Antipsychotics

Antipsychotics are used for schizophrenia and other psychotic disorders, for acute mania in bipolar disorder, and as adjuncts in several other psychiatric conditions. Their shared mechanism is antagonism at dopamine D2 receptors, and blockade in the mesolimbic pathway is what reduces the positive symptoms of psychosis. Because dopamine pathways serve other functions, the same blockade elsewhere in the brain produces the class's characteristic adverse effects.

First-generation (typical) agents include high-potency drugs such as haloperidol and fluphenazine and low-potency drugs such as chlorpromazine. Potency predicts the side effect profile: high-potency agents cause more movement disorders, while low-potency agents cause more sedation, anticholinergic effects, and orthostatic hypotension from histamine, muscarinic, and alpha-adrenergic blockade. Second-generation (atypical) agents such as risperidone, olanzapine, quetiapine, ziprasidone, and aripiprazole add serotonin 5-HT2A antagonism, which lowers the risk of movement disorders but shifts the burden toward metabolic effects — weight gain, hyperglycemia, and dyslipidemia, most pronounced with olanzapine and clozapine. Aripiprazole is distinctive as a D2 partial agonist rather than a pure antagonist.

Extrapyramidal symptoms follow a recognisable timeline: acute dystonia within hours to days, akathisia over days to weeks, drug-induced parkinsonism over weeks to months, and tardive dyskinesia after months to years of exposure. Dopamine blockade in the tuberoinfundibular pathway removes the inhibition normally exerted on prolactin release, so hyperprolactinemia with galactorrhea, amenorrhea, or gynecomastia is a class effect, prominent with risperidone. Neuroleptic malignant syndrome is the emergency to recognise: fever, lead-pipe rigidity, autonomic instability, altered mental status, and elevated creatine kinase.

Two agents carry specific monitoring burdens. Clozapine is reserved for treatment-resistant schizophrenia because of agranulocytosis risk and requires scheduled absolute neutrophil count monitoring; it also lowers the seizure threshold. Ziprasidone and thioridazine prolong the QT interval. Antipsychotics are not controlled substances, so they carry no DEA schedule.

Coverage differs across exams. USMLE Step 1 tests receptor mechanisms, the EPS timeline, hyperprolactinemia, and neuroleptic malignant syndrome. The PTCE places antipsychotics among nervous system drugs, expecting brand and generic recognition and correct classification. NCLEX approaches them through the nursing care of psychotic disorders, focusing on monitoring, side effects, and patient teaching.