Pharm 101: Olanzapine

Class

Second generation antipsychotic (SGA)
Other examples include: clozapine, quetiapine, risperidone

Pharmacodynamics

• Thienobenzodiazepine
• Greater blockade of 5-HT-2a receptors than D2 (low D2/5-HT2A ratio)
• Some alpha blockade and M receptor blockade
• Effective against negative and positive symptoms
• Clinical effects:
  • High clinical potency
  • Medium sedative action
  • Low hypotensive action
  • Very low EPS

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 – improvement of both positive and negative symptoms
• Bipolar disorder (adjunctive with lithium)
• Agitation
• Route and dosage:
  • PO, SL, IM, depot IM
  • 10-20mg

Adverse effects

• Weight gain
• Sedation (but less than typical antipsychotics)
• Metabolic syndrome (diabetes, high cholesterol)
• Dose-related lowering of seizure threshold
• Some anticholinergic effects

Precautions

• Elderly
• Hepatic/renal impairment

Further reading

• Long N. Olanzapine Toxicity. LITFL
• Nickson C. Chemical Restraint. LITFL

References

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