Study Guide for Medication Treatment of Schizophrenia Spectrum and Other Psychosis Disorders – Chlorpromazine

Description of the Psychopharmacological Medication Agent (Brand and Generic Names)
and FDA Indication Uses
Chlorpromazine (generic name) is an antipsychotic drug used in managing and treating
psychoses like schizophrenia and bipolar I acute disorder (the manic-depressive type). Chlorpromazine is
also an FDA-approved drug for treating persistent singultus, a clinical condition characterized by nonstop
hiccupping that extends beyond 48 hours, plus nausea and vomiting. The drug is marketed and sold
under different brands, depending on the manufacturer. The common brands name the drug is sold
under include Chlor-PZ, Largactil, and Thorazine.
Non-FDA Uses
Other than treating persistent singultus and psychoses like schizophrenia, chlorpromazine has
also been found to be effective in treating acute agitation characterized by explosive hyperexcitable
behavior, acute intermittent porphyria, migraine headaches, Tourette’s syndrome, and agitation/anxiety
in dementia. It has also been used to relief apprehension following surgery and as an adjust medication
of serotonin syndrome and tetanus (Mann & Marwaha, 2022). However, these uses are often off-label
and not approved by the FDA.
Drug Classification
Chlorpromazine is a member of phenothiazines or antipsychotics, a class of drugs primarily used
to treat psychoses. In particular, chlorpromazine is classified as a “1 st -generation” or a “typical”
antipsychotic, meaning it was developed in the 1950s.
Mechanism of Action
Although chlorpromazine’s mechanism of action remains unknown, scientists believe the drug
functions by producing antipsychotic effects. This is achieved by blocking dopamine at the post-synaptic
receptors located in the brain. Blocking the dopamine receptors in the brain alleviates psychotic
symptoms, such as delusions and delusions. Chlorpromazine also works by blocking the muscarinic M1
receptors located in the brain’s vomiting center. This alleviates the feeling of nausea and vomiting
(Mann & Marwaha, 2022).
The Medication’s Pharmacokinetics
Chlorpromazine’s activity in the body within a specified period (pharmacokinetics), including
absorption, distribution, localization in tissues, and excretion depends on the drug’s route of
administration. Typically, the drug can be administered through the oral route or through injection
(intramuscular or intravenous). After a patient ingests chlorpromazine (oral administration), the drug is
absorbed quickly through the GIT and proceeds straight to the liver for first-pass metabolism through
conjugation and oxidation processes. The metabolites or end-products of metabolism (N-
desmethylchlorpromazine, 7-hydroxychlorpromazine, 2-hydroxychlorpromazine, 3-
hydroxychlorpromazine, and chlorpromazine sulfoxide) are excreted through urine.

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The kidneys excrete between 43% and 65% of the daily dosage within twenty-four hours. The
onset of action is thought to be within thirty to sixty minutes after ingestion, with peak plasma
concentrations achieved within 1-2 hours. The drugs bioavailability is between 25% and 30%.
Chlorpromazine’s elimination half-life occurs in a series of phases, with the first phase occurring
between 2-3 hours, the intermediate phase fifteen hours, and late phase taking up to sixty days. The
production and excretion of chlorpromazine metabolizes are influenced by factors like drug interaction,
liver function, and age. The drug can also be administered intramuscularly, providing a reliable and rapid
absorption. The onset of action through this route is between 15 and 30 minutes.
The Medication’s Pharmacodynamics
Chlorpromazine’s pharmacodynamics primarily entails its impacts on three key
neurotransmitters in the brain: dopamine, norepinephrine, and serotonin. The drug acts by antagonizing
dopamine in the neocortical and mesolimbic brain areas – regions that essentially produce psychotic
clinical manifestations like delusions and hallucinations. Chlorpromazine alleviates these psychotic
manifestations by blocking or antagonizing dopamine-2 receptors. In the absence of chlorpromazine,
the dopamine release from presynaptic terminals stimulates postsynaptic D-2 receptors, causing a
downstream signal transduction. Chlorpromazine attaches to these receptors without stimulating them,
preventing dopamine from binding to the receptors and blocking downstream signal transduction (See
images A and B).

Images A and B. Schematic diagram A shows the chemical structure of chlorpromazine while B shows
the effects of chlorpromazine on dopaminergic neurotransmission in the brain.
Chlorpromazine can also affect the action of serotonin receptors, especially the 5-HT2A
receptors, in the brain. This produces antipsychotic, antiemetic, and sedative properties. Moreso, the
drug can block alpha-adrenergic receptors, producing antipsychotic, orthostatic, and hypotensive
effects. Chlorpromazine can also act on other neurotransmitters in the brain like acetylcholine and
histamine. It can antagonize the action of H1 receptors (histamine), producing anticholinergic and
sedative effects. The drug can also antagonize muscarinic acetylcholine receptors, producing
anticholinergic symptoms.

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Appropriate Dosing, Administration Route, and Considerations for Dosing Alterations
Chlorpromazine can be administered orally (available in tablets of 200 mg, 100 mg, 50 mg, 25
mg, and 10 mg) or through injections (intravenous or intramuscular). Dosage decisions vary by age and
purpose of treatment. For treating schizophrenia, the patient is started on a dose of 25-75 mg twice a
day. This should be maintained at 200 mg/day depending on the patient’s symptoms and response to
the treatment. The maximum dose through the oral route is 800 mg/day. However, if administered
intramuscularly or intravenously, the starting dose is 25 mg, followed by 25-50 mg after 1-4 hours
depending on the need. The usual dose ranges between 300 mg and 800 mg per day (Mann & Marwaha,
2022).
For treating vomiting and nausea, chlorpromazine’s oral dose can range between 10-25 mg
every four to six hours as required. If administered through injection (intravenous or intramuscular), the
dose can range between 25-50 mg each four to six hours as required. For persistent singultus, the initial
oral chlorpromazine dose is 25-50 mg every six to eight hours. The drug is switched to the intravenous
or intramuscular route if hiccups persist after two to three days of oral treatment. Finally, for
preoperative apprehension, the oral dose typically ranges between 25-50 mg and the intramuscular
dose ranges between 12.5-25 mg every two to three hours before the patient is wheeled for surgery
(Mann & Marwaha, 2022).
Considerations of Use and Dosing in Specific Specialty Populations
consider children, adolescents, elderly, pregnancy, suicidal behaviors,
Definition of Half-life, why half-life is important, and the half-life for your assigned
medication
Side effects/adverse reaction potentials
Contraindications for use including significant drug to drug interactions
Overdose Considerations
Diagnostics and labs monitoring
Comorbidities considerations
Legal and ethical considerations
Pertinent patient education considerations

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References

Mann, S. K., & Marwaha, R. (2022). Chlorpromazine. StatPearls [Internet].
https://www.ncbi.nlm.nih.gov/books/NBK553079/