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| [[Category: Drugs]][[Category: Conventional Antipsychotic]] | | [[Category: Drugs]][[Category: Typical Antipsychotic ]] |
| '''Chlorpromazine''' (中文:[[氯丙嗪]]) is a typical antipsychotic medication. It is used to treat psychotic disorders such as
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| *schizophrenia
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| *Bipolar disorder
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| *Severe anxiety
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| *Attention deficit hyperactivity disorder
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| *Hiccups that do not improve following other measures
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| ==Pronunciation==
| | [[:Category: Antipsychotic Drug | '''Antipsychotic Drug''']] |
| ===Chlorpromazine 50mg===
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| [[File:Chlorpromazine 50mg.mp3]] | |
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| ==Drug Names==
| | '''Drug class: [[:Category: Typical Antipsychotic | Typical Antipsychotic]] |
| {| class="wikitable"
| | |
| !Generic Name 藥名
| | '''Chlorpromazine (LARGACTIL)'''（中文：[[氯丙嗪]]） |
| !HA Code 藥物代碼
| | ==Common Strengths of Chlorpromazine Tablet== |
| !Classification藥物分類
| | Chlorpromazine are available in the following strengths: |
| |-
| | *Tablets: 25 mg, 50 mg, 100 mg |
| |Chlorpromazine Tablet 25 mg
| | |
| |CHLO44
| | ==Drug Trade Names of Chlorpromazine Tablet== |
| |P1S1S3
| | Largactil |
| |-
| | |
| |Chlorpromazine Tablet 50 mg
| | ==Drug Usage== |
| |CHLO46
| | Treatment of schizophrenia and other psychotic disorders |
| |P1S1S3
| |
| |}
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|
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| ==Mechanism of Action== | | ==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. | | Chlorpromazine acts s an antagonist on various postsynaptic receptors: |
| In addition, chlorpromazine also acts as an antagonist (blocking agent) on different postsynaptic and presynaptic receptors:
| | *Blocks dopamine D<sub>1</sub>, D<sub>2</sub>, D<sub>3</sub>, and D<sub>4</sub> receptors |
| *Dopamine receptors (subtypes D1, D2, D3 and D4), which account for its antipsychotic properties | | *Blocks serotonin 5-HT<sub>1</sub> and 5-HT<sub>2</sub> receptors |
| *Serotonin receptors (5-HT2, 5-HT6 and 5-HT7), with anxiolytic, antidepressant, and anti-aggressive properties | | *Blocks histamine H<sub>1</sub> receptors |
| *Histamine receptors (H1 receptors) accounting for sedation, antiemetic effect | | *Blocks alpha-1 and alpha-2 adrenergic receptors |
| *α1- and α2-adrenergic receptors accounting for lowering of blood pressure, reflex tachycardia, vertigo, sedation, hypersalivation and incontinence as well as sexual dysfunction | | *Blocks muscarinic acetylcholine receptors |
| *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. | |
|
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| ==Dosage== | | ==Route of Administration== |
| | Oral |
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| | ==Dosages== |
| | For schizophrenia in adults: |
| | *Initial: 25 - 50 mg orally 3 times daily |
| | *Maintenance: 200 - 400 mg daily in divided dose |
| | *Maximum: 1000 mg daily |
| | |
| | ==Side Effects== |
| {| class="wikitable" | | {| class="wikitable" |
| !style="text-align: left"| Indication | | !style="text-align: left"| Frequency |
| !style="text-align: left"| Dose | | !Adverse reactions |
| | |- |
| | | rowspan="10" | '''Common |
| | | Drowsiness and sedation |
| |- | | |- |
| !style="text-align: left"|
| | | Dizziness |
| *Acute and chronic schizophrenia
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| *Reduce acute mania in bipolar disorder
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| *Control severely violent behaviour
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| *Adjunctive management of severe anxiety
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| |By ''mouth
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| ADULT:
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| *Initially 25 mg 3 times a day, adjusted according to response
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| *Or initially 75 mg once daily, taken at night, adjusted according to response
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| *Maintenance 75 – 300 mg daily
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| ELDERLY or debilitated patients:
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| *A third to half adult dose
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| By ''rectum
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| ADULT: 25 – 50 mg 3 – 4 times a day
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| |- | | |- |
| !style="text-align: left"| Intractable hiccup
| | | Dry mouth |
| |By ''mouth
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| ADULT: 25 – 50 mg 3-4 times a day
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| |- | | |- |
| !style="text-align: left"| Nausea and vomiting of terminal illness
| | | Blurred vision |
| |By ''mouth
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| ADULT: 10 – 25 mg every 4-6 hours
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| CHILD 1-5 years: 500 micrograms/kg every 4-6 hours; max. 40 mg per day
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| CHILD 6-11 years: 500 micrograms/kg every 4-6 hours; max. 75 mg per day
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| CHILD 12-17 years: 10 – 25 mg every 4-6 hours
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| By ''rectum
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| ADULT: 100 mg every 6-8 hours
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| |}
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| Chlorpromazine is given orally as the hydrochloride and the embonate.
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| For both salts, the doses are expressed as the hydrochloride. Chlorpromazine embonate 144 mg is equivalent to 100 mg of chlorpromazine hydrochloride.
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| If the oral route is not suitable, it may be given rectally as suppositories containing 100 mg of chlorpromazine base
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| ==Side Effects==
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| 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.
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| Possible side effects include:
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| {| class = "wikitable"
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| !style="text-align: left"| It has antimuscarinic properties and may cause the following side effects such as
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| *Dry mouth
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| *Constipation
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| *Difficulty to urinate
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| *Blurred vision
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| *Mydriasis
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| *Tachycardia
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| *ECG changes (particularly Q- and T-wave abnormalities)
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| *Orthostatic hypotension is common
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| |- | | |- |
| !style="text-align: left"| Other adverse effects include
| | | Constipation |
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| *Delirium
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| *Agitation
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| *sedation
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| *Insomnia
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| *Nightmares
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| *Glaucoma
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| *Inhibition of ejaculation
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| *Impotence
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| |- | | |- |
| !style="text-align: left"| Hypersensitivity reactions include
| | | Weight gain |
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| *Urticaria
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| *Exfoliative dermatitis
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| *Prolonged therapy may lead to deposition of pigment, producing a bluish-purple discoloration in the skin
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| *Corneal and lens opacities
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| *Photosensitivity reaction
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| |- | | |- |
| !style="text-align: left"| Haematological disorders
| | | Increased appetite |
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| *Haemolytic anaemia
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| *Thrombocytopenic purpura
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| *Most cases of agranulocytosis occurred within 4 to 10 weeks starting treatment
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| |- | | |- |
| !style="text-align: left"| Extrapyramidal dysfunction include
| | | Nausea |
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| *Acute dystonia
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| *A parkinsonism-like syndrome
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| *Tardive dyskinesia
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| *Neuroleptic malignant syndrome
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| |- | | |- |
| !style="text-align: left"| Altered endocrine and metabolic functions
| | | Difficulty urinating |
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| *Developed amenorrhoea, galactorrhoea and gynaecomastia due to hyperprolactinaemia
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| *Weight gain
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| *Hyperglycaemia
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| *Body temperature regulation is impaired and may result in hypo- or hyperthermia depending on environment.
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| |}
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| ==Pharmacokinetics==
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| {|class="wikitable"
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| !style="text-align: left"| Oral bioavailability
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| |Chlorpromazine is readily, although sometimes erratically absorbed after oral doses.
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| |- | | |- |
| !style="text-align: left"| Onset of action
| | | Skin sensitivity to sunlight |
| |Peak plasma concentrations occur about 2 to 4 hours after ingestion.
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| |- | | |- |
| !style="text-align: left"| Metabolism
| | | rowspan="9" | '''Serious |
| |It is subject to considerable first-pass metabolism in the gut wall and is also extensively metabolized in the liver. | | | a. Exterapyramidal symptoms (movement disorders): |
| | *Muscle stiffness or spasms |
| | *Tremors |
| | *Restlessness (akathisia) |
| | *Parkinson-like symptoms |
| |- | | |- |
| !style="text-align: left"| Elimination half-life
| | | b. Tardive dyskinesia (potentially irreversible involuntary movements of face and tongue) |
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| It is excreted in the urine and faeces.
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| Owing to the first-pass effect, plasma concentrations after oral doses are much lower than those after intramuscular doses.
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| The plasma half-life of chlorpromazine occurs about 30 hours.
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| |}
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| ==Drug Management==
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| ====onitoring===
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| The following populations must be closely monitored after administration of chlorpromazine:
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| *Epileptics, since chlorpromazine may lower the seizure threshold. Treatment must be stopped if seizures occur.
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| *Elderly persons with susceptibility to orthostatic hypotension, sedation, and extrapyramidal effects; chronic constipation and prostatic hypertrophy.
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| *Patients with cardiovascular disease since chlorpromazine can induce tachycardia and hypotension. Regular BP and pulse monitoring are recommended.
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| *Patients with severe liver and/or renal failure because of the risk of accumulation.
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| *Patients on long-term treatment should receive regular eye examinations.
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| *Diabetic patients who are started on chlorpromazine should get glycemic monitoring during treatment.
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| *Chlorpromazine commonly causes increased susceptibility to sunburn and individuals should avoid undue exposure to direct sunlight.
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| *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.
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| ===Drug interaction===
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| The most common interactions encountered with chlorpromazine result from use with drugs that have similar pharmacological actions
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| {| class="wikitable"
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| !Drugs given with chlorpromazine
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| !Potential Effect
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| |- | | |- |
| |style="text-align: left"| | | | c. Neuroleptic malignant syndrome (fever, muscle rigidity, altered mental state) |
| *CNS-depressant drugs including alcohol, hypnotics, anxiolytics, and opioids.
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| |Potentiates the sedative effect.
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| |- | | |- |
| |style="text-align: left"| | | | d. Low white blood cell count (agranulocytosis) |
| *Lithium
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| |Concomitant use can cause confusion, with a rapid increase in serum lithium.
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| |- | | |- |
| |style="text-align: left"| | | | e. Seizures |
| *Drugs with antimuscarinic actions such as tricyclic antidepressants
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| |As chlorpromazine has antimuscarinic actions, they can potentiate the adverse effects.
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| |- | | |- |
| |style="text-align: left"| | | | f. QT prolongation leading to dangerous heart arrhythmias |
| *Antiparkinsonian drugs (amantadine, bromocriptine, levodopa, ropinirole)
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| |In theory, antipsychotics with dopamine-blocking activity and dopaminergic drugs such as those used to treat parkinsonism may be mutually antagonistic.
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| |- | | |- |
| |style="text-align: left"| | | | g. Difficulty regulating body temperature |
| *metoclopramide
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| |May increase the risk of antipsychotic-induced extrapyramidal effects.
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| |- | | |- |
| |style="text-align: left"| | | | h. Hormonal changes: |
| *Drugs that prolong the QT interval e.g. amiodarone, verapamil, sotalol and quinidine | | *Increased prolactin levels |
| |An increased risk of ventricular arrhythmias – avoid concomitant use.
| | *Breast enlargement or milk production |
| | *Menstrual changes |
| |- | | |- |
| |style="text-align: left"| | | | i. Sever low blood pressure |
| *Antacids (magnesium, aluminum and calcium salts, oxides and hydroxides)
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| |Decreased GI absorption of chlorpromazine. Administer chlorpromazine and antacid more than 2 hours apart if possible.
| |
| |} | | |} |
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| ===Caution=== | | ==Pharmacokinetics== |
| *In patients with impaired liver, kidney, cardiovascular and respiratory function | | *Absorption: Well absorbed orally, but undergoes extensive first-pass metabolism |
| *In those with angle-closure glaucoma | | *Metabolism: Extensively metabolized in the liver |
| *In patients with a history of jaundice, parkinsonism | | *Elimination: Mainly in urine as metabolites |
| *In those with diabetes mellitus, hypothyroidism | | *Onset: 30 - 60 minutes after oral administration |
| *In patients with myasthenia gravis, paralytic ileus | | *Duration: 4 - 6 hours (single dose), up to 24 hours (multiple doses) |
| *In patients with prostatic hyperplasia or urinary retention
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| *Care is required in patients with epilepsy
| | ==Drug Precautions== |
| *Debilitated patients, the elderly, especially those with dementia.
| | '''Pregnancy |
| | |
| | Use only if potential benefit outweighs risk. May cause extrapyramidal symptoms in newborns if used in 3rd trimester. |
| | |
| | '''Breastfeeding |
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| | Use caution. Chlorpromazine is excreted in breast milk. |
|
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| ===Contra-indications===
| | '''Children and Elderly |
| Use of chlorpromazine should be avoided in individuals with: | | *Children: Use caution. Safety and efficacy not established in children < 1 year old. |
| *CNS depression or coma | | *Elderly: Start at lower doses and titrate slowly due to increased sensitivity to side effects. |
| *Bone-marrow suppression
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| *Pheochromocytoma (tumour of the adrenal gland)
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|
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| ===Hepatic impairment===
| | '''Renal Impairment |
| *Chlorpromazine is hepatotoxic
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| *Can precipitate coma.
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|
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| ===Renal impairment===
| | Use with caution. No specific dosage adjustments required. |
| *Start with small doses in severe impairment.
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|
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| '''Handling and Storage''' Owing to the risk of contact sensitization, pharmacists, nurses and other health workers should avoid direct contact with chlorpromazine; tablets should not be crushed. | | '''Monitoring Requirements |
| | *Blood pressure |
| | *Body temperature |
| | *Complete blood count |
| | *Liver function tests |
| | *Eye examinations |
| | *ECG in patients at risk of QT prolongation |
|
| |
|
| ===Pregnancy===
| | '''Drug Interactions |
| Should be avoided in pregnancy unless the physician considers it essential.
| | *Increased CNS depression with alcohol, barbiturates, opioids |
| | *Increased risk of arrhythmias with drug that prolong QT interval |
| | *Decreased effectiveness of levodopa |
| | *Increased risk of extrapyramidal symptoms with metoclopramide |
|
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| ===Breast-feeding=== | | ==FAQ== |
| Use during breast feeding is not recommended.
| | '''How Should I Take the Tablet? |
|
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| ===Driving and skilled tasks===
| | Take with or without food. |
| Drivers and machine operators should be told about the risk of drowsiness with this medication especially at the start of treatment. Affected patients should not drive or operate machinery.
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|
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|
| == FAQ ==
| | '''What Should I Avoid While Taking? |
| === How should I take the tablet? ===
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| You will be prescribed the lowest dose needed to control your symptoms. Do not stop taking chlorpromazine suddenly, or you could have unpleasant withdrawal symptoms. The tablet should be swallowed with a glass of water.
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| === What should I avoid while taking? ===
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| Avoid drinking alcohol while taking chlorpromazine because it may enhance the side effects of sedation.
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|
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| Avoid driving or hazardous activity until you know how chlorpromazine will affect you. | | Avoid alcohol, driving or operating machinerty until you know how it affect you. Avoid excessive sun exposure. |
|
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| Avoid getting up too fast from a sitting or lying position, or you may feel dizzy.
| | '''What Happens if I Miss a Dose? |
|
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| Avoid exposure to sunlight or tanning beds. Chlorpromazine can make you sunburn more easily. Wear protective clothing and use sunscreen (SPF 30 or higher) when you are outdoors.
| | Take the missed dose as soon as you remember unless it is almost time for your next dose. Do not double doses. |
| === What happen if I overdose? ===
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| Contact your primary care doctor.
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| If emergency situation, call 999
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| === What happen if I miss a dose? ===
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| Take it as soon as you remember. If it is near the time of the next dose, skip the missed dose. Take your next dose at the regular time. Do not double the dose to catch up.
| |
Antipsychotic Drug
Drug class: Typical Antipsychotic
Chlorpromazine (LARGACTIL)（中文：氯丙嗪）
Common Strengths of Chlorpromazine Tablet[edit]
Chlorpromazine are available in the following strengths:
- Tablets: 25 mg, 50 mg, 100 mg
Drug Trade Names of Chlorpromazine Tablet[edit]
Largactil
Drug Usage[edit]
Treatment of schizophrenia and other psychotic disorders
Mechanism of Action[edit]
Chlorpromazine acts s an antagonist on various postsynaptic receptors:
- Blocks dopamine D1, D2, D3, and D4 receptors
- Blocks serotonin 5-HT1 and 5-HT2 receptors
- Blocks histamine H1 receptors
- Blocks alpha-1 and alpha-2 adrenergic receptors
- Blocks muscarinic acetylcholine receptors
Route of Administration[edit]
Oral
Dosages[edit]
For schizophrenia in adults:
- Initial: 25 - 50 mg orally 3 times daily
- Maintenance: 200 - 400 mg daily in divided dose
- Maximum: 1000 mg daily
Side Effects[edit]
| Frequency
|
Adverse reactions
|
| Common
|
Drowsiness and sedation
|
| Dizziness
|
| Dry mouth
|
| Blurred vision
|
| Constipation
|
| Weight gain
|
| Increased appetite
|
| Nausea
|
| Difficulty urinating
|
| Skin sensitivity to sunlight
|
| Serious
|
a. Exterapyramidal symptoms (movement disorders):
- Muscle stiffness or spasms
- Tremors
- Restlessness (akathisia)
- Parkinson-like symptoms
|
| b. Tardive dyskinesia (potentially irreversible involuntary movements of face and tongue)
|
| c. Neuroleptic malignant syndrome (fever, muscle rigidity, altered mental state)
|
| d. Low white blood cell count (agranulocytosis)
|
| e. Seizures
|
| f. QT prolongation leading to dangerous heart arrhythmias
|
| g. Difficulty regulating body temperature
|
h. Hormonal changes:
- Increased prolactin levels
- Breast enlargement or milk production
- Menstrual changes
|
| i. Sever low blood pressure
|
Pharmacokinetics[edit]
- Absorption: Well absorbed orally, but undergoes extensive first-pass metabolism
- Metabolism: Extensively metabolized in the liver
- Elimination: Mainly in urine as metabolites
- Onset: 30 - 60 minutes after oral administration
- Duration: 4 - 6 hours (single dose), up to 24 hours (multiple doses)
Drug Precautions[edit]
Pregnancy
Use only if potential benefit outweighs risk. May cause extrapyramidal symptoms in newborns if used in 3rd trimester.
Breastfeeding
Use caution. Chlorpromazine is excreted in breast milk.
Children and Elderly
- Children: Use caution. Safety and efficacy not established in children < 1 year old.
- Elderly: Start at lower doses and titrate slowly due to increased sensitivity to side effects.
Renal Impairment
Use with caution. No specific dosage adjustments required.
Monitoring Requirements
- Blood pressure
- Body temperature
- Complete blood count
- Liver function tests
- Eye examinations
- ECG in patients at risk of QT prolongation
Drug Interactions
- Increased CNS depression with alcohol, barbiturates, opioids
- Increased risk of arrhythmias with drug that prolong QT interval
- Decreased effectiveness of levodopa
- Increased risk of extrapyramidal symptoms with metoclopramide
How Should I Take the Tablet?
Take with or without food.
What Should I Avoid While Taking?
Avoid alcohol, driving or operating machinerty until you know how it affect you. Avoid excessive sun exposure.
What Happens if I Miss a Dose?
Take the missed dose as soon as you remember unless it is almost time for your next dose. Do not double doses.
