An autopsy case of poisoning with ethanol and psychotropic drugs.

A case of fatal poisoning involving ethanol with psychotropic drugs is presented. Quantitative toxicological analysis showed that the concentrations of ethanol, amoxapine and phenobarbital in the femoral blood were 2.86 mg/ml, 0.41 microg/ml and 6.80 microg/ml, respectively. We concluded that the cause of death was due to the combination use of ethanol, amoxapine and phenobarbital.

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.

Amoxapine-associated acute renal failure.

Acute renal failure, a brief seizure, and mild rhabdomyolysis developed in a 27-year-old man following overdosage with the tricyclic antidepressant, amoxapine. Renal function returned to normal approximately ten days following drug ingestion. Strikingly, of 111 cases of amoxapine overdosage reported to the manufacturer, acute renal failure has occurred in 12. Of these 12 patients, seizures were documented in seven, and presumptive or definitive evidence of rhabdomyolysis or myoglobinuria was documented in eight. Three possible mechanisms of the renal failure are (1) acute tubular necrosis secondary to nontraumatic rhabdomyolysis; (2) hypotension-induced acute tubular necrosis; and (3) direct nephrotoxic reaction from amoxapine. Rapid hydration with intravenously administered saline is proposed as a means of reducing the substantial incidence of acute renal failure following amoxapine overdosage.

Amoxapine: a review of its pharmacology and efficacy in depressed states.

Amoxapine is an N-demethylated dibenzoxazepine closely related in the neuroleptic loxapine. Its tricyclic structure appears to give it antidepressant properties resembling imipramine and amitriptyline. In uncontrolled trials it was shown to have antidepressant activity in usual doses up to 200 to 400mg daily. In placebo and double-blind controlled studies comparing amoxapine with the standard tricyclic antidepressants imipramine and amitriptyline, it was shown to be comparable in efficacy with a possibly somewhat faster onset of improvement of selected symptoms of depression in some studies. Because of the small study groups and lack of placebo control, many reports do not show statistically significant differences of treatment over standard drugs. To date there have been no studies comparing amoxapine with electroconvulsive therapy. Side effects were qualitatively similar to standard drugs with a suggestion that in standard doses or overdose myocardial effects are mild. However, the final place of amoxapine in the therapy of depressed states is still to be decided.

Amoxapine-associated rhabdomyolysis and acute renal failure: case report.

Amoxapine, a new tricyclic antidepressant, has been recently released in the United States and Europe. There has been limited experience with amoxapine overdose, and no serious reactions or sequelae were observed in the reported cases. A case of amoxapine overdose associated with rhabdomyolysis and acute renal failure is reported. Amoxapine overdose could cause convulsions or prolonged coma leading to atraumatic rhabdomyolysis and myoglobinuric renal failure. Direct muscle or renal toxicity from this drug and its metabolites should not be excluded until evidence to the contrary is available. Acute renal failure should be looked for in cases of amoxapine overdose.

Amoxapine overdose in a young man: a transient mitochondrial abnormality?

Amoxapine is a second-generation tricyclic antidepressant structurally related to the neuroleptic loxapine. It was previously marketed as an alternative to traditional tricyclic antidepressants because of alleged shorter onset of action and fewer cardiotoxic effects. However, various adverse reactions, including cardiac dysrhythmias, renal failure, coma, seizures, and neuroleptic malignant syndrome, were reported during therapy or after acute overdose. A 14-year-old boy ingested 1900 mg of amoxapine and developed seizures, hypertension, hyperpyrexia, altered mental status, myoglobinuria, renal failure, and transient magnetic resonance imaging (MRI) changes suggestive of hypertensive encephalopathy and neuroleptic malignant syndrome. Since mitochondrial disorders can cause multisystem failure, including encephalopathy, renal tubular dysfunction, and myopathy, a transient, toxic disorder of mitochondrial function was considered as the basis for the patient's clinical and MRI changes.

Amoxapine fatalities: three case studies.

Amoxapine (Asendin), a recently introduced dibenzoxazepine, has been effective in clinical studies for the treatment of various types of depression. Three amoxapine-related deaths are reported. Quantitation of amoxapine was carried out by gas chromatography using 3% OV-17 column. Blood amoxapine concentrations were 11.5 mg/l, 2.8 mg/l, and 0.89 mg/l. The concentrations are many-fold higher than the reported therapeutic serum concentrations of 0.21 mg/l. These cases illustrate the potential toxicity and lethality of amoxapine overdose and the need for caution in prescribing a large amount of amoxapine to patients with suicidal tendencies.

Toxicological findings in amoxapine overdose.

Tissue concentrations of amoxapine, a new antidepressant with antipsychotic properties, were determined in two cases in which amoxapine was taken in overdose. Two extractions and GLC procedures, UV spectra, and TLC properties of amoxapine are described. The concentrations of amoxapine are described. The concentrations of amoxapine in brain tissue (52 micrograms/g and 53.2 micrograms/g) were about equal to concentrations found in liver (77 micrograms/g and 50 micrograms/g) and higher than blood concentrations (6 micrograms/mL and 1.5 micrograms/mL). The two metabolites of amoxapine, 8-hydroxyamoxapine and 7-hydroxyamoxapine, were not detected by TLC or GLC.

The determination of amoxapine in human fatal overdoses.

Amoxapine, a recently introduced dibenzoxazepine, has been found effective in clinical studies for the treatment of various types of depression. Two amoxapine related deaths, a 53-year-old white male and a 21-year-old white female, have been investigated by this office. Both had been prescribed amoxapine for depression. Quantitation of amoxapine was by gas chromatography using a 3% OV-17 column with confirmation by ultraviolet spectrophotometry and thin layer chromatography. Blood amoxapine concentrations were found to be 18 mg/L in the first subject, and 6.7 mg/L in the second subject. These concentrations are many-fold higher than the therapeutic serum concentrations of up to 0.21 mg/L reported in a clinical study. These cases illustrate the potential lethality of amoxapine overdosage and the need for caution in prescribing amoxapine to patients with suicidal tendencies.

Amoxapine in human overdose.

Amoxapine, a tricyclic antidepressant, is metabolized to 8-hydroxyamoxapine and 7-hydroxyamoxapine. There are few reports on the metabolism of this drug and correlation of clinical symptoms in overdose patients. Five such patients admitted to the Emergency Unit of the University of Cincinnati Hospital were studied. Clinically, all had seizures and evidence of altered cardiac function. The amounts of the parent drug and the 7- and 8-hydroxy metabolites were measured and, in all cases, the parent and 8-hydroxy metabolite were present in both urine and serum. In contrast, the 7-hydroxyamoxapine was found in trace amounts in the serum of only two patients, but in the urine of all the patients observed. These observations were confirmed by gas chromatographic/mass spectroscopic analysis. The pattern of metabolism was analogous to that found in patients on maintenance doses of the drug. In two overdose patients, it was possible to monitor the levels as a function of time. The elimination curve of parent and metabolite was first order with a half-life of 8.5 to 15.0 and 48 hr, respectively.

Amoxapine overdose: report of two cases.

Two deaths are described involving amoxapine. Toxicological analysis in Case 1 revealed an amoxapine blood concentration of 5.7 micrograms/mL, and in Case 2, a concentration of 3.2 micrograms/mL. Qualitative analysis of other body fluids were performed.

Detection of a novel compound after overdoses of aspirin and amoxapine.

The identification of a novel by-product in the tissue and fluid extracts of a victim of fatal overdoses of the tricyclic antidepressant amoxapine and aspirin is presented. Gas chromatography/mass spectrometry suggested that amoxapine was transacetylated by aspirin to form N-acetylated amoxapine. When standard N-acetylated amoxapine was prepared and subjected to the same analytical testing as extracted tissues and fluids, the metabolite was identified as N-acetylamoxapine. Quantitation of N-acetylamoxapine was obtained by gas chromatography. Concentrations of N-acetylamoxapine compared to those of amoxapine and salicylates in blood, liver, stomach, and small bowel are given.

Generalized convulsions as the presenting sign of amoxapine intoxication.

Two infants presented for medical evaluation with sudden onset of seizures or coma, without obvious cause. Suspicious circumstances led to toxicological screening analysis. Amoxapine, a recently released antidepressant, was found in the gastric contents of both children an undetermined time after the putative ingestion, but elevated serum concentrations were noted only in one. The pharmacokinetics are described. There were no obvious cardiotoxic or anticholinergic effects in these infants. Thus, they, like older children and adults, manifest mainly central nervous system toxicity rather than the cardiotoxicity and anticholinergic effects of overdose seen with tricyclic antidepressants.

Analysis of blood and tissue for amoxapine and trimipramine.

A method for the identification and quantitation of two tricyclic antidepressants, amoxapine (Asendin) and trimipramine (Surmontil) is presented here. Samples were extracted with hexane at pH 10, back-extracted with 1.0N sulfuric acid. The acidic layer was adjusted to pH 10 and re-extracted with hexane. Electron impact mass spectra were obtained. The base peak and molecular ion for amoxapine were at m/z 245 and 313, respectively. The base peak and molecular ion for trimipramine were at m/z 58 and 294, respectively. There were three forensic toxicology cases involving amoxapine in Cook County, IL, in 1980 and 1981. The concentrations of amoxapine in blood for these three cases were 1.66 mg/L, 7.16 mg/L, and 2.95 mg/L, respectively.

Simultaneous determination of 5 psychotropic drugs of various types in an autopsy case of acute multiple drug poisoning.

We attempted the simultaneous determination of 5 drugs, mirtazapine, sertraline, chlorpromazine, amoxapine and zolpidem, detected in a gas chromatography-mass spectrometry screening test in an autopsy case. The solid-phase extraction of the analytes from biological samples was achieved using Oasis(®)HLB cartridges (Waters, Milford, MA, USA). Gas chromatography was performed on a HP-5MS fused silica capillary column (30 m × 0.25 mm i.d., 0.25 µm film thickness, Agilent Technologies). The mass spectrometer was operated with an electron energy of 70 eV in electron impact mode. The qualitative and quantitative analyses were performed in full-scan mode and the selected ion monitoring mode, respectively. The total ion chromatogram showed good separation of these drugs. Linear graphs were obtained with good correlation coefficients for these drugs from 0.001 to 2.0 µg/mL (r(2)=0.9909-0.9986) using imipramine-d6 as an internal standard. The recoveries of these drugs were found to be 62.8-88.0% in spiked whole blood. Mirtazapine, sertraline, chlorpromazine, amoxapine and zolpidem were found in post-mortem samples of the deceased at concentrations of 2.67, 0.07, 0.25, 0.32 and 0.68 µg/mL, respectively. The concentration of mirtazapine was within the lethal level and those of amoxapine and zolpidem were within the toxic level. We diagnosed that the cause of death was acute multiple drug poisoning. The simple and practical procedure used in this study is useful for the simultaneous determination of psychotropic drugs of various types in post-mortem biological samples.