Clozapine

Question 1

What can be said about dose-response in clozapine overdose?

Answer 1

Not well defined, poisoning including coma can occur in doses as low as 100 mg in adults

Question 2

Describe clozapine overdose in children.

Answer 2

A single tablet will usually cause some symptoms. >2.5 mg/kg is associated with sedation, hypersalivation, tachycardia, ataxia and agitation. Extrapyramidal side effects in the following days.

Question 3

How does clozapine work?

Answer 3

Tricyclic dibenzodiazepine atypical antipsychotic. Antagonist at the mesolimbic dopamine, serotonin and peripheral alpha-1 receptors. It is potent at muscarinic, histamine and GABA receptors

Question 4

Describe the clinical features of clozapine overdose.

Answer 4

CNS depression, lethargy, tachycardia, orthostatic hypotension, anticholinergic side effects, mydriasis and miosis (both have been described), hypersalivation, extrapyramidal effects in children, uncommonly QT prolongation

Question 5

What is pathognomonic for clozapine overdose?

Answer 5

Hypersalivation, sedated patient with features of anticholinergic poisoning but with small pupils

Question 6

What can therapeutic use of clozapine sometimes be associated with?

Answer 6

Agranulocytosis and myocarditis. Not in an acute toxidrome.