Chlorpromazine

Chlorpromazine (中文:[[ ]]) is a typical antipsychotic medication. It is used to treat psychotic disorders such as

• schizophrenia
• Bipolar disorder
• Severe anxiety
• Attention deficit hyperactivity disorder
• Hiccups that do not improve following other measures

Pronunciation

Chlorpromazine 50mg

Drug Names

Generic Name 藥名	HA Code 藥物代碼	Classification藥物分類
Chlorpromazine Tablet 25 mg	CHLO44	P1S1S3
Chlorpromazine Tablet 50 mg	CHLO46	P1S1S3

Mechanism of Action

Chlorpromazine and other typical antipsychotics are primarily blockers of D2 dopamine receptor. The presumed effectiveness of antipsychotic drugs relied on their ability to block dopamine receptors. This assumption arose from the dopamine hypothesis that maintains that both schizophrenia and bipolar disorder are a result of excessive dopamine activity. In addition, chlorpromazine also acts as an antagonist (blocking agent) on different postsynaptic and presynaptic receptors:

• Dopamine receptors (subtypes D1, D2, D3 and D4), which account for its antipsychotic properties
• Serotonin receptors (5-HT2, 5-HT6 and 5-HT7), with anxiolytic, antidepressant, and anti-aggressive properties
• Histamine receptors (H1 receptors) accounting for sedation, antiemetic effect
• α1- and α2-adrenergic receptors accounting for lowering of blood pressure, reflex tachycardia, vertigo, sedation, hypersalivation and incontinence as well as sexual dysfunction
• M1 and M2 muscarinic acetylcholine receptors causing anticholinergic symptoms such as dry mouth, blurred vision, constipation, difficulty to urinate, sinus tachycardia, and loss of memory.

Dosage

Indication	Dose
Acute and chronic schizophrenia Reduce acute mania in bipolar disorder Control severely violent behaviour Adjunctive management of severe anxiety	By mouth ADULT: Initially 25 mg 3 times a day, adjusted according to response Or initially 75 mg once daily, taken at night, adjusted according to response Maintenance 75 – 300 mg daily ELDERLY or debilitated patients: A third to half adult dose By rectum ADULT: 25 – 50 mg 3 – 4 times a day
Intractable hiccup	By mouth ADULT: 25 – 50 mg 3-4 times a day
Nausea and vomiting of terminal illness	By mouth ADULT: 10 – 25 mg every 4-6 hours CHILD 1-5 years: 500 micrograms/kg every 4-6 hours; max. 40 mg per day CHILD 6-11 years: 500 micrograms/kg every 4-6 hours; max. 75 mg per day CHILD 12-17 years: 10 – 25 mg every 4-6 hours By rectum ADULT: 100 mg every 6-8 hours

Chlorpromazine is given orally as the hydrochloride and the embonate.

For both salts, the doses are expressed as the hydrochloride. Chlorpromazine embonate 144 mg is equivalent to 100 mg of chlorpromazine hydrochloride.

If the oral route is not suitable, it may be given rectally as suppositories containing 100 mg of chlorpromazine base

Side Effects

Chlorpromazine generally produces less central depression than the benzodiazepines, and tolerance to its initial sedative effects develops quickly in most patients. Tardive dyskinesia (involuntary, repetitive body movements) and akathisia (a feeling of inner restlessness and inability to stay still) are less commonly seen with chlorpromazine than they are with high potency typical antipsychotics such as haloperidol or trifluoperazine.

Possible side effects include:

It has antimuscarinic properties and may cause the following side effects such as	Dry mouth Constipation Difficulty to urinate Blurred vision Mydriasis Tachycardia ECG changes (particularly Q- and T-wave abnormalities) Orthostatic hypotension is common
Other adverse effects include	Delirium Agitation sedation Insomnia Nightmares Glaucoma Inhibition of ejaculation Impotence
Hypersensitivity reactions include	Urticaria Exfoliative dermatitis Prolonged therapy may lead to deposition of pigment, producing a bluish-purple discoloration in the skin Corneal and lens opacities Photosensitivity reaction
Haematological disorders	Haemolytic anaemia Thrombocytopenic purpura Most cases of agranulocytosis occurred within 4 to 10 weeks starting treatment
Extrapyramidal dysfunction include	Acute dystonia A parkinsonism-like syndrome Tardive dyskinesia Neuroleptic malignant syndrome
Altered endocrine and metabolic functions	Developed amenorrhoea, galactorrhoea and gynaecomastia due to hyperprolactinaemia Weight gain Hyperglycaemia Body temperature regulation is impaired and may result in hypo- or hyperthermia depending on environment.

Pharmacokinetics

Oral bioavailability	Chlorpromazine is readily, although sometimes erratically absorbed after oral doses.
Onset of action	Peak plasma concentrations occur about 2 to 4 hours after ingestion.
Metabolism	It is subject to considerable first-pass metabolism in the gut wall and is also extensively metabolized in the liver.
Elimination half-life	It is excreted in the urine and faeces. Owing to the first-pass effect, plasma concentrations after oral doses are much lower than those after intramuscular doses. The plasma half-life of chlorpromazine occurs about 30 hours.

Drug Management

Monitoring

The following populations must be closely monitored after administration of chlorpromazine:

• Epileptics, since chlorpromazine may lower the seizure threshold. Treatment must be stopped if seizures occur.
• Elderly persons with susceptibility to orthostatic hypotension, sedation, and extrapyramidal effects; chronic constipation and prostatic hypertrophy.
• Patients with cardiovascular disease since chlorpromazine can induce tachycardia and hypotension. Regular BP and pulse monitoring are recommended.
• Patients with severe liver and/or renal failure because of the risk of accumulation.
• Patients on long-term treatment should receive regular eye examinations.
• Diabetic patients who are started on chlorpromazine should get glycemic monitoring during treatment.
• Chlorpromazine commonly causes increased susceptibility to sunburn and individuals should avoid undue exposure to direct sunlight.
• Chlorpromazine impairs body temperature regulation. The elderly or hypothyroid patient may be particularly susceptible to hypothermia. The hazard of hyperthermia may be increased by hot weather.

Drug interaction

The most common interactions encountered with chlorpromazine result from use with drugs that have similar pharmacological actions

Drugs given with chlorpromazine	Potential Effect
CNS-depressant drugs including alcohol, hypnotics, anxiolytics, and opioids.	Potentiates the sedative effect.
Lithium	Concomitant use can cause confusion, with a rapid increase in serum lithium.
Drugs with antimuscarinic actions such as tricyclic antidepressants	As chlorpromazine has antimuscarinic actions, they can potentiate the adverse effects.
Antiparkinsonian drugs (amantadine, bromocriptine, levodopa, ropinirole)	In theory, antipsychotics with dopamine-blocking activity and dopaminergic drugs such as those used to treat parkinsonism may be mutually antagonistic.
metoclopramide	May increase the risk of antipsychotic-induced extrapyramidal effects.
Drugs that prolong the QT interval e.g. amiodarone, verapamil, sotalol and quinidine	An increased risk of ventricular arrhythmias – avoid concomitant use.
Antacids (magnesium, aluminum and calcium salts, oxides and hydroxides)	Decreased GI absorption of chlorpromazine. Administer chlorpromazine and antacid more than 2 hours apart if possible.