- These are generally benign in OD, requiring only supportive care. Mild sedation, HR, & orthostatic hypoBP common. E.g. Clozapine, risperidone, olanzapine, quetiapine, amisulpride.
- D2, 5HT, peripheral 1, H1, M1 antagonism. Risperidone & amisulpride have affinity for H1, M1.
- Clozapine, risperidone, olanzepine: Rapidly abs. 1st pass metabolism – Cyt P450.
- Olanzapine: Large Vd. Abs by SL route too and also has some hepatic conjugation to glucuronide.
- Quetiapine: Large Vd. Protein bound. Hepatic met by Cyt P450
- Amisulpride: 2 abs peaks (1hr, 4hr). Mod Vd. Most excreted unchanged in faeces & urine.
- All but amisulpride: Intoxication within 4hrs. Mild confusion, sedation, HR, & orthostatic hypoBP common. Miosis. Coma & _cardiotoxicity, rare. EPE more common in children.
- Clozapine: Hypersalivation, anticholinergic effects (incl mydriasis). Fits in 5–10%.
- Olanzapine: agitated delirium & urine retention common with mod OD. 15% have non-specific ST-T wave changes.
- Quetiapine: <5% fit. Although may have QT, torsade de pointes very rare.
- Amisulpride: Higher risk of cardiotoxicity with QT & HR → risk of torsade de pointes up to 36h. BBB possible. Coma uncommon. Large ingestions may delay onset of toxicity.
- Screening: BSL, ECG, paracetamol
- Other: Rpt ECG, cardiac monitoring. QT can occur with some ODs. UEC if ECG abnormal.
Clozapine & risperidone
- Usually benign. OD>2.5mg/kg clozapine may significant symptoms.
- Therapeutic sedation and antipsychotic effects
- 40–100mg (child>0.5mg/kg)
- Mild-mod sedation with possible anticholinergic effects
- Sedation with intermittent marked agitation
- Coma possible, hypoBP with peripheral alpha blockade, rarely seizures
- Mild-mod sedation and sinus tachycardia
- Risk of CNS depression, coma & BP. Delirium or seizures possible
- Mild-mod sedation and sinus tachycardia. QTc & TdP reported >4g
- Risk of delayed CNS depression, cardiotoxicity (BP,QRS,QTc,BBB & TdP)
- Expected delayed CNS depression, cardiotoxicity (BP,QRS,QTc,BBB & TdP)
- Resus, supportive care & monitoring:
- ABCs incl. fluid management for BP.
- Watch for urinary retention.
- Manage delirium with non-pharmacological & BDZ rather than physostigmine.
- Treat seizures with BDZ and acute dystonic reactions (EPE) with benztropine ± BDZ.
- Treat Na blockade cardiotoxicity with **bicarbonate ± hyperventilation, and TdP with MgSO4/pacing.
- Activated charcoal not advised except if >4g amisulpride ingested within 1–2h.
- If remain asymptomatic at 4–6h (16h for amisulpride) post OD with normal ECG can be d/c else monitor until normal & below QT nomogram line. Advise child’s parents of risk of EPE for 1wk.