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1.
J Anal Toxicol ; 45(1): 8-20, 2021 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-33325503

RESUMO

Synthetic stimulants are the largest class of novel psychoactive substances identified each year by forensic laboratories internationally. While hundreds of these drugs appear in drug powders, only a few proliferate in use among forensically relevant populations and eventually emerge in postmortem and clinical investigations. Beta-keto-methylenedioxyamphetamines (i.e., novel psychoactive substances with names ending in "ylone") are currently the most popular subclass of synthetic stimulants. Leading up to its federal scheduling in 2018, N-ethyl pentylone was the most encountered synthetic stimulant. The popularity of N-ethyl pentylone declined once it was scheduled, but it was quickly replaced by eutylone (bk-EBDB), a structurally related analog from the same family. In cases encountered between January 2019 and April 2020, eutylone was quantitatively confirmed in 83 forensic investigations, including postmortem cases and driving under the influence of drugs cases. Matrix types included blood, urine and tissue. Eutylone was identified in cases submitted from 13 states, demonstrating proliferation around the United States; Florida accounted for 60% of the positive cases. The mean concentration of eutylone in postmortem blood was 1,020 ng/mL (standard deviation = ±2,242 ng/mL; median = 110 ng/mL, range = 1.2-11,000 ng/mL, n = 67). The mean concentration of eutylone in blood from driving under the influence of drugs cases was 942 ng/mL (standard deviation = ±1,407 ng/mL; median = 140 ng/mL, range = 17-3,600 ng/mL, n = 7). This report includes cause and manner of death data for 22 postmortem cases. Further analysis of authentic human specimens revealed the presence of three eutylone metabolites, including one unique biomarker and one metabolite in common with butylone. Laboratories should be aware that eutylone may be present in cases of suspected Ecstasy, "Molly" and/or methylenedioxymethamphetamine use, causing or contributing to impairment or death.


Assuntos
Drogas Ilícitas/toxicidade , Detecção do Abuso de Substâncias , Medicamentos Sintéticos/toxicidade , Condução de Veículo , Autopsia , Estimulantes do Sistema Nervoso Central , Cromatografia Líquida , Florida , Toxicologia Forense , Humanos , Drogas Ilícitas/metabolismo , N-Metil-3,4-Metilenodioxianfetamina , Medicamentos Sintéticos/metabolismo , Espectrometria de Massas em Tandem
2.
Toxicol Lett ; 331: 42-52, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32464236

RESUMO

Synthetic cathinones abuse remains a serious public health problem. Kidney injury has been reported in intoxications associated with synthetic cathinones, but the molecular mechanisms involved have not been explored yet. In this study, the potential in vitro nephrotoxic effects of four commonly abused cathinone derivatives, namely pentedrone, 3,4-dimethylmethcatinone (3,4-DMMC), methylone and 3,4-methylenedioxypyrovalerone (MDPV), were assessed in the human kidney HK-2 cell line. All four derivatives elicited cell death in a concentration- and time-dependent manner, in the following order of potency: 3,4-DMMC >> MDPV > methylone ≈ pentedrone. 3,4-DMMC and methylone were selected to further elucidate the mechanisms behind synthetic cathinones-induced cell death. Both drugs elicited apoptotic cell death and prompted the formation of acidic vesicular organelles and autophagosomes in HK-2 cells. Moreover, the autophagy inhibitor 3-methyladenine significantly potentiated cell death, indicating that autophagy may serve as a cell survival mechanism that protects renal cells against synthetic cathinones toxicity. Both drugs triggered a rise in reactive oxygen and nitrogen species formation, which was completely prevented by antioxidant treatment with N­acetyl­L­cysteine or ascorbic acid. Importantly, these antioxidant agents significantly aggravated renal cell death induced by cathinone derivatives, most likely due to their autophagy-blocking properties. Taken together, our results support an intricate control of cell survival/death modulated by oxidative stress, apoptosis and autophagy in synthetic cathinones-induced renal injury.


Assuntos
Alcaloides/toxicidade , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Drogas Ilícitas/toxicidade , Rim/efeitos dos fármacos , Alcaloides/química , Benzodioxóis/química , Benzodioxóis/toxicidade , Técnicas de Cultura de Células , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Humanos , Rim/metabolismo , Rim/patologia , Metanfetamina/análogos & derivados , Metanfetamina/química , Metanfetamina/toxicidade , Metilaminas/química , Metilaminas/toxicidade , Pentanonas/química , Pentanonas/toxicidade , Pirrolidinas/química , Pirrolidinas/toxicidade , Espécies Reativas de Nitrogênio/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Fatores de Tempo
3.
Rev Mal Respir ; 37(1): 34-44, 2020 Jan.
Artigo em Francês | MEDLINE | ID: mdl-31862136

RESUMO

Illicit psychoactive substance (IPAS) use can lead to a number of respiratory complications, including acute eosinophilic pneumonia (AEP). Systematic literature review of data on AEP in IPAS users (cannabis, cocaine, heroin and amphetamine). Of two cases of cannabis and tobacco users reported to have developed AEP, one, a teenage15 year old boy presented with acute respiratory distress syndrome (ARSD) which necessitated extracorporeal membrane oxygenation (ECMO). Five cases of AEP in cocaine smokers (crack) are reported, one of which was fatal. The patient presented with acute pulmonary edema and ARDS which progressed to ventricular fibrillation and asystole. A 24-year-old woman presented with AEP after repeated inhalation of heroin. Finally, a case of an amphetamine abuser who developed AEP and ARDS after amphetamine inhalation is reported. The time between the first IPAS use and admission in cases reported ranged from 7 days to 4 years, while time between the last IPAS use and admission was short (less than 15 days). IPAS use must be sought in case of AEP, especially in young adults, and practitioners must advise and help users to stop their consumption.


Assuntos
Drogas Ilícitas/toxicidade , Psicotrópicos/toxicidade , Eosinofilia Pulmonar/induzido quimicamente , Doença Aguda , Adolescente , Adulto , Feminino , Humanos , Masculino , Eosinofilia Pulmonar/diagnóstico , Eosinofilia Pulmonar/epidemiologia , Transtornos Relacionados ao Uso de Substâncias/complicações , Transtornos Relacionados ao Uso de Substâncias/diagnóstico , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Adulto Jovem
5.
Pediatr Clin North Am ; 66(6): 1121-1134, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31679602

RESUMO

Club drugs and "other" abusable substances are briefly overviewed as a reminder about the wide variety of known and unknown substances used by adolescents, the high potential for direct and interactive substance use effects to manifest acutely and chronically, and the vigilance needed to anticipate and recognize the new effects and drug-drug interactions arising as novel substances continue to be custom "designed," manufactured, and marketed to meet substance use trends. This article discusses dextromethorphan, flunitrazepam (Rohypnol), gamma-hydroxybutyrate, inhalants, ketamine, lysergic acid diethylamide, methylenedioxymethamphetamine, phencyclidine, Salvia divinorum (salvia), synthetic cannabinoids, and synthetic cathinones (bath salts).


Assuntos
Drogas Ilícitas/toxicidade , Transtornos Relacionados ao Uso de Substâncias , Adolescente , Comportamento do Adolescente/psicologia , Humanos , Transtornos Relacionados ao Uso de Substâncias/diagnóstico , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Transtornos Relacionados ao Uso de Substâncias/psicologia , Transtornos Relacionados ao Uso de Substâncias/terapia , Estados Unidos/epidemiologia
6.
Pediatr Clin North Am ; 66(6): 1135-1147, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31679603

RESUMO

Cocaine use by adolescents and young adults continues to be a significant public health issue and the cause of medical and psychological morbidity and mortality. Although use rates are lower than those seen with alcohol, tobacco, and other illicit substances such as marijuana, cocaine is highly addictive and presents significant acute and long-term medical and psychological effects. This article reviews the epidemiology of cocaine use among adolescents and young adults, discusses the pharmacology and neurobiology of cocaine use and dependence, provides information regarding acute intoxication and systemic effects seen with more chronic use, and describes current assessment and treatment approaches.


Assuntos
Transtornos Relacionados ao Uso de Cocaína , Adolescente , Comportamento do Adolescente/psicologia , Cocaína/toxicidade , Transtornos Relacionados ao Uso de Cocaína/diagnóstico , Transtornos Relacionados ao Uso de Cocaína/epidemiologia , Transtornos Relacionados ao Uso de Cocaína/terapia , Humanos , Drogas Ilícitas/toxicidade , Estados Unidos/epidemiologia , Adulto Jovem
7.
Curr Neuropharmacol ; 17(9): 818-822, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31577198

RESUMO

In the last few years, a wide range of new psychoactive substances (NPS) have been produced and marketed to elude the controlled substance lists. These molecules enter the traditional illegal and web market with poor knowledge about their toxicity, mechanism of action, metabolism, abuse potential so that they are directly tested by the consumers. This perspective highlights the main issues connected with NPS: the celerity they enter and leave the market once included in the banning laws to be substituted by new legal analogues; the unavailability of analytical screening tests and certified standards to perform toxicological analyses; the time lag between NPS identification and inclusion in the controlled substances lists. Finally, the authors take a snapshot of the commitment of the Italian Early Warning System in highlighting the recent seizures of NPS as well as the distribution of NPS related intoxication and deaths as an example of what is happening in the European countries and internationally.


Assuntos
Drogas Desenhadas/toxicidade , Drogas Ilícitas/toxicidade , Psicotrópicos/toxicidade , Humanos , Itália
8.
Bull Environ Contam Toxicol ; 103(5): 710-716, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31482305

RESUMO

The manufacturing and consumption of drugs of addiction has increased globally and their widespread occurrence in the environment is an emerging concern. This study evaluated the phytotoxicity of three compounds: methamphetamine, codeine and morphine; commonly reported in Australian urban water, to the aquatic plant Lemna minor under controlled conditions. L. minor was sensitive to lower drug concentrations when administered in multi-compound mixtures (100-500 µg L-1) than when applied individually (range 600-2500 µg L-1), while no adverse effects were observed at environmentally-relevant concentrations (1-5 µg L-1) detected in wastewater effluent. In conclusion, the results show that the concentrations of these compounds discharged into the environment are unlikely to pose adverse phytotoxic effects. These three compounds are known to be the most stable of their group under such conditions indicating that with this respect it is safe to use recycled water for existing regulated reclaimed purposes including agricultural or parklands irrigation or replenishing surface and groundwater. However, more research on the analysis of methamphetamines and opiates in municipal effluents is needed to reassure the likely environmental hazard of these neuroactive drug classes to aquatic organisms. Given the ever-growing production and aquatic disposal of discharge wastewater globally, this study provides timely and valuable insights into the likely drug-related impacts of effluent disposal on aquatic plants in receiving environments.


Assuntos
Araceae/efeitos dos fármacos , Codeína/toxicidade , Drogas Ilícitas/toxicidade , Metanfetamina/toxicidade , Morfina/toxicidade , Poluentes Químicos da Água/toxicidade , Irrigação Agrícola , Austrália , Codeína/análise , Relação Dose-Resposta a Droga , Monitoramento Ambiental , Drogas Ilícitas/análise , Metanfetamina/análise , Morfina/análise , Reciclagem , Águas Residuárias/química , Poluentes Químicos da Água/análise
9.
J Mol Cell Cardiol ; 136: 102-112, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31526813

RESUMO

The use of recreational drugs, including new psychoactive substances (NPS), is paralleled by emergency department visits of drug users with severe cardiotoxicity. Drug-induced cardiotoxicity can be the (secondary) result of increased norepinephrine blood concentrations, but data on potential drug-induced direct effects on cardiomyocyte function are scarce. The presence of hundreds of NPS therefore calls for efficient screening models to assess direct cardiotoxicity. We investigated effects of four reference compounds (3-30 nM dofetilide, nifedipine and isoproterenol, and 1-10 µM mexiletine) and six recreational drugs (0.01-100 µM cocaine, 0.01-1000 µM amphetamine, MDMA, 4-fluoroamphetamine, α-PVP and MDPV) on cardiomyocyte function (beat rate, spike amplitude and field potential duration (FPD ≈ QT interval in ECGs)), using Pluricyte® human-induced pluripotent stem cell (hiPSC)-derived cardiomyocytes cultured on ready-to-use CardioPlate™ multi-well microelectrode arrays (mwMEAs). Moreover, the effects of exposure to recreational drugs on cell viability were assessed. Effects of reference compounds were in accordance with the literature, indicating the presence of hERG potassium (dofetilide), sodium (mexiletine) and calcium (nifedipine) channels and α-adrenergic receptors (isoproterenol). All recreational drugs decreased the spike amplitude at 10-100 µM. All amphetamine-type stimulants and α-PVP decreased the beat rate at 300 µM, while cocaine and MDPV did so at 10 µM and 30 µM, respectively. All drugs increased the FPD, however at varying concentrations. MDMA, MDPV and amphetamine affected cardiomyocyte function at concentrations relevant for human exposure, while other drugs affected cardiomyocyte function only at higher concentrations (≥ 10 µM). Cell viability was only mildly affected at concentrations well above the lowest concentrations affecting cardiomyocyte function. We demonstrate that MEA recordings of hiPSC-derived cardiomyocytes enable screening for acute, direct effects on cardiomyocyte function. Our data further indicate that tachycardia in patients exposed to recreational drugs is likely due to indirect drug effects, while prolonged repolarization periods (prolonged QTc interval) could (partly) result from direct drug effects on cardiomyocyte function.


Assuntos
Cardiotoxicidade/etiologia , Avaliação Pré-Clínica de Medicamentos/métodos , Drogas Ilícitas/toxicidade , Miócitos Cardíacos/efeitos dos fármacos , Psicotrópicos/toxicidade , Alcaloides/toxicidade , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Cocaína/toxicidade , Relação Dose-Resposta a Droga , Avaliação Pré-Clínica de Medicamentos/instrumentação , Humanos , Indóis/toxicidade , Células-Tronco Pluripotentes Induzidas , Síndrome do QT Longo/induzido quimicamente , Microeletrodos , Miócitos Cardíacos/metabolismo , Testes de Toxicidade/instrumentação , Testes de Toxicidade/métodos
11.
Sci Total Environ ; 689: 141-148, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31271983

RESUMO

Illicit drugs and their metabolites have been identified as emerging aquatic pollutants. Cocaine (COC) is one of the most used illicit drug worldwide. After human consumption, COC enters the aquatic ecosystems, where it is commonly detected in ng L-1 concentration range. Although a number of studies have shown that the exposure to environmental concentrations of COC can induce diverse biochemical, molecular and histological effects on aquatic organisms, the information of COC-induced behavioral alterations is scant. Thus, the present study aimed at exploring both biochemical and behavioral effects induced by the exposure to two environmental concentrations (50 ng L-1 and 500 ng L-1) of COC on the freshwater cladoceran Daphnia magna. Specimens were exposed to selected COC concentrations for 21 days and the effects on the oxidative status, including the amount of reactive oxygen species and the activity of antioxidant (SOD, CAT and GPx) and detoxifying (GST) enzymes, and swimming activity were investigated after 7, 14 and 21 days of treatment, while effects on reproductive success was assessed after 21-days only.. Exposure to COC induced an overproduction of reactive oxygen species and a modulation of the activity of defense enzymes. Moreover, COC affected the swimming behavior and altered the reproductive success of treated specimens. Our results highlighted that environmental concentrations of COC can cause adverse effects at different levels of the biological hierarchy in a zooplanktonic species, confirming the potential threat due to this illicit drug for the aquatic community.


Assuntos
Cocaína/toxicidade , Daphnia/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Poluentes Químicos da Água/toxicidade , Animais , Daphnia/fisiologia , Relação Dose-Resposta a Droga , Drogas Ilícitas/toxicidade , Reprodução/efeitos dos fármacos
12.
Food Chem Toxicol ; 132: 110653, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31265866

RESUMO

Methamphetamine (MA) and ketamine (KET) are widely abused drugs individually. Previous surveys have revealed that the combined consumption of MA and KET were prevalent in illicit drugs abusers. However, few studies on the toxic effects induced by the combination of MA and KET have been reported. In this study, combined treatments were carried out using 3 × 3 full factorial design to determine the combined effects of MA and KET on apoptosis, oxidative stress and genotoxicity in HepG2 cells. Higher apoptosis and oxidative damage were observed in the MA treatments groups. Compared with control groups, the maximum apoptotic rate and level of malondialdehyde were ∼7.7 fold and ∼5.5 fold respectively. The mechanism that excessive oxidative stress resulted in cell apoptosis and DNA damage was inferred. For the joint effects, synergistic or additive interactions were found at different biological endpoints for various combinations, likely due to the mechanism in which MA promotes the metabolism of KET, which together provokes even greater oxidative stress. In conclusion, synergistic or additive interactions between MA and KET enhance cytotoxicity, oxidative damage and genotoxicity in HepG2 cells more than either of the drugs alone, which implies higher risk for abusers when exposed to the polydrug situation.


Assuntos
Apoptose/efeitos dos fármacos , Quebras de DNA/efeitos dos fármacos , Drogas Ilícitas/toxicidade , Ketamina/toxicidade , Metanfetamina/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Catalase/metabolismo , Combinação de Medicamentos , Sinergismo Farmacológico , Glutationa/metabolismo , Células Hep G2 , Humanos , Peroxidação de Lipídeos/efeitos dos fármacos , Testes de Mutagenicidade , Superóxido Dismutase/metabolismo
13.
Br J Clin Pharmacol ; 85(9): 2098-2107, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31173392

RESUMO

AIMS: We aim to calculate 2 metrics of relative lethal toxicity; the fatal toxicity index (FTI; number of deaths per year of a daily dose) and the case fatality (CF; number of deaths per overdose) with a focus on opioids, antidepressants, antipsychotics, benzodiazepines and illicit drugs. METHODS: This descriptive cohort study used the Australian National Coronial Information System (NCIS) to identify a population of individuals with drug-associated deaths in the Greater Newcastle Hunter Area between January 2002 and December 2016. This was combined with Australian medicine dispensing data and corresponding data from the Hunter Area Toxicology Service to calculate FTI and CF. RESULTS: There were 444 drug-related deaths and 21,296 overdoses during the study period. FTI and CF were well correlated (Spearman's rho 0.64, P < .001). Of the classes of interest, opioids had the highest FTI (40.3 95% confidence interval [CI] 35.2-45.4 deaths per 100 years of use at the defined daily dose or deaths/DDD/100 years) and CF (12.4% 95%CI 11.0-13.9). Fentanyl, methadone and morphine had the highest relative fatal toxicity within this class. Tricyclic antidepressants had the highest relative fatal toxicity of all antidepressants (FTI 14.5 95%CI 9.7-19.3 deaths/DDD/100 years and CF 7.1% [95%CI 4.8-9.3]) and benzodiazepines appeared to be more associated with multiple agent deaths than single. Of the illicit drugs, heroin had the highest CF (26.4%, 95%CI 19.1-33.7). CONCLUSION: Knowledge of relative lethal toxicity is useful to prescribers and medicines and public health policy makers in restricting access to more toxic drugs and may also assist coroners in determining cause of death.


Assuntos
Overdose de Drogas/mortalidade , Drogas Ilícitas/toxicidade , Medicamentos sob Prescrição/toxicidade , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Austrália/epidemiologia , Criança , Pré-Escolar , Estudos de Coortes , Conjuntos de Dados como Assunto , Relação Dose-Resposta a Droga , Overdose de Drogas/etiologia , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Adulto Jovem
14.
Neurotoxicology ; 74: 28-39, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31078573

RESUMO

The use of new psychoactive substances (NPS) is increasing despite associated health risks and limited pharmacological and toxicological knowledge. Information is available mainly for acute effects on specific targets like monoamine transporters and receptors. Recently, we have shown the ability of several NPS and illicit drugs to modulate neuronal activity during acute exposure. While these acute measurements provide valuable information regarding the potency and possible structure-activity relationships, an exposure scenario more representative of human exposure would increase insight and aid translation to the human situation. Therefore, we investigated the effects on neuronal activity after acute (30 min) and prolonged (5 h) exposure to amphetamine-type stimulants, cathinones, hallucinogens, piperazines and cocaine using rat primary cortical cultures grown on multi-well microelectrode arrays. To investigate the reversibility of effects, activity was also measured after a washout period of 19 h. During acute exposure, all compounds concentration-dependently decreased neuronal activity. Compared to acute exposure, prolonged exposure did not further decrease neuronal activity. Following washout, effects of 3 out of 11 drugs (methamphetamine, cocaine, and benzylpiperazine) were fully reversible, whereas effects induced by MDMA, PMMA and α-PVP were partially reversible. Neuronal activity did not recover after 19 h washout following exposure to the highest concentration of MDPV, 2C-B, 25B-NBOMe, and TFMPP. On the contrary, exposure to low concentrations of methylone, and to some extent of 2C-B, increased neuronal activity after the washout period. Hazard characterization of emerging NPS should include at least an acute exposure to determine a potency rank order. Supplementing the (acute and prolonged) exposure scenario with a washout period allows investigation of the reversibility of effects. The possibility of a neuronal network to regain activity after drug exposure appears independent of drug class or IC50 values for acute and prolonged exposure. Even though neuronal activity (partly) recovers after washout following exposure to most drugs, it is perturbing that complete recovery of neuronal activity is observed only for a minority of the tested drugs.


Assuntos
Córtex Cerebral/efeitos dos fármacos , Drogas Ilícitas/toxicidade , Neurônios/efeitos dos fármacos , Psicotrópicos/toxicidade , Anfetaminas/toxicidade , Animais , Sobrevivência Celular/efeitos dos fármacos , Estimulantes do Sistema Nervoso Central/toxicidade , Córtex Cerebral/citologia , Drogas Desenhadas/química , Drogas Desenhadas/toxicidade , Humanos , Drogas Ilícitas/química , Cultura Primária de Células , Psicotrópicos/química , Ratos , Relação Estrutura-Atividade
15.
Environ Int ; 129: 595-606, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31053240

RESUMO

Multiple classes of environmental contaminants have been found in aquatic environments, globally. Understanding internalised concentrations in the organism could further improve the risk assessment process. The present study is concerned with the determination of several contaminant classes (107 compounds) in Gammarus pulex collected from 15 sites covering 5 river catchments across Suffolk, UK. Quantitative method performance was acceptable for 67 compounds including pharmaceuticals, pesticides, illicit drugs and drugs of abuse. A total of 56 compounds were detectable and ranged from

Assuntos
Monitoramento Ambiental/métodos , Drogas Ilícitas/química , Invertebrados/química , Praguicidas/química , Poluentes Químicos da Água/química , Animais , Água Doce , Humanos , Drogas Ilícitas/toxicidade , Praguicidas/toxicidade , Testes de Toxicidade
16.
Pharmacotherapy ; 39(4): 508-513, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30811628

RESUMO

OBJECTIVE: We describe a multicenter descriptive case series of six patients admitted with synthetic cannabinoid (SC) intoxication displaying similar symptoms and sequelae, all resulting in multiple organ failure. METHODS: Patients were included in this report if they presented with known SC use and experienced multiple organ failure between March 1, 2016, and July 19, 2016, to the intensive care units of three hospitals in Maryland. Patients were followed to either discharge or death, and complications related to SC were documented. RESULTS: All six patients presented with altered mental status and severe rhabdomyolysis, with a peak creatine phosphokinase ranging from 4000 to >320,000 units/L. The majority of patients (five of six) presented with acute kidney injury, with most (four of six) requiring continuous renal replacement therapy. Most patients experienced fever (five of six) and myocardial injury, as evidenced by a troponin elevation (three of six). Seizures occurred in half of patients (three of six patients). Two patients required emergent fasciotomies of the bilateral lower extremities for acute compartment syndrome. Two patients developed fulminant hepatic failure that necessitated liver transplant evaluation, one requiring Molecular Adsorbent Recirculating System (MARS) therapy as a bridge to successful transplant, while the patient without it did not survive. Delirium, severe rhabdomyolysis, acute kidney injury, and fever are common in patients with synthetic cannabinoid intoxication. CONCLUSIONS: Given the growing abuse of these substances, clinicians should consider their use in the differential of such patient presentations. To our knowledge, only a few published case reports discuss multiple organ failure associated with SC toxicity, and only two have described an associated acute liver failure. Our report describes the first case of SC-associated acute liver failure requiring organ transplantation. Clinicians should be aware of life-threatening complications and consider SC ingestion in the differential diagnosis of patients presenting with multiple organ failure.


Assuntos
Canabinoides/toxicidade , Drogas Ilícitas/toxicidade , Insuficiência de Múltiplos Órgãos/induzido quimicamente , Adolescente , Adulto , Evolução Fatal , Feminino , Humanos , Masculino , Insuficiência de Múltiplos Órgãos/terapia , Resultado do Tratamento
17.
J Anal Toxicol ; 43(3): 155-160, 2019 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-30796807

RESUMO

This article is intended as a brief review or primer about cocaethylene (CE), a pharmacologically active substance formed in the body when a person co-ingests ethanol and cocaine. Reference books widely used in forensic toxicology contain scant information about CE, even though this cocaine metabolite is commonly encountered in routine casework. CE and cocaine are equi-effective at blocking the reuptake of dopamine at receptor sites, thus reinforcing the stimulant effects of the neurotransmitter. In some animal species, the LD50 of CE was lower than for cocaine. CE is also considered more toxic to the heart and liver compared with the parent drug cocaine. The plasma elimination half-life of CE is ~2 h compared with ~1 h for cocaine. The concentrations of CE in blood after drinking alcohol and taking cocaine are difficult to predict and will depend on the timing of administration and the amounts of the two precursor drugs ingested. After an acute single dose of cocaine and ethanol, the concentration-time profile of CE runs on a lower level to that of cocaine, although CE is detectable in blood for several hours longer. A strong case can be made for adding together the concentrations of cocaine and CE in forensic blood samples when toxicological results are interpreted in relation to acute intoxication and the risk of an overdose death.


Assuntos
Cocaína/análogos & derivados , Etanol/toxicidade , Toxicologia Forense , Drogas Ilícitas/sangue , Drogas Ilícitas/toxicidade , Consumo de Bebidas Alcoólicas/sangue , Animais , Cocaína/sangue , Cocaína/toxicidade , Etanol/sangue , Meia-Vida , Humanos , Dose Letal Mediana , Testes de Toxicidade
18.
Neurotoxicology ; 73: 40-49, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30802467

RESUMO

Mephedrone (4-methylmethcathinone) is a new and popular drug of abuse and also widely available on the internet and still legal in some parts of the world. The central nervous system is the target of mephedrone and recent evidence suggested that mephedrone could affect mitochondria in brain tissue. However, the underlying mechanisms of mephedrone toxicity in brain mitochondria have not yet been well understood. In this study, mitochondria from three separate parts of rat brain hippocampus, cortex, and cerebellum were obtained using differential centrifugation and were incubated with different concentrations of mephedrone (3, 6 and 12 µM). Then, the mitochondrial parameters toxicity were determined. The results showed that mephedrone (3, 6 and 12 µM) induced impairment in the activity of the mitochondrial complex II and IV. Also, mephedrone (3, 6 and 12 µM) increased mitochondrial reactive oxygen species (ROS) level, collapsed mitochondria membrane potential (MMP), induced swelling in the mitochondria and damaged the mitochondrial outer membrane (MOM) in the mitochondria obtained from hippocampus, cortex, and cerebellum, which in all cases is associated with the cytochrome c release. Furthermore, increased disturbance in oxidative phosphorylation was also shown by the decrease in ATP level in mephedrone-treated mitochondria indicating mitochondrial dysfunction in separate parts of the brain. This study suggests that mephedrone via increasing oxidative stress and impairment of the mitochondrial respiratory chain in the hippocampus, cortex, and cerebellum may play a key role in the neurotoxicity.


Assuntos
Cerebelo/efeitos dos fármacos , Córtex Cerebral/efeitos dos fármacos , Hipocampo/efeitos dos fármacos , Drogas Ilícitas/toxicidade , Metanfetamina/análogos & derivados , Mitocôndrias/efeitos dos fármacos , Animais , Cerebelo/metabolismo , Cerebelo/patologia , Córtex Cerebral/metabolismo , Córtex Cerebral/patologia , Citocromos c/metabolismo , Relação Dose-Resposta a Droga , Complexo II de Transporte de Elétrons/metabolismo , Complexo IV da Cadeia de Transporte de Elétrons/metabolismo , Hipocampo/metabolismo , Hipocampo/patologia , Masculino , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Metanfetamina/toxicidade , Mitocôndrias/metabolismo , Mitocôndrias/patologia , Dilatação Mitocondrial/efeitos dos fármacos , Fosforilação Oxidativa/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismo , Medição de Risco
20.
J Appl Toxicol ; 39(8): 1083-1095, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30723925

RESUMO

Benzofurans, also known by users as benzo fury or benzofury, are synthetic phenethylamines and constitute the third most prominent group of new psychoactive substances (NPS). As the use of these substances has been spread as an alternative to the classic illicit psychostimulants, such as amphetamines, their legal status was reviewed, resulting in an utter prohibition of these NPS in many countries worldwide. Herein, the prevalence of abuse, chemistry, biological effects, metabolism, and the potential harms and risky behaviors associated with the abuse of benzofurans are reviewed. The congeners of this group are mainly consumed recreationally at electronic dance music parties, in polydrug abuse settings. Benzofurans preferentially act by disturbing the functioning of serotonergic circuits, which induces their entactogenic and stimulant effects and is the reason behind the considerable number of recent benzo fury-related deaths. The slight interaction of these drugs with the dopaminergic system justifies the rewarding effects of these drugs. To date, published evidence on the mechanisms of toxicity of benzo fury is very limited but a body of research is now beginning to emerge revealing an alarming public health threat regarding the abuse of these NPS.


Assuntos
Benzofuranos/toxicidade , Uso Indevido de Medicamentos/tendências , Drogas Ilícitas/toxicidade , Psicotrópicos/toxicidade , Transtornos Relacionados ao Uso de Substâncias , Benzofuranos/metabolismo , Uso Indevido de Medicamentos/estatística & dados numéricos , Comportamentos de Risco à Saúde/efeitos dos fármacos , Humanos , Drogas Ilícitas/metabolismo , Psicotrópicos/metabolismo , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Transtornos Relacionados ao Uso de Substâncias/etiologia , Transtornos Relacionados ao Uso de Substâncias/psicologia
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