Pharmacology Of Parkinsons Flashcards

1
Q

Dopamine precursors eg levodopa,fos levodopa action

A

Levodopa is taken up in the terminals of nigrostriatal neurones. It is decarboxylated into dopamine by dopa decarboxylase (useful to think of levodopa as a prodrug for dopamine). This compensates for the loss of endogenous dopamine in nigrostriatal neurones.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Drug target for dopamine

A

No classical drug target for levodopa. Once converted into dopamine, then the targets are the dopamine receptors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Side effects of dopamine precursor

A

Nausea and vomiting
Dizziness
Headache
Gastrointestinal discomfort
Somnolence
Dyskinesias

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Extra info on dopamine

A

Onset of somnolence can be rapid and without warning. Caution advised when driving.

Fos-levodopa is a phosphate pro-drug of levodopa. It is more water soluble than levodopa, which makes it more suitable for constant sub-cutaneous infusion.
Rapid withdrawal of levodopa can lead to neuroleptic malignant syndrome
In 2020 – Co-careldopa was the 113th most commonly prescribed drug in West London area

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Dopa decarboxylase inhibitors eg carbidopa, benserazide mechanism of action

A

Dopa decarboxylase inhibitors block the dopa decarboxylase enzyme and prevent the conversion of dopa to dopamine. These drugs cannot enter the brain and only exert their effects peripherally. As a result, they only reduce dopamine side effects in the periphery e.g. nausea. This increases amount of levodopa available for nigrostriatal neurons

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Drug target for dopa decarboxylase

A

Dopa decarboxylase enzyme

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Dopa decarboxylase side effects

A

Dyskinesias (facial twitching, head bobbing)

Vitamin deficiencies (B3 & B6)

Peripheral monoamine depletion

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Dopa decarboxylase extra info

A

Maximum dose of carbidopa is 200mg.
Carbidopa is rarely administered alone, which makes it more difficult to identify specific adverse effects/contraindications specifically associated with carbidopa. Given with levodopa to reduce affects in periphery
In 2020 – Co-careldopa was the 113th most commonly prescribed drug in West London area

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Dopamin receptor agonists eg ropinorole, rotigotine mechanism

A

Dopamine receptor agonists bind to post-synaptic dopamine receptors (i.e. independently of dopaminergic neurone activation).

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Dopamine receptor agonists target

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Side effects of dopamine receptors agonists side effects

A

Nausea and vomiting
Dizziness
Headache
Gastrointestinal discomfort
Somnolence
Hallucinations
Dyskinesias

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Extra info on dopamine receptor agonists

A

Dopamine receptor agonists tend to be used as add-on therapy with levodopa.
Newer dopamine agonists are more selective for D2/D3 receptors. D3 receptors mediate drug seeking behaviours so these drugs are more associated with impulsive behaviours and compulsive gambling
Anti-PD drugs don’t tend to be prescribed in primary care so are less commonly prescribed than other drugs. As an add on therapy, dopamine agonists are not within the top 250 most prescribed drugs.
Doesn’t cross the blood brain barrier

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Local anaethetic eg lidocaine mechanism of action

A

Uncharged form of local anaesthetics diffuse through the neurone to bind to the sodium channel from the inside. This locks them in the open state and prevents nerve depolarisation.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Target of local anesthetic

A

Voltage gated sodium channels

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Side effects in anaethetics

A

Mild side effecs:
Redness, swelling at site of injection
Numbness

Severe toxicity (uncommon):
Fear/anxiety
Anaphylaxis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Extra info of lidocaine

A

Lidocaine’s efficacy is reduced at sites of inflammation. pH is lower at these sites, so basic lidocaine exists in a more polarised (charged) state so less can diffuse across neurones.
Lidocaine is also classified as a class 1b anti-arrythmic – slows conduction in the heart due to decreasing permeability of sodium channel to sodium
In 2020 – lidocaine was the 162nd most commonly prescribed drug in West London area