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
Pharmacology 101
Top 200 drugs
Adult/Paediatric Emergency Medicine Advanced Trainee in Melbourne, Australia. Special interests in diagnostic and procedural ultrasound, medical education, and ECG interpretation. Co-creator of the LITFL ECG Library. Twitter: @rob_buttner
Note that the “Pharmacokinetics of antipsychotic drugs (general)” regarding absorption doesn’t apply to haloperidol – which has high bioavailability and low first pass metabolism.