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PR3153 FINALS > IC17 Parkinson's Disease > Flashcards

IC17 Parkinson's Disease Flashcards

1
Q

What are the 4 characterpstic features of PD (which ones are cardinal signs)?

A
  1. Tremors (resting)
  2. Rigidity (lead pipe or cogwheel)
  3. Akinesia (bradykinesia)
  4. Postural instability
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2
Q

How do tremors manifest and what should be excluded?

A

resting tremors that disappear with movement and increases with stress

exclude generalised anxiety that can be triggered by certain activities

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3
Q

What must be present for a PD diagnosis?

A

Clinical signs, physical exam and history

2/3 of the cardinal signs (T,R,A)

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4
Q

What are the characteristic features of idiopathic PD? Which ones manifest upon diagnosis and which ones show up later on?

A

Upon dx:
assymetry

Later on:
positive response to levodopa or apomorphine
less rapid progression
may present with impaired olfaction

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5
Q

What are the possible factors that could lead to loss of dopaminergic neurons in PD? (3)

A

age-related factors

environmental toxins or insults (MPTP-MPP+, pesticides, herbicides)

genetic factors (predisposition to toxins or insults and genetic abnormalities)

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6
Q

Which 2 scoring systems can be used used for PD staging?

A

Hoehn and Yahr (H&Y)
MDS-UPDRS

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7
Q

What are the 5 non-motor symptoms of PD?

A
  1. Cognitive impairment → dementia
  2. Psychiatric symptoms → depression, psychosis
  3. Sleep disorders → REM sleep behaviour disorder
  4. Autonomic dysfunction → constipation, GI motility, sialorrhea and orthostatic hypotension
  5. Other symptoms → fatigue
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8
Q

Differentiate between the features in early onset PD and typical PD? (3)

A

slower disease progression
less cognitive decline
earlier motor complications

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9
Q

What are the 2 goals of therapy for PD?

A

manage symptoms
maintain function and autonomy

no neuroprotective treatment yet

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10
Q

Which 2 symptoms of PD are levodopa good for managing?

A

rigidity and akinesia

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11
Q

What is an important counselling point for taking levodopa?

A

Space apart from heavy meal

If got n&v, can take w light snacks

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12
Q

What is the DCI dosing required to saturate DOPA?

A

75-100mg daily

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13
Q

What are the levodopa to DCI ratios?

A

Sinemet 1:4 or 1:10
Madopar 1:4

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14
Q

What are the side effects of levodopa (5)

A
  1. nausea, vomiting (especially in new treatment)
  2. orthostatic hypotension
  3. drowsiness and sudden sleep onset
  4. hallucinations, psychosis
  5. dyskinesias (usual onset 3-5 years of starting levodopa)
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15
Q

What is the “on-off” phenomenon in levodopa treatment?

A

ON refers to levodopa response
OFF refers to no levodopa response

unpredictable and not related to dose or dosing intervals

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16
Q

What is the “wearing off” phenomenon in levodopa treatment?

A

effect of levodopa wanes before the end of the dosing interval with a shortened ON time, associated with disease progression

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17
Q

How can “wearing off” be managed?

A

modifying times of administration or replacing with modified-release preparations

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18
Q

How can peak dose dyskinesia be managed?

A

manage by decreasing dose and increasing frequency

alternatively can be managed by adding amantadine or replacing levodopa with specific doses or MR-levodopa

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19
Q

How should dose of levodopa/DCI be adjusted with switching from IR to CR form?

A

Increase dose by 25-50%

20
Q

What are the DDIs with levodopa?

A
  1. Pyridoxine (vitamin B) → cofactor for DOPA decarboxylase, possibility of interactions with high dose B6
  2. Iron → space out administration
  3. Protein → space out administration
  4. Dopamine antagonists → such as risperidone, FGA and metoclopramide/prochlorperazine (domperidone is antiemetic of choice in PD)
21
Q

What dosage forms are rotigotine and apomorphine available in

A

rotigotine: transdermal patch
apomorphine: SC injection

22
Q

What are the peripheral dopaminergic side effects of dopamine agonists?

A

Dopaminergic (peripehral) → nausea, vomiting, orthostatic hypotension, leg edema

23
Q

What are the central dopaminergic side effects of dopamine agonists?

A

Dopaminergic (central) → hallucinations (visual > auditory), somnolence, day-time sleepiness, compulsive behaviours (gambling, shopping, eating, hypersexuality)

24
Q

What are the non-dopaminergic side effects of dopamine agonists?

A

Non-dopaminergic → fibrosis, valvular heart disease

25
Q

Compare between the efficacy and side effect profile of dopamine agonists and levodopa

A

Dopamine agonists result in less motor complications than levodopa

but shows a higher instance of hallucinations, sleep dsiturbances, eg. edema and orthostatic hypotension

26
Q

What is the place in therapy for dopamine agonists

A

Monotherapy in young-onset PD

Adjunct to levodopa in moderate to severe PD

27
Q

Which two dopamine agonists are available as both IR and SR forms?

A

Pramipexole and Ropinorole

28
Q

Which neurotransmitters do MAO-A and MAO-B act on

A

MAO-A (peripheral) → NA and 5-HT
MAO-B (central) → DA

29
Q

What type of drugs are selegiline and rasagiline?

A

irreversible MAO-B inhibitors

30
Q

Describe the half life and duration of action for selegiline and rasagiline

A

Short half-life of 1.5-4h
Long duration of action due to irreversibility

31
Q

When are MAO-B inhibitors indicated in PD treatment?

A

Early stages of disease
Can use as monotherapy

32
Q

How should selegiline be dosed

A

0.5mg OM to BD
second dose in the afternoon because metabolite (amphetamine) is stimulating

33
Q

How should rasagiline be dosed

A

0.5 to 2mg OD

34
Q

What are DDIs with MAO-B inhibitors?

A

SSRIs, SNRIs, TCAs (washout period recommended for these 3)

pethidine, tramadol, linezolid, dextrometorphan, dopamine, sympathomimetics (eg. nasal decongestants like pseudoephedrine and phenylephrine) and other MAOis

35
Q

What are COMTi drugs

A

Entacapone
Tolcapone (not used anymore due to ADRs)

36
Q

How do COMTi drugs help in PD?

A

They help to decrease “off” time

37
Q

How should COMTi drugs be administered?

A

At the same time as levodopa (not effective as monotherapy)

38
Q

What kind of a COMTi is entacapone

A

Reversible

39
Q

What are DDIs with COMTis?

A
  1. iron, calcium
  2. concurrent nonselective MAOi (but safe w MAOBi)
  3. any catecholamine drug
  4. warfarin (enhances anticoagulant effect)
40
Q

What are side effects of COMTis? (3)

A

diarrhea
urine discolouration (orange)
may cause dyskinesia and potentiate other dopaminergic effects (ortho hypotension, n&v)

41
Q

In which populations should entacapone be used with caution?

A

Pts w hepatic impairment

42
Q

What symptoms do anticholinergics help with

A

Tremors

43
Q

What are the side effects of NMDA antagonists? (6)

A

nausea, light-headedness, insomnia, confusion, hallucinations, livedo reticularis

44
Q

What is memantine’s place in PD therapy?

A

Mostly adjunctive to manage levodopa-induced dyskinesia

45
Q

What are the features of drug-induced parkinsonism

A

symptoms tend to occur bilaterally
drug withdrawal usually leads to sx improvement

46
Q

What are high risk drugs that can cause drug-induced parkinsonism?

A
  1. Dopamine receptor blockers → typical antipsychotics (eg. haloepridol, prochlorperazine), high dose atypical antipsychotics (eg. risperidone, olanzapine, aripiprazole)
  2. Dopamine depleters
  3. Dopamine synthesis blockers → α-methyldopa

PR3153 FINALS (8 decks)

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