A fatal case of amoxapine poisoning under the influence of chronic use of psychotropic drugs.

A 43-year-old woman was found dead in a car in the supine position. She had been suffering from depression for 2 years and hesitation wounds on the left forearm and wrist were observed. On microscopic examination, pulmonary congestion and edema were observed with heart failure cells in many alveoli, thereby suggesting not only acute but also chronic heart failure. Drug screening in the blood by gas chromatography-mass spectrometry (GC-MS) revealed the presence of amoxapine and levomepromazine, and their concentrations in tissues were determined by GC-MS with three-step solvent extraction followed by acetylation. The concentration of amoxapine in the blood and liver was 0.86-1.77 and 18.76microg/ml, respectively; the levels were much higher than the therapeutic level but did not reach the lethal level. The concentrations of levomepromazine in tissues were within the therapeutic level. Based on the pathological and toxicological findings, the cause of death was determined to be amoxapine poisoning on the basis of chronic heart failure due to the chronic use of psychotropic drugs.

[Hair analysis as a document of oxcarbazepine therapy in fatal levomepromazine poisoning]. / Analiza wlosów jako dokument terapii okskarbazepina w smiertelnym zatruciu lewomepromazyna.

A development of contemporary analytical methods makes possible to use hairs in toxicological analysis for documentation history of drug administration. An undertaken subject has been illustrated by a suicidal fatal poisoning of 58-year-old man with a neuroleptic drug--levomepromazine. Toxicological analysis carried out by HPLC/APCI/MS, besides of standardized postmortem specimen as blood, urine, liver and cerebrospinal fluid included also victim hairs. As a result of analytical procedure levomepromazine at high concentrations was revealed, which may be responsible for death. Moreover, and antiepileptic drug--oxcarbazepine and two main metabolites at therapeutic concentrations were revealed parallel. In three 2-cm segments of hair oxcarbazepine and two metabolites were detected, levomepromazine, in contrary, was not detected in this specimen. Complex chemical-toxicological investigation confirmed information that victim was an epileptic patient and was treated with oxcarbazepine at least 6 months before death while toxic dose of levomepromazine, as one could suppose, he took to commit suicide.

Intentional overdose of Large Animal Immobilon.

We describe a case of voluntary self-injection with Large Animal Immobilon, a veterinary anaesthesia product containing etorphine, a very strong opioid, and acepromazine, a phenothiazine. This resulted in cardiorespiratory arrest and the need for sustained haemodynamic support after resuscitation. Large Animal Immobilon is used under specific conditions only, mainly in zoo and wildlife medicine. Primary toxicological analysis, although guided by the presumed toxin, could only detect a metabolite of acepromazine in the urine. Further analysis was able to show some traces of etorphine. A number of topics are treated, including the apparent potency of the etorphine and the selection of a suitable antidote, taking into account the different properties of the respective agents.

A previously unidentified acepromazine metabolite in humans: implications for the measurement of acepromazine in blood.

High-performance liquid chromatography-diode-array detection results obtained during the investigation of two cases involving acepromazine prompted us to study the stability of the drug in blood. It was found that acepromazine can undergo in vitro conversion by human red blood cells to 2-(1-hydroxyethyl)promazine, a product that has been reported as a minor urinary metabolite in horse urine but not previously identified in humans. Further, our analytical findings in the two cases examined suggest that 2-(1-hydroxyethyl)promazine may be the major unconjugated metabolite of acepromazine in humans. These findings have important implications for the analytical toxicology of acepromazine.

Analysis of etorphine in postmortem samples by HPLC with UV diode-array detection.

Etorphine is a synthetic narcotic analgesic usually used in veterinary medicine. It possesses an analgesic potency up to 1000 times greater than morphine and is therefore used in low doses, primarily for tranquilising large animals. For veterinary use, etorphine is usually available in its commercial formulation as Immobilon, when in combination with acepromazine or methotrimeprazine. Due to the potency of etorphine, only very low doses are required to produce adverse or fatal effects. This paper describes a method for detecting and quantifying etorphine using HPLC with UV diode array detection (HPLC-DAD) and demonstrates the advantage of the technique for the detection of Immobilon at low doses. In a forensic case involving Immobilon, the etorphine concentrations measured in postmortem femoral vein and heart blood specimens were 14.5 and 23.5 micrograms/l, respectively. No etorphine was detected in the urine. To our knowledge this is the first time postmortem etorphine concentrations have been reported.

A fatal case of methotrimeprazine overdose.

Fatal ingestion of methotrimeprazine is unusual, and while therapeutic drug levels are established as concentrations between 0.02 to 0.14 mg/L, fatal levels are not. The following describes a case of fatal suicidal ingestion of methotrimeprazine in which the measured concentration of methotrimeprazine in the blood was 4.1 mg/L. In addition, the major metabolites of methotrimeprazine, desmethylmethotrimeprazine, and methotrimeprazine sulfoxide were also measured at 2.0 and 1.8 mg/L, respectively. Methotrimeprazine and its metabolites were also measured in urine, bile, and vitreous humor. These results are compared with other case reports of methotrimeprazine fatalities reported in the literature.

[Analysis of combined phenothiazine-opiate poisoning]. / Uber die Analyse kombinierter Phenothiazin-Opiat-Vergiftungen.

Report about 2 death cases due to an overdosage of phenothiacine derivates. The EMIT-test showed positive results concerning opiates for both cases. But morphine only was detected in one case by a fluorimetric method. The EMIT-test for opiates can show positive results in error, if there exist phenothiacines in the specimen at the same time.

Phenothiazine treatment and respiratory distress syndrome in a child.

An 11-year-old boy who was treated with a relatively high dose of methotrimeprazine meleate (Levemepromazine) a phenothiazine antipsychotic drug, was admitted to the pediatric intensive care unit suffering from respiratory distress syndrome. He required intensive treatment and support for 13 days. The persistent effects of methotrimeprazine meleate on various organs are typical of the prolonged biological action of the phenothiazine metabolites. The association of phenothiazine overdose and respiratory distress syndrome merits consideration.

Tratamiento de intoxicaciones / Treatment of the intoxications

Se trataron 8 pacientes intoxicados por diferentes métodos: hemoperfusión, hemodiálisis, diálisis peritoneal afectados de diferentes tóxicos (se desarrolla botulismo, bromato de potasio y metanol), se discuten las indicaciones de tratamiento

Tratamiento de intoxicaciones / Treatment of the intoxications

Se trataron 8 pacientes intoxicados por diferentes métodos: hemoperfusión, hemodiálisis, diálisis peritoneal afectados de diferentes tóxicos (se desarrolla botulismo, bromato de potasio y metanol), se discuten las indicaciones de tratamiento

Tratamiento de intoxicaciones / Treatment of the intoxications

Se trataron 8 pacientes intoxicados por diferentes métodos: hemoperfusión, hemodiálisis, diálisis peritoneal afectados de diferentes tóxicos (se desarrolla botulismo, bromato de potasio y metanol), se discuten las indicaciones de tratamiento

[Delirium syndrome in biperiden poisoning]. / Delirantes Syndrom bei Biperiden-Intoxikation.

We report on two cases of self-induced intoxication with the anticholinergic agent biperiden (oral ingestion of at least 200 mgs. in case 1, and of 60 mgs. in combination with 300-400 mgs levomepromazine in case 2). An acute delirious state and other somatic symptoms of a toxic anticholinergic action dominated the clinical picture. Serial measurements of biperiden serum levels revealed values up to 50-fold (case 1) and 15-fold (case 2) of those usually observed under therapeutic doses of biperiden. In both cases, the intoxication was controlled by the application of physostigmine and general therapeutic measures. We discuss the prognosis of biperiden intoxications, and the clinical symptomatology and therapy of drug-induced anticholinergic syndromes.

Resin haemoperfusion in levomepromazine poisoning: evaluation of effect on plasma drug and metabolite levels.

Plasma levels of levomepromazine and two of its major metabolites N-desmethyl-levomepromazine and levomepromazine sulphoxide were studied in two poisoned patients treated with resin haemoperfusion at a constant blood flow of 200 ml/min. The mean haemoperfusion clearance of levomepromazine, N-desmethyl-levomepromazine and levomepromazine sulphoxide was 114, 123 and 151 ml/min, respectively, in patient no. 1, and 153, 148 and 184 ml/min, respectively, in patient no. 2. Patient no. 2 had also ingested amitriptyline, and the mean haemoperfusion clearance of amitriptyline and its metabolite nortriptyline was 183 and 183 ml/min respectively. Haemoperfusion did not seem to alter the elimination profile of levomepromazine or the two metabolites in either patient. We conclude that haemoperfusion is of little value in removing levomepromazine, N-desmethyl-levomepromazine or levomepromazine sulphoxide from the body. This is probably due to the large apparent volume of distribution and the high intrinsic hepatic metabolic clearance of these compounds.

Plasma immunoreactive insulin and somatotropin in delirium tremens and alcoholic hallucinosis.

The glucose tolerance curve in alcoholics in delirium tremens was similar to that seen in hepatogenic diabetes. The secretion of immunoreactive insulin and somatotropin after glucose was similar in patients with delirium tremens and alcoholic hallucinosis.