Antiparkinsons drugs Flashcards
parkinsons disease affects what region of the brain?
It is a disorder of the basal ganglia function: caudate nucles and putamen
what are the symptoms of parkinsons?
slowness/poverty of voluntary movement
muscular rigidity
tremor at rest
abnormal posture
shuffling gait
inability to perform skilled tasks
cognitive/speech impairment
What neurotransmitter is effected in parkinsons?
dopamine (leads to dopamine deficiency)
it also leads to a loss of pigmented cells in the substantia nigra
what are the different targets of parkinson’s treatment?
Dopamine replacement therapy - (L-Dopa)
Dopamine receptor agonists - (Bromocriptine)
monoamine oxidase B inhibitors (selegiline)
catechol-O-methyltransferase inhibitors (entacapone)
How does L-dopa work?
It is a precursor to Dopamine - so it is converted to dopamine by AAAD once in the body
However, many tissues contain AAAD - so it’s not very specific, and once converted dopamine cannot cross the BBB
how does Carbidopa work?
it is often combined with L-dopa b/c it is a AAAD inhibitor that does not cross the BBB
therefore L-dopa is not converted in peripheral tissues, and the AAAD is not inhibited in the brain
What are the major side effects of L-dopa?
L-dopa dyskinesia - abnormal involuntary movement of limbs, trunk and orofacial regions-
nausea/vomiting
psychosis/anxiety
sleep disturbances
hypotension
what are the “on-off” effects related to fluctuations in clinical state due to L-dopa?
off = variable transitions from lack of movement
on = normal movement or dyskinesia
what are the issues with chronic L-dopa treatment?
reduced effectiveness, dyskinesias and on-off fluctuations
What is the MOA of Dopamine receptor agonists?
in parkinsons the loss of dopamine nerve terminals may limit long term effect of L-dopa, but Dopamine receptor agonistts do not require intact dopamine neurons
it is used to treat the ‘on-off’ effects of L-dopa
They have similar side effects to L-dopa though
how do monoamine Oxidase B inhibitors work?
monoamine oxidase B normally inactivates dopamine in humans, so this inhibitor reduces the breakdown of dopamine
how do catechol-O-methyltransferase inhibitors work?
COMT normally inactivates L-dopa and dopamine, so if we inhibit it it reduces the breakdown of L-dopa and dopamien
