**_💊Pharmacology💊 - Parkinson's Flashcards

1
Q

What is the first line treatment for Parkinson’s?

A

Levodopa (dopamine precursor) combine with carbidopa

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2
Q

Why does levodopa help with Parkinson’s treatment?

A

Acts as a precursor to dopamine, converted to dopamine in the brain by dopa decarboxylase
By increasing dopamine levels in the brain, levodopa compensates for the loss of dopamine caused by the degeneration of dopaminergic neurons in Parkinson’s disease

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3
Q

Why is levodopa given, not dopamine directly?

A

Dopamine unable to cross the blood-brain barrier - levodopa can
Levodopa only converted to dopamine where dopa decarboxylase can be found - keeps dopamine to the areas of the body where dopamine should be found - reduces off target effects

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4
Q

What is carbidopa?

A

Inhibitor of dopa decarboxylase

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5
Q

Why is levodopa usually combined with carbidopa?

A

Carbidopa can’t cross the blood-brain barrier, so inhibits extra-cerebral dopa decarboxylase
Prevents extra-cerebral presence of dopamine

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6
Q

What is the recommended dosage of combined carbidopa/levodopa?

A

Initially 25/100mg 3x daily
Increase in increments of 12.5/50 per day
Dose can increase up to 200/800 daily
When co-careldopa is used (combination levodopa/carbidopa) minimum 70mg carbidopa required - less will not fully inhibit extra-cerebral dopa decarboxylase

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7
Q

What can Parkinson’s medication cause in patients, particularly those of moderate or advanced stage disease?

A

Motor fluctuations
Dyskinesias

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8
Q

What are some of the classic symptoms of motor fluctuations?

A

Freezing of gait
Difficulty standing

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9
Q

What are dyskinesias?

A

Involuntary, jerky movements
Caused by sensitization of the brain to dopamine

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10
Q

Why do dyskinesias and motor fluctuation occur?

A

When giving a patient levodopa, causes rising peaks and troughs of dopamine levels (fluctuations)
On periods, where dopamine is very high, leads to dyskinesias
Off periods, where dopamine is too low, leads to motor fluctuations

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11
Q

What are the options for treating patients who develop dyskinesias?

A

Using controlled-release preparations of levodopa
Replace levodopa with a D2 receptor agonist

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12
Q

How does a D2 receptor agonist differ from levodopa, with regard to the treatment of Parkinson’s?

A

Dopamine agonists directly stimulate D2 receptors
Mimic the action of dopamine
Do not require conversion into dopamine to be effectuve
Bypass the need for dopaminergic neurons (no need for dopa decarboxylase)
Have a longer half-life, more stable and prolonged dopaminergic stimulation (less doses per day, so less peaks and troughs)

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13
Q

What is the mechanism of action of dopamine precursors (e.g. levodopa)?

A

Taken up in terminals of nigrostriatal neurons, decarboxylated into dopamine
Compensates for loss of endogenous dopamine

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14
Q

What is the mechanism of action of dopa decarboxylase inhibitors?

A

Inhibits extra-cerebral dopa decarboxylase
Prevents presence of extra-cerebral dopamine, thus less off target and side effects (e.g. nausea)

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15
Q

What is the mechanism of action of dopamine receptor agonists?

A

Binds to post-synaptic dopamine receptors, independently of dopaminergic neurone activity

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16
Q

What is the mechanism of action of local anaesthetics?

A

Uncharged form of local anaesthetics diffuse through the neurone to bind to the sodium channel, from the inside
Locks them in open state, prevents nerve depolarisation

17
Q

What is the drug target of dopa decarboxylase inhibitors?

A

Dopa decarboxylase enzyme

18
Q

What is the drug target of dopamine precursors?

A

No classical drug target
Converted by enzymes to dopamine

19
Q

What is the drug target of dopamine receptor agonists?

A

Dopamine receptors (D2/D3 receptors key in Parkinson’s)

20
Q

What is the drug target of local anaesthetics?

A

Voltage gated sodium channels

21
Q

What are the main side effects of dopamine precursors?

A

Nausea and vomiting
Dizziness
Headache
GI discomfort
Somnolence (strong desire to sleep)
Dyskinesias

22
Q

What are the main side effects of dopa decarboxylase inhibitors?

A

Dyskinesias (facial twitching, head bobbing)
Vitamin deficiencies (B3 & B6)
Peripheral monoamine deficiency

23
Q

What are the main side effects of dopamine receptor agonists?

A

Nausea and vomiting
Dizziness
Headache
GI discomfort
Somnolence (strong desire to sleep)
Dyskinesias
Hallucinations
i.e. Same as levodopa + hallucinations

24
Q

What are the main side effects of local anaesthetics?

A

Mild side effects:
Redness, swelling at site of injection
Numbness
Uncommon:
Severe toxicity
Fear/anxiety
Anaphylaxis