Pharm 101: Chlorpromazine

Class

First generation antipsychotic (FGA)


Pharmacodynamics
  • Aliphatic phenothiazine derivative
  • Greater blockade of D2 receptors than 5-HT-2a receptors (high D2/5-HT2A ratio)
  • Alpha1-receptor, M receptor and H1 receptor blockade (especially extensive alpha1 blockade, causing many autonomic adverse effects)
  • Clinical effects:
    • Low clinical potency
    • Medium extrapyramidal toxicity
    • High sedative action
    • High hypotensive action

Pharmacokinetics of antipsychotic drugs (general)
  • Characteristics of most antipsychotic drugs:
    • Readily but incompletely absorbed
    • Significant first-pass metabolism
    • Highly lipid soluble and protein bound (92-99%)
    • Large volumes of distribution (usually > 7L/kg)
    • Much longer duration of action than estimated from their plasma half-lives
    • Hepatic metabolism by oxidation or demethylation, catalysed by CYP450 enzymes

Clinical uses
  • Schizophrenia (alleviates positive symptoms)
  • Bipolar disorder (manic phase)
  • Antiemetic
  • Agitation

Adverse effects of antipsychotic drugs
  • Muscarinic cholinoceptor blockade:
    • Loss of accomodation, dry mouth, difficulty urinating, constipation
    • Tachycardia
    • Toxic-confusional state
  • Alpha-adrenoceptor blockade:
    • Postural hypotension
    • Impotence, failure to ejaculate
  • Dopamine-receptor blockade:
    • Parkinson’s syndrome
    • Akathisia, dystonias
    • Neuroleptic malignant syndrome
    • Amenorrhoea, galactorrhoea, infertility, impotence due to hyperprolactinaemia resulting from dopamine receptor blockade
  • Supersensitivity of dopamine receptors:
    • Tardive dyskinesia
  • H1 receptor blockade:
    • Sedation
  • Combined H1 and 5-HT2 blockade:
    • Weight gain
  • Specific to chlorpromazine:
    • Extensive alpha blockade causing hypotension
    • Seizures
    • Corneal deposits

Precautions/contraindications
  • Combination with other drugs producing extrapyramidal dysfunction, sedative effects, alpha-blockade, anti-cholinergic effects

Further reading

References

Pharm 101 700

Pharmacology 101

Top 200 drugs

Emergency Medicine Trainee, educationalist, and ultrasound enthusiast. Currently based at Sir Charles Gairdner Hospital in Perth, Western Australia | Top 200 Drugs | De-eponymificationTwitter

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