Chlorpromazine

Chlorpromazine is a first-generation low-potency typical antipsychotic agent. It exerts its antipsychotic effect by blocking dopaminergic receptors (D1-D4 but especially D2) in mesolimbic and mesocortical pathways. It is approved for use in humans as an antipsychotic agent to manage psychotic disorders, such as mania, schizophrenia, and bipolar disorder. Miscellaneous other uses are in the treatment of intractable hiccup, nausea, vomiting, preoperative anxiety, and severe behavioral problems in children. It is also useful as a treatment of psychogenic pruritus. Chlorpromazine's use is associated with major adverse effects, such as extrapyramidal side effects, orthostatic hypotension, sedation, and ocular complications. Chlorpromazine has been associated with a greater risk of seizures among first-generation antipsychotics. Long-term use of chlorpromazine has been associated with corneal deposits and hepatoxicity, which includes abnormal liver function tests (increased serum aminotransferase levels), acute cholestatic liver injury, and jaundice. Chlorpromazine can cross the blood-brain barrier. With the development of second-generation antipsychotics that have a lower side-effect profile, chlorpromazine is now rarely used. It is extensively metabolized in the liver and kidneys (by isozymes CYP2D6, CYP1A2 and CYP3A4), yielding to many metabolites. This drug chapter aims to illustrate the uses (FDA-approved and Off-label), acute and chronic toxicity, and clinical management of the adverse and toxic effects associated with chlorpromazine. It also highlights the exposure routes, toxicokinetics, immunotoxicity, reproductive toxicity, genotoxicity, carcinogenicity, and ecotoxicity associated with chlorpromazine. There is no known antidote for this compound, and poisoned patients should receive prompt supportive care.