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May 2023 > Parkinson's disease > Flashcards

Parkinson's disease Flashcards

1
Q

Parkinson
PD

A

pas dopamine (neurotransmitter responsible for initiating and controlling movement)

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2
Q

Parkinson
Risk factor (non-modifiable 4, modifiable 4)

A
  • Non-modifiable
    Age, gender, family hx, gene
  • Modifiable
    1. Low estrogen level
    2. Low vitamin B and folic acid level
    3. Head trauma
    4. Agricultural work
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3
Q

Parkinson
Symptoms (4)

A

TRAP
1. Tremor resting (70%)
2. Rigidity
3. Akinesia, Bradykinesia
4. Postural instability: inability to stand straight
Aki=w/o
Dys=abnormal
Brady = slow
kinesia = movement

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4
Q

Parkinson
Diagnosis
Bradykinesia + eliminate + response
No lab test

A
  1. Bradykinesia with at least 1:
    - limb muscle rigidity
    - resting tremor
    - postural instability
  2. Eliminate 2nd causes:
    - neoplasm
    - stroke, trauma
    - infection
    - drug causes
    - dementia
  3. pt’s responsiveness to therapy
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5
Q

Parkinson
Drug-induced parkinsonism
Symptom

A
  1. Bilateral
  2. Symptoms start and gone together with the starting and finishing of drug. Poorly/not responds to L-dopa
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6
Q

Parkinson
Drugs induced parkinson

A
  1. Dopamine antagonist (antipsychotic, 1st gen: phenothiazines, risperidone, butyrophenones)
  2. Block dopamine centrally and peripherally (antiemetics: metoclopramide, prochlorperazine) + release from synapse (reserpine, alpha-methydopa)
  3. Valproic, lithium: cause tremor
  4. Antidepressant: TCAs, SSRI: dyskinesia
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7
Q

Parkinson
Goals of therapy

A

No cure
Slow progression of disease
Management of symptoms

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8
Q

Parkinson
Dopamine metabolism

A
  1. L-dopa => inactive by: COMT, MAO-B ==> COMTi (entacapone), MAOBi (selegiline/rasagiline)
  2. L-dopa => dopamine by DDC (dopamine decarboxylase inhibitor). Combination: Levodopa + carbidopa, levodopa + benserazide
  3. NMDA receptor antagonists (amantadine): increase dopamine avail
  4. Dopamin agonists (cause pulmonary fibrosis, withdawn from market?): bromocriptine, ropinirole, pramipexole, rotigotine, pergolide
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9
Q

Parkinson
anticholinergic: benztropine, ethopropazine.. used for what?

A

not often
treat tremors

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10
Q

Parkinson
Non-pharm
exercising allied health

A

SLP = speech language pathologist
PT = physical therapist
OT = occupational therapist

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11
Q

Parkinson
When to initiate treatment?

A

Disease begins interfere with activities of daily living, employment, quality of life

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12
Q

Parkinson
How to initiate treatment? Consider + Avoid 2

A
  1. Consider: age, cognitive function, safety, tolerability of drug therapy
  2. Avoid: dopamine agonists in elderly (psychiatric SE)
  3. Avoid: anticholinergics in elderly (SE: urinary retention, confusion)
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13
Q

Parkinson
Mild/early PD

A
  1. MAOBi: more potent
  2. Dopamine precursor (tiền chất) + DOPA decarboxylase inh
  3. Dopamine agonist: not use ergot-derived DAs as 1st line
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14
Q

Parkinson
Moderate/ Severe PD: add to the drug in mild/early PD

A
  1. COMTi
  2. Amantadine: use in later stages, not effect in early
    Memantine not used in PD.
    Anticholinergics: no longer = 1st line
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15
Q

Parkinson
Non-selective MAOi

A

Selegiline: slow progression of PD (neuroprotective effect)
1. amphetamine metabolite: avoid sympathomimetics (pseudophedrine)
2. BID
3. avail: disintegrating tablet => avoid 1st pass (increase bioavailability). Take late afternoon before 4pm to minimize insomnia
4. DI: tyramine (fermented, cheese, yogurt..)

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16
Q

Parkinson
Selective MAOi

A

Rasagiline (more potent): improve motor, wearing off
1. not amphetamine metabolite
2. DIE
3. No DI with tyramine
Safinamide = irreversible MAOBi and modulator of glutamate ~ Rasagiline
4. CYP1A2 substrate => adjust dose with CYP1A2 inh (ciprofloxacin)

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17
Q

Parkinson
Drug of choice to treat drug-induced Parkinson

A

Benztropine = anticholinergic
1. qHS
2. Against resting tremor, no effects on bradykinesia
3. Avoid: elderly (>65)
4. CI: glaucoma, BPH, patients with dementia (due to cognitive impairment)
5. AE: confusion, memory impairment, hallucinations
dry mouth, blurred vision, urinary retention, constipation
somnolence

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18
Q

Parkinson
Antiviral with anticholinergic and antiglutamate properties (block acetylcholine receptor)

A

amantadine
1. Later stage reduce choreic movement (L-dopa induced dyskinesia)
2. Adjust: renal dysfunction
3. Rebound if d/c w/o taper
4. confusion, nightmares, insomnia, leg edema, drug mouth, nausea..

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19
Q

Parkinson
Dopamine agonist medications

A
  1. Ergot: bromocriptine (pulmonary fibrosis), pergolide (cardiac valvopathy => withdraw)
  2. Non-ergot: pramipexole, ropinirole, rotigotine
    Safer, favorable SE but compulsive behavior (gambling or shopping)
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20
Q

Parkinson
Benefit of Dopamine agonist = active dopamine receptor = mimicking Dopamine

A
  1. younger pt.(<60)
  2. Cannot tolerate high dose L-dopa,
  3. Reduce the risk of motor complications long term with levodopa.
    Titrate 4-6 wks
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21
Q

Parkinson
Combine Levodopa with ? to cross the BBB

A

Peripheral decarboxylase inh
Carbidopa (more common Sinemet)
Benserazide (Prolopa)

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22
Q

Parkinson
Most effective medication for PD

A

Levodopa
Initial: > 60
SE: * dyskinesia (peak-dose). Mangage:
1. change to CR
2. Use smaller dose + more frequently
3. Use COMT inh
4. Decrease Ldopa
* wearing-off/ end-of-dose effect:
1. + COMT inh
2. + MAOBi
3. + dopamine agonist

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23
Q

Parkinson
Which medication needs to be taken separate from meals containing protein (decrease bioavailability)

A

levodopa

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24
Q

Parkinson
Combined to reduce dose of levodopa 30%

A

+ COMT inh
Entacapone
Tolcapone (withdrawn d/t hepatotoxicity)
Benefit: extend L-dopa duration => manage wear-off
Given TID with L-dopa
SE: dyskinea, psychosis, diarrhea, abdominal pain, brownish-orange urinary discolouration

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25
Q

Parkinson
Levodopa complication 4

A
  1. Delayed on response
  2. End of dose wearing off
  3. Freezing
  4. Off-period dystonia
26
Q

Parkinson complication

A
  1. NV
  2. Constipation
  3. Depression
27
Q

Parkinson
Delay-on response of L-dopa due to delayed gastric emptying /decreased absoption in duodenum

A
  1. Chew/crush tablet with full glass of water
  2. Regular tablet on empty stomach to facilitate gastric emptying
  3. Reduce protein intake with L-dopa
28
Q

Parkinson
After 5 years of levodopa

A

50% pt will develop motor fluctuation

29
Q

Parkinson
End-of-dose wearing off: Levodopa

A
  1. Increase levodopa dose/ dose frequency
    • dopamine agonist (pramipexole, ropinirole)
    • Entacapone (must combine with Levodopa)
    • rasagiline
  5. Bedtime Levodopa CR or dopamine agonists
  6. Subcutaneous short-acting dopamine agonist (apomorphine), rapid onset of action
30
Q

Parkinson
Freezing of Levodopa

A

sudden inh of movement
Non-pharm: physiotherapy

31
Q

Parkinson
Off-period dystonia: muscle contraction early morning

A
  1. Bedtime administration of controlled-release products
  2. Baclofen use (muscle relaxant)
  3. Selective chemical denervation with inj of botulinum toxin
32
Q

Parkinson
Peak-dose dyskinesias

A
  1. Decrease L-dopa dose by small amount
  2. Decrease L-dopa dose, + dopamine agonist or increase dose of concurrent DA
  3. If on MAOBi, gradually decrease and d/c
  4. If recent + COMTi, decrease L-dopa by 15-30%
    • amantadine
  6. If on immediate L-dopa, change to modified release L-dopa
33
Q

Parkinson
Disease complications: drug-induced psychosis

A
  1. Monitor electrolytes, signs of infection
  2. Simplify regimen: d/c in order:
    - D/c anticholinergic, TCAs, antihistamines
    - Taper & d/c amantadine
    - Taper & d/c dopamine agonist
    - d/c MAOBi and COMTi
    - reduce L-dopa
    • atypical antipsychotic (quetiapine, preferred > clozapine b/c avoid blood monitoring requirements with clozapine) if disruptive hallucinations and psychosis persists
34
Q

Parkinson
Manage NV

A

1, Domperidone (peripheral dopamine antagonist)
2, Avoid metoclopramide b/c cross BBB

35
Q

Parkinson
Constipation mngt

A

Osmotic laxative (Lactulose, PEG)
Increase fiber & fluid
Docusate (soft)

36
Q

Parkinson
Depression

A

Avoid SSRI/SNRI/bupropion if on MAOBi
(risk of serotonin)

37
Q

Parkinson
Urinary frequency/ incontinence

A

Trospium/Darifenacin (more selective on bladder, less cross BBB)/ Mirabegron (nonanticholinergic)
Solifenacin worsen constipation and xerostomia

38
Q

myrxtx How is disease progression and longer-term treatment

A
  1. motor fluctuations
    - end-of-dose “wearing off” of effectiveness
    - periods of fluctuating response known as “on-off” phenomena
    - a variety of patterns of dyskinesia
    + peak-dose dyskinesia (occurring during the peak effect of the dose)
    + diphasic dyskinesia (occurring at the beginning and/or end of a dosing interval)
    + off-period dystonia (painful spasms, usually of the feet, occurring upon morning rising or when a dose is wearing off)
  2. increasing recognition that nonmotor symptoms
    excessive perspiration, anxiety, cognitive changes and shortness of breath
39
Q

myrxtx Management of Levodopa-Associated Motor Complications
Mild or no dyskinesia

A
  1. Increase frequency of levodopa
  2. Add entacapone
  3. Add dopamine agonist
  4. Add rasagiline / safinamide
  5. Change to slow-release levodopa
40
Q

myrxtx Management of Levodopa-Associated Motor Complications
Moderate dyskinesia

A
  1. Add amantadine
  2. Increase frequency but smaller doses of levodopa
  3. Decrease levodopa and add dopamine agonist
41
Q

myrxtx Management of Levodopa-Associated Motor Complications
Mild or no “wearing-off”

A
  1. Add amantadine
  2. Decrease levodopa
  3. D/c anticholinergic
  4. D/c MAO-B inh
42
Q

myrxtx Dopamine agonists used when?

A
  1. Monotherapy in the early stages
  2. As adjunctive therapy with levodopa with pt. with more advanced motor complications
43
Q

myrxtx Which dopamine agonist available as a transdermal patch formulation

A

rotigotine
stable plasma concentrations (avoid pulsatile stimulation of dopamine receptors) => an alternative to reduce oral med, improve adherence

44
Q

myrxtx non-ergot dopamine agonists?

A

pramipexole
ropinirole
rotigotine

45
Q

myrxtx SE of dopamine replacement meds (dopamine agonist&raquo_space; levodopa)

A

daytime sleepiness
sudden irresistible attacks of sleep
impulse control disorders: hypersexual behaviour/ pathologic gambling/ GI upset/ orthostatic hypotension/ psychiatric reactions (hallucination and confusion)

46
Q

myrxtx dopamine agonist available subcutaneous inj and sublingual film

A

apomorphine
Indication: during an off-episode that has not responded to adjustments to other meds

47
Q

myrxtx MAO-B inh

A

selegiline: benefit during 1st year of treatment, mild effect, not delay dyskinesia/fluctuation with chronic levodopa
rasagiline: more potent MAO-B inh: initial treatment/improve motor symptoms, pt with wearing-off, no slow disease progress
safinamide: irreversible MAO-B inh + modulator of glutamate: approved in Canada as an add-on treatment for wearing-off

48
Q

myrxtx amantadine

A

improve levodopa-induced dyskinesia in the LATER stages
unclear mechanism
N-methyl-D-aspartate (NMDA) antagonist = antiparkinsonian efficacy
SE: anticholinergic SE, leg edema, erythema and livedo reticularis (a reversible)
CI: patients with cognitive deficits

49
Q

myrxtx anticholinergics

A

benztropine, ethopropazine and trihexyphenidyl
major putative effect is on tremor
not be used as first-line and in patients with dyskinesias and/or motor fluctuations

50
Q

myrxtx Entacapone = COMT inh
COMT = an enzyme that helps metabolize levodopa in both the brain and in the peripheral nervous system

A

prevent peripheral metabolism of
increases levodopa availability to the brain, and has no effect if not used in conjunction with levodopa
SE: increased dopaminergic activity in the brain such as dyskinesia, and less often, confusion and/or hallucinations

51
Q

myrxtx 1st line

A
  1. Levodopa: initial therapy in most pt.
  2. Dopamine agonist: Was typically used as initial therapy in patients younger at onset (<60 y)
  3. MAO-B inh: May improve, typically used in mild disease
52
Q

myrxtx Treatment of nonmotor issues
Depression

A

Mainstay:
- SSRIs
- tricyclic antidepressants (TCAs): used cautiously because their anticholinergic effects:
+ delirium, especially in memory-impaired patients,
+ aggravate orthostatic hypotension, which can increase the risk of falls

53
Q

myrxtx Treatment of nonmotor issues
Rapid eye movement (REM) sleep behaviour disorder

A

Clonazepam (0.25–1 mg)&raquo_space; effective but SE
melatonin (3–12 mg) given before sleep

54
Q

myrxtx Treatment of nonmotor issues
Psychosis
All medications used to treat motor symptoms can contribute to psychosis in a dose-related fashion

A

PD medications often need to be reduced or withdrawn because of worsening of the patient’s cognitive status.
1. anticholinergics are withdrawn first
2. MAO-B inh: selegiline, rasagiline
3. amantadine
4. dopamine agonists
5. COMT inhibitors
6. reducing the dose of levodopa

55
Q

myrxtx Treatment of nonmotor issues
For patients in whom an optimum balance cannot be found by adjusting PD medications

A

antipsychotics quetiapine&raquo_space; clozapine are sometimes used
all other antipsychotics should be avoided in PD psychosis
recent addition: pimavanserin, a selective serotonin 5-hydroxytryptamine 2A (5-HT2a) inverse agonist; however, this is not yet available in Canada

56
Q

myrxtx Treatment of nonmotor issues
Dementia

A

Cholinesterase inhibitors (e.g., donepezil, rivastigmine) have a modest impact on improving dementia, but careful observation for deterioration in motor function is required

57
Q

myrxtx Treatment of nonmotor issues
Autonomic dysfunction

A
  1. Orthostatic hypotension: adding domperidone, midodrine and/or fludrocortisone may be considered
  2. Urinary urgency and incontinence: darifenacin, trospium, mirabegron
  3. Erectile dysfunction: sildenafil, tadalafil and vardenafil may all be used
  4. Constipation: proper hydration with a high fibre diet and exercise before considering treatments like polyethylene glycol, lactulose or fibre supplements such as psyllium
  5. Sialorrhea: onabotulinumtoxinA
58
Q

myrxtx When levodopa or a dopamine agonist are initiated, add ? to reduce gastric upset or orthostatic hypotension

A

domperidone (10–20 mg 30 min prior to each dose)
Caution: history of cardiovascular disease => increased risk of ventricular arrhythmia and sudden cardiac death

59
Q

myrxtx levodopa with food or w/o food

A

Early in therapy: with food => ease nausea
Advanced disease: w/o food => manage motor fluctuations

60
Q

myrxtx Parkinsonism-hyperpyrexia syndrome (similar to neuroleptic malignant syndrome) is a potentially fatal complication associated with

A

abrupt reduction or discontinuation of dopaminergic drugs
Hyponatremia is also a risk factor.
Medications should be reduced or withdrawn slowly
“Drug holidays” to reduce motor complications are not a recommended practice

61
Q

myrxtx Anticholinergic SEs

A

Dry mouth, blurred vision, constipation, urinary retention, precipitation of angle-closure glaucoma, confusion, memory impairment.

62
Q

myrxtx levodopa/​carbidopa may increase hypotensive action when using with

A

Antihypertensives,
diuretics,
tricyclic antidepressants

May 2023 (9 decks)

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