An autopsy case of intoxication caused by drug interaction with multiple psychotropic drugs, fluvoxamine, levomepromazine, and trihexyphenidyl.

A case of death due to combined use of multiple drugs is reported, and the pharmacokinetic interactions are discussed. A woman in her thirties was found dead in her home. A medico-legal autopsy found no findings suggestive of injury or natural disease. Toxicological analysis using liquid chromatography tandem mass spectrometry (LC-MS/MS) identified a toxic level of fluvoxamine (0.947 µg/mL), and concentrations greater than the therapeutic levels of levomepromazine (0.238 µg/mL) and trihexyphenidyl (0.225 µg/mL) were present, while bromazepam, haloperidol, sulpiride, and 7-aminoflunitrazepam were within or below their therapeutic ranges. Fluvoxamine is mainly metabolized by cytochrome P450 2D6 (CYP2D6), and levomepromazine is a potent CYP2D6 inhibitor. A high concentration of levomepromazine may increase the blood fluvoxamine level. Since the combined use of levomepromazine and fluvoxamine induces seizures, it may have been involved in causing the subject's death. In addition, combined use of trihexyphenidyl may potentiate anticholinergic effects of fluvoxamine overdose, including convulsions and coma. It was concluded that the cause of the subject's death was the interaction of multiple drugs.

Kerosene condenses in the trachea following inhalation.

PURPOSE: We have investigated the absorption dynamics of petroleum fuel components from the analytical results of autopsy samples. METHODS: Post-mortem samples of the severely burned case, including femoral blood, intratracheal contents (mucus) and intratracheal gas-phase samples were collected, and analysed by gas chromatography-mass spectrometer with head-space solid-phase microextraction. RESULTS: The composition of flammable substances in the tracheal gas phase differed slightly from that in mucus. CONCLUSION: High-boiling point components are retained in the trachea, whereas relatively lower-boiling point components are detected predominantly in the tracheal gas phase and blood.

An autopsy case of BRONTM overdose with multiple drug ingestion.

A man in his forties was found dead in his friend's home, with moderate putrefaction. Quantitative toxicological analysis showed that concentrations of caffeine, chlorpheniramine, dihydrocodeine, and methylephedrine were 183.3 µg/mL, 0.533 µg/mL, 2.469 µg/mL and 8.336 µg/mL, respectively. Ephedrine, amitriptyline, nortriptyline, etizolam, fluvoxamine and 7-aminoflunitrazepam were detected in an aortic blood sample. Caffeine, chlorpheniramine, dihydrocodeine and methylephedrine are the main components of BRONTM, an over-the-counter antitussive sold in Japan. Those concentrations in blood were within fatal ranges. Caffeine is classified as a methylxanthine and is mainly metabolized by cytochrome P450 (CYP)1A2. Fluvoxamine is a potent CYP1A2 inhibitor. Blood fluvoxamine concentration was within the therapeutic range, but would have increased blood caffeine level by the inhibition of caffeine metabolism. The conclusion was that his death was caused by BRONTM overdose. Inhibition of caffeine metabolism may increase blood caffeine concentrations. This suggests that more attention should be paid to potential interactions between multiple drugs.

Case report: Fatal poisoning caused by additive effects of two barbiturates.

A case of fatal poisoning involving multiple psychotropic drugs is presented. Quantitative toxicological analysis showed femoral blood concentrations of pentobarbital, phenobarbital, duloxetine, acetaminophen and tramadol were 10.39, 22.57, 0.22, 0.61 and 0.22 µg/ml, respectively. We concluded that the death was due to the additive effects of two barbiturates. As both pentobarbital and phenobarbital act on gamma-aminobutyric acid (GABA) receptors, central nervous system activity was suppressed, causing respiratory depression. Additive pharmacological effects should be considered in cases of massive ingestion of multiple drugs.