Recherche et dosage de la nitrendipine dans un cas mortel d'intoxication polymédicamenteuse

La nitrendipine est un inhibiteur calcique utilisé dans le traitement de l'hypertension. Nous présentons dans ce travail une procédure analytique, effectuée en routine au laboratoire, permettant l'analyse toxicologique de la nitrendipine. Nous rapportons ensuite les résultats obtenus dans un cas mortel d'intoxication polymédicamenteuse où la nitrendipine était impliquée. Des échantillons autopsiques de sang, d'urine et de contenu gastrique, prélevés sur la victime ont été analysés par chromatographie en phase gazeuse couplée à la spectrométrie de masse (CPG-SM) et par chromatographie en phase liquide à haute performance avec détecteur à barrette de diodes (CLHP-DBD). Le dosage sanguin de la nitrendipine a été réalisé par CLHP-DBD. La méthode de dosage a été validée et la stabilité du produit a été vérifiée. La dégradation in vitro et in vivo de la nitrendipine a été discutée. La concentration de la nitrendipine dans le sang périphérique (0,750 mg/L) était 15 fois plus élevée que la valeur extrême de la fourchette thérapeutique. Les concentrations sanguines des autres composés mis en évidence (paracétamol et triazolam) étaient également toxiques. L'association de ces trois composés était vraisemblablement à l'origine du décès

Trends in Fatal Poisoning Among Drug Users in France From 2011 to 2021

Importance The DRAMES (Décès en Relation avec l’Abus de Médicaments Et de Substances) register is a database of drug-related deaths with the aim of identifying the psychoactive substances associated with and estimating the trends in these deaths. Our novel approach is based on the collection of data on all deaths for which toxicology experts have performed analyses. Objective To describe drug-related deaths in France and report trends over an 11-year period. Design, Setting, and Participants This case series used a national register to assess 4460 drug-related deaths that occurred from 2011 to 2021 in France. Data analyses were performed from January 1, 2012, to December 31, 2022. Main Outcomes and Measures Demographic characteristics; medical and substance abuse history; forensic autopsy findings; and toxicology reports. Results Among the 4460 deceased individuals (mean [SD] age, 37.8 [10.5] years), the mortality rate was highest among men (sex ratio, 4.4:1). Of the deaths involving a single or predominant drug, the legal substitution product, methadone, was the leading cause of death during the entire study period, ahead of heroin—44.7% and 35.9% for methadone vs 15.8% and 21.8% for heroin in 2011 and 2021, respectively. Between 2011 and 2021, most of the drug-related deaths shifted from licit to illicit drugs, and statistically significant variations were found for buprenorphine, cocaine, heroin, methadone, and other licit opioids. Deaths related to polydrug use increased from 23.2% in 2011 to 30.6% in 2021. In this context, opioids remained associated with most deaths, with at least 1 opioid being involved in approximately 9 of 10 cases (85.9%) in 2021. However, the main trend was the dramatic increase in drug combinations with cocaine, from less than one-third of cases in 2011 (30.8%) to more than half in 2021 (57.8%). Conclusions and Relevance This case series assessment of 4460 drug-related deaths found that opioids used alone or in combination were the main contributor to drug-related deaths, despite having a lower prevalence than other drugs. This finding is similar to that of other countries; however, in France licit methadone was the leading cause of opioid-related deaths (ahead of heroin) during the study period. Deaths associated with use of cannabis, new psychoactive substances, and stimulants (including amphetamine-type stimulants and cocaine, especially in combination) have increased and should be closely monitored