Usage
Prochlorperazine is prescribed for the management of:
- Severe nausea and vomiting: This includes nausea and vomiting associated with surgery, chemotherapy, and gastroenteritis.
- Schizophrenia: Prochlorperazine helps manage psychotic symptoms like hallucinations and delusions.
- Generalized non-psychotic anxiety: It’s important to note that this is not a first-line treatment for anxiety and usage should be limited to low doses for short periods (less than 20 mg/day or 12 weeks).
- Vertigo and dizziness associated with inner ear disorders like Meniere’s disease.
- Migraine: (off-label use)
Pharmacological Classification: Prochlorperazine is a first-generation antipsychotic (also known as a typical antipsychotic or neuroleptic) belonging to the phenothiazine class. It also possesses antiemetic properties.
Mechanism of Action: Prochlorperazine primarily acts as a dopamine receptor antagonist, blocking dopamine D2 receptors in the brain. This action is responsible for its antipsychotic and antiemetic effects. It also exhibits anticholinergic, antihistaminic, and antiadrenergic properties, contributing to its clinical effects and side effect profile.
Alternate Names
- International Nonproprietary Name (INN): Prochlorperazine
- Other Names: Prochlorperazine maleate, prochlorperazine mesylate, prochlorperazine edisylate (depending on the specific salt form)
Brand Names: Compazine, Stemetil, Buccastem, and various generic formulations are available.
How It Works
Pharmacodynamics: Prochlorperazine’s effects are primarily mediated through dopamine D2 receptor antagonism in various brain regions. This leads to:
- Antipsychotic Effect: Reduced dopaminergic activity in the mesolimbic pathway, alleviating positive symptoms of schizophrenia.
- Antiemetic Effect: Dopamine receptor blockade in the chemoreceptor trigger zone (CTZ) in the medulla oblongata suppresses nausea and vomiting.
- Other Effects: The drug’s anticholinergic, antihistaminic, and alpha-adrenergic blocking properties contribute to its side effect profile.
Pharmacokinetics:
- Absorption: Well-absorbed orally, rectally, and intramuscularly. Oral bioavailability is relatively low due to first-pass metabolism.
- Metabolism: Extensively metabolized in the liver, primarily by CYP2D6.
- Elimination: Excreted in urine and feces as metabolites.
Mode of Action: Prochlorperazine binds to and blocks dopamine D2 receptors, preventing dopamine from binding and exerting its effects. This results in decreased dopaminergic neurotransmission.
Receptor Binding: Primarily a dopamine D2 receptor antagonist. Also exhibits some affinity for other receptors, including alpha-adrenergic, histamine H1, and muscarinic cholinergic receptors.
Elimination Pathways: Primarily hepatic metabolism followed by renal and biliary excretion.
Dosage
Standard Dosage
Adults:
- Oral: 5-10 mg every 6-8 hours, not exceeding 150 mg/day. Extended-release: 10 mg every 12 hours or 15 mg every morning.
- Intramuscular: 5-10 mg every 3-4 hours, not exceeding 40 mg/day.
- Intravenous: 2.5-10 mg every 3-4 hours, not exceeding 10 mg/dose or 40 mg/day (administer slowly).
- Rectal Suppository: 25 mg every 12 hours.
Children (over 2 years of age):
Dosing is based on weight and requires careful titration. Generally starting at 2.5 mg one to three times daily, not exceeding specific weight-based limits. Use in children under 2 years is generally not recommended.
Special Cases:
- Elderly Patients: Lower starting doses are recommended due to increased sensitivity to side effects.
- Patients with Renal Impairment: Dosage adjustments may be needed in severe renal dysfunction.
- Patients with Hepatic Dysfunction: Dose reduction may be required.
- Patients with Comorbid Conditions: Caution and dose adjustments may be needed in patients with cardiovascular disease, seizure disorders, etc.
Clinical Use Cases
- Intubation/Surgical Procedures/Mechanical Ventilation/ICU Use: Prochlorperazine can be used for pre- and postoperative nausea and vomiting prevention and management. Dosage and route of administration depend on the specific clinical situation.
- Emergency Situations: May be used in emergency settings for the management of severe nausea and vomiting or acute agitation.
Dosage Adjustments
Dose modifications are crucial in:
- Renal/Hepatic Dysfunction: Reduced doses are typically necessary.
- Metabolic Disorders: Consider patient-specific factors.
- Genetic Polymorphisms: Patients with certain CYP2D6 variations may have altered drug metabolism.
Side Effects
Common Side Effects:
- Drowsiness, dizziness, lightheadedness
- Dry mouth, blurred vision, constipation
- Nasal congestion
- Extrapyramidal symptoms (EPS): tremors, restlessness, muscle stiffness or spasms (dystonia), parkinsonism
Rare but Serious Side Effects:
- Neuroleptic malignant syndrome (NMS): high fever, muscle rigidity, altered mental status
- Tardive dyskinesia: involuntary movements of the face, tongue, and limbs
- Agranulocytosis: low white blood cell count
- Seizures
- Severe allergic reactions
Long-Term Effects:
- Tardive dyskinesia can become permanent if not addressed promptly.
- Metabolic changes, including weight gain and dyslipidemia, may occur with prolonged use.
Adverse Drug Reactions (ADR):
Any signs of NMS, tardive dyskinesia, agranulocytosis, or severe allergic reactions require immediate discontinuation of the drug and supportive medical care.
Contraindications
- Hypersensitivity to prochlorperazine or other phenothiazines
- Coma or severe CNS depression
- Bone marrow depression
- Subcortical brain damage
- Parkinson’s disease
- Severe liver disease
- Phaeochromocytoma
Drug Interactions
Prochlorperazine interacts with numerous medications, including:
- CNS Depressants: Alcohol, opioids, benzodiazepines, barbiturates – increased sedation
- Anticholinergics: Atropine, scopolamine – additive anticholinergic effects
- Antihypertensives: Increased risk of hypotension
- Lithium: Increased risk of EPS
- CYP2D6 Inhibitors/Inducers: Fluoxetine, paroxetine, rifampin – altered prochlorperazine levels
Pregnancy and Breastfeeding
- Pregnancy: Use with caution. While not strictly contraindicated, it’s generally avoided, especially during the first trimester. Discuss risks and benefits with a physician.
- Breastfeeding: Small amounts of prochlorperazine may be present in breast milk. Monitor infant for drowsiness and other potential side effects. If possible, alternative medications are preferred during breastfeeding.
Drug Profile Summary
- Mechanism of Action: Dopamine D2 receptor antagonist.
- Side Effects: Drowsiness, dizziness, dry mouth, EPS, NMS (rare), tardive dyskinesia (rare).
- Contraindications: Hypersensitivity, coma, bone marrow depression, severe liver disease.
- Drug Interactions: CNS depressants, anticholinergics, antihypertensives, lithium, CYP2D6 inhibitors/inducers.
- Pregnancy & Breastfeeding: Use with caution. Generally avoided during pregnancy, monitor infant during breastfeeding.
- Dosage: See detailed dosage section above.
- Monitoring Parameters: Blood pressure, complete blood count (CBC), liver function tests, extrapyramidal symptoms.
Popular Combinations
Prochlorperazine may be combined with other antiemetics in specific clinical situations, but the need for combinations should be carefully evaluated.
Precautions
- General Precautions: Assess for allergies, underlying medical conditions (especially cardiovascular, hepatic, and renal), and concomitant medications.
- Specific Populations: Use cautiously in the elderly, pregnant/breastfeeding women, and children.
- Lifestyle Considerations: Avoid alcohol. May impair alertness, so caution with operating machinery.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Prochlorperazine?
A: See the detailed dosage section above, as it varies depending on age, indication, and route of administration.
Q2: What are the most common side effects?
A: Drowsiness, dizziness, dry mouth, blurred vision, and extrapyramidal symptoms (EPS) are common.
Q3: What are the serious side effects to watch out for?
A: Neuroleptic malignant syndrome (NMS), tardive dyskinesia, agranulocytosis, and severe allergic reactions are rare but serious.
Q4: Can Prochlorperazine be used in pregnancy?
A: It is generally avoided, particularly in the first trimester, but it is not strictly contraindicated. Consult with a doctor to assess the risks and benefits.
Q5: Can Prochlorperazine be used during breastfeeding?
A: Small amounts can be excreted in breast milk. Monitor the infant for side effects like drowsiness. If possible, choose alternative medications while breastfeeding.
Q6: How does Prochlorperazine work for nausea and vomiting?
A: It blocks dopamine receptors in the chemoreceptor trigger zone (CTZ) of the brain, which plays a key role in the vomiting reflex.
A: Consider reducing the dose or switching to an antipsychotic with a lower risk of EPS. Anticholinergic medications can be used to manage EPS acutely.
Q8: What are the contraindications to using Prochlorperazine?
A: Contraindications include hypersensitivity to phenothiazines, coma, severe CNS depression, bone marrow depression, and severe liver disease.
Q9: Does Prochlorperazine interact with other medications?
A: Yes, it interacts with many drugs, including CNS depressants, anticholinergics, antihypertensives, and lithium. Always check for drug interactions before prescribing.
Q10: What are the long-term risks of Prochlorperazine use?
A: Tardive dyskinesia is a potentially irreversible long-term side effect. Metabolic changes can also occur with chronic use.
