MH PHARM | Chlorpromazine [Thorazine]

Chlorpromazine (Thorazine): Essential Clinical Profile1. Mechanism of Action & Pharmacology Chlorpromazine is a first-generation phenothiazine antipsychotic and antiemetic. It blocks postsynaptic dopamine D2 receptors in the mesolimbic system, reducing psychosis but causing extrapyramidal symptoms (EPS). Dopamine blockade in the chemoreceptor trigger zone produces antiemetic effects. It exhibits strong anticholinergic and alpha-1-adrenergic receptor blocking properties, causing sedation and cardiovascular effects like profound hypotension.2. Pharmacokinetics & Metabolism Oral bioavailability averages 32% due to extensive first-pass metabolism. It is 90% to 99% plasma protein-bound, and undergoes biphasic metabolism with a terminal half-life of 30 hours. Metabolism is primarily via CYP2D6, which chlorpromazine inhibits. Only 1% of the drug is excreted unchanged in urine, and it is not dialyzable. Peak antipsychotic effects may take 6 weeks to 6 months.3. Core Indications & Dosing Parameters Approved for schizophrenia (adults start at 10-25 mg PO; up to 1000 mg/day max), severe pediatric behavioral problems (ADHD), intractable hiccups, tetanus adjunct, acute intermittent porphyria, and acute nausea/vomiting. Off-label uses include acute migraines, neonatal abstinence syndrome, and ICU agitation. It is a last-line option for pregnancy-induced nausea.4. High-Risk Administration Protocols Intravenous (IV) administration is restricted to surgical nausea, severe hiccups, or tetanus. It must NEVER be injected undiluted. Dilute with 0.9% NaCl to 1 mg/mL; maximum infusion rate is 1 mg/min for adults (0.5 mg/min for children). IM injections must be given slowly and deeply into the upper outer buttock. Blood pressure monitoring is mandatory; patients must remain completely recumbent for at least 30 minutes following IM/IV doses to prevent severe orthostatic hypotension.5. Boxed Warning & Geriatric Precautions A strict Boxed Warning notes it is not approved for dementia-related psychosis in the elderly due to significantly increased mortality risks (heart failure, sudden death, infections) and stroke. The Beers Criteria classifies it as a potentially inappropriate medication (PIM) due to risks of tardive dyskinesia, falls, and anticholinergic toxicity. Long-term care use is regulated by OBRA guidelines, requiring gradual dose reduction attempts in two separate quarters in the first year.6. Major Adverse Reactions Life-threatening reactions require immediate intervention: neuroleptic malignant syndrome (NMS), tardive dyskinesia, QT prolongation, seizures, and agranulocytosis. Common effects include drowsiness, xerostomia, photosensitivity, and severe hypotension. Discontinue therapy immediately if jaundice develops. Monitor sodium closely due to SIADH risk.