Week 7 Antipsychotics Flashcards
List the brain circuit that is malfunctioning to the symptoms of schizophrenia.
- Positive symptoms: hyperactive mesolimbic circuit
- Negative symptoms: hypoactive mesocortical
- Affective symptoms: ventromedial prefrontal cortex
- Agressive: orbitofrontal cortex and amygdala
- cognitive symptoms: dorsolateral prefrontal cortex
What is the nigrostriatal DA pathway? Role in schizophrenia?
- projects from substantial negra to striatum or BG, part of extrapyramidal nervous system and controls motor function and movement
- normal in schizophrenia
What is the mesolimbic DA pathway? Role in schizophrenia?
- projects from midbrain ventral tegmental area to nucleus accumbens
- involved in behaviors associated with pleasurable sensations, drugs, delusions, hallucinations
- hyperactive in schizophrenia
What is the mesocortical DA pathway? Role in schizophrenia?
- projects from midbrain ventral tegmental area to prefrontal cortex
- mediating cognitive and affective sysmptoms (dorsolateral prefrontal cotex and ventromedial prefrontal cortex)
- hypoactive in schizophrenia
What is the tuberinfundibular DA pathway? Role in schizophrenia?
- projects from hypothalamus to anterior pituitary gland and controls prolactin secretion
- normal in schizophrenia
Define typical antipsychotics.
- Dopamine D2 receptor antagonism.
- Extrapyramidal side effects: blocking alpha-1, causing CV side effects such as hypotension and drowsiness
Define atypical antipsychotics
- D2 receptor antagonism with serotonin-2A antagonism
- rapid dissociation of D2 antagonism
What is the mechanism of typical antipsychotics in treating schizophrenia? What are its effects in the different DA pathways?
MESOLIMBIC
-blocks dopamine from binding to the D2 receptor
-decreases hyperactivity
MESOCORTICAL
-A d2 antagonist could further reduce activity in this pathway and worsen cognitive, negative, and affective symptoms
NEGROSTRIATAL
-can cause motor side effects are are called extrapyramidal symptoms (EPS)
-tardive dyskinesia–>long term effect: tongue protrusions, facial grimaces, chewing, quick jerky limb movements like Parkinsons
-long term blockage of D2 can cause up regulation of those receptors, lead to hyperkinetic motor condition
Summarize the effects of typical antipsychotics on a schizophrenia patient.
- reduce positive symptoms of psychosis but may reduce experience of pleasure or reward
- no improvement in cognitive, negative, or affective symptoms, may worsen them
- nigrostriatal and tuberoinfundibular pathways: reduction of dopamine can cause extrapyramidal symptoms and prolactin elevation
How does serotonin regulate dopamine release from nigrostriatal dopamine neuron?
- Serotonin inhibits dopamine release at the level of dopamine cell bodies in substantial nigra and at level of axon terminals in basal ganglia-neostriatum
- 5HT2A antagonists stimulate DA release by blocking the action of serotonin inhibition of DA release
What is the mechanism of atypical antipsychotics in treating schizophrenia? What are its effects in the different DA pathways?
- Mesolimbic DA pathway: same as for typical antipsychotics
- mesocortical: blockade of 5HT2A receptors leads to DA release, could improve affective, cognitive, and negative symptoms
- nigrostriatal: 5HT2A antagonisms reverses that action of D2 antagonism. DA is released when 5HT can no longer inhibit its release. DA competes with atypical antipsychotic for D2 receptors and reverses inhibition there
- cause little EPS symptoms or tar dive dyskinesia
Summarize the effects of atypical antipsychotics on a schizophrenia patient.
- reduce positive symptoms of psychosis, may also reduce experience of pleasure and reward
- any potential increase in DA in mesocortical may be offset by 5HT2A antagonism, net effect may be increase in DA in cortex. Could reduce cognitive, negative, or affective symptoms
- Nigrostriatal and tuberoinfundibular: net effect may be DA output unchanged. reduces risk of EPS.
What are some adverse effects of typical and atypical antipsychotics?
- Clozapine: can cause agranulocytosis (lowered WBCs)
- atypical antipsychotics: risk of hyperglycemia and diabetes
- risperadone: EPS and hypotension at higher doses, low EPS at low doses
