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Poisoning Caused by Medicines and Drugs of Abuse

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A special issue of Toxics (ISSN 2305-6304). This special issue belongs to the section "Drugs Toxicity".

Deadline for manuscript submissions: closed (31 May 2022) | Viewed by 51754

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Dr. Elisabetta Bertol

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Guest Editor

U.R.I.To.N—Unit of Research, Department of Health Science, University of Florence, 50121 Florence, Italy
Interests: forensic toxicology; DUID; DFSA; forensic pathology; legal medicine
Special Issues, Collections and Topics in MDPI journals

Dr. Claudia Trignano

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Guest Editor

Università degli Studi di Sassari, Sassari, Italy

Special Issue Information

Dear Colleagues,

Poisoning has always been a part of human life. The causes and scientific understanding of poisoning has changed over time, and with them the opportunities for its correct diagnosis and treatment.

Drug poisoning causes harmful effects on the health of certain therapeutic drugs, resulting either from overdose or from the sensitivity of specific body tissues to regular doses (side effects).

Chronic poisoning is by far the most common “intoxication” affecting our society in this broad sense of the term, but also acute intoxication represents an ongoing challenge.

If tobacco and alcohol are mainly involved in the first case, in the second case, the causes of acute poisoning change over time. Some substances that were once very common causes of poisoning are now only rarely so. Newer medications, illegal drugs, technical products, such as cleaning agents and cosmetics, and new consuming habits (both intentional and unintentional) have also changed the overall picture substantially.

This Special Issue aims to highlight and collect research on the established knowledge, as well as on open issues, regarding drug poisoning; it aims to depict the state of art and also provide new starting points for future advances.

This Special Issue welcomes any original research articles, reviews and short communications (without limits to word length) that focus on the mechanisms of poisoning (accidental or not accidental); acute or chronic exposure; identifications of medicine or illicit drugs; diagnosis and therapeutic options; medical and social solutions. Studies that use metagenomics and metabolomics are encouraged, as well as those establishing predictive tools for monitoring health impacts.

We look forward to receiving your contributions.

Prof. Dr. Elisabetta Bertol
Dr. Claudia Trignano
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Toxics is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

poisoning
forensic toxicology
pharmacology
drugs of abuse
illegal drugs
medicine
chronic poisoning
acute poisoning
metagenomics
metabolomics

Published Papers (12 papers)

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Editorial

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3 pages, 198 KiB

Open AccessEditorial

Poisoning Caused by Medicines and Drugs of Abuse

by Elisabetta Bertol and Claudia Trignano

Toxics 2022, 10(9), 515; https://doi.org/10.3390/toxics10090515 - 31 Aug 2022

Cited by 1 | Viewed by 1408

Abstract

We believe it is necessary to state a premise on the framing of poison and poisoning in the context of Forensic Toxicology as an important contribution to this Special Issue, which is composed of articles about this discipline—the discipline of “poison” [...] Full article

(This article belongs to the Special Issue Poisoning Caused by Medicines and Drugs of Abuse)

Research

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10 pages, 435 KiB

Open AccessArticle

Clinical Presentations and Predictors of In-Hospital Mortality in Illicit Drug Users in the New Psychoactive Substances (NPS) Endemic Era in Taiwan

by Hsin-Tzu Yeh, Hsien-Yi Chen, Sung-Wei Liu, Te-I Weng, Cheng-Chung Fang, Jiun-Hao Yu, Yen-Chia Chen, Yu-Jang Su, Shi-Ying Gao and Chih-Chuan Lin

Toxics 2022, 10(7), 386; https://doi.org/10.3390/toxics10070386 - 12 Jul 2022

Cited by 3 | Viewed by 1659

Abstract

Predictors of mortality in illicit drug users involving Novel Psychoactive Substances (NPS) and multiple substances have not been elucidated. We aimed to define predictors of mortality in the NPS endemic era’s illicit drug users to strengthen patient care in emergency treatment. This was a retrospective study. LC-MS/MS-confirmed positive illicit drug users who visited the emergency departments (ED) of six medical systems were enrolled. Demographic information, physical examinations, and laboratory data were abstracted for mortality analysis. There were 16 fatalities in 355 enrolled patients. The most frequently used illicit drugs were amphetamines, followed by opioids, cathinones, and ketamine. The most frequently detected cathinones among the 16 synthetic cathinones were eutylone, followed by mephedrone. The combined use of cathinones and ketamine was most commonly observed in our results. Univariate analysis revealed that the mortality patients were older, with deep coma, faster heart rate and respiratory rate, lower blood pressures and O₂ room air saturation, more seizures, abnormal breath sounds, and had urine incontinence compared to the survivor patients. The mortality patients also had acute kidney injury, higher potassium, blood sugar, liver function test, and lactate level. The results of multiple logistic regression demonstrated that SBP < 90 mmHg, dyspnea, blood sugar > 140 mg/dl, and HCO₃ < 20.6 mmHg were independent predictors of in-hospital mortality. Regardless of the pattern of the use of illicit drugs, the predictors allow for risk stratification and determining the optimal treatment. Full article

(This article belongs to the Special Issue Poisoning Caused by Medicines and Drugs of Abuse)

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20 pages, 3596 KiB

Open AccessArticle

Effects of Chronic Inhalation of Electronic Cigarette Vapor Containing Nicotine on Neurobehaviors and Pre/Postsynaptic Neuron Markers

by Fawaz Alasmari, Farraj M. Alotibi, Faleh Alqahtani, Tahani K. Alshammari, Aban A. Kadi, Abdullah M. Alghamdi, Bassil S. Allahem, Abdullah F. Alasmari, Shakir D. Alsharari, Salim S. Al-Rejaie and Musaad A. Alshammari

Toxics 2022, 10(6), 338; https://doi.org/10.3390/toxics10060338 - 20 Jun 2022

Cited by 6 | Viewed by 4285

Abstract

Nicotine-exposed animal models exhibit neurobehavioral changes linked to impaired synaptic plasticity. Previous studies highlighted alterations in neurotransmitter levels following nicotine exposure. Vesicular glutamate transporter (VGLUT1) and vesicular gamma-aminobutyric acid (GABA) transporter (VGAT) are essential for the transport and release of glutamate and GABA, respectively, from presynaptic neurons into synapses. In our work, an e-cigarette device was used to deliver vapor containing nicotine to C57BL/6J mice for four weeks. Novel object recognition, locomotion, and Y-maze tests were performed to investigate the behavioral parameters. Protein studies were conducted to study the hippocampal expression of VGLUT1, VGAT, and postsynaptic density protein 95 (PSD95) as well as brain cytokine markers. Long-term memory and locomotion tests revealed that e-cigarette aerosols containing nicotine modulated recognition memory and motor behaviors. We found that vapor exposure increased VGLUT1 expression and decreased VGAT expression in the hippocampus. No alterations were found in PSD95 expression. We observed that vapor-containing nicotine exposure altered certain brain cytokines such as IFNβ-1 and MCP-5. Our work provides evidence of an association between neurobehavioral changes and altered hippocampal VGLUT1 and VGAT expression in mice exposed to e-cigarette vapors containing nicotine. Such exposure was also associated with altered neurobehaviors, which might affect neurodegenerative diseases. Full article

(This article belongs to the Special Issue Poisoning Caused by Medicines and Drugs of Abuse)

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17 pages, 2097 KiB

Open AccessArticle

Suicidal Behavior and Its Relationship with Postmortem Forensic Toxicological Findings

by Aurelia Collados-Ros, Carmen Torres-Sánchez, María Dolores Pérez-Cárceles, Aurelio Luna and Isabel Legaz

Toxics 2022, 10(6), 319; https://doi.org/10.3390/toxics10060319 - 11 Jun 2022

Cited by 6 | Viewed by 2680

Abstract

Suicide affects all sociodemographic levels, age groups, and populations worldwide. The factors that can increase the risk of suicidal tendencies are widely studied. The aim of this study was to analyze the types and combinations of toxics found in fatal suicide victims with different suicide mechanisms. A total of 355 autopsies were retrospectively studied, and 26 toxics were determined and related to mechanisms of suicide. Hanging (55%), drug overdose (22.7%), and jumping from a height (17.8%) were most represented suicide mechanisms with positive toxicology. Hanging was the most represented in men (50.3%; p = 0.019), while jumping from a height was more represented in women (29.7%, p = 0.028). Drugs of abuse were the most frequent toxics found in men (55.5%; p < 0.001), while medicines were the most frequent type found in women (70.3%, p < 0.001). Alcohol, nordiazepam, cocaine, and venlafaxine were the most consumed toxics. Benzodiazepines and venlafaxine were found in suicides involving drug overdose, hanging, and jumping from a height. In conclusion, most suicides were associated with drug abuse in men. Hanging was more represented in men and jumping from a height in women. Alcohol was present in combination with other toxics and medicines. The toxicological analysis is fundamental to understanding consumption patterns and establishing strategies and protocols for detecting and preventing suicide. Full article

(This article belongs to the Special Issue Poisoning Caused by Medicines and Drugs of Abuse)

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16 pages, 844 KiB

Open AccessArticle

A Forensic Diagnostic Algorithm for Drug-Related Deaths: A Case Series

by Antonina Argo, Stefania Zerbo, Roberto Buscemi, Claudia Trignano, Elisabetta Bertol, Giuseppe Davide Albano and Fabio Vaiano

Toxics 2022, 10(4), 152; https://doi.org/10.3390/toxics10040152 - 22 Mar 2022

Cited by 17 | Viewed by 5839

Abstract

The best evidence provided in the literature worldwide suggests the importance of harmonizing the investigation in drug-related fatalities. In this study, the application of a multidisciplinary approach in eight cases of drug-related deaths is presented. Although death scene findings could be highly suggestive of drug intoxication, external examination and toxicological screening test alone are insufficient. There are several variables, and it is not always easy to give the proper interpretation of the drug detection. A complete autopsy is necessary to correctly complete organ and tissues sampling for further histological and toxicological studies and obtain body fluids. The use of peripheral blood is recommended to avoid artifacts. The collection of many specimens is warranted to get more responses. The sampling aims to provide a picture of the distribution of the substance in the body. The sample and the selection of the drugs and the matrices to investigate are case-dependent. The presented diagnostic algorithm provides the coroner with all the elements to investigate drug-related deaths and cooperate with toxicologists. Toxicological forensic diagnosis is still extremely heterogeneous in regional and national contexts. Funding for method development, research, networking, facilities, and technologies improvement is mandatory to standardize the toxicological investigation. Full article

(This article belongs to the Special Issue Poisoning Caused by Medicines and Drugs of Abuse)

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9 pages, 246 KiB

Open AccessArticle

The Clinical Presentations of Nitrous Oxide Users in an Emergency Department

by Jhe-Ping Lin, Shi-Ying Gao and Chih-Chuan Lin

Toxics 2022, 10(3), 112; https://doi.org/10.3390/toxics10030112 - 26 Feb 2022

Cited by 5 | Viewed by 2669

Abstract

Today, the concomitant abuse of nitrous oxide (N₂O) and illicit drugs is evident and problematic. However, there are few reports regarding the clinical manifestations of N₂O users when they present to the emergency department (ED). The purpose of this study was to describe the clinical presentations, the associated illicit substances used in combination, and the outcomes in N₂O users visiting the ED. This was a retrospective observational cohort study. All N₂O adult users admitted to the ED at Linkou Chang Gung Memorial Hospital between 2012 and 2020 were included. Demographic variables, clinical symptoms, and examination results were collected from medical records. Univariate comparisons were conducted between pure N₂O users and combined illicit drug users. A total of 40 patients were included, 24 of which were pure N₂O users. Limb weakness and numbness accounted for the majority of chief complaints. Neurologic symptoms were the most common clinical manifestations (90%). A more severe ED triage level, faster heart rate, greater agitation, and cardiovascular symptoms were significantly noted in combined illicit drug users. In ED, limb numbness/weakness should arouse physicians’ awareness of patients using N₂O. Combined use of N₂O and illicit drugs can cause great harm to health. Full article

(This article belongs to the Special Issue Poisoning Caused by Medicines and Drugs of Abuse)

15 pages, 3806 KiB

Open AccessEditor’s ChoiceArticle

Neuronal and Astrocytic Morphological Alterations Driven by Prolonged Exposure with Δ9-Tetrahydrocannabinol but Not Cannabidiol

by Elisa Landucci, Costanza Mazzantini, Daniele Lana, Maria Grazia Giovannini and Domenico E. Pellegrini-Giampietro

Toxics 2022, 10(2), 48; https://doi.org/10.3390/toxics10020048 - 21 Jan 2022

Cited by 6 | Viewed by 3598

Abstract

Cannabis derivatives are largely used in the general population for recreational and medical purposes, with the highest prevalence among adolescents, but chronic use and abuse has raised medical concerns. We investigated the prolonged effects of Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) in organotypic hippocampal slices from P7 rats cultured for 2 weeks. Cell death in the CA1 subregion of slices was quantified by propidium iodide (PI) fluorescence, pre-synaptic and post-synaptic marker proteins were analysed by Western blotting and neurodegeneration and astrocytic alterations by NeuN and GFAP by immunofluorescence and confocal laser microscopy. The statistical significance of differences was analysed using ANOVA with a post hoc Dunnett w-test (PI fluorescence intensities and Western blots) or Newman–Keuls (immunohistochemistry data) for multiple comparisons. A probability value (P) of < 0.05 was considered significant. Prolonged (72 h) THC or CBD incubation did not induce cell death but caused modifications in the expression of synaptic proteins and morphological alterations in neurons and astrocytes. In particular, the expression of PSD95 was reduced following incubation for 72 h with THC and was increased following incubation with CBD. THC for 72 h caused disorganisation of CA1 stratum pyramidalis (SP) and complex morphological modifications in a significant number of pyramidal neurons and in astrocytes. Our results suggest that THC or CBD prolonged exposure induce different effects in the hippocampus. In particular, 72 h of THC exposure induced neuronal and glia alterations that must draw our attention to the effects that relatively prolonged use might cause, especially in adolescents. Full article

(This article belongs to the Special Issue Poisoning Caused by Medicines and Drugs of Abuse)

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9 pages, 2133 KiB

Open AccessFeature PaperArticle

Peroxisome Proliferator-Activated Receptor Delta Agonist (PPAR- δ) and Selective Androgen Receptor Modulator (SARM) Abuse: Clinical, Analytical and Biological Data in a Case Involving a Poisonous Combination of GW1516 (Cardarine) and MK2866 (Ostarine)

by Pascal Kintz, Laurie Gheddar, Camille Paradis, Mickael Chinellato, Alice Ameline, Jean-Sébastien Raul and Magali Oliva-Labadie

Toxics 2021, 9(10), 251; https://doi.org/10.3390/toxics9100251 - 7 Oct 2021

Cited by 15 | Viewed by 5325

Abstract

A 43-year-old male, sport coach, presented him-self at the Emergency unit of a local hospital for epigastric pain, myalgia pain and severe headache. He claimed having used for some days a combination of GW1516 (cardarine), a peroxisome proliferator-activated receptor delta agonist (PPAR- δ) and MK2866 (ostarine), a selective androgen receptor modulator (SARM) to gain skeletal muscles. Cytolysis with marked increase of alanine aminotransferase or ALT (up to 922 UI/L) and aspartate aminotransferase or AST (up to 2558 UI/L) and massive rhabdomyolysis with elevated creatine phosphokinase or CPK (up to 86435 UI/L) were the main unusual biochemistry parameters. Using a specific liquid chromatography coupled to tandem mass spectrometry method, cardarine and ostarine tested positive in blood at 403 and 1 ng/mL, respectively. In urine, due to extensive metabolism, the parent GW1516 was not identified, while ostarine was at 88 ng/mL. Finally, both drugs were identified in hair (2 cm in length, brown in colour), at 146 and 1105 pg/mg for cardarine and ostarine, respectively. This clearly demonstrates repetitive abuse over the last 2 months. Asthenia was persistent for 2 weeks and 6 weeks after the admission, the subject fully recovered. Full article

(This article belongs to the Special Issue Poisoning Caused by Medicines and Drugs of Abuse)

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Review

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19 pages, 1318 KiB

Open AccessReview

Is Illicit Substance Use Gender-Specific? The Basic Points of Mental and Health Disorders

by Ekaterina Georgieva, Krasimira Benkova, Nadya Vlaeva, Yanka Karamalakova, Radostina Miteva, Hristo Abrashev and Galina Nikolova

Toxics 2022, 10(7), 344; https://doi.org/10.3390/toxics10070344 - 22 Jun 2022

Cited by 3 | Viewed by 2353

Abstract

Among the groups of users of illicit substances, a high percentage are persons deprived of their liberty; at the same time, each social and age group is also affected, to one degree or another. The purpose of this study is to provide general data on the relationship between different psychostimulants, clinical and socio-demographic studies, and gender, both among the general population and in one of the most at-risk groups. This review identifies the use of illicit substances as gender-specific in the general population. A detailed study of the causal relationship between the use of illicit substances and gender was carried out. Electronic databases Academic Search Complete, PubMed, HealthCare, Web of Science, and Google Scholar were searched for relevant studies up to 2022 associated with drug abuse and mental and health disorders. The analysis indicated that the human population showed significant differences between the sex of the consumer as to the type of drug consumers, development of addiction, and relapse. We focus on the pathological changes caused by drug use, the personal and physiological individual traits that influence drug choice, and the extent of use in one of the most affected groups of individuals. The study may provide some guidance in developing gender-specific treatment and prevention, including response to some pharmacological and behavioral therapies. The review is intended for a wide audience of social workers, toxicologists, and pharmacologists. Full article

(This article belongs to the Special Issue Poisoning Caused by Medicines and Drugs of Abuse)

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Other

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7 pages, 8438 KiB

Open AccessCase Report

Overdose of Quetiapine—A Case Report with QT Prolongation

by Elisabetta Bertol, Fabio Vaiano, Antonina Argo, Stefania Zerbo, Claudia Trignano, Simone Protani and Donata Favretto

Toxics 2021, 9(12), 339; https://doi.org/10.3390/toxics9120339 - 7 Dec 2021

Cited by 5 | Viewed by 9748

Abstract

Quetiapine is an atypical antipsychotic drug used to treat bipolar disorder, schizophrenia, and major depressive disorder. Although several studies describe the adverse effects of intoxication with Quetiapine, only a few report an extreme overdose without comedications that lead to a life threat. We present a case of a 75-year-old male who tried to attempt suicide by ingesting 28 g of Quetiapine. During the management in the emergency department, both serum and urine samples were collected, allowing a complete pharmacokinetic analysis to be conducted, from the admission to the discharge. Full article

(This article belongs to the Special Issue Poisoning Caused by Medicines and Drugs of Abuse)

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17 pages, 1404 KiB

Open AccessSystematic Review

Oxidative Stress and Cocaine Intoxication as Start Points in the Pathology of Cocaine-Induced Cardiotoxicity

by Ekaterina Georgieva, Yanka Karamalakova, Radostina Miteva, Hristo Abrashev and Galina Nikolova

Toxics 2021, 9(12), 317; https://doi.org/10.3390/toxics9120317 - 24 Nov 2021

Cited by 7 | Viewed by 6449

Abstract

Psychomotor stimulants are the most commonly used prohibited substances after cannabis. Globally, their use reaches epidemiological proportions and is one of the most common causes of death in many countries. The use of illicit drugs has negative effects on the cardiovascular system and is one of the causes of serious cardiovascular pathologies, ranging from abnormal heart rhythms to heart attacks and sudden cardiac death. The reactive oxygen species generation, toxic metabolites formation, and oxidative stress play a significant role in cocaine-induced cardiotoxicity. The aim of the present review is to assess acute and chronic cocaine toxicity by focusing on the published literature regarding oxidative stress levels. Hypothetically, this study can serve as a basis for developing a rapid and effective method for determining oxidative stress levels by monitoring changes in the redox status of patients with cocaine intoxication. Full article

(This article belongs to the Special Issue Poisoning Caused by Medicines and Drugs of Abuse)

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18 pages, 1279 KiB

Open AccessSystematic Review

Pharmacogenetics and Forensic Toxicology: A New Step towards a Multidisciplinary Approach

by Nunzio Di Nunno, Massimiliano Esposito, Antonina Argo, Monica Salerno and Francesco Sessa

Toxics 2021, 9(11), 292; https://doi.org/10.3390/toxics9110292 - 4 Nov 2021

Cited by 25 | Viewed by 4277

Abstract

Pharmacogenetics analyzes the individual behavior of DNA genes after the administration of a drug. Pharmacogenetic research has been implemented in recent years thanks to the improvement in genome sequencing techniques and molecular genetics. In addition to medical purposes, pharmacogenetics can constitute an important tool for clarifying the interpretation of toxicological data in post-mortem examinations, sometimes crucial for determining the cause and modality of death. The purpose of this systematic literature review is not only to raise awareness among the forensic community concerning pharmacogenetics, but also to provide a workflow for forensic toxicologists to follow in cases of unknown causes of death related to drug use/abuse. The scientific community is called on to work hard in order to supply evidence in forensic practice, demonstrating that this investigation could become an essential tool both in civil and forensic contexts. The following keywords were used for the search engine: (pharmacogenetics) AND (forensic toxicology); (pharmacogenetics) AND (post-mortem); (pharmacogenetics) AND (forensic science); and (pharmacogenetics) AND (autopsy). A total of 125 articles were collected. Of these, 29 articles were included in this systematic review. A total of 75% of the included studies were original articles (n = 21) and 25% were case reports (n = 7). A total of 78% (n = 22) of the studies involved deceased people for whom a complete autopsy was performed, while 22% (n = 6) involved people in good health who were given a drug with a subsequent pharmacogenetic study. The most studied drugs were opioids (codeine, morphine, and methadone), followed by antidepressants (tricyclic antidepressants and venlafaxine). Furthermore, all studies highlighted the importance of a pharmacogenetics study in drug-related deaths, especially in cases of non-overdose of drugs of abuse. This study highlights the importance of forensic pharmacogenetics, a field of toxicology still not fully understood, which is of great help in cases of sudden death, deaths from overdose, deaths after the administration of a drug, and also in cases of complaint of medical malpractice. Full article

(This article belongs to the Special Issue Poisoning Caused by Medicines and Drugs of Abuse)

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