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PR3136 CA1 > L4 Antiparkinsons > Flashcards

L4 Antiparkinsons Flashcards

1
Q

What is the function of basal ganglia and its significance in the pathophysiology of PD?

A

Facilitates and modulates motor movements initiated by motor cortex
- PD: degeneration of dopaminergic neurons with Lewy body inclusions in substantial nigra, which has dopaminergic projections to basal ganglia

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2
Q

Lewy bodies

A

aggresome, containing a-synuclein and ubiquitin

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3
Q

What is the main cause of parkinsonism?

A

PD

- but 10-25% of patients with parkisonian syndromes do not have PD

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4
Q

What are some common differential diagnoses of PD?

A

Atypical parkinsonian disorders

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5
Q

Diagnosis and diagnostic criteria of PD are based on? (3)

A
  • Presence of clinical features (movement disorders)
  • Exclusion of alternative diagnoses
  • Neuroimaging
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6
Q

What are the 3 cardinal features of PD?

A

rest tremors, rigidity, bradykinesia

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7
Q

What is often neglected in PD management?

A

Non-motor manifestations

  • autonomic, neuropsychiatric, olfactory, sensory
  • common in PD, more prominent in later stages of PD - cause significant disability
  • relatively resistant to, and may be worsened by dopaminergic agents
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8
Q

When will significant disability be experienced over the course of PD?

A

significant disability 10-15yrs after onsent

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9
Q

Motor fluctuation, dyskinesias and non-motor symptoms are common at later stages:

A

falls, postural instability, postural hypotension, confusion, dementia, suboptimal nutrition, speech and sleep disorders

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10
Q

What does treatment has to be individualised according to? (6)

A

age, stage of disease, level of activity, assoc physiological factors, assoc medical conditions, patient factors

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11
Q

Does a patient with early symptomatic PD without complications require any oral medications?

A

No, if coping well

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12
Q

Non-pharmacologicals for PD

A
  • Physiotherapy and exercise regime (stretching, maintain balance and posture)
  • Healthy and balanced diet
  • Knowledge on disease
  • Social support
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13
Q

What is the gold standard medication used for PD?

A

Levodopa

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14
Q

Examples of ‘2-in-1’ preparation with levodopa

A

and peripheral decarboxylase inhibitors

  • Levodopa + benserazide = Madopar
  • Levodopa + carbidopa = Sinemet
  • available as regular form or long acting form (HBS or CR)
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15
Q

What is a potentially serious side effect of levodopa?

A

Dyskinesia (10%/yr) - chronic SE that is accumulative, does not fade away even if dose is later reduced

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16
Q

What is the most efficacious drug for the symptomatic management of both early and late PD?

A

Levodopa

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17
Q

What is the dose of levodopa that should be used?

A

Lowest effective dose! Should be kept to the minimum necessary, to achieve good motor function

18
Q

Example of an anticholinergic (and dose) used in PD

A

Artane (trihexyphenidyl) 2-15mg/day

19
Q

What are the common side effects of anticholinergics and which group of population is the most susceptible to it?

A

Dry mouth, constipation, urinary retention, sedation, delirium, confusion, halucinations
- ELDERLY

20
Q

What are the advantages of anticholinergiccs?

A
  • May be effective in controlling tremor

- Peripherally acting agents may be useful in treating sialorrhoea

21
Q

How are anticholinergic agents used in PD treatment?

A

symptomatic monotherapy or as an adjunct to levodopa to treat tremors and stiffness

22
Q

Examples of MAO-B inhibitors used in PD

A

Selegiline (Jumex), rasagiline

23
Q

Anticholinergic MOA

A

Does not act directly on the dopaminergic system, correct the imbalance between acetylcholine and dopamine in PD

24
Q

MAO-B inhibitors MOA

A
  • inhibit enzyme MAO, interferes with breakdown of dopamine

- lab studies suggest that it may delay the nigral brain cell degeneration

25
Q

How are MAO-B inhibitors used in PD treatment?

A

Symptomatic monotherapy, used in early stages

26
Q

Examples of COMT inhibitors

A

Entacapone (Comtan) and Tolcapone (Tasmar)

27
Q

COMT inhibitors MOA

A

only effective if used with levodopa: blocks an enzyme that converts levodopa into an inactive form, hence more levodopa is available to enter the brain -> increases duration of each dose of levodopa, beneficial in treating ‘wearing off’ responses

28
Q

What are the side effects of COMT inhibitors? (6)

A
  1. increase abnormal movements (bradykinesias)
  2. liver dysfunction (esp Tolcapone)
  3. nausea, diarrhea
  4. urinary discoloration
  5. visual hallucinations
  6. daytime drowsiness, sleep disturbances
29
Q

Dopamine agonists MOA

A
  • act directly on dopamine receptors in the brain to reduce the symptoms of PD: prevent or delay onset of motor complications
30
Q

Examples of dopamine agonists

A
  • Bromocriptine (Parlodel)
  • Pergolide (Celance, Permax)
  • Piribedil (Trivastal Retard)
  • Ropinirole (Requip)
  • Pramipexole (Sifrol)
31
Q

Is dopamine agonist or levodopa a better class of drug for PD?

A

Levodopa, still the gold standard

32
Q

What is a side effect specific to Pergolide

A

restrictive valvular heart disease

33
Q

What is a side effect specific to ropinirole, pramipexole

A

somnolence (incr sleepyness)

34
Q

Side effects of dopamine agonists (general)

A

similar to levodopa, fibrosis, arrhythmia

35
Q

Recognising that levodopa and dopamine agonists have similar SE, which is milder?

A

Dopamine agonist - can be used in younger patients

36
Q

In younger patients with PD, which drug class should be commenced first?

A

Dopamine agonists

37
Q

How are dopamine agonists used in PD treatment?

A

symptomatic monotherapy, adjunct to levodopa

38
Q

What can be considered a therapy to reduce dyskinesia in patients with PD who have motor fluctuations?

A

Amantadine

39
Q

Amantadine MOA

A
  • enhance release of stored dopamine
  • inhibit presynaptic uptake of catecholamine
  • dopamine receptor agonist
  • NMDA receptor anatagonist (anti-glutamate)
40
Q

How are amantadine used in PD treatment

A

monotherapy or adjunct to levodopa

41
Q

What is an important function of Amantadine?

A

Antidyskinetic

42
Q

Amantadine’s usefulness as anti-PD drug is often limited by

A
  • side effects

- need to screen patient for history of seizures and psychiatric smx

PR3136 CA1 (8 decks)

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