Drugs used in Parkinson's disease Flashcards
Parkinson’s sx
- Resting tremor - 4-6Hz
- Bradykinesia
- Rigidity
Why is neuromelanin in substantial nigra good?
Protects neurones from oxidative stress
Components of dopamine
Tyrosine and levo-dopa
How is dopamine made?
- Made from tyrosine and levo-dopa
- Tyrosine acquires hydroxyl group to form thyrosine hydroxylase
- L-dopa loses carboxylic acid group to form dopamine by DOPA decarboxylase
How do you increase dopamine levels?
- At presynaptic membrane, dopamine released into cleft and can either attach to postsynaptic membrane, be re-uptaken by presynaptic neurone, or be degraded by MAO or COMT
- To increase dopamine: increase tyrosine, L-dopa, decrease degradation, stimulate dopamine receptor
What happens to cause Parkinson’s sx
Less dopamine means less inhibitory effect on cholinergic and GABA-inergic neurones so glutaminergic neurones are less inhibited
What happens when you have too much glutamate ?
Excitiotoxicity
Glutamate is excitatory - causes neuronal damage, ischaemia and brain injury
NMDA mediates glutamate and causes Ca2+ influx to mediate destructive cell processes
How does levodopa work?
Passes through BBB and moves into CNS where it is converted to dopamine
combined effect of levodopa and carbidopa
Inhibits AAD in periphery (less side effects and more dopamine in CNS)
Sx too much dopamine
Hallucinations, behaviour changes (gambling, hyper sexuality etc )
Dopamine agonists examples
Pramiopexole, ropinirole
Side effects of dopamine agonists
Impulse control disorders, tiredness, hallucinations
MAO-B inhibitor examples
Rasagiline, selegiline
Where is MAOB found ?
Striatum
Function of mAOBi
Inhibit MAOB to increase dopamine conc
