Usage
Chlorpromazine is prescribed for a range of conditions, including:
- Psychotic disorders: Schizophrenia, schizoaffective disorder, manic episodes associated with bipolar disorder.
- Nausea and vomiting: Including that associated with surgery, chemotherapy, and gastroenteritis.
- Intractable hiccups: Persistent hiccups unresponsive to other treatments.
- Preoperative apprehension and anxiety: To promote relaxation before surgical procedures.
- Behavioral disorders and hyperactivity in children: Especially in hospitalized settings.
- Acute intermittent porphyria: A rare metabolic disorder.
- Tetanus: As an adjunct to other treatments.
Pharmacological Classification: Chlorpromazine is classified as a first-generation (typical) antipsychotic, also known as a neuroleptic. It belongs to the phenothiazine class of medications.
Mechanism of Action: Chlorpromazine primarily acts as a dopamine receptor antagonist, specifically blocking D2 receptors in the brain. This action is believed to be responsible for its antipsychotic effects. It also has anticholinergic, antihistaminic, and alpha-adrenergic blocking properties, contributing to its sedative and other effects.
Alternate Names
- Chlorpromazine hydrochloride
- Largactil (brand name)
- Thorazine (brand name)
- Thoradol (brand name)
How It Works
Pharmacodynamics: Chlorpromazine’s primary effect is the blockade of dopamine D2 receptors in various brain regions. This blockade impacts dopaminergic pathways, leading to a reduction in psychotic symptoms. Its anticholinergic, antihistaminic, and alpha-adrenergic blocking actions contribute to sedative, antiemetic, and hypotensive effects, respectively.
Pharmacokinetics:
- Absorption: Well-absorbed orally, but bioavailability is reduced by first-pass metabolism. Intramuscular (IM) and intravenous (IV) routes provide higher bioavailability.
- Metabolism: Extensively metabolized in the liver, primarily by CYP2D6. Numerous metabolites are formed, some of which are active.
- Elimination: Excreted in urine and bile, with a half-life of approximately 30 hours.
Mode of Action: Chlorpromazine binds to and blocks dopamine D2 receptors, preventing dopamine from binding and exerting its effects. This receptor blockade disrupts dopaminergic neurotransmission, which is thought to be overactive in psychotic disorders. It also influences other neurotransmitter systems, including acetylcholine, histamine, and norepinephrine, through receptor blockade.
Elimination Pathways: Primarily hepatic metabolism followed by renal and biliary excretion. CYP2D6 is the major enzyme involved in its metabolism.
Dosage
The dosage of chlorpromazine varies depending on the indication, patient age, and other factors. It’s important to note that the information below is for general guidance and should be tailored to individual patients.
Standard Dosage
Adults:
- Oral: Initially 30-75 mg per day divided every 6-12 hours, gradually increasing to a maintenance dose of 200 mg per day. Higher doses (up to 800 mg or more) may be required in some cases.
- IM/IV: Initially 25 mg, followed by 25-50 mg every 1-4 hours as needed, up to a maximum of 400 mg every 4-6 hours. Usual dosage is 300-800 mg per day.
Children:
- Under 6 months: Safety and efficacy not established.
- 6 months and older: Dosage based on weight (0.5-1 mg/kg) or age. Dosing frequency is typically every 4-6 hours. Maximum daily doses are usually limited (40 mg for 1-5 years, 75 mg for 6-12 years).
Special Cases:
- Elderly Patients: Lower initial doses are recommended (typically 1/3 to 1/2 the adult dose), with gradual titration based on response and tolerability.
- Patients with Renal Impairment: Dose adjustment may be needed based on renal function.
- Patients with Hepatic Dysfunction: Dose reduction is usually required due to impaired metabolism.
- Patients with Comorbid Conditions: Careful monitoring and dose adjustment may be necessary, particularly for patients with cardiovascular disease, diabetes, or other conditions.
Clinical Use Cases
Dosing for specific clinical situations varies and should be guided by clinical protocols and patient response:
- Intubation: Chlorpromazine is not typically used for intubation itself but may be used to manage agitation or nausea/vomiting associated with the procedure.
- Surgical Procedures: May be used preoperatively for anxiety and postoperatively for nausea and vomiting.
- Mechanical Ventilation: Not routinely indicated but may be used to manage agitation or delirium.
- Intensive Care Unit (ICU) Use: May be used to manage delirium or agitation.
- Emergency Situations: IM or IV administration may be used to rapidly control severe agitation or psychotic symptoms.
Dosage Adjustments
Dosage adjustments are based on individual patient factors, including renal and hepatic function, other medical conditions, concomitant medications, and response to therapy. Therapeutic drug monitoring may be helpful in some cases.
Side Effects
Common Side Effects:
- Drowsiness
- Dizziness
- Dry mouth
- Blurred vision
- Constipation
- Orthostatic hypotension (low blood pressure upon standing)
- Extrapyramidal symptoms (EPS): Tremor, rigidity, restlessness, dystonia
- Weight gain
- Photosensitivity
Rare but Serious Side Effects:
- Neuroleptic malignant syndrome (NMS): A life-threatening condition characterized by fever, muscle rigidity, altered mental status, and autonomic instability.
- Tardive dyskinesia (TD): A potentially irreversible movement disorder.
- Agranulocytosis (low white blood cell count): Increasing the risk of infections.
- Jaundice (liver dysfunction)
- Seizures
- Severe allergic reactions
Long-Term Effects:
- Tardive dyskinesia
- Metabolic syndrome (weight gain, elevated cholesterol and triglycerides, insulin resistance)
Adverse Drug Reactions (ADR):
- NMS
- Agranulocytosis
- Anaphylaxis
Contraindications
- Hypersensitivity to chlorpromazine or other phenothiazines
- Coma
- Severe CNS depression
- Severe hypotension
- Bone marrow suppression
- Phaeochromocytoma
- Hepatic failure
- Subcortical brain damage
- Poorly controlled seizure disorder
- Circulatory collapse
Drug Interactions
Chlorpromazine interacts with numerous medications, including:
- CNS depressants (alcohol, benzodiazepines, opioids): Increased sedation and respiratory depression.
- Anticholinergics (antihistamines, tricyclic antidepressants): Enhanced anticholinergic effects.
- Antihypertensives: Increased risk of hypotension.
- Dopamine agonists (levodopa): Reduced effectiveness of dopamine agonists.
- CYP2D6 inhibitors and inducers: Alterations in chlorpromazine metabolism.
Pregnancy and Breastfeeding
- Pregnancy: Not contraindicated but should be used with caution, especially in the first and third trimesters. May cause extrapyramidal symptoms in newborns.
- Breastfeeding: Chlorpromazine is excreted in breast milk. Monitor infants for drowsiness and developmental milestones. Use the lowest effective dose if necessary. Consider alternative medications.
Drug Profile Summary
- Mechanism of Action: Dopamine D2 receptor antagonist, also has anticholinergic, antihistaminic, and alpha-adrenergic blocking properties.
- Side Effects: Drowsiness, dizziness, dry mouth, EPS, orthostatic hypotension, NMS, TD.
- Contraindications: Hypersensitivity, coma, severe CNS depression, severe hypotension, bone marrow suppression.
- Drug Interactions: CNS depressants, anticholinergics, antihypertensives, dopamine agonists, CYP2D6 inhibitors/inducers.
- Pregnancy & Breastfeeding: Use with caution; monitor infant.
- Dosage: Varies by indication and age; adjust for renal/hepatic impairment.
- Monitoring Parameters: Blood pressure, mental status, liver function tests, complete blood count, EPS.
Popular Combinations
Chlorpromazine may be used in combination with other medications for specific conditions, but its use in combinations is becoming less common due to the availability of newer antipsychotics with fewer side effects.
Precautions
- General Precautions: Monitor for EPS, NMS, TD, hypotension, and other adverse effects.
- Specific Populations: Adjust dosage for elderly, renally impaired, and hepatically impaired patients. Avoid in children under 6 months.
- Lifestyle Considerations: Avoid alcohol, protect skin from sun exposure, avoid operating machinery until effects are known.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Chlorpromazine?
A: The dosage varies based on the indication and patient characteristics. Refer to the “Dosage” section above for detailed information.
Q2: What are the most common side effects of Chlorpromazine?
A: The most common side effects are drowsiness, dizziness, dry mouth, blurred vision, constipation, orthostatic hypotension, and EPS.
A: Neuroleptic malignant syndrome (NMS), tardive dyskinesia (TD), agranulocytosis, severe allergic reactions, and seizures are serious side effects requiring immediate medical attention.
Q4: Can Chlorpromazine be used during pregnancy and breastfeeding?
A: Chlorpromazine should be used cautiously during pregnancy, particularly in the first and third trimesters. During breastfeeding, use the lowest effective dose if necessary and monitor the infant closely.
Q5: What are the contraindications for Chlorpromazine use?
A: Contraindications include hypersensitivity to phenothiazines, coma, severe CNS depression, severe hypotension, bone marrow suppression, phaeochromocytoma, and hepatic failure.
Q6: How does Chlorpromazine interact with other medications?
A: Chlorpromazine can interact with CNS depressants, anticholinergics, antihypertensives, dopamine agonists, and drugs that affect CYP2D6 metabolism.
Q7: How should Chlorpromazine be administered?
A: Chlorpromazine can be administered orally, intramuscularly (IM), or intravenously (IV). The choice of route depends on the specific clinical situation and patient condition.
Q8: What monitoring parameters are essential during Chlorpromazine therapy?
A: Monitoring blood pressure, mental status, liver function tests, complete blood counts, and observing for extrapyramidal symptoms is essential during Chlorpromazine therapy.
Q9: What is the mechanism of action of Chlorpromazine?
A: Chlorpromazine primarily blocks dopamine D2 receptors. It also has anticholinergic, antihistaminic, and alpha-adrenergic blocking effects.
Q10: What patient education is essential for individuals taking Chlorpromazine?
A: Patients should be educated about potential side effects, drug interactions, precautions regarding sun exposure, and the importance of avoiding alcohol and operating machinery until the drug’s effects are fully understood. They should also be advised to report any unusual symptoms to their healthcare provider immediately.
