Pharm 101: Haloperidol

Class

First generation antipsychotic (FGA)

Pharmacodynamics

• 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

Precautions/contraindications

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

Further reading

• Buttner R. Pharm 101: Olanzapine. LITFL
• Nickson C. Acute Dystonic Reaction. LITFL
• Nickson C. Chemical Restraint. LITFL

References

• Katzung BG. Basic and Clinical Pharmacology. 14e. 2018: 515-529