CHLOROPROMAZINE 100MG TABLETS

Indications

• Schizophrenia
• Severe anxiety
• Acute psychotic episodes
• Severe agitation
• Nausea and vomiting
• Preoperative sedation

Dosage

Adults: The initial dose is typically 25 mg to 50 mg taken orally, which may be increased gradually based on clinical response. The maximum recommended dose is generally 800 mg per day, but maintenance doses are often lower. Refer to the BNF for specific dosing guidelines.

Mechanism of action

Chlorpromazine acts as an antagonist on various postsynaptic receptors, including dopaminergic (D1, D2, D3, D4), serotonergic (5-HT1, 5-HT2), histaminergic (H1), and alpha1/alpha2 receptors. It also interacts with muscarinic (M1/M2) receptors and acts as a weak presynaptic inhibitor of dopamine reuptake. These actions contribute to its antipsychotic effects, as well as sedation, antiemesis, and various side effects including weight gain and anticholinergic symptoms.

Pharmacodynamics

Chlorpromazine is a psychotropic agent with sedative and antiemetic activities. It primarily affects the central nervous system at subcortical levels, exhibiting strong antiadrenergic effects and weaker peripheral anticholinergic activity. It has slight antihistaminic and antiserotonin effects, making it versatile in treating various symptoms associated with psychosis and agitation.

Pharmacokinetics

Chlorpromazine is well absorbed following oral administration, with a peak plasma concentration typically reached within 1 to 4 hours. It undergoes extensive hepatic metabolism, primarily via the cytochrome P450 system, and has a long half-life, allowing for once-daily dosing in many cases. It is excreted mainly in urine as metabolites, with less than 1% excreted unchanged.

Contra-indications

• Hypersensitivity to chlorpromazine or any of its components
• Severe CNS depression
• Bone marrow depression
• Comatose states
• Severe liver impairment
• Pheochromocytoma

Adverse effects

• Sedation
• Weight gain
• Hypotension
• Extrapyramidal symptoms
• Anticholinergic effects (dry mouth, blurred vision)
• Sexual dysfunction
• Tachycardia
• Jaundice
• Seizures

Interactions

• CNS depressants (increased sedation)
• Antihypertensives (enhanced hypotensive effects)
• Anticholinergics (additive anticholinergic effects)
• Dopamine agonists (reduced effectiveness of agonists)
• Alcohol (enhanced CNS depression)

Precautions

• Monitor for signs of tardive dyskinesia
• Caution in patients with history of seizures
• Use with caution in elderly patients, particularly those with dementia
• May lower seizure threshold
• Regular monitoring of blood pressure is advised

Pregnancy

Chlorpromazine should only be used during pregnancy if the potential benefit justifies the risk to the fetus. Animal studies have shown adverse effects.

Breast-feeding

Chlorpromazine is excreted in breast milk; caution should be exercised when administering to nursing mothers.

Storage

Store in a cool, dry place, away from light. Keep out of reach of children.

Formulations

• Tablets: 10 mg, 25 mg, 50 mg, 100 mg
• Oral solution: 25 mg/5 mL
• Injection: 25 mg/mL, 50 mg/mL

Mechanism of action

Chlorpromazine acts as an antagonist (blocking agent) on different postsysnaptic receptors -on dopaminergic-receptors (subtypes D1, D2, D3 and D4 - different antipsychotic properties on productive and unproductive symptoms), on serotonergic-receptors (5-HT1 and 5-HT2, with anxiolytic, antidepressive and antiaggressive properties as well as an attenuation of extrapypramidal side-effects, but also leading to weight gain, fall in blood pressure, sedation and ejaculation difficulties), on histaminergic-receptors (H1-receptors, sedation, antiemesis, vertigo, fall in blood pressure and weight gain), alpha1/alpha2-receptors (antisympathomimetic properties, lowering of blood pressure, reflex tachycardia, vertigo, sedation, hypersalivation and incontinence as well as sexual dysfunction, but may also attenuate pseudoparkinsonism - controversial) and finally on muscarinic (cholinergic) M1/M2-receptors (causing anticholinergic symptoms like dry mouth, blurred vision, obstipation, difficulty/inability to urinate, sinus tachycardia, ECG-changes and loss of memory, but the anticholinergic action may attenuate extrapyramidal side-effects). Additionally, Chlorpromazine is a weak presynaptic inhibitor of Dopamine reuptake, which may lead to (mild) antidepressive and antiparkinsonian effects. This action could also account for psychomotor agitation and amplification of psychosis (very rarely noted in clinical use). The principal pharmacologic effects of chlorpromazine are similar to those of other propylamino derivatives of phenothiazine. Chlorpromazine has strong anticholinergic and sedative effects and moderate extrapyramidal effects. Chlorpromazine has strong antiemetic and adrenergic blocking activity and weak ganglionic blocking, antihistaminic, and antiserotonergic activity. The development of phenothiazine derivatives as psychopharmacologic agents resulted from the observation that certain phenothiazine antihistaminic compounds produced sedation. In an attempt to enhance the sedative effects of these drugs, promethazine and chlorpromazine were synthesized. Chlorpromazine is the pharmacologic prototype of the phenothiazines. The pharmacology of phenothiazines is complex, and because of their actions on the central and autonomic nervous systems, the drugs affect many different sites in the body. Although the actions of the various phenothiazines are generally similar, these drugs differ both quantitatively and qualitatively in the extent to which they produce specific pharmacologic effects. /Phenothiazine General Statement/ In the CNS, phenothiazines act principally at the subcortical levels of the reticular formation, limbic system, and hypothalamus. Phenothiazines generally do not produce substantial cortical depression; however, there is minimal information on the specific effects of phenothiazines at the cortical level. Phenothiazines also act in the basal ganglia, exhibiting extrapyramidal effects. The precise mechanism(s) of action, including antipsychotic action, of phenothiazines has not been determined, but may be principally related to antidopaminergic effects of the drugs. There is evidence to indicate that phenothiazines antagonize dopamine-mediated neurotransmission at the synapses. There is also some evidence that phenothiazines may block postsynaptic dopamine receptor sites. However, it has not been determined whether the antipsychotic effect of the drugs is causally related to their antidopaminergic effects. Phenothiazines also have peripheral and/or central antagonistic activity against alpha-adrenergic, serotonergic, histaminic (H1-receptors), and muscarinic receptors. Phenothiazines also have some adrenergic activity, since they block the reuptake of monoamines at the presynaptic neuronal membrane, which tends to enhance neurotransmission. The effects of phenothiazines on the autonomic nervous system are complex and unpredictable because the drugs exhibit varying degrees of alpha-adrenergic blocking, muscarinic blocking,

Pharmacodynamics

Chlorpromazine is a psychotropic agent indicated for the treatment of schizophrenia. It also exerts sedative and antiemetic activity. Chlorpromazine has actions at all levels of the central nervous system-primarily at subcortical levels-as well as on multiple organ systems. Chlorpromazine has strong antiadrenergic and weaker peripheral anticholinergic activity; ganglionic blocking action is relatively slight. It also possesses slight antihistaminic and antiserotonin activity.