Neurological Pharmacology Flashcards
What are some of the key clinical features of Parkinsonism
- Tremor
- Rigifity
- Bradykinesia
- Postural instability
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What are some of the non motor manifestations of Parkinsonism?
- Mood changes
- Pain
- Cognitive change
- Urinary symptoms
- Sleep disorders
- Sweating
- Swallowing problems
What is the underlying pathological basis of Parkinson’s Disease?
Low Dopamine due to loss of neurones in the substantia nigra
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How is idiopathic Parkinson’s Disease diagnosed?
Based on:
- Clinical features
- Exclude other causes e.g. drug induced, vascular, progressive supranuclear palsy etc
- Responding to treatment
- Normal structural neuro imaging
Explain how a decrease in dopamine leads to the motor symptoms seen in Parkinsons
- A decrease in Dopamine leads to less inhibition on the neurostriatum
- Less inhibition = increased acetyl choline production
- Signals ot the motor cortex are altered; indirect pathway (inhibitory) is overstimulated and direct pathways (excitatory) is understimulated → reduced movement
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Describe the synthesis of Dopamine
- L- Tyrosine precursor converted to L-DOPA
- L-DOPA converted to Dopamine by DOPA decarboxylase
- Further conversion turn dopamine into norepinephrine/ epinephrine
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How is dopamine degraded?
Dopamine converted to Homovanillic acid via enzymes monoamine oxidase and catechol-O-methyl transferases (COMT)
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What is measured on a DAT scan?
A type of PET scan measuring the re-uptake of neurotransmitters
In Parkinson’s re-uptake is reduced as there are less neurones to release neurotransmitter in the first place
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Why can Parkinson’s disease not be treated by simply giving dopamine directly? What is given instead?
Dopamine cannot cross the blood brain barrier
L-DOPA is a dopamine pre-cursor that can cross the blood brain barrier (by active transport)
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Why does L-DOPA start as a good treatment for Parkinson’s but then become less reliable over time?
- Levodopa needs to be taken up by dopamingergic cells in the substantia nigra to be converted to dopamine
- Over time, the number of neurones becomes less and less so the effect is not as great
Describe the pharmacokinetics if L-DOPA
- Orally administered
- 90% in inactivated in the intestinal wall due to MOA and DOPA decarboxylase
- T 1/2 of 2 hours → need frequent dosing 3-5x day
- 9% broken down peripherally by DOPA decarboxylase
- <1% enters the CNS
What should patients taking L-DOPA be mindful of when taking their medication and why?
Need to avoid meals with large protein content at the same time as taking drug
Why?: L-DOPA is taken up by active transport , amino acids from protein compete with L-DOPA and less L-DOPA can be absorbed
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Why is L-DOPA used in combination with a peripheral DOPA decarboxylase inhibitor?
The DOPA decarboxylase inhibitor will reduce the amount of L-DOPA broken down in the periphery before reaching the brain
Allows for:
- Reduced doses required
- Reduced side effects
- Increased amount of L-DOPA reaching the brain
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Give the name of 2 L-DOPA and DOPA decarboxylase inhibitor combinations
- Sinemet (Co-careldopa)
- Madopar (Co-beneldopa)
What are the advantages of L-DOPA to treat Parkinsonism?
- Highly efficacious
- Low side effects, the ones that do exist:
- Nausea and anorexia
- Hypotension central and peripheral
- Psychosis (hallucinations, delusion, paranoia)
- Tachycardia