Antipsychotics Flashcards
action in mesolimbic pathway
D2 block –> reduced positive sx
action in mesocortical pathway
poorly responsive to D2 block. Atypicals with 5HT2A block –> decreased negative sx
action in nigrostriatal pathway
D2 block –> basal ganglia EPS effects
action in tuberoinfundibular pathway
DA neurons in hypothalamus –> DA to pituitary –| prolactin release
D2 block –> hyperprolactinemia, poikilothermia, weight gain
serotonin hypothesis
Activation of 5HT2A on DA in PFC –> decreased DA release –> negative sx
activation of 5HT2A on glu pyramidal cells in PFC –> stimulation of DA neurons in VTA –> increased DA release in mesolimbic pathway –> positive sx
glutamate and mesolimbic system
cortical glu neurons to VTA –> DIRECT stimulation of mesolimbic DA neurons
NMDA receptors on cortical GABA interneurons –> inhibited cortical glu output
glutamate and positive sx
lost cortical GABA inhibition –> increased activity of cortical glu neurons –> HYPERactivity of mesolimbic path –> positive sx
glutamate and mesocortical pathway
cortical glu neurons –> GABA interneurons in VTA –> inhibition of mesocortical DA neurons
NMDA receptors on cortical GABA interneurons in VTA –> inhibited glu output
glutamate and negative sx
hypofunction of NMDA receptors on GABA interneurons –> loss of cortical GABA inhibition –> increased activity of cortical glu neurons –> HYPOactivity in mesocortical path –> negative sx
typical antipsychotic receptor selectivity
D2»_space; 5HT2A
chlorpromazine
low potency –> less EPS risk
need larger doses for comparable antipsychotic effects –> antimuscarinic, a1 blockade, antihistamine effects
haloperidol
higher potency –> greater D2 block –> greater EPS risk
atypical antipsychotic receptor selectivity
5HT2A»_space; D2
EPS potential
haloperidol»_space; chlorpromazine > risperidone > olanzapine, clozapine, aripiprazole
EPS symptoms and treatment
acute dystonia (antimuscarinics), akathesia (reduce dose; add anticholinergic and/or B-blocker, benzo), pseudoparkinsonism (anticholinergic, amantadine), tardive dyskinesia (no treatment)
