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chlorpromazine

Chlorpromazine is an antipsychotic drug belonging to the class of phenothiazines and - as such - has neuroleptic activity, ie it is able to depress the central nervous system.

Chlorpromazine is also known as torazine.

Chlorpromazine - Chemical Structure

It was discovered by the chemist Paul Charpentier in 1950, in an attempt to synthesize analogues of promethazine, a phenothiazine with both neuroleptic and antihistamine activity.

Later, the French surgeon Laborit and his collaborators discovered the ability of this drug to enhance the effects of anesthesia. They noted that chlorpromazine itself did not produce loss of consciousness, but favored a tendency to sleep and a marked disregard for the surrounding environment.

In 1952 the psychiatrists Delay and Deniker hypothesized that chlorpromazine was not only an agent capable of symptomatically resolving agitation and anxiety, but that it could also have a therapeutic effect in the treatment of psychoses.

Indications

For what it uses

The use of chlorpromazine is indicated for the treatment of:

  • Schizophrenia;
  • Paranoid states;
  • Mania;
  • Toxic psychoses (induced by amphetamines, LSD, cocaine, etc.);
  • Organic mental syndromes accompanied by delirium;
  • Severe anxiety disorders resistant to therapy with typical anxiolytics;
  • Depression accompanied by agitation and delirium (in association with antidepressants);
  • Pre-anesthetic medication;
  • Uncontrollable vomiting and hiccups;
  • Intense pain (generally, in association with opioid analgesics).

Warnings

Patients treated with chlorpromazine should be kept under medical supervision.

Co-administration of chlorpromazine and other neuroleptics should be avoided.

The use of chlorpromazine in infants with infectious diseases - or undergoing surgery - should be carried out with caution, as there may be an increased incidence of extrapyramidal effects (Parkinson's-like symptoms).

The antiemetic effect of chlorpromazine may mask the symptoms of overdose of other drugs, the onset of diseases of the digestive tract or of the central nervous system.

Chronic chlorpromazine treatment can cause persistent late dyskinesias, so this treatment should only be performed in patients where alternative therapies cannot be undertaken.

Abrupt discontinuation of chlorpromazine therapy may cause withdrawal symptoms.

Chlorpromazine can cause the onset of neuroleptic malignant syndrome, in the event of the onset of this syndrome, treatment must be stopped immediately (see the "Side effects" section).

Chlorpromazine should be used with caution in elderly patients and in patients with the following conditions:

  • Cardiovascular disorders;
  • Acute or chronic lung diseases;
  • Glaucoma;
  • Prostatic hypertrophy;
  • Parkinson's disease, as chlorpromazine increases the muscle stiffness induced by this disease;
  • Hypotension;
  • Patients with a family history of prolongation of the QT interval (the interval of time required by the ventricular myocardium to depolarize and repolarize).

Chlorpromazine can cause an increase in the hormone prolactin in the bloodstream (hyperprolactinemia), therefore, caution should be used in the use of the drug by patients with breast cancer.

Because of the adverse effects that chlorpromazine can cause, it is necessary to carry out periodic checks to verify the state of health of the central nervous system, bone marrow, eyes, liver, kidneys and the cardiovascular system.

Since chlorpromazine can cause changes in blood formation, it is necessary to carry out appropriate checks throughout the duration of the treatment.

Patients on chlorpromazine therapy who need to undergo surgery need a lower dose of anesthetics.

Chlorpromazine can lower the seizure threshold and promote the appearance of epileptic seizures. In patients with epilepsy an adjustment of the dose of antiepileptic drugs may be necessary.

Patients on chlorpromazine therapy should avoid direct exposure to the sun and use special protective creams.

Chlorpromazine can cause hyperglycaemia, therefore, in diabetic patients, an adjustment in the dose of insulin or oral hypoglycemic agents may be necessary.

Chlorpromazine may compromise thermoregulation, therefore the drug should be administered with caution in subjects exposed to very low or very high temperatures.

In patients with dementia, chlorpromazine treatment increases the risk of cerebrovascular events.

Since chlorpromazine increases the risk of clot formation, care must be taken when administering it to patients with a history - including family history - of coagulation disorders.

Chlorpromazine causes sedation and drowsiness, therefore driving vehicles and / or using machinery is not recommended.

Interactions

The combination of chlorpromazine and other depressants in the central nervous system (such as, barbiturates, hypnotics, anxiolytics, anesthetics, antihistamines and opioid analgesics ) must be carried out with caution, in order to avoid excessive sedation of the patients.

The co-administration of chlorpromazine and lithium (a drug used for bipolar disorders) can decrease the plasma concentration of chlorpromazine itself and - at the same time - increase the extrapyramidal effects.

Chlorpromazine may increase the activity of antihypertensive drugs.

Anticholinergic drugs can decrease the antipsychotic action of chlorpromazine.

The combination of chlorpromazine and other myelosuppressive drugs (which suppress bone marrow) should be avoided.

Metrizamide (a compound used as a contrast agent) increases the risk of convulsions induced by chlorpromazine.

Alcohol intake during chlorpromazine therapy is not recommended.

Anti-Parkinson's drugs (such as lisuride, pergolide and levodopa ) can antagonize the effect of chlorpromazine.

Concomitant administration of chlorpromazine and antiarrhythmics increases the risk of cardiac arrhythmias.

Co-administration of chlorpromazine and tricyclic antidepressants ( TCA ) increases antimuscarinic effects.

Chlorpromazine increases the plasma concentration of valproic acid (an antiepileptic).

Other drugs that can interact with chlorpromazine are:

  • Some antibiotics, such as streptomycin and erythromycin ;
  • Anticoagulants, such as warfarin which increases the plasma concentration of the antipsychotic;
  • Anti-migraine, such as ergot derivatives and eletriptan ;
  • Antivirals, such as ritonavir (used to treat HIV) and amantadine (used in Parkinson's disease);
  • Drugs used for the treatment of Alzheimer's disease, such as donepezil, galantamine and rivastigmine ;
  • Naltrexone, an opiate receptor antagonist;
  • Tamoxifen, an anticancer;
  • Drugs that alter the concentration of electrolytes;
  • Drugs that inhibit liver enzymes, as chlorpromazine is mainly metabolised in the liver.

Side effects

Chlorpromazine can cause a long series of side effects, although not all patients experience them.

The following are the main adverse effects that may occur following chlorpromazine therapy.

Nervous system disorders

Chlorpromazine therapy may cause:

  • Sedation;
  • Drowsiness;
  • Dizziness;
  • Insomnia;
  • Anxiety;
  • Restlessness;
  • Psychomotor agitation;
  • Euphoria;
  • Mood depression;
  • Worsening of psychotic symptoms;
  • Convulsions;
  • Changes in body temperature;
  • Parkinson-like symptoms;
  • Akathisia (inability to stand still).

Cardiovascular disorders

Treatment with chlorpromazine may cause hypotension, syncope, arrhythmias, prolonged QT interval, atrioventricular block, cardiac arrest and sudden death.

Blood and lymphatic system disorders

Chlorpromazine can cause disorders of the system responsible for the synthesis of blood cells (hemolymphopoietic system), this can cause:

  • Anemia (reduced amount of hemoglobin in the blood);
  • Leukopenia (reduced number of white blood cells) with consequent increased susceptibility to infection contraction;
  • Plateletopenia (reduced number of platelets) leading to bruising and abnormal bleeding with an increased risk of bleeding.

Skin and subcutaneous tissue disorders

Chlorpromazine therapy can cause hypersensitivity and photosensitivity reactions that occur in the form of hives, eczema and exfoliative dermatitis.

Endocrine disorders

Chlorpromazine can cause hyperprolactinaemia and decreased estrogen, progesterone and pituitary gonadotropins.

Reproductive system and breast disorders

Chlorpromazine in women can cause breast enlargement and tension, amenorrhea (lack of menstruation) and abnormal lactation.

In men, however, the drug can cause gynecomastia (abnormal development of the breasts), impotence and a decrease in testicular volume.

Hepatobiliary disorders

Chlorpromazine can cause liver damage and jaundice.

Malignant Neuroleptic Syndrome

Neuroleptic Malignant Syndrome is a neurological disorder characterized by:

  • Temperature;
  • Dehydration;
  • Muscle stiffness;
  • akinesia;
  • Sweating;
  • Tachycardia;
  • Arrhythmia;
  • Changes in the state of consciousness that can progress to stupor and coma.

If these symptoms appear, chlorpromazine therapy should be stopped immediately and the doctor should be contacted.

Other side effects

Other adverse effects that may arise following chlorpromazine therapy are:

  • Anaphylactic reactions;
  • Thrombosis;
  • Visual deficits;
  • Kidney damage;
  • bronchospasm;
  • Laryngospasm.

Overdose

There is no specific antidote against chlorpromazine hyper-dosing. Gastric lavage may be useful. The symptoms that can occur consist of an exacerbation of the side effects. In case of suspected overdose, contact a doctor immediately or contact the nearest hospital.

Action mechanism

Chlorpromazine performs its antipsychotic action by blocking the postsynaptic D2 dopamine receptors. Furthermore, chlorpromazine also has a non-specific antihistamine effect and this causes patients to feel sleepy.

Mode of Use - Posology

Chlorpromazine is available for oral (os) administration in the form of oral tablets or drops. The drug is also available in vials for intramuscular (im) or intravenous (IV) administration.

The dosage must be established by the doctor on a strictly individual basis, depending on the age of the patient, the type and severity of the disease, the therapeutic response and tolerability of the drug.

The following are some indications on the usual doses of chlorpromazine.

Psychiatric disorders

In ambulatory patients the doses are 30-75 mg of chlorpromazine per day, per os. Treatment can also be started im with 25 mg of medication.

In hospitalized patients, higher doses may be necessary (either by mouth or by im).

In children, the recommended dose is 1 mg / kg body weight per day.

Uncontrollable vomiting and hiccups

The dose is 25-50 mg of chlorpromazine, to be administered 2-3 times a day intramuscularly. Once the therapeutic effect is reached - if necessary - the therapy can be continued orally.

Pre-anesthetic medication

The recommended dose is 25-50 mg of chlorpromazine taken by mouth; 12.5-25 mg for im or ev a few hours before surgery.

Pregnancy and breastfeeding

Chlorpromazine should not be administered during the first trimester of pregnancy due to possible damage to the fetus. During the second and third trimester, the drug should be used only if the doctor considers it absolutely essential, due to the adverse effects that may occur in the newborn.

Chlorpromazine is excreted in breast milk, therefore breast-feeding mothers should not take the drug.

Contraindications

The use of chlorpromazine is contraindicated in the following cases:

  • Known hypersensitivity to chlorpromazine;
  • Comatose states, especially those caused by alcohol, barbiturates, opiates, etc .;
  • Patients with subcortical brain damage;
  • Severe depressive states;
  • In patients suffering from blood dyscrasias;
  • In patients suffering from liver and / or kidney diseases;
  • In patients with pheochromocytoma, a tumor that affects the adrenal gland;
  • Myasthenia gravis, a neuromuscular plaque disorder;
  • In patients with untreated epilepsy;
  • In early childhood;
  • In the first trimester of pregnancy and during breastfeeding.

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