Antipsychotics
We can classify antipsychotics based on the receptor that they act on. Older ‘classical’ antipsychotics (e.g. phenothiazines, thioxanthenes) act on the dopamine (D1 and D2) receptors as antagonists, while the newer ‘atypical’ antipsychotics (e.g. amisulpride, clozapine, olanzapine, risperidone) are weaker D2 antagonists and have effects on serotonin (5HT2A) and other CNS receptor systems.
Lets consider the mechanisms of toxicity here:
- Antidopaminergic effects (classic antipsychotics) have strong extrapyramidal activity, increasing muscle tone, movement disorders and acute dystonia in overuse
- Anticholinergic effects are found in the newer ‘atypical’ drugs, resulting in sedation, dry mouth and urinary retention. Additionally the atypicals send to act as alpha-adrenoceptor antagonists and cause dose related vasodilation with hypotension and reflex tachycardia.
The older antipsychotics are absorbed slowly, with erratic peak concentrations often taking hours. Most antipsychotics are lipid soluble, with large volumes of distribution and are eliminated by hepatic metabolism with long half lives. Most have metabolites which may contribute to toxicity.
Risk factors for toxicity include being young, female and patients with liver disease and coingestion of drugs with other CNS depressants (increases the risk for respiratory depression).
Management is mostly supporti e, activated charcoal may be used in the first four hours. If patients become agitated, consider diazepam, and dystonic reactions should be managed with anticholinergics (procyclidine 5-10mg IV or IM) if required.