Parkinson's Disease Flashcards

1
Q

Pathophysiology of Parkinson’s?

A

degeneration & loss of dopaminergic neurons with Lewy body inclusions in substantial nigra

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2
Q

Does dopamine and levodopa pass thru BBB?

A

Dopamine: no
Levodopa: yes

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3
Q

Lifecycle of dopamine?

A

L-tyrosine -> levodopa by tyrosine hydroxylate -> dopamine by DOPA decarboxylase -> breakdown to HVA by COMT & MAO-B or recycled

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4
Q

Symptoms of Parkinson’s?

A

Motor: TRAP:
Tremors
Rigidity
Akinesia / bradykinesia
Postural instability & gait

Non-Motor:
- cognitive impairment (dementia, confusion)
- psychiatric sx (depression, psychosis)
- sleep disorders
- autonomic dysfunction (constipation, OH)
- others (fatigue, choking etc)

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5
Q

Non Pharm of Parkinson’s?

A
  • physiotherapy
  • occupational therapy
  • speech & swallowing
  • surgery
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6
Q

1st line treatment for Parkinson’s? Other treatment options?

A

1st line: levodopa-DCI (carbidopa, benserazide)
Other options: dopamine agonists, MAO-B inhibitors, COMT inhibitors

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7
Q

Examples of dopamine agonists used for Parkinson’s?

A

Ropinirole, pramiprexole

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8
Q

Examples of MAO-B inhibitors used for Parkinson’s?

A

Selegiline, rasagiline

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9
Q

Examples of COMT inhibitors used for Parkinson’s?

A

Entacopone

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10
Q

MOA of:
- levodopa-DCI
- dopamine agonists
- MAO-B inhibitor
- COMT inhibitor

A
  • levodopa-DCI: covered to dopamine, DCI prevents peripheral conversion of levodopa to dopamine by DOPA decarboxylase/MAO/COMT
  • dopamine agonists: mimic dopamine (act on D2 receptors)
  • MAO-B inhibitor: irreversibly inhibits MAO-B -> inhibit breakdown of dopamine
  • COMT inhibitor: selectively & reversibly inhibit COMT conversion -> inhibit breakdown of dopamine
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11
Q

Special adm instructions for levodopa-DCI?

A
  • Space apart from heavy meals (less absorption with high fat / protein meals)
  • space apart from iron
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12
Q

Dose adjustment when switching b/w immediate & controlled release forms of levodopa-DCI?

A
  • IR to CR: increase dose
  • CR to IR: decrease dose
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13
Q

Ratio of levodopa:DCI for Madopar?

A

4:1

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14
Q

What dose of DCI is required to prevent conversion of levodopa into dopamine outside the brain?

A

75-100mg/day

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15
Q

SE of levodopa-DCI?

A
  • N/V
  • OH
  • drowsy
  • hallucinations
  • dyskinesias (reduce with amantadine or CR)
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16
Q

What antiemetic is preferred for pts with Parkinson’s? Why not the others?

A

Domperidone
(metoclopramide and prochlorperazine cross BBB)

17
Q

When is dopamine agonists indicated?

A
  • monotherapy in young-onset PD
  • adjunct to levodopa in moderate/severe PD
  • management of motor complications caused by levodopa
18
Q

SE of dopamine agonists?

A
  • N/V
  • OH
  • drowsy
  • hallucinations
  • leg edema
  • compulsive behaviours (e.g. gambling, shopping, eating etc)
19
Q

If selegiline is taken BD, when should the second dose be taken and why?

A

2nd dose in the afternoon; hepatically metabolised to amphetamines (stimulant), cause insomnia

20
Q

SE of MAO-B inhibitors?

A
  • heartburn, loss of appetite
  • anxiety, palpitation
  • insomnia, nightmares, visual hallucination
21
Q

If switching from MAO inhibitors to SSRIs, SNRIs and TCAs, what should be done?

A

washout period of 14D

22
Q

Major interaction of MAO-B inhibitors with what food item?

A

Tyramine (e.g. aged cheese) -> HTN crisis

23
Q

When are COMT inhibitors indicated?

A

Adjunct to levodopa (must be used together with levodopa)

24
Q

SE of COMT inhibitors?

A
  • diarrhoea
  • urine discolouration (orange)
  • visual hallucinations
  • drowsy
25
Q

What are anticholinergics used for in Parkinson’s? Examples?

A
  • symptomatic tx for tremors & stiffness (not bradykinesia)
  • benztropine, trihexyphenidyl (benzhexol)
26
Q

What is amantadine used for in Parkinson’s?

A

Adjunct to manage levodopa-induced dyskinesias

27
Q

What drugs can cause Parkinsonism?

A
  • antipsychotics
  • ASM
  • metoclopramide, prochlorperazine
  • non-DHP CCB