Overview

1. Include the phenothiazines: chlorpromazine, fluphenazine, thioridazine (discontinued in Aus) and the butyrophenones: haloperidol & droperidol. These neuroleptics cause CNS depression, orthostatic hypoBP, anticholinergic effects in OD.
   1. Thioridizine was the most cardiotoxic.

Toxic mechanism

1. Main action is central D2 antagonism, but they have unwanted effects at other receptors (H1, GABA-A, M1, 1, 2, 5HT). They also have Na & K channel-blocking effects.

Toxicokinetics

1. Rapidly abs but more erratically in OD. 1st pass metabolism.- Cyt P450. Many have active metabolites and long elimination half-lives.

Clinical features

1. Intoxication: within 2–4hrs.
2. CNS depression: LOC, coma from large OD. Seizures & EPE uncommon.

Orthostatic hypotension.

1. Anticholinergic effects: agitated delirium, urinary retention, HR, mydriasis, etc
2. Cardiotoxicity: QRS, QTc, Torsade & other arrhythmias (mainly thioridazine)
3. NB: Neuroleptic Malignant Syndrome occurs rarely in OD.

Investigations

1. Screening: BSL, ECG, paracetamol
2. Other: Serial ECGs & cardiac monitoring for 6hrs, longer for thioridazine

Risk assessment

1. Only significant risk of cardiac toxicity with thioridazine, otherwise relatively low risk.
2. Thioridazine coma & cardiotoxicity likely with OD >5g
3. Torsade risk if QTc>500ms
4. Chlorpromazine coma likely with OD >5g

Management

1. Resus: ABCs

Supportive care

1. Fluid management for BP
2. Treat NaBlockade with bicarbonate.
3. Treat TdP by correcting hypoxia, hypoK and give MgSO4 or, if HR<100, give isoprenaline 1–10µg/min IV infusion or overdrive pace to 100–120bpm.
4. Manage delirium with non-pharmacological & BDZ rather than physostigmine.
5. Treat seizures with BDZ.
6. Treat acute dystonic reactions (EPE) with benztropine ± BDZ.

Decontamination

1. Activated charcoal indicated if intubated.

Disposition

1. If remain asymptomatic at 6hr post OD with normal ECG can be d/c.