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clozapine p. 591
agranulocytosis with p. 249
clozapine use and p. 591
Antipsychotics, as their name implies, are mainly used to treat schizophrenia and other psychotic conditions.
Even though the exact cause of schizophrenia is still unknown, there's some evidence that suggests it’s related to altered levels of the neurotransmitter dopamine.
Now, antipsychotics are subdivided into two main categories: the first generation or typical antipsychotics, and the second generation or atypical antipsychotics.
Alright, within the brain, dopamine is found in 4 main dopamine pathways: the mesolimbic pathway, which controls motivation and desire; mesocortical pathway, which helps regulate emotions; nigrostriatal pathway, which contains motor neurons that bypass the medullary pyramids, to control involuntary movements and coordination; and lastly, tuberoinfundibular pathway, which releases dopamine to limit the secretion of prolactin.
Other regions of the central nervous system that are rich in dopamine receptors, include the chemoreceptor trigger zone, which initiates the vomiting reflex; and the medullary periventricular pathway, which regulates eating behavior.
However, in schizophrenia, altered levels of dopamine mainly affect the mesolimbic pathway and mesocortical pathway.
There’s usually high levels of dopamine in the mesolimbic pathway, which cause positive symptoms of schizophrenia, such as delusions, hallucinations, and disorganized thought.
On the other hand, low levels of dopamine in the mesocortical pathway cause negative symptoms of schizophrenia, such as lack of motivation, social withdrawal and “flat affect”, which basically means lack of emotions.
Now, in conditions such as schizophrenia, atypical antipsychotics block dopamine D2 receptors in the mesolimbic pathway, thereby alleviating positive symptoms of schizophrenia.
But, they also block serotonin 5-HT2A receptors in the mesocortical pathway.
These receptors are found on inhibitory neurons that regulate dopaminergic neurons and decrease dopamine release.
Atypical antipsychotics are a newer class of medications used to treat schizophrenia and bipolar disorder. Unlike the older typical antipsychotics, atypical antipsychotics are not as likely to cause movement disorders like tardive dyskinesia. However, atypical antipsychotics can sometimes cause other side effects, such as weight gain, high blood sugar, and heart problems such as myocarditis.
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