Pharmacology of psychoses Flashcards
dopamine theory of SCHIZOPHRENIA
abnormality in brain function in schizophrenia due to overactivity in dopaminergic pathways esp MESOLIMBIC PATHWAY
drugs block D2 recpeotrs treat schizo
schizophrenics have decr D2 in prefrontal lobe but incr D2 in striatum
support for dopamine hypothesis
1) all antipsychotics block CNS postsynap D2
2) drugs that incr DA (L-dopa, cocaine, amphetamine) aggravate/prod schizo
3) PET shows decr D2 density in prefrontal but incr in caudate
evidence against dopamine hypothesis
1) block D2 occurs immediately while antipsych effect = 3-6 weeks
2) clozapine = weak D2 block but effective antipsych
3) glut and serotonin also involved
Nigrostriatal path
1) structure involve
2) normal function
3) role in schizo
4) pharm intervention
1) subst nigra + striatum
2) planning and coord movement
3) not affected in schizo
4) antipsych (D2 block) –> extrapyramidal parkinson sign
mesolimbic path
1) structure involve
2) normal function
3) role in schizo
4) pharm intervention
1) VTA, nucleus accumbens, amygdala, hippocampus, VMPFC
2) integrate sensory input + motor response with emotional resonse
3) hyperactivity –> positive sx
4) antipsych (D2 block) decr positive sx
mesocortical path
1) structure involve
2) normal function
3) role in schizo
4) pharm intervention
1) dorsolat and VM prefrontal cortex
2) comm and social skills
3) hypoactivity –> negative sx (lack of motiv, social isolation)
4) poor response to antipsych
responsive to atypical antipsych
tuberoinfundibular path
1) structure involve
2) normal function
3) role in schizo
4) pharm intervention
1) hypothalamus and pituitary
2) hypothalamic neurons release DA into pituitary to inhib prolactin release
3) not affected
4) antipsych (D2 block) in hypothal –> hyperprolactinemia, poikilothermia, weight gain
role of cortical glutamate neurons in causing schizo
effect on mesolimbic
1) cortical glut
2) incr GABA from brainstem neuron
3) inhib mesolimbic path
in schizo, decr inhib mesolimbic from hypofunction of NMDA-glu cortical neurons–> positive sx
role of cortical glutamate neurons in causing schizo
effect on mesocortical path
1) cortical glut
2) incr release of DA from brainstem neuron
3) excitation of mesocortical path
in schizo, decr excitation of mesocortical from hypofunction of NMDA-glu cortical neuron –> negative sx
role of cortical-striatal-thalamic-cortical loop in causing schizo
1) cortical glut
2) incr GABA activity of striatum
3) decr thalamic excitation
4) decr incoming sensory to cortex
in schizo, overactivity of mesolimbic –> incr DA release from VTA into nucleus accumbens –> disinhib of thal
or decr activity of glutamate neurons –> decr GABA outflow from striatum –> disinhib of thal
role of 5HT2A -receptor on DA neurons in striatum and PFC
1) activate 5HT2A receptor in striatum and prefrontal cortex
2) decr DA release (negative sx)
role of 5HT2A -receptor on pyramidal cells in PFC
1) activation of 5-H2A
2) stim VTA
3) incr DA release = positive sx
Typical antipsych
1) ratio of D2 to 5HT2A block ratio
2) positive or negative sx use?
3) side effect
4) which pathway affects?
1) high D2/5HT2A ratio
2) decr positive symptoms
3) incr extrapyramidal toxicity
4) decr DA in mesolimbic pathway
Atypical antipsych
1) ratio of D2 to 5HT2A block ratio
2) positive or negative sx use?
3) side effect
4) which pathway affects?
1) low D2/5HT2A ratio
2) decr negative sx
3) decr extrapyramidal side effect
4) incr DA release in mesocortical pathway
Chlorpromazine
1) uses
2) NT and receptor involved
3) side effects
4) treatment of side effects
1) treat positive sx
2) block most D2 but some muscarinic, alpha1, and H1
3) low EP signs,
high dose = dry mouth, hypotension, sedation
4) n/a
