Pharm 101: Haloperidol


First generation antipsychotic (FGA)

  • Butyrophenone derivative
  • Greater blockade of D2 receptors than 5-HT-2a receptors (medium D2/5-HT2A ratio)
  • Some alpha blockade, minimal M receptor blockade
  • Clinical effects:
    • High clinical potency
    • Very high extrapyramidal toxicity
    • Low sedative action (much less than phenothiazines)
    • Very low 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)
  • Huntington’s chorea
  • Tourette syndrome
  • Behavioural disturbance
  • Cannabis hyperemesis syndrome
  • Nausea/vomiting in palliative care
  • Route:
    • PO, SC, IM, IV, IM depot
    • Variable dosage depending on route
Adverse effects of antipsychotic drugs
  • Muscarinic cholinoceptor blockade:
    • Loss of accomodation, dry mouth, difficulty urinating, constipation
    • Toxic-confusional state
  • Alpha-adrenoceptor blockade:
    • Postural hypotension
    • Impotence, failure to ejaculate
  • Dopamine-receptor blockade:
    • Parkinson’s syndrome
    • Akathisia, dystonias
    • Amenorrhoea, galactorrhoea, infertility, impotence due to hyperprolactinaemia resulting from dopamine receptor blockade
  • Supersensitivity of dopamine receptors:
    • Tardive dyskinesia
  • Combined H1 and 5-HT2 blockade:
    • Weight gain
  • Specific to haloperidol:
    • Extrapyramidal dysfunction is major adverse event
    • Neuroleptic malignant syndrome
    • Agranulocytosis, cholestatic jaundice, and skin eruptions occur rarely with the high-potency antipsychotics used
  • Combination with other drugs producing extrapyramidal dysfunction, sedative effects, alpha-blockade, anti-cholinergic effects
Further reading

Pharmacology 101

Top 200 drugs

MBBS (UWA) CCPU (RCE, Biliary, DVT, E-FAST, AAA) Adult/Paediatric Emergency Medicine Advanced Trainee in Melbourne, Australia. Special interests in diagnostic and procedural ultrasound, medical education, and ECG interpretation. Editor-in-chief of the LITFL ECG Library. Twitter: @rob_buttner

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