describe the main neurochemical theory leading to schizophrenia?
dopamine theory:
- amphetamine, a drug which increases dopamine, NA and 5-HT produces sx similar to acute schizophrenia
- it is the most important theory basis for pharmacotherapy that all antipsychotics are D2 antagonists
- affects mesocortical pathway and nigrostratial pathway (off-target effects)
describe the 2 other theories relating to positive sx of schizo
5-HT: LSD which acts primarily as 5-HT agonist, produces sx similar to acute schizo
glutamate theory: drugs which block the NMDA receptor channel produce sx similar to acute schizo
list the examples of typical antipsychotic drugs
chlorpromazine, haloperidol, trifluoperazine
describe EPS
extrapyrimidal side effects
- acute dystonia: parkinsonism-like syndrome occurring within the first few weeks of tx (reversible)
- tardive dyskinesia and akathisia: involuntary movements & compulsion to act associated with restlessness, anxiety & agitation
what are the general ADR of typical antipsychotics
- dry mouth, consti, blurred vision (only in chlorpromazine)
- postural HoTN, dizziness (only in chlorpromazine)
- sedation, weight gain
what is the core characteristic of atypical antipsychotics?
serotonin-dopamine antagonism (SDA)
list some examples of atypical antipsychotics
clozapine, amisulpride, olanzapine, risperidone, aripiprazole
what is an ADR of clozapine which limits its use clinically?
clozapine-induced agranulocytosis
what is the ADR unique to amisulpride?
effect on mammary glands and tissues:
- increase prolactin secretion due to block of dopamine receptors in anterior pituitary glands
- breast swelling, pain & lactation
- presents as gynecomastia in males
what is the moa of aripiprazole
partial agonist which has antagonistic effects in the presence of an agonist
what are the additional ADRs of atypicals
- new onset or exacerbation of diabetes (irreversible even when drug is stopped; does not occur in amisulpride)
- drug induced weight gain (unlikely in amisulpride)
why do atypicals produce less EPS
- clozapine: potent 5-HT antagonism vs weak D2 antagonism; and high D4 vs D2 favours action in prefrontal cortex rather than striatum
- olanzapine: potent 5-HT vs weak D2
- amisulpride: high D3 vs D2 favours action on nucleus accumbens over striatum; high D2 vs D1 reduces impact of antagonism in striatum
what are the additional benefits of atypicals?
clozapine, risperidone and olanzapine are more effective against negative sx & better at mood stabilisation
- clozapine & risperidone may ameliorate cognitive dysfunction
