pharmacology of parkinsons Flashcards
production sequence of dopamine
tyrosine -> Dopa -> dopamine
enzyme that converts tyrosine to dopa
tyrosine hydroxylase
enzyme that converts dopa to dopamine
L-amino acid decarboxylase
2 pathways of dopamine metabolism
MAO-B
COMT
enzyme that converts dopa into 3-o-methoxy dopa
catechol-o-methyl transferase
PK of L-dopa
- very rapid onset
- benefits may exceed duration of the drug in plasma due to recycling
MoA of L-dopa
gets taken up into dopamine neurons and converted to dopamine and then released
too little dopamine being produced leads to
- wearing off
- on-off phenomenon
too much dopamine being produced leads to
- dyskinesias
- hallucinations/psychosis
when dopamine neurons are almost all degenerated how is dopamine still produced
- L-dopa is taken up into serotonin neurons
- aromatic amino acid decarboxylase can convert dopa to dopamine
- dopamine gets released abnormally
where dyskinesias stem from
loss of dopamine neurons to reuptake dopamine so there is hyperexcitation of D1 receptors
COMT inhibitor drugs
- entacapone
- entacapone + L-dopa + carbidopa
MAO-B inhibitor drugs
- rasagiline
- selegiline
COMT inhibitor MoA
prevent metabolic breakdown of dopa in the periphery so it can get to where it needs to be
MAO-B inhibitor MoA
inhibits metabolism of dopamine in dopamine neurons to increase the amount that is available for release
Dopamine agonists
- pramipexole
- ropinirole
- rotigotine
dopamine agonist MoA
agonize D2 receptors in the indirect pathway
antimuscarinic drugs
- trihexyphenidyl
- benztropine mesylate
amantadine use
reduce dyskinesias
amantadine MoA
- blockade of NMDA receptors and thus hyperactivity in subthalamic nucleus/internal Globus Pallidus pathway
- causes reduced release of glutamate in SN which ultimately increases activation of the cerebral cortex
cofactor for L-amino acid decarboxylase
pyridoxal phosphate
