Pharmacology of Movement Flashcards
what does parkinson’s disease histologically look like
- Loss of dopaminergic cells in substantia nigra pars compacta
- And presence in neurones of Lewy bodies ( these are intracellular formation that are enriched in the protein alpha-synuclein)
- These Lewy bodies are also presence in other conditions such as dementia
- There are also losses of cells throughout the nervous system
How can you monitor the loss of dopaminergic nigral cells in parkinsons
- This imaging of the transporter is known as the DAT scan
- The transporter is a marker of dopaminergic projections and can be labelled with SPECT ligands
What are the motor features of parkinsons
Features of the disease
- Resting tremor – specific frequency of around 4-6hz
- Bradykinesia (akinesia)
- Rigidity
They also have
- Difficulty initiating and stopping movement
- Altered gait and postural changes (flexed posture)
Other symtpoms
- Gradual development of micrographia
What are the non motor features of parkinsons
- olfactory dysfunction
- depression
- psychotic symptoms
- cognitive dysfunction
- dementia (late phase)
- sleep disturbance
- autonomic dysfunction
what features of parkinsons arise first normally motor or non motor
non-motor features may precede by 12-15 years the onset of typical parkinsonian motor symptoms, this premotor phase is likely to involve multiple regions of the peripheral and central nervous system
describe the scoring phase of parkinsons
- 100%-Completely independent. Able to do all chores w/o slowness, difficulty, or impairment.
- 90%-Completely independent. Able to do all chores with some slowness, difficulty, or impairment. May take twice as long.
- 80%-Independent in most chores. Takes twice as long. Conscious of difficulty and slowing
- 70%-Not completely independent. More difficulty with chores. 3 to 4X along on chores for some. May take large part of day for chores.
- 60%-Some dependency. Can do most chores, but very slowly and with much effort. Errors, some impossible
- 50%-More dependant. Help with 1/2 of chores. Difficulty with everything
- 40%-Very dependant. Can assist with all chores but few alone
- 30%-With effort, now and then does a few chores alone of begins alone. Much help needed
- 20%-Nothing alone. Can do some slight help with some chores. Severe invalid
- 10%-Totally dependant, helpless
- 0%-Vegetative functions such as swallowing, bladder and bowel function are not functioning. Bedridden.
what protein is associated with parkinsons
protein alpha-synuclein
what gene is associated with parkinson’s disease
- SNCA- codes for the protein alpha-synuclein – increases significantly the risk of developing Parkinson’s
- Duplications, or triplications can cause autosomal dominant familial parkinsons disease
describe how neurotoxins and dopamine receptors can lead to parkinsons
- there can be mitochondrial toxicity
- MPTP this can be transformed into the metabolite MPP+ which is neurotoxic for dopaminergic neurones
- dysfunction of complex I of the mitochondrial respiratory chain can lead to increased oxidative stress
Why is oxidative stress increased in parkinsons disease
- Dopamine is highly oxidizable and its metabolism produces free radicals and oxidation products such as H2O2
- MAO – monoamine oxidase (B isoform) is critically involved in oxidation
processes
describe the pathway of dopamine synthesis
- L tyrosine is made into L dopa via tyrosine hydroxylase
- L dopa is made into dopamine via DOPA decarboxylase
describe the pathway of dopamine being degraded
- MAO coverts dopamine to DOPA
- then COMT coverts DOPA to its inactive form
why is dopamine given as L dopa in a drug
- dopamine does not go straight through the blood brain barrier as it is hydrophilic
- when it is taken in high amounts it also makes you sick
- it is inactivated as well
What type of receptors are dopamine receptors
G protein coupled receptors
name the two dopamine family receptors and there subtypes
- D1-like (D1 family) receptor subtypes: D1 and D5
- D2-like (D2 family) receptor subtypes: D2, D3, D4
