quetiapine

Introduction

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