Pharmacology Of Parkinsons Flashcards
Dopamine precursors eg levodopa,fos levodopa action
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.
Drug target for dopamine
No classical drug target for levodopa. Once converted into dopamine, then the targets are the dopamine receptors
Side effects of dopamine precursor
Nausea and vomiting
Dizziness
Headache
Gastrointestinal discomfort
Somnolence
Dyskinesias
Extra info on dopamine
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
Dopa decarboxylase inhibitors eg carbidopa, benserazide mechanism of action
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
Drug target for dopa decarboxylase
Dopa decarboxylase enzyme
Dopa decarboxylase side effects
Dyskinesias (facial twitching, head bobbing)
Vitamin deficiencies (B3 & B6)
Peripheral monoamine depletion
Dopa decarboxylase extra info
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
Dopamin receptor agonists eg ropinorole, rotigotine mechanism
Dopamine receptor agonists bind to post-synaptic dopamine receptors (i.e. independently of dopaminergic neurone activation).
Dopamine receptor agonists target
Dopamine receptors (D2/D3 receptors key targets in Parkinson’s disease)
Side effects of dopamine receptors agonists side effects
Nausea and vomiting
Dizziness
Headache
Gastrointestinal discomfort
Somnolence
Hallucinations
Dyskinesias
Extra info on dopamine receptor agonists
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
Local anaethetic eg lidocaine mechanism of action
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.
Target of local anesthetic
Voltage gated sodium channels
Side effects in anaethetics
Mild side effecs:
Redness, swelling at site of injection
Numbness
Severe toxicity (uncommon):
Fear/anxiety
Anaphylaxis