Typical/first-generation

• Examples:

  • Chlorpromazine
  • Prochlorperazine
  • Haloperidol
• Common indications:

  • Schizophrenia
  • Mania
  • Agitation
  • Acute psychosis
• MOA:

  • Dopamine receptor antagonists that work by inhibiting dopaminergic neurotransmission
  • Block post-synaptic dopamine D2-receptors
  • Increase dopamine levels
  • Also have noradrenergic, cholinergic, and histaminergic blocking properties
  • Most useful at treating positive symptoms of psychosis
• Side effects:

  • ESPEs - more so than atypical
  • Anticholinergic - dry skin, blurred vision, tachycardia, constipation
  • Sedation - antihistamine effects
  • Lower seizure threshold
  • Neuroleptic malignant syndrome
  • May cause prolongation of QT interval - more common with atypical antipsychotics
• High-potency antipsychotics:

  • Fluphenazine, haloperidol and loxapine
  • Have very low activity on the histaminic and muscarinic receptors - do not carry significant sedation, weight gain or anticholinergic activity
  • Higher risk of EPSEs
• Low potency antipsychotics:

  • Chlorpromazine and thioridazine
  • High histaminic and muscarinic activity - increased sedation and anticholinergic effects
  • Lower risk of EPSEs
• Typical antipsychotics should be prescribed with caution in patients with:

  • Concurrent use of anticholinergic medication
  • Severe cardiac abnormalities
  • History of seizure disorders
  • History of tardive dyskinesia
  • Concurrent use of CNS depressants - benzodiazepines, opioids
• haloperidol can cause abnormal heart rhythms, ventricular arrhythmia, torsades de pointes, and even sudden death if injected intravenously.
• Route:

  • All typical antipsychotics are available for oral administration
  • Haloperidol can be delivered orally and IM for rapid tranquilization
  • Haloperidol and fluphenazine can be delivered as long-acting depot parenteral shots