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Pharmacotherapeutics IV CA1 > Parkinson’s Disease > Flashcards

Parkinson’s Disease Flashcards

1
Q

Pathophysiology of PD?

A

Impaired clearing of abnormal or damaged intracellular proteins by ubiquitin proteasomal system -> failure to clear toxic proteins -> accumulation of aggresomes -> apoptosis

Degeneration of dopaminergic neurona with Lewy body (aggresome) inclusions in substantia nigra

  • substantia nigra has dopaminergic projections to basal ganglia (impt for controlling movement) -> movement disorders
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2
Q

What 3 features characterise parkinsonism?

A

Parkinsonism refers to the presence of rest remors, rigidity and bradykinesia.

= 3 cardinal features of PD

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3
Q

What are the non-motor manifestations of PD?

A
  • autonomic, neuropsychiatric, olfactory and sensory
  • common in PD
  • more prominent in later stages of PD
  • relatively resistant to and may be worsened by dopaminergic agents
  • causes significant disability
  • often neglected in PD management
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4
Q

How should we treat PD?

A

Go slow, start low. Bc PD is a chronic condition and its lifelong.

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5
Q

What to do in early symptomatic disease without complications?

A 
May not need oral medications if coping well. 
Use non pharmaco: 
- physiotherapy and exercise 
- healthy diet 
- knowledge on disease 
- social support
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6
Q

What is Levodopa’s MOA?

A
  • gold standard treatment for PD
  • it is a dopamine precursor -> converted into dopamine in the brain
  • available in 2 in 1 preparations with peripheral decarboxylase inhibitors (benserazide or carbidopa) -> prevents levodopa from being converted into dopamine in the periphery, csn reduce the dose of levodopa needed -> reduce dyskinesia
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7
Q

Side effects of levodopa?

A

Short term: nausea, vomiting and postural hypotension

Long term: motor fluctuations and dyskinesia (v serious)

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8
Q

How to dose levodopa?

A

Keep to lowest necessary dose of levodopa to achieve good motor function. Cannot be too high bc want to avoid dyskinesia.

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9
Q

What is an example of an anticholinergic used in PD?

What are anticholinergics used for in PD?

A

Example is artane

  • effective in controlling tremors
  • useful for sialorrhoea (excessive secretion of saliva) bc anticholinergic
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10
Q

Side effects of anticholinergics?

A

Especially in elderly:

Dry mouth, sedation, constipation, urinary retention, delirium, confusion and hallucinations

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11
Q

How is anticholinergics used in PD?

A

Can be used as symptomatic monotherapy OR
As adjunct to levodopa to treat tremors and stiffness in PD (combi treatment can lower dose of levodopa and prevent dyskinesia)

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12
Q

What is an example of a MAOB inhibitor used in PD?

MOA of MAOB inhibitor in PD?

A
  • Example: selegiline
  • inhibits MAOB -> prevents breakdown of dopamine -> more dopamine available in synapse
  • may delay nigral brain cell degeneration
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13
Q

Side effects of MAOB inhibitors?

A

Heartburn, loss of appetite, nausea, constipation

Dizziness, anxiety, headache, palpitation, insomnia, confusion, nightmares, visual hallucination

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14
Q

How is selegiline (MAOBI) used in PD treatment?

A

Symptomatic monotherapy and may be used in early stages of PD.

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15
Q

What is COMT?
What are examples of COMT inhibitors?
What is the MOA of COMT inhibitors?
How is COMT inhibitor used in PD?

A

COMT - Catechol- O-methyltransferase (COMT)

  • examples are entacapone and tolcapone
  • COMT inhibitors block enzyme that converts levodopa into an inactive form -> more levodopa is available to enter the brain
  • only effective if used with levodopa (not used as monotherapy)
  • increases duration of each dose of levodopa -> beneficial in treating “wearing off” responses
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16
Q

What are the side effects of COMT inhibitors?

A
  • increased abnormal movements (dyskinesias)
  • liver dysfunction (tolcapone)
  • nausea, diarrhoea
  • urinary discolouration
  • visual hallucinations
  • daytime drowsiness, sleep disturbances
17
Q

What arw examples of dopamine agonists?

What are examples of dopamine agonists in PD?

How are dopamine agonists used in PD?

MOA of dopamine agonists?

How are dopamine agonists used in younger PD patients?

A

bromocriptine, pergolide, piribedil, ropinirole, and pramipexole

  • used as adjunct (with levodopa to lower dose of levodopa) or monotherapy
  • acts directly on dopamine receptors in the brain to reduce symptoms of PD
  • anti parkinsonian effects not superior to levodopa (levodopa still the gold standard)
  • prevents or delays onset of motor complications

In younger PD patients, therapy should commence first with dopamine agonists rather than levodopa (bc side effects are rather mild compared to dyskinesia in levodopa)

18
Q

What are the side effects of dopamine agonists?

A
  • similar to levodopa
  • ergot derivative- fibrosis
  • pedal edema
  • somnolence with ropinirole and pramipexole
  • arrhythmia
  • pregolide can cause restrictive valvular heart disease
19
Q

How is Amantadine used in PD?

A
  • antiviral agent accidentally discovered to have antiparkinsonian effect (tremor, rigidity, bradykinesia and dyskinesia)
  • given as monotherapy or adjunct to levodopa (to reduce side effect of dyskinesia bc amantadine is anti dyskinetic)
  • may be considered as therapy to reduce dyskinesia in patients with PD who have motor fluctuations
20
Q

MOA of amantadine?

A
  • enhance release of stored dopamine
  • inhibit presynaptic uptake of catecholamines
  • dopamine receptor agonist
  • NMDA recepter antagonist
21
Q

What are the side effects of amantadine?

A

Its side effects limit its use in advanced disease:

  • cognitive impairment
  • hallucinations
  • insomnia
  • nightmares
  • livedo reticularis (venule swelling due to thromboses) -> mottled reticulated discolouration of limbs
  • rare cases of severe skin rash like SJS or suicidal ideation have been reported
22
Q

What are the key drugs to remember?

A 
Dopaminergic:
 Levodopa (+/- carbidopa)
 Entacapone / Tolcapone
 Selegiline / rasagiline
 Bromocriptine / pergolide / ropinirole

Non-dopaminergic / Mixed MoA:
 Amantadine
 Trihexyphenidyl (artane)

Pharmacotherapeutics IV CA1 (8 decks)

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