1. Besides D2 receptors in the mesolimbic pathway, atypical antipsychotics also block dopamine receptors in the tuberoinfundibular pathway, causing hyperprolactinemia.
High levels of prolactin indirectly decrease levels of GnRH, LH, and FSH, causing oligomenorrhea, galactorrhea, and gynecomastia.
Risperidone is the most likely to cause hyperprolactinemia.
2. Atypical antipsychotics block dopamine receptors in the nigrostriatal pathway causing extrapyramidal symptoms.
These symptoms can be subdivided into 2 main groups: a. acute extrapyramidal symptoms, which include dystonia, akathisia, and pseudoparkinsonism, also known as drug-induced Parkinsonism; and tardive, or
b. delayed extrapyramidal symptoms, which include tardive dyskinesia.
3. The most dangerous side effect is neuroleptic malignant syndrome or NMS, which is characterized by confusion, agitation, muscle rigidity, seizures, and hyperthermia.
Treatment of neuroleptic malignant syndrome includes application of dantrolene, which is a muscle relaxant; and dopamine agonists, such as bromocriptine, which mimics the effect of dopamine.
4. Besides dopamine D2 receptors and serotonin 5-HT2A receptors, atypical antipsychotics also block: histamine H1 receptors causing sedation; alpha-1 receptors, causing orthostatic hypotension; and muscarinic receptors, causing atropine-like (anticholinergic) side effects, such as dry mouth, blurred vision, urinary retention, and constipation.
5. Atypical antipsychotics can also cause metabolic syndrome, which includes weight gain, diabetes, dyslipidemia, and increased cardiovascular risk.
People treated with olanzapine and clozapine tend to gain the most weight, while aripiprazole has the least impact on weight.
Clozapine can also cause seizures and agranulocytosis, which is a condition where a person's white blood cells are depleted, resulting in frequent and overwhelming infections.
Because of this, the white blood cell count (WBC) and absolute neutrophil count (ANC) need to be monitored, so it's only used in individuals that don't respond to other antipsychotics.
6. Finally, atypical antipsychotics, especially ziprasidone, can prolong the Q-T interval and should be avoided in people with arrhythmias.