Chlorpromazine 💊

💊 Key Clinical Tip: Chlorpromazine was the first widely used antipsychotic and remains an archetype for understanding dopaminergic blockade. ⚠️ Do not crush tablets - may cause contact hypersensitivity. Use cautiously in older adults due to profound sedation, orthostatic hypotension, and anticholinergic burden.

🧠 About

• Chlorpromazine is a first-generation (typical) antipsychotic of the phenothiazine class.
• It exerts broad receptor blockade: D₂ dopaminergic, 5-HT₂ serotonergic, H₁ histaminergic, α₁-adrenergic, and muscarinic receptors.
• Historically transformative - it allowed de-institutionalisation of many patients with schizophrenia.

⚙️ Mechanism of Action

• D₂ receptor blockade in the mesolimbic pathway ↓ positive psychotic symptoms (delusions, hallucinations).
• However, D₂ blockade in the nigrostriatal pathway → extrapyramidal side effects (EPSE).
• Antagonism at H₁ and α₁ receptors causes sedation and hypotension.
• Muscarinic blockade → dry mouth, constipation, urinary retention, blurred vision.
• 5-HT₂ antagonism gives minor mood-stabilising effect and sedation.

🎯 Indications & Typical Doses

• Schizophrenia and other psychoses: Chlorpromazine 25 mg TDS (or 75 mg nocte), titrate gradually to maintenance 75–300 mg/day; severe cases up to 1 g/day (use specialist supervision). In elderly: start at half adult dose.
• Intractable hiccup: 25–50 mg TDS–QDS PO.
• Acute sedation (IM): 25–50 mg deep IM every 6–8 h PRN.

🔗 Interactions

• ↑ Sedation with alcohol, benzodiazepines, opioids, or other CNS depressants.
• ↑ Risk of QT prolongation with amiodarone, sotalol, macrolides, quinolones, or other QT-prolonging psychotropics.
• ↑ Hypotension when combined with antihypertensives.
• See BNF for comprehensive list.

⚠️ Cautions

• Parkinson’s disease (may worsen rigidity and tremor).
• Epilepsy (lowers seizure threshold).
• Long-QT or concurrent QT-prolonging drugs.
• Myasthenia gravis, prostatic hypertrophy, angle-closure glaucoma.
• Severe chest disease or cardiovascular instability.
• Blood dyscrasias or hypotension.

🚫 Contraindications

• Comatose or CNS-depressed states (e.g. alcohol intoxication).
• Dementia-related psychosis in elderly (↑ mortality).
• History of agranulocytosis or bone-marrow suppression.

💥 Adverse Effects

• 😴 Sedation (H₁ blockade).
• 🦵 Extrapyramidal symptoms: dystonia, akathisia, parkinsonism, tardive dyskinesia (due to D₂ blockade).
• 🧠 Neuroleptic malignant syndrome (NMS): rigidity, fever, autonomic instability - medical emergency.
• 🧴 Antimuscarinic: dry mouth, constipation, urinary retention, blurred vision.
• 💧 Endocrine: ↑ prolactin → galactorrhoea, amenorrhoea, sexual dysfunction.
• ⚡ Cardiac: QT prolongation, arrhythmia, hypotension, syncope.
• 🧊 Temperature dysregulation: hypothermia or hyperthermia in overdose.
• 🩸 Haematological: leucopenia, agranulocytosis (rare).
• 🌈 Dermatological: rash, photosensitivity, bluish skin pigmentation (“slate-grey discoloration” with chronic use).

🧾 Monitoring

💡 Teaching Tip

• Chlorpromazine exemplifies “broad-spectrum blockade” - it targets multiple receptors, explaining both efficacy and side effects.
• Mnemonic: DAM-HA → Dopamine, Adrenergic, Muscarinic, Histamine, (5-HT₂A) - the five main receptor targets.
• Compare with haloperidol (potent D₂, minimal H₁/M blockade) - helps illustrate the trade-off between EPS and sedation.
• Always emphasise early recognition of NMS - rigidity + fever + raised CK.

📚 References

• BNF: Chlorpromazine
• MHRA Drug Safety Update (2021): Antipsychotics and QT prolongation.
• NICE NG222 (2023): Psychosis and schizophrenia in adults.
• Stahl SM. Essential Psychopharmacology, 5th ed. Cambridge University Press, 2021.