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PR3153 > IC16 Parkinson's Disease > Flashcards

IC16 Parkinson's Disease Flashcards

1
Q

What is Parkinson’s Disease?

A

Parkinson disease (PD) - a neurodegenerative brain condition that causes problems with movement, mental health, sleep, pain and other health issues.

PD is a neurodegenerative disease that exhibits extrapyramidal motor symptoms, due to doperminergic striatal deficiency.

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2
Q

What are the 4 key features of Parkinson’s Disease (PD)?

A
  1. Tremor
  2. Rigidity
  3. Akinesia - slowness of movement
  4. Postural instability

Acronym: TRAP

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3
Q

How to diagnose a pt with Parkinson’s Disease?

A

A pt must present with 2 out of 3 cardinal signs of PD.

2 out of these 3:
1. Tremor
2. Rigidity
3. Akinesia - slowness of movement

Postural instability is not considered as a cardinal sign.

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4
Q

What are initial presentations of PD?

A
  1. Asymmetric
  2. Positive response to levodopa
  3. No postural instability
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5
Q

What is the most believed pathophysiology of PD?

A
  1. Misfolding of alpha-synuclein protein, leading to formation of Lewy body
  2. Long term overexpression and aggregation of Lewy bodies lead to ↓ dopamine & mitochondria to fail.
  3. This leads to neuroinflammation as a result of microglia activation.
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6
Q

How is PD progression measured?

A

It is measured using 2 scales:
1. Hoehn and Yahr Staging
2. UPDRS - Unified Parkinson’s Disease Rating Scale

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7
Q

What is the preferred agent to use in younger patients w PD?

A

Dopaminergic agonists.

Dopaminergic agonists are preferred over levodopa.

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8
Q

What are goals of therapy for PD?

A
  1. Manage PD symptoms
  2. Maintain function & autonomy
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9
Q

What are the pharmacological therapies for PD?

A
  1. Drugs that ↑ Dopamine levels
    - Levodopa
    - Dopaminergic agonists (e.g Pramiprexole)
    - MAO-B inhibitors (e.g Selegiline, Rasagiline)
    - COMT inhibitors (e.g Entacapone, Tolcapone)
  2. Drugs that correct imbalances in other pathways
    - Anticholinergics
    - NMDA antagonists
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10
Q

What are some patient counselling points for taking levodopa?

A

Pt should take levodopa on an empty stomach.

Never take it with high fat or high protein meals, as it decreases levodopa absorption.

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11
Q

Levodopa absorption is poor when taken alone (33%).

However, when it is taken together with DOPA decarboxylase inhibitors (DCIs), absorption improves significantly.

What are 2 examples of DCIs?

A
  1. Benserazide
  2. Carbidopa

These two DCIs are often used as adjunctive agents to levodopa to increase absorption.

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12
Q

What are the ADRs of levodopa?

A
  1. N&V
  2. Orthostatic hypotension
  3. Hallucinations, psychosis
  4. Dyskinesia - involuntary & uncontrolled jerking
  5. Drowsiness
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13
Q

The use of levodopa undergoes this complication known as “on-off” phenomenon.

The effects of levodopa wears off before the next dose.

As the disease progresses, it has shorter “ON” time. where effects of levodopa last a shorter time.

How should we go about managing this?

A
  1. We can modify times of administration to optimise dosing.
  2. We can use other agents, such as dopaminergic agonists, MAO-B inhibitors, COMT inhibitors as adjunct therapy to levodopa
  3. We can also replace current dosing with modified release preparations.
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14
Q

What medication can we use to manage dyskinesia?

Dyskinesia can develop due to the use of levodopa.

A

Amantadine can be used to help manage dyskinesia.

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15
Q

What are the benefits of sustained release dosage forms of levodopa?

A

Sustained release levodopa is useful for:
1. ↓ stiffness on waking
2. Reduced dosing interval

Do not crush tablets or open capsules for sustained release dosage forms.

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16
Q

What are some DDIs that occur w levodopa?

A
  1. Pyridoxine
  2. Iron
  3. Protein (food or protein powder)
  4. Dopaminergic antagonist - metoclopramide
  5. 1st gen antipsychotics
  6. Risperidone - atypical antipsychotic
17
Q

Dopaminergic agonist, such as pramipexole, act on dopamine receptors in the basal ganglia.

What ADRs are associated with dopaminergic agonists?

A

Effects on the PNS:
- N&V
- Orthostatic hypotension
- Leg oedema

Effects on the CNS:
- Hallucinations
- Somnolence, day time drowsiness
- Compulsive behaviour - e.g. gambling, shopping, eating

Others:
- Fibrosis
- Valvular heart disease

18
Q

What are the pros and cons of dopamine agonists, as compared to levodopa?

A

Pros:
- Lesser motor complications than levodopa
- Preferred in younger pts
- Can be used as adjunct therapy w levodopa in moderate to severe PD pts.

Cons:
- More hallucination, sleep disturbances, leg oedema, orthostatic hypotension

Dopamine agonist and levodopa are equally efficacious.

19
Q

What is the difference in site of action between MAO-A inhibitors and MAO-B inhibitors?

A

MAO-A inhibitors: Peripheral acting, targets noradrenaline & 5HT

MAO-B inhibitors: Central acting, targets dopamine

Examples of MAO-B inhibitors: Selegeline & Rasagiline

20
Q

How are MAO-B inhibitors used in PD?

A

They are used as monotherapy.

21
Q

What are DDIs that are associated w MAOB inhibitors?

A
  1. SSRIs, SNRIs, TCAs
  2. Tramadol
  3. Linezolid
  4. Dextromethorphan
  5. Dopamine
  6. Sympathomimetics
  7. Other MAOis
22
Q

How are COMT inhibitors used in PD?

A

They are used as adjunctive therapy to levodopa. Entacapone must be taken at the same time as levodopa.

COMT inhibitors are ineffective as monotherapy

COMT inhibitors help to decrease “off” time when using levodopa.

23
Q

What cautions must we take note of when using COMT inhibitors?

A
  1. Use w caution in hepatic impairment- tolcapone
  2. May cause dyskinesia upon initiation - ↓ levodopa dose
  3. May also cause other dopaminergic effects - such as N&V, orthostatic hypotension
24
Q

How are anticholinergics used in PD?

A

Anticholinergics have limited use in PD. They are primarily used to control tremor.

25
Q

What are examples of NMDA antagonists?

A
  1. Amantadine
  2. Memantine

NMDA antagonists can be used in PD, but we do not know the exact MOA.
NMDA antagonists are used as adjunctive therapy to levodopa to manage dyskinesia.

26
Q

What are the differences between drug-induced PD VS PD?

A
  1. Drug-induced PD symptoms tend to occur bilaterally as compared to unilaterally in normal PD.
  2. Withdrawal of the drug usually leads to improvement in symptoms in 80% of pt in 8 weeks
  3. Treatment for drug-induced PD is to withdraw the offending drug
27
Q

What are drugs that can cause drug-induced PD?

A

All drugs that decreases dopamine levels have high risk of causing drug-induced PD.

  1. Dopamine antagonist (e.g typical antipsychotics - haloperidol)
  2. Dopamine depleters (e.g reserpine)
  3. Dopamine synthesis blockers (e.g a-methyldopa)
  4. Ca channel blocker (e.g flunarizine, cinnarizine)
28
Q

What is the role of pharmacist in PD pts?

A
  1. Ensure correct levodopa preparations - regular release VS modified release
  2. Check if pt can swallow pills whole
  3. DDIs
  4. Timing of administration
    - educate pt that entacapone must take same time as levodopa
29
Q

What non-pharmacological therapy are there for PD?

A
  1. Physiotherapy
  2. Occupational therapy
  3. Speech therapy
  4. Deep brain stimulation

PR3153 (18 decks)

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