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  • [Prolonged toxic coma and anisocoria secondary to doxepin, lorazepam and phenobarbital poisoning--case study].

[Prolonged toxic coma and anisocoria secondary to doxepin, lorazepam and phenobarbital poisoning--case study].

Przeglad lekarski (2012-12-19)
Małgorzata Kołodziej, Magdalena Majewska, Anna Krajewska, Jarosław Szponar
ABSTRACT

Doxepin is a tricyclic antidepressant from the group of dibenzoxepines. Apart from the antidepressant effect, it has also the sedative and anxiolytic effect, so it is used in the treatment of anxiety disorder in the course of psychosis, organic diseases and alcoholism. Doxepin increases concentration of norepinephrine and serotonin in the brain by preventing inactivation and blocking their reuptake. In addition, the drug has an antagonistic effect on receptors in CNS (muscarinic M1, histamine H1, alpha-1adrenergic, serotonergic 5-HT2) and also blocks sodium and potassium channels in cardiomyocytes. In this paper we present a case of severe poisoning by various drugs, including doxepin. The dominating symptom was prolonged toxic coma. Slow return of consciousness was observed from the fifth day after intoxication, logical verbal contact with the patient was possible on the seventh day. It seems that this symptom results from the pharmacokinetic properties of doxepin as well as the high drug dose and a synergistic effect of lorazepam and phenobarbital. Transient anisokoria was an unusual symptom that appeared in the course of intoxication. The patient was examined by a neurologist and underwent CT of the head twice - no organic causes were revealed. This phenomenon can be explained by physiological anisokoria, caused by asymmetry in the sympathetic innervation of pupil rectractor muscle, exacerbated by a complete parasympathetic conduction block as a result of anticholinergic action of doxepin. Tricyclic antidepressants are often used by patients for the purpose of suicide. Because of the serious cardiological and neurological symptoms the course of doxepin intoxication may be severe.

MATERIALS
Product Number
Brand
Product Description

Supelco
Lorazepam solution, 1.0 mg/mL in acetonitrile, ampule of 1 mL, certified reference material, Cerilliant®
Supelco
Phenobarbital solution, 1 mg/mL in methanol, ampule of 1 mL, certified reference material, Cerilliant®
Doxepin for system suitability, European Pharmacopoeia (EP) Reference Standard
Supelco
Doxepin hydrochloride solution, 1.0 mg/mL in methanol (as free base), ampule of 1 mL, certified reference material, Cerilliant®
Sigma-Aldrich
(±)-Lorazepam
Sigma-Aldrich
Phenobarbital
Sigma-Aldrich
Phenobarbital sodium salt
Sigma-Aldrich
Doxepin hydrochloride, ~85% E-isomer basis, ≥98% (GC), 15% Z-isomer basis, powder