
Q

Catechol-O-methyl transferase inhibitors – MOA, role, SE

A
  • Entacapone (produced as single or w/ levodopa & carbidopa – triple product expensive & not used often)
  • Reversible peripheral COMT inhibitor
  • Reduces GI metabolism of levodopa
    • Prolongs levodopa t1/2 & increase bioavailability
  • No effect w/o levodopa
  • May provide up to 1-2 h of extended “on” time for px w/ “wearing off” of levodopa
  • Typically used later on as add-on
  • SE = N/V, abdominal pain, brown-orange urine/ sweat discolouration, delayed onset diarrhea, hypotension, NMS
26
Q

Dopamine agonists – MOA, SE

A
  • Directly stimulates dopamine receptors (mimics real dopamine)
  • Moderate clinical effect (not as potent as levodopa)
  • Less motor complications but more side effects than levodopa
  • May be preferred over levodopa in younger px (who can tolerate SE) to delay levodopa dyskinesias
  • Reduce frequency of “off” periods & may allow levodopa dose reductions
  • SE = nausea, cognitive impairment (esp > 70 y/o), lower extremity edema; serious = impulsivity, sleep attacks; erythromelalgia/ cardiac valve fibrosis (ergot derived); can increase frequency & severity of levodopa-induced dyskinesia
    • Abrupt withdrawal/ significant dose reduction => risk of NMS & not resolved w/ other PD drugs (need to resume previous dopamine agonist)
27
Q

Titration of dopamine agonists

A
  • Must be titrate slowly & up to therapeutic dose; otherwise will just cause SE w/o much clinical benefit
    • Pramipexole –> initiate at low dose & increase slowly over 4-6 weeks; usual dose = 0.5 – 1.5 mg TID w/ meals
28
Q

Types of dopamine agonists

A
  1. Ergot-derived agonist (bromocriptine) –> not 1st line b/c cardiac valve disease
  2. Non-ergot agonist (pramipexole, ropinirole, rotigotine) –> used alone in mild PD or adjunct to levodopa in px w/ motor fluctuations
29
Q

Rotigotine

A
  • Steady release of drug from patch, but not proven to achieve better control of Parkinson’s sx
  • Use based on pt preference
30
Q

Levodopa – MOA, role, SE

A
  • Most effective therapy for Parkinson’s disease
    • Virtually all px respond
    • Improves disability, prolongs capacity to maintain employment and ADL
    • Reduced mortality rate
  • Superior motor benefit but associated w/ dyskinesias
    • May not be appropriate to delay solely based on concern for dyskinesia
  • Levodopa (L-dopa) –> dopamine
  • Combined w/ dopamine decarboxylase inhibitors (carbidopa or benserazide)
    • Allows more L-dopa to cross BBB (increases t1/2)
    • Prevents conversion to dopamine in periphery
    • Minimizes acute peripheral SE (nausea, hypotension)
  • MOA –> levodopa in periphery converted to dopamine by L-aromatic amino acid decarboxylase which causes SE (N/V, low BP); levodopa cross BBB to CNS & is then converted to dopamine which causes movement (SE = headache, vivid dreams, insomnia)
  • SE = nausea (ensure 75-200 mg carbidopa is being used; take w/ low protein food); hypotension (ensure adequate water/ salt intake, consider domperidone); hallucination, nightmares, motor fluctuations
31
Q

Benefit of regular release levocarb

A
  • Better absorption if taken before meals

- Can be taken w/ meals if nausea (protein rich foods decrease absorption)

32
Q

When to use controlled release LevoCarb?

A
  • No evidence that CR is better than regular release
  • Should not be used as initial therapy b/c:
    • Less well absorbed
    • Less noticeable response since reaches CNS more slowly
  • Makes evaluating & monitoring initial response more difficult
  • Generally ineffective for “wearing off” effect in most middle of night/ very early AM sx
  • Likely adds about 90 min to duration of effect
  • CR 70% bioavailable compared to regular release
  • Delayed onset may require supplemental regular release LevoCarb for optimal control in the mornings
33
Q

Duodopa Gel

A
  • Levodopa/carbidopa in a 100 mL cassette
  • Intraduodenal infusion
  • Indicated for severe, debilitating motor fluctuation and hyper-/dyskinesia despite optimized tx w/ available meds
34
Q

Motor fluctuations in Parkinson’s

A
  • PD is progressive
    1. End-of-dose “wearing off” / “on-off”
    2. “Delayed-on” and “no-on” response
    3. “Freezing”
    4. Peak-dose (“on” period) dyskinesias
    5. Early morning “off-period” dystonia
35
Q

End-of-dose “wearing off” / “on-off” – onset and management

A
  • Onset 5-6 months (often 1-5 years) after starting levodopa
  • Progressive loss of neuronal dopamine storage & short levodopa t1/2
  • Waning effect of levodopa w/in 4 h of last dose
    Management:
  • Smaller & more frequent levodopa dosing (take next dose 30-60 mins earlier) –> watch for dyskinesia
  • Consider adding dopamine agonist, COMT inhibitor (entacapone), or MAO-B inhibitor (rasagiline) –> watch for dyskinesia (abnormal movement as a result of too much dopamine)
  • Reduce protein in diet
36
Q

“Delayed-on” and “no-on” response

A
  • Delayed gastric emptying or decreased absorption in the duodenum
  • Management –> chew/crush tablet & drink full glass of water
37
Q

“Freezing”

A
  • Sudden or episodic inhibition of lower-leg motor function
    • Feet suddenly feel stuck to the floor
    • Anxiety/ perceived obstacles encountered
    • Fall risk**
  • Physical therapy, assistive walking devices, sensory cues
  • Changes to drug regimen may not be helpful
38
Q

Peak-dose (“on”) dyskinesias

A
  • Too much dopamine
  • Involuntary repetitive, rapid/jerky movements – usually neck, trunk, and lower/upper extremities
  • Management:
    • Add amantadine (antidyskinesia effect)
    • Decrease levodopa & add dopamine agonist –> watch for worsening of Parkinson’s sx
    • Decrease or d/c COMT inhibitor/ MAO-B inhibitor –> watch for worsening of Parkinson’s sx
39
Q

“Off-period” dystonia

A
  • Sustained muscle contractions – normally in distal lower extremities (ex: clenching of toes, turning of foot)
  • Early morning hours (waning drug levels)
  • Improve w/ first levodopa dose of the day
  • Management:
    • Chew regular release LevoCarb tablets and take w/ carbonated drink to increase absorption
    • Controlled-release LevoCarb (esp at bedtime)
40
Q

Principles of pharmacotherapy for Parkinson’s

A
  • Initial drug choice must be individualized based on sx severity and other comorbidities
  • Treat px w/ each drug (increasing doses weekly) until desired effect is seen, the maximum dose is achieved, or adverse effects become intolerable **start low, go slow
  • If partial response (w/ acceptable level of SE) has been seen w/ the initial drug, continue this drug and add the next drug in the sequence
  • As disease progresses, often w/in 6 months to 1 year of starting therapy, pharmacologic response to levodopa will deteriorate
  • When adding adjuvant therapy to levodopa/ carbidopa, reduce the dose of levodopa
  • No role for drug holidays as any benefit is usually short-lived and risks include immobility, aspiration/ pneumonia, severe depression
  • Therapy shouldn’t be d/c abruptly (parkinsonian crisis & neuroleptic malignant syndrome have been reported)
41
Q

Initial pharmacologic management for Parkinson’s

A
  • Only initiate therapy if functional impairment
  • If < 60 y/o w/ tolerable sx –> dopamine agonists, MAO-B inhibitors, levodopa
    • If pt has unacceptable SE or lack of efficacy –> use levodopa
  • If 60 years & older, or severe impairment –> levodopa
42
Q

Levodopa-associated motor complications

A
  • Predominant end-of-dose “wearing off” w/ mild/no dyskinesia –> increase levodopa frequency, add entacapone, add dopamine agonist, add MAO-B inhibitor, or change to slow release levodopa
  • Predominant end-of-dose “wearing off” w/ moderate dyskinesia –> increase smaller dose levodopa frequency, add amantadine, or decrease levodopa & add dopamine agonist
  • Predominant dyskinesia w/ mild/no “wearing off” –> decrease levodopa, add amantadine, d/c anticholinergic, or d/c MAO-B or COMT inhibitor
43
Q

Monitoring for Parkinson’s

A
  • Efficacy for parkinsonian sx – weekly during titration period, then q3months once pt has been stabilized
  • Safety
    • CNS psychosis –> monitor confusion, agitation, hallucinations, depression
    • Abnormal involuntary movements (AIMs) –> sx are dose-related (minimized w/ dose reduction); must titrate dose to minimize AIMs
    • CV –> orthostatic hypotension (especially when initiating therapy, usually decreases w/ continued therapy)
    • GI –> N/V (especially w/ initiating therapy; usually decreases w/ continued therapy); take w/ food/milk
  • Convenience –> swallowing/ motor fluctuation management
44
Q

Pt counselling for Parkinson’s

A
  • Medication administration times –> IR carbidopa/ L-dopa is absorbed best on an empty stomach but commonly taken w/ food to minimize nausea
  • Ensure pt and/or caregivers understand the prescribed medication regimen
  • Inquire specifically about dose-by-dose effects of medication
  • Inquire about concerns that caregivers may have about the pt
  • Monitor for non-adherence
  • Monitor for presence of drugs that can exacerbate idiopathic Parkinson’s disease motor features and anticholinergic agents causing cognitive impairment
45
Q

Non-drug interventions for Parkinson’s

A
  • Pt/family education and support
  • Physical therapy (improve gait)
  • Speech therapy (improve volume)
  • Occupational therapy (for mobility, safety, driving skills, maintain social/ family/ work roles)
  • Nutrition counselling
  • Sleep hygiene