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PHA333 > Wk 29 - Parkinson's disease 2 > Flashcards

Wk 29 - Parkinson's disease 2 Flashcards

1
Q

Which drugs restore dopamine levels in nigrostriatal dopaminergic tract?

A
  • Levodopa (L-dopa) + carbidopa/benserazide
  • Dopamine agonists
  • MAO-B inhibitors
  • COMT inhibitors
  • Miscellaneous (Amantadine)
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2
Q

Which drug restore dopamine-acetylcholine balance?

A

Antimuscarinic

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3
Q

Levodopa

A
  • Therapeutic + adverse effects result from decarboxylation to DA
  • Given w/ peripheral decarboxylase inhibitor to prevent peripheral break down (Carbidopa , Benserazide)
  • Nausea + vom red by DOPA decarboxylase inhibitors
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4
Q

Outline the therapeutic effectiveness of Levodopa

A
  • Best results: 1st few years
  • 80%: marked initial improvement
  • 20%: normal motor function
  • Effectiveness dec overtime
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5
Q

Why does the effectiveness of levodopa dec overtime?

A
  • Progressive loss of dopaminergic neurons
  • Down-reg of D1/D2 receptors on post-synaptic terminals
  • Some require red dose but inc freq
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6
Q

Dyskinesias occur in what percentage of patients on long-term levodopa therapy?

A

80%

  • Excessive + abnormal involuntary movements
  • Higher dose = inc risk
  • Frequently in younger patients
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7
Q

What are the side effects of levodopa?

A
  • Anorexia, N+V
  • Dry mouth
  • Postural hypotension
  • Drowsiness + Sudden onset of sleep
  • Dystonia + dyskinesia
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8
Q

How is levodopa taken?

A
  • Empty stomach, 45 mins before meal

- Food inhibit absorption from gut

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9
Q

Outline the interactions of levodopa

A
  • Inc postural hypotension w/ antihypertensives
  • Risk of hypertensive crisis due to inc catecholamine w/ MAOIs
  • Pyridoxine inc peripheral break down of L-dopa
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10
Q

What do bromocriptine + pergolide mesylate dopamine-receptor agonists do?

A
  • Bromocriptine - selective D2 receptor agonist + partial agonist at D1 receptors
  • Pergolide mesylate - directly stims D1 + 2 receptos
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11
Q

What is Pergolide mesylate associated w/?

A
  • Cardiac valve fibrosis

- Loses efficacy over time

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12
Q

What is the clinical use of bromocriptine + pergolide mesylate dopamine-receptor agonists?

A
  • Used as individual
  • Combination w/ levodopa
  • Patients who are refractory to + can’t tolerate levodopa
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13
Q

What are the side effects of bromocriptine + pergolide dopamine-receptor agonists?

A
  • GI disturbances:anorexia,nausea + vomiting
  • Cardiac arrhythmias
  • Postural hypotension
  • Drowsiness + Sudden onset of sleep
  • Dyskinesia
  • Pulmonary infiltrates + erythromelalgia
  • Impulse control disorder
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14
Q

What does ropinirole + pramipexole dopamine-receptor agonists do?

A
  • Affinity for D2 sub class especially at D2 + D3 receptors
  • Early management of PD
  • Pramipexole: neuroprotective - scavenge H2O2
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15
Q

What does rotigotine dopamine-receptor agonists do?

A
  • Used to treat sign + symptom of early PD

- Admin as OD transdermal patch

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16
Q

What are the side effects of ropinirole + pramipexole + rotigotine?

A
  • GI disturbances: N + V
  • Sleepiness + fatigue
  • Marked hypotension
  • Drowsiness + Sudden onset of sleep
  • Dyskinesia
  • Neuropsychiatric: hallucination,
    confusion, insomnia
17
Q

What does apomorphine dopamine-receptor agonists do?

A
  • Potent dopamine agonist
  • High affinity for D4 receptors
  • Low affinity for D1 receptors
  • Given via SC injection to provide temp relief of ‘off periods’ of akinesia
18
Q

What does MAO-A metabolize?

A

NA + 5-HT

19
Q

What does MAO-B metabolize?

A

Dopamine

20
Q

What does selegiline + rasagiline do (MAOIs)?

A
  • Selective, irreversible inhibitors of MAO-B
  • Prevent break down of both naturally occurring DA + DA formed from levodopa
  • Doesn’t inhibit MAO-A
21
Q

What is selegiline metabolised to?

A
  • Methamphetamine

- Amphetamine

22
Q

Outline the therapeutic effectiveness of MAOIs

A
  • Early PD

- Enables red in levodopa dose or smooth on-off fluctuations

23
Q

What are the side effects of MAOIs?

A
  • Blocks MAO-A at high dose - hypertensive crisis due to peripheral accumulation of NA
  • Fatal hyperthermia when admin w/ meperidine, cocaine or fluoxetine
24
Q

Give examples of COMT inhibitors + what they do?

A

Diminish peripheral metabolism of levodopa + red on-off fluctuations

  • Tolcapone
  • Entacapone
  • Opicapone
25
Q

What are the adverse effects of COMT inhibitors?

A
  • Inc plasma conc of levodopa
  • Dyskinesias
  • Nausea
  • Confusion
  • Diarrhea
  • Sleep disorders
  • Tolcapone - hepatoxic
26
Q

What is the main treatment for PD before levodopa?

A

Anticholinergics

27
Q

What is the clinical use of anticholinergics?

A
  • Control tremor in early stage
  • Used: drug induced PD
  • Not used in idiopathic PD (cause cog impairment)
28
Q

What are the side effects of anticholinergics?

A
  • Constipation
  • Blurred vision
  • Dry mouth
  • Urinary retention
29
Q

What is amantadine used for?

A
  • Prophylaxis + treatment of influenza A
  • For latter stages if problem w/ dyskinesia induced by levodopa
  • Inc DA release in striatum
  • Anticholinergic properties
  • Blocks NMDA glutamate receptors
30
Q

What are the side effects of amantadine?

A
  • Difficulty in concentrating
  • Confusion
  • Nightmares
  • Leg swelling
  • Livedo reticularis

PHA333 (35 decks)

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