Flashcards in 3.1 Psychosis: Basic Sciences Deck (18):
What brain morphology is associated with poorer outcomes in schizophrenia?
-Reduced frontal lobe volume and frontal lobe grey matter
-Enlarged lateral ventricle volume
-Reduced temporal cortex volume- superior temporal gyrus
-Reduced temporal cortex and median temporal lobe volumes
What is the dopamine hypothesis of schizophrenia?
-Dopamine releasing drugs (amphetamines) or D2 receptor agonists produce psychotic state
-dopamine receptor antagonists treat symptoms of schizophrenia
-schizophrenia due to overactivity of dopamine pathways
What do the dopamine receptor subtypes do in the brain?
D1/F5: stimulate cAMP
D2/3/4: inhibit adenylyl cyclase, inhibit voltage activated Ca2+ channels and open K+ channels (makes cell more -)
What is the distribution of D1 receptors? D2 receptors?
D1: neostriatum, cerebral cortex, olfactory tubercle, nucleus accumbens
D2: neostriatum, olfactory tubercle, nucleus accumbens
What is an agonist and antagonist of dopamine D2 receptor?
Agonist: bromocriptine (can tx parkinsons, pit tumour, hyperprolactinemia)
Antagonist: raclopride, haloperidol
What receptor does clozapine block?
Clozapine is a D4 antagonist
What is the reformulated Dopamine hypothesis?
Psychosis: due to subcortical dopamine hyperactivity
Negative/cognitive symptoms: due to mesocortical dopamine hypoactivity.
Failure to activate ventral striatum during rewarding cues associated with stronger negative symptoms
What is the glutamatergic hypothesis of schizophrenia?
Due to altered NMDA receptor subunit expression
Evidence: ketamine can cause psychotic symptoms
What is the Serotonergic hypothesis of schizophrenia?
Due to abnormal serotonin NA binding potential in frontal cortex
Evidence: this binding potential is smaller in pts with schizophrenia
What genes are implicated in schizophrenia brain pathology?
neuregulin- role in growth and development of organs
dysbindin- essential for neural plasticity
DISC-1- neurite outgrowth and cortical development role
Name some typical antipsychotics, and the definition
drugs without atypical properties
What is the definition of atypical antipsychotic? What are some examples?
1. Less likely to cause extrapyramidal side effects
2. High 5HT-2A to D2 blockade ratio
3. Better efficacy vs. negative symptoms
4. Effective in pts not responsive to typical drugs
What do extrapyramidal effects mean?
(Tardive dyskinesia- the presentation of these effects after several months)
Do not occur with clozapine
Less prominent with atypical antipsychotics
-Result from D2 blockade in the nigrostriatal pathways
What is the principle SE of 5HT-2 blockade in antipsychotics?
-related to antagonism/inverse agonist activity at 5HT2C receptors
What is the principle SE of histamine blockade in antipsychotics?
What is the principle SE of alpha-1 adrenergic blockade in antipsychotics?
Due to lack of sympathetic stimulation that should cause increased HR and BP.
What are the principle SE of muscarinic blockade in antipsychotics?
Increased ocular pressure
CNS muscarinic blockade may also cause confusion