O-CHLOPROMAZINE 75 TABLETS

Indications

• Schizophrenia
• Acute psychosis
• Severe behavioral problems in children
• Nausea and vomiting
• Preoperative sedation

Dosage

Children: Dosing in children should be determined carefully, considering age, weight, and clinical condition. Refer to BNF for Children for specific dosing recommendations.

Adults: Dosage varies based on the condition being treated and patient response. Initiation of therapy typically starts at lower doses, which can be gradually increased as needed, with careful monitoring for efficacy and side effects.

Mechanism of action

Chlorpromazine exerts its therapeutic effects primarily by blocking dopamine D2 receptors in the central nervous system. This antagonism reduces dopaminergic activity, which is implicated in the pathophysiology of psychotic disorders. Additionally, chlorpromazine exhibits antagonistic effects on various other receptors, including alpha-adrenergic, histaminergic, and muscarinic receptors, contributing to its diverse clinical effects.

Pharmacodynamics

Chlorpromazine has a complex pharmacodynamic profile. Its antipsychotic effects are primarily due to dopamine receptor blockade, which alleviates symptoms of psychosis such as hallucinations and delusions. The drug also possesses sedative properties, as it can cause CNS depression, making it useful in treating agitation and anxiety. However, its use may lead to extrapyramidal side effects due to interference with dopaminergic pathways involved in motor control.

Pharmacokinetics

Chlorpromazine is well absorbed after oral administration, with peak plasma concentrations typically occurring within 2 to 4 hours. It undergoes extensive hepatic metabolism, primarily through the cytochrome P450 system, resulting in various active metabolites. The elimination half-life can range from 30 to 70 hours, and the drug is primarily excreted in the urine. Its pharmacokinetic profile may be affected by factors such as age, liver function, and concurrent medications.

Contra-indications

• Hypersensitivity to chlorpromazine or any component of the formulation
• Severe central nervous system depression
• Comatose states
• Bone marrow depression
• Pheochromocytoma
• Jaundice due to liver dysfunction

Adverse effects

• Sedation
• Hypotension
• Extrapyramidal symptoms (e.g., tremors, rigidity)
• Tardive dyskinesia
• Anticholinergic effects (e.g., dry mouth, constipation)
• Weight gain
• Photosensitivity
• Neuroleptic malignant syndrome
• Agranulocytosis

Interactions

• Increased CNS depression with alcohol, sedatives, and opioids
• Antihypertensive agents may have enhanced effects
• Anticholinergic drugs may increase anticholinergic side effects
• Dopamine agonists may reduce the effectiveness of chlorpromazine
• Certain antidepressants may increase the risk of serotonin syndrome

Precautions

• Monitor for signs of agranulocytosis, especially in patients with pre-existing conditions
• Use caution in patients with cardiovascular disease
• Use in elderly patients may increase the risk of adverse effects
• Caution in patients with a history of seizures
• Regular monitoring of metabolic parameters is advised due to the risk of weight gain and diabetes

Pregnancy

Chlorpromazine should only be used in pregnancy if the potential benefits justify the potential risks to the fetus. It is classified as category C.

Breast-feeding

Chlorpromazine is excreted in breast milk. Caution should be exercised when administered to a breastfeeding woman.

Storage

Store at room temperature, away from light and moisture. Keep out of reach of children.

Formulations

• Tablets (various strengths)
• Oral suspension
• Injectable solution (intramuscular)