💊Pharmacology💊 - Parkinson's Flashcards
What is the first line treatment for Parkinson’s?
Levodopa (dopamine precursor) combine with carbidopa
Why does levodopa help with Parkinson’s treatment?
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
Why is levodopa given, not dopamine directly?
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
What is carbidopa?
Inhibitor of dopa decarboxylase
Why is levodopa usually combined with carbidopa?
Carbidopa can’t cross the blood-brain barrier, so inhibits extra-cerebral dopa decarboxylase
Prevents extra-cerebral presence of dopamine
What is the recommended dosage of combined carbidopa/levodopa?
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
What can Parkinson’s medication cause in patients, particularly those of moderate or advanced stage disease?
Motor fluctuations
Dyskinesias
What are some of the classic symptoms of motor fluctuations?
Freezing of gait
Difficulty standing
What are dyskinesias?
Involuntary, jerky movements
Caused by sensitization of the brain to dopamine
Why do dyskinesias and motor fluctuation occur?
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
What are the options for treating patients who develop dyskinesias?
Using controlled-release preparations of levodopa
Replace levodopa with a D2 receptor agonist
How does a D2 receptor agonist differ from levodopa, with regard to the treatment of Parkinson’s?
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)
What is the mechanism of action of dopamine precursors (e.g. levodopa)?
Taken up in terminals of nigrostriatal neurons, decarboxylated into dopamine
Compensates for loss of endogenous dopamine
What is the mechanism of action of dopa decarboxylase inhibitors?
Inhibits extra-cerebral dopa decarboxylase
Prevents presence of extra-cerebral dopamine, thus less off target and side effects (e.g. nausea)
What is the mechanism of action of dopamine receptor agonists?
Binds to post-synaptic dopamine receptors, independently of dopaminergic neurone activity
