quetiapine

see also:

• anti-psychotic medications

• quetiapine is an atypical benzothiazepine antipsychotic agent introduced in the late 1990's.
• it is an antagonist at multiple neurotransmitter receptors in the brain.
• it has been proposed that it's antipsychotic activity is mediated through a combination of dopamine type 2 (D2) and serotonin type 2 (5-HT2) antagonism
• it also has a high affinity for alpha-adrenergic and histamine receptors but low affinity for muscarinic receptors

• well absorbed from the gastrointestinal tract and reaches peak plasma levels within 2 h after oral administration
• Vd 8-10 L/kg
• 83% bound to plasma proteins
• extensively metabolized by the liver (including via CYP3A4 and CYP2D6) to over 20 metabolites, with only 5% of the drug being excreted unchanged

• starting dose in adults 25mg bd then titrate every 2 days to a target dose of 75-150mg bd within a week

• appears to have greater safety in overdose than traditional antipsychotic agents
• lethality has occurred with doses above 13g

• usually are evident within 4 hours and may last 72 hours
• most likely to display toxicity at doses above 3g in adults and over 100mg in children
• prolonged QTc
• sinus tachycardia
• hypokalaemia
• 1st degree heart block
• orthostatic hypotension
• mild-mod anticholinergic effects
• children may develop extra-pyramidal symptoms up to 3 days later
• dose-related decreased conscious state and if coma occurs it usually lasts 24-48hrs

• ABC's as per usual with cardiac monitoring and may require mechanical restraints
• if reduced GCS then consider early intubation and consider charcoal once airway protected
• Mx of seizures:
  • excluding arrhythmia as a cause
  • titrated benzodiazepines
• Mx of hypotension
  • IV crystalloid as per shock (eg. 10-20mL/kg)
  • consider inotropes
    • WARNING: adrenaline is C/I due to possible paradoxical hypotension due to beta 2 adrenergic vasodilatation
    • noradrenaline appears to be the preferred agent
• check for urinary retention