Pharmacology of Psychoses - Mood Disorders Flashcards
Explain the dopamine theory of schizophrenia and its limitations.
hypothesis = abnormality in brain function in schizophrenics is due to overactivity in
brain dopaminergic pathways, especially in mesolimbic pathway
limits = a) Postmortem and in vivo imaging studies show diminished DA activity in cortical and hippocampal regions that may underlie negative symptoms and cognitive impairment
b) Clozapine is weak D2 blocker but still is an effective antipsychotic agent
c) Evidence exists for role of serotonin (5-HT) and glutamate neurotransmitter systems (via modulation of dopamine neurotransmission)
Describe the mechanism of antipsychotic drug action.
Virtually all effective antipsychotics block CNS dopamine receptors (postsynaptic D2).
Name the brain dopamine systems affected by antipsychotic drugs.
1: Mesolimbic pathway
2: Mesocortical pathway
3: Nigrostriatal pathway
4: Tuberoinfindibular pathway
Describe the mesolimbic pathway.
integration of sensory input and motor responses with affective or emotional data
Hyperactivity in this pathway is believed to
contribute to the occurrence of positive symptoms
Tx = antipsychotics (via D2 receptor blockade)
Describe the mesocortical system.
Cortical structures (dorsolateral prefrontal cortex and ventromedial prefrontal cortex) are involved in communication and social abilities.
Hypoactivity due to cell loss in the prefrontal cortex contributes to presence of negative symptoms.
Tx = atypical antipsychotic agents such as clozapine or olanzapine (via additional block of 5HT2A receptors)
Describe the nigrostriatal system.
This dopaminergic tract is part of a larger subcortical circuit known as the basal ganglia and plays a central role in planned, coordinated movement.
Loss of dopamine in this region results in dysregulation of movement (Parkinson’s disease –> hypoactivity,
bradykinesia, and tremor).
Tx = dopaminergics
Describe the tuberoinfundibular system.
Hypothalamic neurons release DA in pituitary to inhibit prolactin release.
What integrates sensory input and motor responses with affective or emotional data?
the mesolimbic pathway
Collectively, these cortical structures (dorsolateral prefrontal cortex and ventromedial prefrontal cortex) are involved in communication and social abilities.
the mesocortical system
Loss of dopamine in this region results in dysregulation of movement (Parkinson’s disease –> hypoactivity,
bradykinesia, and tremor).
the nigrostriatal system
_____ drug use (via ______) can result in unwanted extrapyramidal side effects
Antipsychotic via D2 dopamine receptor blockade
What are antipsychotic drug side effects called?
extrapyramidal side effects
What are extrapyramidal side effects?
antipsychotic drug side effects
______ neurons release DA in pituitary to inhibit prolactin release.
Hypothalamic
Hypothalamic neurons release ______ in pituitary to inhibit prolactin release.
DA
Hypothalamic neurons release DA in pituitary to inhibit ______.
prolactin release
Antipsychotic drug use (via ______) can cause side effects of hyperprolactinemia as well as interference with regulation of body temperature (poikilothermia) and alteration of eating behavior (weight gain).
D2 dopamine receptor blockade
Chlorpromazine NTs and receptors? SEs? Tx for? Choose when? Dosing and extra considerations?
Chlorpromazine
NTs and receptors: high D2 / 5HT2A ratio = good D2 block (typical agent)
SEs: MANY, esp ANS: antimuscarinic, α1-blockade, sedation
Tx for: Schizo, mania, Tourettes, depression. IS AN ANTIEMETIC and treats intractable hiccoughs
Choose when: to treat positive symptoms
Dosing and extra considerations: generic and cheap but high doses; IM
Aripiprazole (Abilify) NTs and receptors? SEs? Tx for? Choose when? Dosing and extra considerations?
Aripiprazole (Abilify)
NTs and receptors: low D2 / 5HT2A ratio= poor D2 block (atypical agent) and good 5-HT, little bit of D4, alpha-1, and H1 block, too
SEs: uncertain, possible novel toxicities
Tx for: Schizo, mania, Tourettes, depression
Choose when: to treat negative symptoms of schizo
Dosing and extra considerations: lower weight gain, long half life; IM
Haloperidol NTs and receptors? SEs? Tx for? Choose when? Dosing and extra considerations?
Haloperidol
NTs and receptors: high D2 / 5HT2A ratio = good D2 block (typical agent) and mild alpha-1 block
SEs: SEVERE extrapyramidal syndrome
Tx for: Schizo, mania, Tourettes, depression
Choose when: to treat positive symptoms
Dosing and extra considerations: generic avail; low doses; IM
Clozapine NTs and receptors? SEs? Tx for? Choose when? Dosing and extra considerations?
Clozapine
NTs and receptors: low D2 / 5HT2A ratio= poor D2 block (atypical agent), medium D4 block, medium alpha-1, medium 5-HT block, medium M block, mild H1 block
SEs: little extrapyramidal tox but can cause AGRANULOCYTOSIS, lowers SZ threshold
Tx for: Schizo, mania, Tourettes, depression
Choose when: treatment resistant otherwise; to treat negative symptoms of schizo
Dosing and extra considerations: Use in otherwise resistant patients. Oral or IM (long acting)
Risperidone NTs and receptors? SEs? Tx for? Choose when? Dosing and extra considerations?
Risperidone
NTs and receptors: low D2 / 5HT2A ratio= poor D2 block (atypical agent); medium D2 block, mild alpha-1, medium 5-HT, mild M, mild H1
SEs: MAJOR EXTRAPYRAMIDALS
Tx for: Schizo, mania, Tourettes, depression
Choose when: to treat negative symptoms of schizo
Dosing and extra considerations: Oral.
Olanzapine NTs and receptors? SEs? Tx for? Choose when? Dosing and extra considerations?
Olanzapine
NTs and receptors: low D2 / 5HT2A ratio= poor D2 block (atypical agent); mild D2 block, mild alpha-1, medium 5-HT, mild M, mild H1
SEs: little to none extrapyramidal, but weight gain, lowers SZ threshold, possible DIABETES
Tx for: Schizo, mania, Tourettes, depression
Choose when: to treat negative symptoms of schizo
Dosing and extra considerations: High dose req’d; can help with insomnia; oral, IM
Activation of the cortical glutamate neurons leads first to activation of the ______, then inhibition of mesocortical DA neurons.
VTA GABA interneurons
Activation of the cortical glutamate neurons leads first to activation of the VTA GABA interneurons, then inhibition of ______.
mesocortical DA neurons
Activation of the _______ leads first to activation of the VTA GABA interneurons, then inhibition of mesocortical DA neurons.
cortical glutamate neurons
