Death of two subjects due to imipramine and desipramine metabolite accumulation during chronic therapy: a review of the literature and possible mechanisms.

In two unrelated cases, a 7-year-old boy and a 21-year-old woman died suddenly while receiving chronic imipramine therapy. In the boy, concentrations of imipramine were: Left femoral blood 0.5 mg/L, right femoral blood 1.2 mg/L, aorta blood 1.0 mg/L, liver 68 mg/Kg, and for the active metabolite, desipramine, left femoral blood 6.7 mg/L, right femoral blood 9.9 mg/L, aorta blood 8.7 mg/L, liver 400 mg/Kg. In the woman, the imipramine concentrations were: Femoral blood 0.6 mg/L, liver 37 mg/Kg, and of the active metabolite, desipramine, femoral blood 3.74 mg/L, liver 261 mg/Kg. In both cases, the scene investigation strongly indicated that neither individual had ingested an acute overdose. The very high ratios of desmethyl metabolite to parent drug are consistent with this observation. Impaired metabolism due to a genetically determined "slow metabolizer" phenotype of cytochrome CYP2D6, and/or concurrent therapy with phenothiazines, is suggested as a possible mechanism for the apparent fatal accumulation of these tricyclic antidepressants.

An acetonitrile-related death.

A 39-year-old female who lived alone was discovered dead in her home. An autopsy produced no cause of death. The blood sedative screen was negative and only diphenhydramine was found by the urine organic base analysis. Examination of the blood and urine for volatiles produced an unexpected peak by GC analysis, which was then identified as acetonitrile by GC/MS. Acetonitrile concentrations were 31 and 56 mg/dL in two separate blood samples and 44 mg/dL in the urine. The blood cyanide concentration was 4.4 micrograms/mL. The cause of death was determined to be acetonitrile poisoning although the source of the acetonitrile was not discovered.

Massive strychnine intoxication: serial blood levels in a fatal case.

A fatal case of strychnine intoxication is reported. The patient expired despite early aggressive management and prevention of metabolic complications. Serial blood levels are reported. In contrast to a previous report describing first order elimination kinetics, our data suggest that strychnine follows Michaelis-Menton elimination kinetics. The case illustrates the rapid, dramatic course of severe strychnine ingestions. A review of the toxicokinetics, mechanism of action and treatment of strychnine intoxication follows.

Evaluation of the Abbott TDx for determination of phenobarbital in forensic blood specimens.

The Abbott TDx was evaluated for determination of phenobarbital (PB) levels in postmortem (PM) blood. Because hemolysis does not interfere with fluorescence polarization assays, the TDx could be a fast, efficient alternative to gas chromatography (GC). The linearity and precision of the TDx assay were evaluated using postmortem blood that was spiked with phenobarbital and serially diluted. The relationship between nominal and measured values was linear for phenobarbital concentrations up to 150 mg/L (r = 0.999) in two separate postmortem bloods. Precision was excellent with run-to-run coefficients of variation of 10% or less. The TDx results for phenobarbital in spiked PM blood were compared to those determined by GC. An excellent correlation (r = 0.999) between the TDx results and GC results was achieved. PM blood specimens from ten forensic cases were assayed for PB by GC and compared with PB results from the TDx. Comparison of these results also showed good correlation (r = 0.959). These data indicate that the Abbott TDx can be used reliably in the estimation of PB levels in postmortem whole blood samples.

Concentrations of morphine and codeine in serum and urine after ingestion of poppy seeds.

We measured morphine and codeine in commercially available poppy seeds and in serum and urine samples from healthy adults who had ingested these poppy seeds. Four brands of black poppy seeds, examined by gas chromatography-mass spectroscopy (GC-MS) with deuterated internal standards, contained from 17 to 294 micrograms of morphine and 3 to 14 micrograms of codeine per gram of seeds. Morphine was detected by GC-MS in hydrolysates of serum as late as 24 h after ingestion, with a maximum mean concentration of 100 ng/mL (range 82-131) measured 2 h after the subjects ingested 25 g of seeds. Opiates were detectable (greater than 300 micrograms/L) in urine by enzyme-multiplied immunoassay (EMIT; Syva Co.) and by radioimmunoassay screening procedures for as long as 48 h after ingestion. The identity and quantities of morphine and codeine in poppy seed extracts and in hydrolysates of serum and urine were confirmed by GC-MS. Therefore a positive finding of morphine or codeine in blood and urine may sometimes be due to ingestion of poppy seeds.