Severe and Fatal Fentanyl Poisonings from Transdermal Systems after On-Skin and Ingestion Application.

In recent years, the administration of fentanyl (FNTL) implicitly in transdermal drug delivery systems (TDDS) has vastly increased in chronic pain treatment. Non-medical and uncontrolled use of FNTL in TFDS (transdermal fentanyl delivery systems) may reveal toxic effects by the route of exposure, dermal or alternative, by ingestion of patches, and drug release in the stomach. The purpose of this study was to present three different cases of FNTL poisonings, two of which resulted in death due to TFDS abuse. The first case is a 66-year-old woman treated for accidental FTNL poisoning resulting in acute respiratory distress syndrome. Two remaining cases are a 31-year-old woman and a 25-year-old man who died as a result of FNTL overdose after on-skin and ingestion application of the drug patches. During the hospitalization of the 66-year-old patient, in blood samples, FNTL was confirmed at a concentration of 10.0 ng/mL. Tests run on blood taken from the corpses of 25- and 31-year-old patients exhibited FNTL presence in concentrations of 29.1 ng/mL and 38.7 ng/mL, respectively. The various routes of administration and ultimately toxic effects are important to present because, in TDDS, fentanyl can be a reason for severe to fatal poisoning, as shown by the three cases above.

Causes of Death during the Intravenous Infusion of Dimethylsulphoxide and Hydrogen Peroxide in the Course of Alternative Medicine Therapy.

Unconventional (alternative, natural) medicine in Poland and worldwide includes hundreds of non-scientifically verified "treatment" modalities. Among the most popular are biological therapies using chemical or natural compounds administered with injection or drip infusion. The latter has found the most excellent use in treating rheumatological and dermatological diseases and certain types of cancer. Vitamin infusions, curcumin, glutathione, perhydrol and dimethylsulphoxide (DMSO) have gained popularity among clients of natural medicine clinics. The present study aims to analyse the case of a 37-year-old woman who was administered infusions containing perhydrol and DMSO (0.5 mL 0.04% hydrogen peroxide/0.5 mL p.d.a DMSO in saline) due to a MTHFR A1298C mutation. After having the next infusion, the woman complained of nausea and then became unconscious. Subsequently, she suffered respiratory and cardiac arrest. Adequate resuscitation was undertaken. After being taken to the hospital, the patient was in critical condition and died due to increasing multiple-organ failure. Initially, there was suspected DMSO poisoning as it was the only compound to have been administered as an intravenous infusion. However, it was not until the analysis of the secured evidence that it became clear that the patient had also been given an intravenous solution of hydrogen peroxide, H2O2, and that there had been a mistake in preparing the intravenous perhydrol solution. The autopsy concluded that the immediate cause of death was an acute cardiopulmonary failure due to the toxic effects of intravenously administered hydrogen peroxide. This conclusion was established after the toxicological testing of the evidence and biological material secured during the patient's treatment and autopsy. Products containing DMSO and perhydrol are not included in the lists of medicinal/therapeutical forms and preparations and thus are not authorised for marketing in Poland. In the case of perhydrol, apart from the topical use of diluted preparations for washing and cleansing wounds, no data on therapeutic use exist in the available scientific literature. Furthermore, "DMSO and perhydrol therapy" cannot even be considered a placebo effect, as both are toxic compounds which could, at most, cause poisoning symptoms rather than improve health.

Oxidative stress and biochemical indicators in blood of patients addicted to alcohol treated for acute ethylene glycol poisoning.

Ethylene glycol (EG), in addition to its neurotoxic and nephrotoxic effects, evokes oxidative stress. The aim of this study was to assess the influence of the ethylene glycol on the biochemical indicators and oxidoreductive balance of patients treated for acute poisoning. The total study group consisted of 56 persons including 26 alcoholics who took EG as a substitute for ethyl alcohol in the course of alcohol dependence syndrome and 30 controls. Severity of poisoning, results of acid-base parameters, biochemical, and toxicological tests as well as biomarkers of the oxidative stress in blood were analyzed during the patients' hospitalization. The key issue was to assess the oxidative stress and biochemical disturbances caused by EG and the type of treatment applied in the course of poisoning. Significant changes in some parameters were found both at time of diagnosis and after treatment initiation (ethanol as an antidote and hemodialysis). The most important differences included the activity of hepatic parameters (aspartate aminotransferase, AST) and oxidative stress markers like catalase (CAT); correlation of the lipid peroxidation products level (TBARS) with urea concentration has been shown. On the last day of the hospitalization, in some cases, the mutual correlation between the evaluated markers were observed, for example, between alanine transaminase (ALT) and glutathione reductase (GR), and urea concentration and glutathione level (GSH/GSSG). The concentration of ions (H+) had a major impact on the oxidoreductive balance, correlating with the elevated GR and GSH/GSSG levels.

New Methods Used in Pharmacokinetics and Therapeutic Monitoring of the First and Newer Generations of Antiepileptic Drugs (AEDs).

The review presents data from the last few years on bioanalytical methods used in therapeutic drug monitoring (TDM) of the 1st-3rd generation and the newest antiepileptic drug (AEDs) cenobamate in patients with various forms of seizures. Chemical classification, structure, mechanism of action, pharmacokinetic data and therapeutic ranges for total and free fractions and interactions were collected. The primary data on bioanalytical methods for AEDs determination included biological matrices, sample preparation, dried blood spot (DBS) analysis, column resolution, detection method, validation parameters, and clinical utility. In conclusion, the most frequently described method used in AED analysis is the LC-based technique (HPLC, UHPLC, USLC) combined with highly sensitive mass detection or fluorescence detection. However, less sensitive UV is also used. Capillary electrophoresis and gas chromatography have been rarely applied. Besides the precipitation of proteins or LLE, an automatic SPE is often a sample preparation method. Derivatization was also indicated to improve sensitivity and automate the analysis. The usefulness of the methods for TDM was also highlighted.

Clonazolam a new designer benzodiazepine intoxication confirmed by blood concentration.

BACKGROUND: Recently the number of new psychoactive substances have significantly increased, becoming popular among experienced users of designer drugs. A significant group includes benzodiazepine derivatives, which have not been introduced as medications but are abused by people experimenting with new and classical psychoactive substances. CASE PRESENTATION: The aim of this paper was to present the case of a clonazolam ingestion by a person who was not habituated to benzodiazepines. The intake caused only prolonged coma, decreased muscle tone, and deep tendon reflexes without any other concomitant toxicity and cardio-respiratory failure. CONCLUSIONS: Clonazolam concentrations in patient's blood, measured three times were 0.077 mg/L, 0.015 mg/L, 0.009 mg/L after 4, 8 and 12 h, respectively. Clonazolam's human toxicity has not been well established, so any case of poisoning should be closely monitored.

Suicidal Carbon Monoxide Poisoning Using Motor Vehicle Exhaust in an Open Space.

OBJECTIVES: A rare case of a suicidal use of gases from the car exhaust system of the car petrol engine in an open space is presented. CLINICAL PRESENTATION AND INTERVENTION: To verify suicidal intent of poisoning, an experimental reconstruction of the crime scene was performed. This demonstrated that appropriately long exposure to carbon monoxide with unfavorable weather conditions can cause acute carbon monoxide poisoning in an open space. CONCLUSIONS: This case was studied to observe the pattern of fatal carbon monoxide poisoning in an open space. This might be helpful for forensic medicine, emergency medicine, and occupational medicine.

Effect of repeated administration of 4-methylpyrazole on renal function and lipid peroxidation products in rat kidney after ethylene glycol poisoning.

Toxic effects of ethylene glycol (EG) and its metabolites are mainly related to metabolic acidosis and kidney damage. EG biotransformation involving CYP2E1 affects the oxidant-antioxidant balance. The study assessed the effect of repeated administration of 4-methylpyrazole (4MP, 15mg/kg b.w. after 2h, followed by 10mg/kg b.w. every 12h) on renal function (creatinine, urea and urinary protein levels) as well as products of kidney's lipid peroxidation (MDA and TBARS levels) in rats poisoned with EG (5745mg/kg b.w.). Serum EG and glycolic acid (GA) concentrations were measured throughout the experiment. Repeated administration of 4MP reduced the rate of EG elimination, extended the period of EG persistence in serum and significantly limited formation of GA. The study showed the temporary intensification of kidney oxidative processes that correlated with changes in kidney function. It was found that the use of 4MP in EG poisoning inhibited its biotransformation to toxic metabolites, but simultaneously intensified oxidative damages in kidneys.