Drug information of Chlorpromazine

Chlorpromazine


Chlorpromazine is a dimethylamin-derivative phenothizine used in the form of the base or the hydrochloride salt that as an antipsychotic agent, antiemetic, and presurgical sedative, and in the treatment of intractable hiccups, acute intermittent prophyria, tetanus, and the manic phase of bipolar disorder. it is also used to treat certain severe behavioral problems in children.

Mechanism of effect

Chlorpromazine acts as an antagonist on different postsysnaptic, on dopaminergic-receptors (different antipsychotic properties on productive and unproductive symptoms), on serotonergic-receptors receptors(with anxiolytic, antidepressive and antiaggressive properties as well as an attenuation of extrapyramidal side-effects, but also leading to weight gain, fall in blood pressure, sedation and ejaculation difficulties),

on histaminergic-receptors(sedation, antiemetic, 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),

 on muscarinic (cholinergic) 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.

Pharmacodynamic

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.

Pharmacokinetics

Absorption

Bioavailability: 20%; extensive 1st-pass metabolism

Onset: 30-60 min

Duration: 4-6 hr; extended release, 10-12 hr

Distribution

Protein bound: 92-97%

Vd: 20 L/kg

Metabolism

Metabolized by hepatic P450 enzyme CYP2D6

Metabolites: 10-12 different compounds

Elimination

Half-life: 30 hr

Excretion: Urine

Dosage

*Adults:

Schizophrenia, Psychotic Disorders

PO: 30-75 mg/day divided q6-12hr initially; maintenance: usually 200 mg/day (up to 800 mg/day in some patients; some patients may require 1-2 g/day)

IV/IM: 25 mg initially, followed PRN with 25-50 mg after 1-4 hours, then increased to maximum of 400 mg q4-6hr until patient is controlled; usual dosage 300-800 mg/day

Nausea & Vomiting

PO: 10-25 mg q4-6hr PRN

IV/IM: 25-50 mg q4-6hr PRN

Preoperative Apprehension

25-50 mg PO 2-3 hours before surgery

12.5-25 mg IM 1-2 hours before surgery

Intraoperative Sedation

12.5 IM q30min or 2 mg IV q2min; total dose not to exceed 25 mg

Intractable Hiccups

25-50 mg PO q6-8hr; if hiccups persist after 2-3 days of oral therapy, administer 25-50 mg IM q3-4hr; if symptoms persist, administer 25-50 mg by slow IV infusion with patient lying flat in bed; monitor BP

Acute Intermittent Porphyria

25-50 mg PO q6-8hr

Migraine Headache (Off-label)

5-50 mg IV as single dose 

*Pediatrics:

Behavioral Disorders, Hyperactivity

<6 months: Safety and efficacy not established

>6 months: 50-100 mg/day PO/IM; 200 mg/day or more may be necessary for older hospitalized patients; for outpatients, may administer 0.55 mg/kg q4-6hr PRN  

Nausea & Vomiting

<6 months: Safety and efficacy not established

>6 months: 0.5-1 mg/kg PO/IM q6-8hr PRN 

Preoperative Apprehension

<6 months: Safety and efficacy not established

>6 months: 0.55 mg/kg PO/IM 1-2 hours before surgery

Alerts

  • Patients with dementia-related psychosis who are treated with antipsychotic drugs are at increased risk for death, as shown in short-term controlled trials; deaths in these trials appeared to be either cardiovascular (eg, heart failure, sudden death) or infectious (eg, pneumonia) in nature.
  • This drug is not approved for treatment of patients with dementia-related psychosis.
  • Avoid using in children with suspected Reye syndrome
  • Use caution in glaucoma, prostatic hypertrophy, stenosing peptic ulcer disease (PUD), history of NMS, Parkinson disease, hypocalcemia, renal or hepatic impairment, history of severe reaction to insulin or electroconvulsive therapy (ECT), history of seizures, asthma, respiratory tract infection, cardiovascular disease, myelosuppression
May cause extrapyramidal symptoms, including akathisia, acute dystonic reactions, and pseudoparkinsonism, and tardive dyskinesia; risk of dystonia greater with increased doses.

Points of recommendation

  • Patient should avoid activities requiring mental alertness, coordination, or visual acuity until drug effects are realized.
  • Drug can cause sun sensitivity. advise patient to use sunscreen and avoid tanning beds.
  • Drug may impair heat regulation. advise patients to use caution with activities leading to an increased core temperature, such as strenuous exercise, exposure to extreme heat or dehydration.
  • Advise patient to report any visual disturbances. Patients receiving moderate to high-dose therapy for long periods of time may need to have period eye exams.
  • When receiving IV or IM injection, instruct patient to rise slowly from a sitting/supine position as drug may cause orthostatic hypotension.
  • This drug may cause anticholinergic effects, diminished sweating, akathisia, or somnolence.
  • Instruct patient to report signs/symptoms of agranulocytosis (eg. sudden appearance of sore throat or other signs of infection). espicially between the forth and tenth weeks of therapy.
  • Advise patient to report signs/symptoms of neuromuscular adverse effects such as parkinsonian extrapyramidal disease, tardive dyskinesia(jerk muscle movement, tongue thrusting, facial grimacing/ticks, random movements of extremities), or neuroleptic malignant syndrome (sweating, fever, stupor, unstable blood pressure, muscular rigidity, autonomic dysfunction).
  • Patients on concurrent antipsychotic therapy should report signs/symptoms of encephalopathic syndrome (weakness, lethargy, fever, tremulousness, confusion).
  • Advise patients against sudden discontinuation of drug.
  • Patients receiving IV or IM injection should remain in bed for at least 1/2h post -injection to minimize hypotension.
  • Patient should not drink alcohol or take additional CNS depressants while taking this drug.
Patient should avoid exposure to organophosphorus insecticides during drug therapy.

Pregnancy level

C


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