pharmacology: parkinson disease Flashcards
nigrostriatal tract
caudate and putamen
DA agonists = initiation of movement
mesolimbic-mesocortical tracts
amygdala and hippocampus
DA agonists = reinforcement “good feelings”
tuberoinfundibular
endocrine (hypothalamus to pituitary)
DA agonists = decreased prolactin
chemoreceptor trigger zone (CTZ)
vomiting (DA agonists)
D1 receptors
Gs couples (increased cAMP)
D2A receptor
Gi coupled (decreased cAMP) - nigrostriatal (movement initiation)
D2C receptor
Gi coupled (decreased cAMP) - mesolimic (mood)
what are the dopaminergic neural pathways?
nigrostriatal tract, mesolimibic-mesocortical tracts, tuberinfundibular, chemoreceptor trigger zone
parkinson disease pathology
degeneration of nigrostriatal dopamine tracts with imbalance between dopamine (decreased) and ACh (increased)
DA and Ach both work on GABA-ergic neuron - Ach will stimulate GABA neuron causing inhibition and DA will inhibit the GABA neuron causing excitatory
what are the drugs used in parkinsons
levodopa, cabidopa, talcapone, entacapone, selegiline, bromocriptine, pramipexole, ropinirole, benztropine, trihexyphenidyl, diphenhydramine, amantadine
levodopa mechanism and side effects
a prodrug converted to dopamine by aromatic amino acid decarboxylase (AAAD)
side effects: dyskinesias, psychosis, hypotension (D1 receptor agonist), vomiting
carbidopa mechanism and use
peripheral inhibitor of AAD (noncompetitive, decrease vmax AAD) - prevents levodopa from being converted to dopamine in periphery - dopamine cannot cross BBB
talcapone and entacapone mechanism and use
COMT inhibitors - COMT converts L-dopa to 3-O-methyldopa (partial agonist at dopamine receptors and competes with Ldopa) - works in both brain and periphery
side effects tolcapone
hepatotoxic
selegiline mechanism
MAO B selective inhibitor (prevents breakdown of dopamine to metabolites) - initial treatment and adjunct to levodopa
