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Chlorpromazine (CPZ) — marketed, as chlorpromazine hydrochloride, in the United States as Thorazine and elsewhere as Largactil and Megaphen — is a dopamine antagonist of the typical anti-psychotic class of medications possessing additional anti-adrenergic, anti-serotonergic, anti-cholinergic and anti-histaminergic properties used to treat schizophrenia. First synthesized on December 11, 1950, chlorpromazine was the first drug developed with specific antipsychotic action and would serve as the prototype for the phenothiazine class of drugs, which comprises several other agents. The introduction of chlorpromazine during the 1950s into clinical use has been described as the single greatest advance in the history of psychiatric care, dramatically improving as it did the prognosis of patients in psychiatric hospitals worldwide.
Chlorpromazine works on a variety of receptors in the central nervous system, producing potent anticholinergic, antidopaminergic, antihistaminic, and antiadrenergic effects. Both the clinical indications and side effect profile of CPZ are determined by the broadness of its action: its anticholinergic properties cause constipation, sedation, and hypotension but also help relieve nausea. It also has anxiolytic (anxiety-relieving) properties. Its antidopaminergic properties can cause extrapyramidal symptoms, such as akathisia (restlessness, aka the 'Thorazine shuffle' where the patient walks almost constantly, despite having nowhere to go due to mandatory confinement, and takes small, shuffling steps) and dystonia. It is known to cause tardive dyskinesia, which can be irreversible.
Tolerance and withdrawal
The British National Formulary recommends a gradual withdrawal when discontinuing antipsychotic treatment to avoid acute withdrawal syndrome or rapid relapse. While withdrawal symptoms can occur, there is no evidence that tolerance develops to the drug's antipsychotic effects. A patient can be maintained for years on a therapeutically effective dose without any decrease in effectiveness being reported. Tolerance appears to develop to the sedating effects of chlorpromazine when it is first administered. Tolerance also appears to develop to the extrapyramidal, parkinsonian and other neuroleptic effects, although this is debatable.
Pharmacodynamics and central effects
Chlorpromazine is a very effective antagonist of D2 dopamine receptors and similar receptors, such as D3 and D5. Unlike most other drugs of this genre, it also has a high affinity for D1 receptors. Blocking these receptors causes diminished neurotransmitter binding in the forebrain, resulting in many different effects. Dopamine, unable to bind with a receptor, causes a feedback loop that causes dopaminergic neurons to release more dopamine. Therefore, upon first taking the drug, patients will experience an increase in activity of dopaminergic neural activity. Eventually, dopamine production of the neurons will drop substantially and dopamine will be removed from the synaptic cleft. At this point, neural activity decreases greatly; the continual blockade of receptors only compounds this effect
Peripheral effects
Chlorpromazine is an antagonist to H1 receptors (provoking antiallergic effects), H2 receptors (reduction of forming of gastric juice), M1 and M2 receptors (dry mouth, reduction in forming of gastric juice) and some 5-HT receptors (different anti-allergic/gastrointestinal actions).
Because it acts on so many receptors, chlorpromazine is often referred to as a "dirty drug", whereas the atypical antipsychotic amisulpride, for example, acts only on central D2 and D3 receptors and is therefore a "clean drug". Research still needs to be done to understand the implications of this fact.
Discontinuation
At regular intervals the treating physician should evaluate whether continued treatment is needed. The drug should never be discontinued suddenly, due to unpleasant withdrawal-symptoms, such as agitation, sleeplessness, states of anxiety, stomach pain, dizziness, nausea and vomiting. Preferably the dose should be gradually reducedc.
History
In 1933, the French pharmaceutical company Laboratoires Rhône-Poulenc began to search for new anti-histamines. In 1947, it synthesized promethazine, a phenothiazine derivative, which was found to have more pronounced sedative and antihistaminic effects than earlier drugs. A year later, the French surgeon Pierre Huguenard used promethazine together with pethidine as part of a cocktail to induce relaxation and indifference in surgical patients. Another surgeon, Henri Laborit, believed the compound stabilized the central nervous system by causing 'artificial hibernation', and described this state as 'sedation without narcosis'. He suggested to Rhône-Poulenc that they develop a compound with better stabilizing properties. The chemist Paul Charpentier produced a series of compounds and selected the one with the least peripheral activity, known as RP4560 or chlorpromazine, on 11 December 1950. Simone Courvoisier conducted behavioural tests and found chlorpromazine produced indifference to aversive stimuli in rats.
Children should not use products that contain codeine after certain surgeries (including tonsil/adenoid removal). Also, for children younger than 12 years, do not use codeine to treat cough or pain unless specifically directed by the doctor. Some children are more sensitive to codeine and have had very serious (rarely fatal) breathing problems such as slow/shallow breathing (see also Side Effects section). Talk with your doctor or pharmacist about the risks and benefits of this medication.
This combination medication is used to relieve symptoms caused by the common cold, flu, allergies, "hay fever," and other breathing illnesses (such as sinusitis, bronchitis). These symptoms include cough, watery eyes, itchy eyes/nose/throat, runny nose, and sneezing. This product contains a cough suppressant (such as chlophedianol) that affects a certain part of the brain, reducing the urge to cough. This product also contains a decongestant (such as pseudoephedrine, phenylephrine), which helps relieve stuffy nose symptoms. It also contains an antihistamine (such as brompheniramine, triprolidine, among others), which helps relieve watery eyes, itchy eyes/nose/throat, runny nose, and sneezing.
This medication is not usually used for ongoing coughs from smoking, asthma, or other long-term breathing problems (such as emphysema), or for coughs with a lot of mucus, unless directed by your doctor.
Cough-and-cold products have not been shown to be safe or effective in children younger than 6 years. Therefore, do not use this product to treat cold symptoms in children younger than 6 years unless specifically directed by the doctor. Some products (such as long-acting tablets/capsules) are not recommended for use in children younger than 12 years. Ask your doctor or pharmacist for more details about using your product safely.
These products do not cure or shorten the length of the common cold and may cause serious side effects. To decrease the risk for serious side effects, carefully follow all dosage directions. Do not use this product to make a child sleepy. Do not give other cough-and-cold medication that might contain the same or similar ingredients (see also Drug Interactions section). Ask the doctor or pharmacist about other ways to relieve cough and cold symptoms (such as drinking enough fluids, using a humidifier or saline nose drops/spray).
How to use Pro-Chlo
Take this medication by mouth with or without food. If stomach upset occurs, take this product with food or milk. Drink plenty of fluids when you use this medication unless otherwise directed by your doctor. The fluid will help loosen the mucus in your lungs.
The dosage is based on your age, medical condition, and response to treatment. Long-acting products are usually taken twice a day. Some products may be taken every 4 to 6 hours as needed. Follow your doctor's directions carefully. Do not increase your dose or take this medication more often than prescribed without your doctor's approval. If you are taking this medication for allergy or hay fever, take it regularly to get the most benefit from it.
If you are using the liquid form, use a medication-measuring device or spoon to carefully measure the prescribed dose. Do not use a household spoon because you may not get the correct dose. If your liquid form is a suspension, shake the bottle well before each dose.
If you are using the chewable form, chew the tablets thoroughly before swallowing.
Tell your doctor if your condition persists for more than 1 week, if it worsens, or if it occurs with fever, rash, or persistent headache. These may be symptoms of a serious medical problem and should be checked by a doctor.
Drowsiness, dizziness, flushing, headache, nausea, nervousness, blurred vision, or dry mouth/nose/throat may occur. If any of these effects persist or worsen, tell your doctor or pharmacist promptly.
To reduce the risk of dizziness and lightheadedness, get up slowly when rising from a sitting or lying position.
To relieve dry mouth, suck on (sugarless) hard candy or ice chips, chew (sugarless) gum, drink water, or use a saliva substitute.
Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.
Tell your doctor right away if you have any serious side effects, including: mental/mood changes (such as hallucinations, confusion), shaking (tremors), trouble urinating, weakness.
Get medical help right away if you have any very serious side effects, including: fast/slow/irregular heartbeat, seizure.
A very serious allergic reaction to this drug is rare. However, get medical help right away if you notice any symptoms of a serious allergic reaction, including: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.
This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.
Before taking this medication, tell your doctor if you are allergic to any of its ingredients; or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.
Before taking this medication, tell your doctor or pharmacist your medical history, especially of: breathing problems (such as asthma, emphysema), diabetes, glaucoma, heart problems, high blood pressure, seizures, overactive thyroid (hyperthyroidism), urination problems (such as trouble urinating due to enlarged prostate, urinary retention).
This drug may make you dizzy or drowsy or cause blurred vision. Do not drive, use machinery, or do any activity that requires alertness or clear vision until you are sure you can perform such activities safely. Limit alcoholic beverages.
Some brands may contain sugar, alcohol, or aspartame. Caution is advised if you have diabetes, alcohol dependence, liver disease, phenylketonuria (PKU), or any other condition that requires you to limit/avoid these substances in your diet. Ask your doctor or pharmacist about using this product safely.
Before having surgery, tell your doctor or dentist about all the products you use (including prescription drugs, nonprescription drugs, and herbal products).
Children may be more sensitive to the side effects of antihistamines. In young children, this medication may cause agitation/excitement instead of drowsiness.
Older adults may be more sensitive to the side effects of this drug, especially dizziness, drowsiness, mental/mood changes, and blood pressure changes.
During pregnancy, this medication should be used only when clearly needed. Discuss the risks and benefits with your doctor.
This drug may pass into breast milk and could have undesirable effects on a nursing infant. Consult your doctor before breast-feeding.
Drug interactions may change how your medications work or increase your risk for serious side effects. This document does not contain all possible drug interactions. Keep a list of all the products you use (including prescription/nonprescription drugs and herbal products) and share it with your doctor and pharmacist. Do not start, stop, or change the dosage of any medicines without your doctor's approval.
Taking MAO inhibitors with this medication may cause a serious (possibly fatal) drug interaction. Avoid taking MAO inhibitors (isocarboxazid, linezolid, methylene blue, moclobemide, phenelzine, procarbazine, rasagiline, selegiline, tranylcypromine) during treatment with this medication. Most MAO inhibitors should also not be taken for two weeks before treatment with this medication. Ask your doctor when to start or stop taking this medication.
Before using this medication, tell your doctor or pharmacist of all prescription and nonprescription/herbal products you may use, especially of: antihistamines applied to the skin (such as diphenhydramine cream, ointment, spray).
Check the labels on all your medicines (such as cough-and-cold products, diet aids) because they may contain the same or similar ingredients that could increase your heart rate or blood pressure or cause drowsiness. Ask your pharmacist about using those products safely.
Tell your doctor or pharmacist if you are taking other products that cause drowsiness including alcohol, other antihistamines (such as cetirizine, diphenhydramine), drugs for sleep or anxiety (such as alprazolam, diazepam, zolpidem), muscle relaxants, and narcotic pain relievers (such as codeine).
If overdose is suspected, contact a poison control center or emergency room immediately.large pupils, flushing, shaking (tremor), hallucinations, confusion, seizures. In children, excitement may occur first, and may be followed by loss of coordination, drowsiness, loss of consciousness, seizures.
Notes
Do not share this medication with others.
Do not take this product for several days before allergy testing because test results can be affected.
Missed Dose
If your doctor directs you to take this medication on a regular schedule and you miss a dose, take it as soon as you remember. If it is near the time of the next dose, skip the missed dose and resume your usual dosing schedule. Do not double the dose to catch up.
Storage
Store in a tightly closed container at room temperature away from light and moisture. Do not store in the bathroom. Do not freeze liquid forms of this medication. Keep all medications away from children and pets.
Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company.
Information last revised October 2013. Copyright(c) 2013 First Databank, Inc.
