Study Guide for Chlorpromazine
CHLORPROMAZINE |
Description |
· Chlorpromazine is an antipsychotic medication mainly used for the treatment of schizophrenia disorder.
· Generic Name: Chlorpromazine · Brand Names: Ormazine, Thorazine spansule and Thorazine. · Approved FDA Indications: Schizophrenia, the acute manic phase of bipolar I disorder, persistent hiccups, acute agitation, relief of anxiety preoperatively, acute intermittent porphyria, and as an adjunctive treatment for tetanus (Mann & Marwaha, 2020). · Off-label Uses: Treatment for migraine-associated nausea and vomiting and treatment for serotonin syndrome. |
Drug Classification |
· Chlorpromazine is a low-potency typical antipsychotic belonging to the class of drugs known as phenothiazines based on their chemical structure (Mann & Marwaha, 2020). |
Pharmacokinetics |
· Has approximately 10-80% bioavailability.
· Half-life: 23 to 37 hours. · About 90-99% is protein bound. · It undergoes hepatic metabolism via the CYPA12 and the CYP2D6 enzymes (Mann & Marwaha, 2020). · Excretion is via urine and feces. |
Pharmacodynamics |
· Chlorpromazine is a dopamine D2 receptor antagonist. The drug works by blocking the dopamine receptors, inhibiting the binding of the neurotransmitter to the forebrain, resulting in decreased neural activity.
· Initially, the patients may experience increased dopaminergic neural activity due to rebound production of dopamine. With the continued blockade, reduced neural activity ensues. |
Mechanism of Action |
· The exact mechanism of action of chlorpromazine is unknown. However, it is thought that chlorpromazine causes post-synaptic blockage of the D2 receptors in the nigrostriatal pathway and mesolimbic pathway. Blockade in the former pathway causes extrapyramidal effects. The antiemetic effects are produced through the combined blockade of muscarinic, histamine, and dopamine receptors. |
Dosing and Administration |
· Chlorpromazine is available for parenteral and enteral route (Keepers et al.,2020).
o Oral intake: Tablets of various dosages between 10–200mg. o Parenteral use: Can be administered intramuscularly and intravenously. · Dosing varies and is dependent on the indication for use. · For schizophrenia, the initial dose is 25-75mg orally twice a day and maintenance of 200 mg once daily. If it is to be administered as an intravenous or intramuscular injection, the initial dose is 25 mg, followed by 25-50 mg every 1-4 hours (Keepers et al., 2020). · Caution should be taken for patients with hepatic failure or liver disease. · No need for dose adjustment for patients with renal disease. |
Special Considerations |
· Breastfeeding: Chlorpromazine has been proven to be safe for use during breastfeeding. However, there should be strict medical supervision and only advised when the benefits for use outweigh the risks.
· Pregnancy: Chlorpromazine can be used but in low doses and when the clinician is certain that the benefits outweigh the risks. |
Half-Life | |
Definition | · The half-life of a drug refers to the time for a drug’s concentration to be reduced by half (Gandhi, 2022). |
Importance | · Knowing the half-life of a drug is important as it determines the rates of excretion and the steady state of specific drugs.
· It also helps in determining the frequency of administration of the drug. |
Half-Life of Chlorpromazine | · Chlorpromazine has a long half-life of approximately 23-37 hours hence the recommended once-daily dosing (Mann & Marwaha, 2020). |
Potential Side Effects/Adverse Reactions |
· Generally, it causes dizziness, constipation, urine retention, and dry mouth due to the blockade of muscarinic receptors (Geddes & Andreasen, 2020).
· D2 receptor blockade causes hyperprolactinemia, hence reducing libido in both males and females (Zhu et al., 2021). In males, there may be associated erectile dysfunction, galactorrhea, and gynecomastia. In females, there may be amenorrhea, oligomenorrhea, galactorrhea, and irregular menses. · Extrapyramidal effects include akathisia, tardive dyskinesia, parkinsonism, neuroleptic malignant syndrome, and dystonia(Geddes & Andreasen, 2020). · Others: headache and hypotension when given parenterally, prolonged QT interval, cholestatic jaundice, and hepatotoxicity. |
Contraindications and Drug Interactions |
· Chlorpromazine is contraindicated for use in patients with allergies or hypersensitivity to phenothiazines.
· Caution should be taken when administered to patients who are on anti-hypertensives due to the risk of developing hypotension. · The drugs should be avoided in patients with uncontrolled seizures and should not be used in combination with drugs suppressing the central nervous system. · Chlorpromazine may affect the therapeutic effects of drugs, causing dopamine agonists such as cabergoline and levodopa. · Concomitant use of chlorpromazine with escitalopram and citalopram is contraindicated. · Caution should be taken when administered to pregnant and breastfeeding mothers. (Geddes & Andreasen, 2020). |
Overdose Considerations |
· Unfortunately, there is no antidote for chlorpromazine, and treatment for overdose toxicity should be aimed at symptom relief. In case of an overdose, ensure proper ventilation with regular assessment of the respiratory and cardiac functions.
· Following ingestion of large doses, gastric lavage should only be attempted within the first four to six hours following ingestions. Another alternative is activated charcoal. · An electrocardiogram is essential to check for prolongation of QT interval and arrhythmias. · In case a patient develops neuroleptic malignant syndrome, offer supportive care, which includes giving dantrolene sodium and cooling the patient. However, when a patient develops tardive dyskinesia, discontinue chlorpromazine and consider switching to second-generation antipsychotics. (Keepers et al., 2020) |
Lab Monitoring and Diagnostics |
· Complete blood count to check for agranulocytosis. Chlorpromazine should be discontinued if agranulocytosis is evident.
· Elecertocardiogram for each visit to check for QT prolongation. · Regular monitoring of the liver enzymes and the bilirubins as chlorpromazine is metabolized in the liver. Caution should be taken in case of liver disease. (Keepers et al., 2020) |
Comorbidities Considerations |
· For hypersensitive individuals who develop anaphylactic reactions, discontinue chlorpromazine and administer antihistamines or steroids.
· Administer with caution for patients with cardiovascular and cerebrovascular disorders. · Avoid concomitant use of chlorpromazine with anti-hypertensive drugs due to the risk of hypotension. · The drug is contraindicated in patients with liver failure. (Mann & Marwaha, 2020) |
Legal and Ethical Consideration |
· Just like any other antipsychotic, before initiation of chlorpromazine, a patient must be informed of the benefits of the drugs and the associated effects for them to make an informed decision.
· It is important to abide by the patient’s decision while on treatment. (Gandhi, 2022) |
Patient Education |
· Patients should be advised on the importance of compliance with chlorpromazine medication for effective treatment.
· Educate the patients on the potential side effects and advise them to seek medical attention once they notice life-threatening adverse reactions or hypersensitivity. · Patients should be advised to quit or reduce alcohol consumption while on medications. · Give nutritional counseling and advice on a healthy diet when taking chlorpromazine. (Gandhi, 2022) |
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References
Gandhi, S. (2022). Textbook of Mental Health and Psychiatric Nursing: Principles and Practice. Elsevier Health Sciences. https://books.google.co.ke/books?hl=en&lr=&id=stN-EAAAQBAJ&oi=fnd&pg=PP1&dq=chlorpromazine+textbook&ots=UvSjR5hTLD&sig=j9mtBiLZ4eMiRl8c-pvC5WhQapE&redir_esc=y#v=onepage&q=chlorpromazine%20textbook&f=false
Geddes, J. R., & Andreasen, N. C. (2020). New Oxford textbook of psychiatry. Oxford University Press, USA. https://books.google.co.ke/books?hl=en&lr=&id=hY_UDwAAQBAJ&oi=fnd&pg=PP1&dq=psychiatry+textbook&ots=xvCIrba7vY&sig=1u6AQQ9rUwKg9HjsHKFU2ErJMLE&redir_esc=y#v=onepage&q=psychiatry%20textbook&f=false
Keepers, G. A., Fochtmann, L. J., Anzia, J. M., Benjamin, S., Lyness, J. M., Mojtabai, R., … & (Systematic Review). (2020). The American Psychiatric Association practice guidelines for the treatment of patients with schizophrenia. American Journal of Psychiatry, 177(9), 868-872. https://doi.org/10.1176/appi.ajp.2020.177901
Mann, S. K., & Marwaha, R. (2020). Chlorpromazine. https://europepmc.org/article/NBK/nbk553079
Zhu, Y., Zhang, C., Siafis, S., Zhuo, K., Zhu, D., Wu, H., & Li, C. (2021). Prolactin levels influenced by antipsychotic drugs in schizophrenia: A systematic review and network meta-analysis. Schizophrenia Research, 237, 20-25. https://doi.org/10.1016/
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