Lecture 2: Movement Disorders (PD & HD) Flashcards
What causes PD?
- Age: most important risk factor!
- Family history
- Male gender
Signs & symptoms of PD
TRAP:
- Tremor
- Rigidity
- Akinesia (difficulty initiating movement)
- Postural problems
Difference between PD & HD
PD: difficulty initiating movement
HD: difficulty suppressing unwanted movements
What is the most common form of PD?
Idiopathic (shaking at rest)
In PD, what is happening to the neurons and where
- In PD, dopaminergic neurons start dying in the SUBSTANTIA NIGRA
(SN is the major origin of dopaminergic innervation of the striatum; a main function is regulation of posture and muscle tone)
Dopamine in CNS synapses
NT (dopamine) synthesized presynaptically -> packaged into vesicles -> vesicles merge with membrane & dopamine is released -> dopamine enters synaptic gap and interacts with receptor -> DAT (transporters located presynaptically that clear the synapse) take left over dopamine & recycles it
What happens in PD in terms of dopamine?
- Dopaminergic neurons decrease, thus dopamine production decreases
- Because healthy people balance dopamine & Atch, the decrease in dopamine will increase atch
What is effective treatment for PD?
Increase dopamine
Decrease atch
Why can’t you just give someone dopamine to reduce PD?
- Dopamine cannot pass the blood-brain barrier
How & why is L-DOPA used in PD treatment?
- It is a precursor of dopamine that CAN cross the blood brain barrier, where it is then taken up by dopaminergic neurons and converted to dopamine for use in the synapse
- Therefore, increasing dopamine levels
What is the downside of L-DOPA?
Only 1-3% of it crosses the blood-brain barrier, which is helpful, but is only SHORT-TERM
How can you maximise L-DOPA?
- Combine it with an antagonist (carbidopa) for the enzyme that converts L-DOPA to dopamine in the periphery & digestive system
- Slows conversion down, increasing the amount of L-DOPA that reaches the brain
What is the challenge with PD treatment? What does this mean for the patient?
- It does nothing to prevent the death of dopaminergic neurons - it only helps to minimise the impact
- Thus, you need to constantly be reassessed to determine effectiveness of treatment
What drugs inhibit the metabolism of dopamine?
- Rasagiline
- Entacapone
Rasagiline mechanism
Slows the normal degradation of dopamine in the brain and preserves it for recycling into vesicles
