RESUMEN
ABSTRACT: Synthetic cathinones are one of the major pharmacological families of new psychoactive substances and 4-methylethcathinone (4-MEC) has emerged in recent years as a recreational psychostimulant. We report a case of a 35-year-old man found dead and naked at home by his friend. Although no anatomic cause of death was observed at autopsy, toxicological analysis identified 4-MEC and hydroxyzine at therapeutic level (160 ng/mL). 4-Methylethcathinone was quantified in autopsy samples by a validated method consisting in liquid-liquid extraction and gas chromatography coupled to tandem mass spectrometry: peripheral blood, 14.6 µg/mL; cardiac blood, 43.4 µg/mL; urine, 619 µg/mL; vitreous humor, right 2.9 µg/mL and left 4.4 µg/mL; bile, 43.5 µg/mL; and gastric content, 28.2 µg/mL. The cause of death was 4-MEC intoxication and the manner of death could be either accidental or suicidal. The literature concerning 4-MEC was reviewed, focusing on distribution in classical postmortem matrices and 4-MEC metabolism and postmortem redistribution and stability.
Asunto(s)
Anfetaminas/envenenamiento , Estimulantes del Sistema Nervioso Central/envenenamiento , Propiofenonas/envenenamiento , Adulto , Anfetaminas/análisis , Bilis/química , Estimulantes del Sistema Nervioso Central/análisis , Sobredosis de Droga , Cromatografía de Gases y Espectrometría de Masas , Contenido Digestivo/química , Humanos , Masculino , Propiofenonas/análisis , Abuso de Sustancias por Vía Intravenosa/complicaciones , Cuerpo Vítreo/químicaAsunto(s)
Sobredosis de Droga/complicaciones , Síndrome de QT Prolongado/inducido químicamente , Parasimpatolíticos/envenenamiento , Propiofenonas/envenenamiento , Torsades de Pointes/inducido químicamente , Electrocardiografía , Femenino , Humanos , Persona de Mediana Edad , Parasimpatolíticos/sangre , Propiofenonas/sangreRESUMEN
We report two fatalities that are related to the cathinone 4-methylethcathinone (4-MEC) and review the current knowledge of 4-MEC. Qualitative and quantitative analysis of 4-MEC was performed by validated high performance liquid chromatography-tandem mass spectrometry methods. In the first case a 22-year-old male died in hospital following collapse and seizures after using 4-MEC. Toxicological analysis of postmortem femoral blood revealed the presence of 4-MEC (0.167 mg/L), ethanol (27 mg/100 mL) and paracetamol (5 mg/L). Death was attributed solely to 4-MEC toxicity. The second case involved a 54-year-old man found with a taped plastic bag over his head. Toxicological analysis of postmortem femoral blood revealed the presence of 4-MEC (1.73 mg/L) along with ethanol (229 mg/100 mL), propranolol (0.036 mg/L), venlafaxine (0.284 mg/L) and its metabolite O-desmethylvenlafaxine (0.205 mg/L), and diazepam (<0.005 mg/L) and its metabolite nordiazepam (0.033 mg/L). Death was attributed primarily to asphyxiation. These cases and a review of the current knowledge of 4-MEC pharmacology/toxicology adds to the body of case material for 4-MEC and will assist with interpretation in postmortem toxicology cases in which 4-MEC is detected.
Asunto(s)
Anfetaminas/metabolismo , Sobredosis de Droga/diagnóstico , Propiofenonas/metabolismo , Anfetaminas/envenenamiento , Resultado Fatal , Toxicología Forense , Humanos , Masculino , Persona de Mediana Edad , Propiofenonas/envenenamiento , Adulto JovenRESUMEN
BACKGROUND: Sixty-one autopsy cases involving cathinones and/or cannabinoids (synthetic cathinones/cannabinoids) use have been reported. However, little is known about the demographics and autopsy findings in fatal synthetic cathinones/cannabinoids users. OBJECTIVES: To elucidate demographic and autopsy findings (i.e. major organ pathology and causes of death) in synthetic cathinones/cannabinoids cases. METHODS: We reviewed forensic autopsy reports in Department of Legal Medicine of Tokyo Women's Medical University (Tokyo, Japan) between 2011 and 2015 (a total of 359). We compared demographic and autopsy findings between synthetic cathinones/cannabinoids and methamphetamine cases (as control subjects). RESULTS: There were 12 synthetic cathinones/cannabinoids cases and 10 methamphetamine cases. Synthetic cathinones/cannabinoids users were significantly younger than methamphetamine users (p < 0.01), and there were no cases that used both synthetic cathinones/cannabinoids and methamphetamine. Acute intoxication and cardiac ischemia were the two most prominent causes of death in both synthetic cathinones/cannabinoids users and methamphetamine users. Excited delirium syndrome and pulmonary aspiration were found only in synthetic cathinones/cannabinoids cases. CONCLUSIONS: The populations of synthetic cathinones/cannabinoids and methamphetamine users who died of an overdose are different in Japan. Acute intoxication, cardiac ischemia, excited delirium syndrome, pulmonary aspiration, and drowning are the major autopsy findings in synthetic cathinones/cannabinoids-related death. Clinicians shuld be aware of these potentially fatal complications in the medical management of synthetic cathinones/cannabinoids users.
Asunto(s)
Alcaloides/envenenamiento , Cannabinoides/envenenamiento , Sobredosis de Droga/mortalidad , Propiofenonas/envenenamiento , Adulto , Causas de Muerte , Demografía , Femenino , Humanos , Japón/epidemiología , Masculino , Metanfetamina/envenenamiento , Persona de Mediana Edad , Adulto JovenRESUMEN
Intravenous injection of self-produced ephedrone (metcathinone) using potassium permanganate as an oxidant can lead to severe, fixed encephalopathy. This risk applies mainly to young individuals experimenting with "home-made" drugs and results in an irreversible aggravation of overall functioning. Besides multiple neurological symptoms and movement disorders, affected individuals also experience cognitive dysfunction. No systematic research has been conducted in this field. Single case reports and small group descriptions show that assessment with screening tools such as the Mini-Mental State Examination (MMSE) is ineffective. Neuropsychological assessment conducted with other tests indicates significant dysarthric speech disorders, psychomotor function impairment, attentional disorders of varying intensity as well as dysfunctions of verbal and visual working memory processes. Some studies of this group of subjects also indicate working memory and executive function disorders. These dysfunctions seem to be permanent and do not recede following manganese use discontinuation and an improvement of the neuroradiological picture in MRI assessment. A standard test battery should be developed enabling the assessment of both cognitive and neurological dysfunctions that otherwise render some tests impossible to administer.
Asunto(s)
Encefalopatía Hipertensiva/inducido químicamente , Drogas Ilícitas/envenenamiento , Intoxicación por Manganeso/complicaciones , Propiofenonas/envenenamiento , Abuso de Sustancias por Vía Intravenosa/complicaciones , Humanos , Intoxicación por Manganeso/diagnóstico , Pruebas Neuropsicológicas , Propiofenonas/administración & dosificación , Asunción de Riesgos , Abuso de Sustancias por Vía Intravenosa/diagnósticoRESUMEN
Ephedrone encephalopathy is referred to as a group of symptoms of manganese deposition within the central nervous system (CNS), resulting from the abuse of ephedrone (methcathinone), obtained in reaction using the excess amount of manganese-containing oxidants. The diagnosis is based on the contrast-enhanced head MRI findings characteristic for this syndrome, clinical manifestation and history of ephedrone use. The syndrome has been reported in recent years in young people from Eastern Europe and Russia with a history of ephedrone overuse. However, no report has ever been published on ephedrone encephalopathy in Polish patients.
Asunto(s)
Encefalopatías/inducido químicamente , Intoxicación por Manganeso/etiología , Intoxicación por Manganeso/patología , Propiofenonas/envenenamiento , Trastornos Relacionados con Sustancias/etiología , Trastornos Relacionados con Sustancias/patología , Adulto , Humanos , Masculino , Adulto JovenRESUMEN
We report here the quantitative analysis of cathinone-type designer drug 3,4-dimethylmethcathinone (3,4-DMMC) in blood and urine using liquid chromatography-tandem mass spectrometry (LC-MS/MS) in a fatal case. Abuse of 3,4-DMMC is widespread and a global issue. However, to date, there have been no reports of 3,4-DMMC-related deaths. We encountered a death in which 3,4-DMMC was thought to play a causative role, and successfully identified this designer drug from biological samples by using LC-MS/MS and QuEChERS (quick, easy, cheap, effective, rugged and safe) extraction method. For standard samples, detection of 3,4-DMMC in human blood and urine samples in the calibration range (5-400 ng/mL) was successful with recoveries of 85.9-89.4% (blood) and 95.8-101% (urine), limits of detection of 1.03 (blood) and 1.37 ng/mL (urine) and limits of quantification of 5.00 (blood) and 5.38 ng/mL (urine). The concentrations of 3,4-DMMC in blood (external iliac vein) and urine in the case were 27 mg/L and 7.6 mg/L, respectively. Some metabolites, including 3,4-dimethylcathione (DMC) and ß-ketone reduced metabolites (ß-OH-DMMC and ß-OH-DMC), were detected in both blood and urine.
Asunto(s)
Drogas de Diseño/análisis , Toxicología Forense/métodos , Propiofenonas/análisis , Detección de Abuso de Sustancias/métodos , Adulto , Alcaloides/análisis , Alcaloides/envenenamiento , Análisis Químico de la Sangre/métodos , Causas de Muerte , Estimulantes del Sistema Nervioso Central/análisis , Estimulantes del Sistema Nervioso Central/envenenamiento , Cromatografía Liquida/métodos , Drogas de Diseño/envenenamiento , Sobredosis de Droga/sangre , Sobredosis de Droga/orina , Humanos , Masculino , Propiofenonas/envenenamiento , Espectrometría de Masas en Tándem/métodos , Urinálisis/métodosAsunto(s)
Anfetaminas/envenenamiento , Drogas de Diseño/envenenamiento , Metanfetamina/análogos & derivados , Propiofenonas/envenenamiento , Adulto , Anfetaminas/sangre , Muerte , Drogas de Diseño/farmacocinética , Humanos , Masculino , Metanfetamina/sangre , Metanfetamina/envenenamiento , Propiofenonas/sangreRESUMEN
AIM: In this study, cognitive functions of 9 patients developing parkinsonism due to chronic manganese intoxication by intravenous methcathinone solution were investigated using detailed neuropsychometric tests. METHOD: Attention deficit, verbal and nonverbal memory, visuospatial function, constructive ability, language, and executive (frontal) functions of 9 patients who were admitted to our clinic with manifestations of chronic manganese intoxication and 9 control subjects were assessed using neuropsychometric tests. Two years later, detailed repeat neuropsychometric tests were performed in the patient group. The results were evaluated using the χ(2) test, Fisher's exact probability test, Student's t test and the Mann-Whitney U test. RESULTS: While there was no statistically significant difference between the two groups in language functions, visuospatial functions and constructive ability, a statistically significant difference was noted between both groups regarding attention (p = 0.032), calculation (p = 0.004), recall and recognition domains of verbal memory, nonverbal memory (p = 0.021) and some domains of frontal functions (Stroop-5 and spontaneous recovery) (p = 0.022 and 0.012). Repeat neuropsychometric test results of the patients were not statistically significant 2 years later. CONCLUSION: It has been observed that cognitive dysfunction seen in parkinsonism secondary to chronic manganese intoxication may be long-lasting and may not recover as observed in motor dysfunction.
Asunto(s)
Trastornos del Conocimiento/inducido químicamente , Intoxicación por Manganeso/complicaciones , Trastornos Parkinsonianos/inducido químicamente , Propiofenonas/envenenamiento , Psicotrópicos/envenenamiento , Adulto , Humanos , Masculino , Pruebas Neuropsicológicas , Trastornos Relacionados con Sustancias/complicaciones , Adulto JovenAsunto(s)
Drogas de Diseño/envenenamiento , Propiofenonas/envenenamiento , Psicosis Inducidas por Sustancias/etiología , Psicotrópicos/envenenamiento , Adulto , Estimulantes del Sistema Nervioso Central/envenenamiento , Diagnóstico Diferencial , Humanos , Hipnóticos y Sedantes/uso terapéutico , Masculino , Trastornos Paranoides/etiología , Agitación Psicomotora/etiologíaAsunto(s)
Alcaloides/envenenamiento , Estimulantes del Sistema Nervioso Central/envenenamiento , Productos Domésticos/envenenamiento , Drogas Ilícitas/envenenamiento , Propiofenonas/envenenamiento , Adulto , Alcaloides/farmacocinética , Estimulantes del Sistema Nervioso Central/farmacocinética , Control de Medicamentos y Narcóticos/legislación & jurisprudencia , Urgencias Médicas , Humanos , Drogas Ilícitas/legislación & jurisprudencia , Drogas Ilícitas/farmacocinética , Masculino , Propiofenonas/farmacocinética , Trastornos Relacionados con Sustancias/prevención & control , Estados UnidosRESUMEN
INTRODUCTION: We report a case of ethcathinone and methylone poisoning with severe clinical toxicity. This is to our knowledge the first case reported in the medical toxicology literature. CASE REPORT: A 22-year-old woman was brought to the emergency department following several episodes of tonicoclonic seizures, a few hours after ingesting "legal ecstasy". The patient needed intubation for recurrent seizures, and she was found to have severe hyponatremia (120 mmol/L) that was corrected with hypertonic saline. The patient's mental status improved rapidly, and she was extubated the day following her admission. However, she developed prolonged rhabdomyolysis (CK 34.537 U/L) that required a 6-day hospitalisation. DISCUSSION: The seizures and the hyponatremia may be explained by the MDMA-like characteristics of methylone that may induce inappropriate secretion of antidiuretic hormone mediated via the serotonin system. The combination of methylone and ethcatinone (both acting like serotonin reuptake inhibitors) might have contributed to neurologic manifestations compatible with serotonin toxicity, although our patient never had autonomic instability. Our patient had a prolonged period of rhabdomyolysis which may also be explained by excessive serotonin activity resulting in an increased motor hyperactivity. The public has to be aware of this growing health problem. Clinicians must report future cases of toxicity related to the use of cathinone synthetic derivatives in order to increase our knowledge of these substances.
Asunto(s)
Alcaloides/envenenamiento , Anfetaminas/envenenamiento , Hiponatremia/inducido químicamente , Metanfetamina/análogos & derivados , Propiofenonas/envenenamiento , Convulsiones/inducido químicamente , Inhibidores Selectivos de la Recaptación de Serotonina/envenenamiento , Adulto , Femenino , Humanos , Metanfetamina/envenenamiento , Rabdomiólisis/inducido químicamente , Adulto JovenAsunto(s)
Parasimpatolíticos/envenenamiento , Centros de Control de Intoxicaciones/estadística & datos numéricos , Propiofenonas/envenenamiento , Quinazolinas/envenenamiento , Enfermedad Aguda , Factores de Edad , Humanos , Japón/epidemiología , Intoxicación/epidemiología , Intoxicación/etiología , Factores de TiempoRESUMEN
We report two fatalities involving the new designer drug methedrone, 4-methoxymethylcathinone. Blood was extracted with ethyl acetate after the addition of sodium hydroxide followed by evaporation and derivatization with TFAA before gas chromatography-mass spectrometry analysis. Hair was decontaminated and cut into segments, and after overnight extraction with acetonitrile/methanol/20 mM ammonium formate buffer (pH 3) (10:10:80), samples were analyzed by liquid chromatography-tandem mass spectrometry. The first case was treated in hospital, and blood was collected for drug screening. The concentration of methedrone in antemortem blood was 13.2 µg/g and in postmortem femoral blood 8.4 µg/g. The second case presented with 9.6 µg methedrone/g femoral blood, and in a hair sample, methedrone was detected in five short segments suggesting exposure to the drug during the months prior to death. In living abusers, the blood concentration range was 0.2-4.8 µg/g (n = 11). We conclude that use of methedrone may result in accidental death owing to its toxic properties and that the blood concentrations found in the two cases are close to those seen in the living. This suggests a rather narrow "therapeutic" window and emphasizes the danger in taking this kind of drug for recreational purposes.
Asunto(s)
Drogas de Diseño/envenenamiento , Propiofenonas/envenenamiento , Psicotrópicos/envenenamiento , Detección de Abuso de Sustancias , Adulto , Métodos Analíticos de la Preparación de la Muestra , Cromatografía Líquida de Alta Presión , Drogas de Diseño/análisis , Drogas de Diseño/química , Resultado Fatal , Toxicología Forense/métodos , Cabello/química , Humanos , Masculino , Estructura Molecular , Narcóticos/análisis , Narcóticos/sangre , Narcóticos/química , Narcóticos/envenenamiento , Propiofenonas/análisis , Propiofenonas/sangre , Propiofenonas/química , Psicotrópicos/análisis , Psicotrópicos/sangre , Psicotrópicos/química , Espectrometría de Masas en Tándem , Adulto JovenRESUMEN
INTRODUCTION: Eperisone hydrochloride is a centrally acting muscle relaxant, and triazolam is a short-acting benzodiazepine. Although commonly prescribed, cardiotoxicity induced by a single overdose of either drug is comparatively rare. A patient receiving nifedipine developed torsades de pointes (TdP) because of prolongation of the corrected QT (QTc) interval after an overdose of eperisone hydrochloride and triazolam. CASE REPORT: A 60-year-old man receiving nifedipine was admitted in a comatose condition 3 h after ingesting 5,000 mg of eperisone and 2.5 mg of triazolam. Electrocardiogram showed sinus rhythm with prolongation of the QTc interval (820 ms). The serum electrolyte levels were as follows: potassium, 3.8 mEq/L; magnesium, 2.4 mg/dL. The serum drug concentrations were high: eperisone, 15,360 ng/mL; triazolam, 110.8 ng/mL. A temporary cardiac pacemaker was implanted immediately after the development of TdP, 11 h after the ingestion. The serum triazolam concentration normalized on day 2. The QTc interval and eperisone concentration normalized on day 6. CONCLUSION: Eperisone and triazolam overdose can cause life-threatening cardiotoxicity. Electrocardiographic monitoring and serial determination of QTc interval are likely the best way to observe these patients and evaluate the risk of cardiotoxicity.
Asunto(s)
Síndrome de QT Prolongado/inducido químicamente , Propiofenonas/envenenamiento , Torsades de Pointes/inducido químicamente , Triazolam/envenenamiento , Ansiolíticos/farmacocinética , Ansiolíticos/envenenamiento , Bloqueadores de los Canales de Calcio/efectos adversos , Coma/inducido químicamente , Interacciones Farmacológicas , Sobredosis de Droga , Electrocardiografía , Humanos , Masculino , Persona de Mediana Edad , Relajantes Musculares Centrales/farmacocinética , Relajantes Musculares Centrales/envenenamiento , Nifedipino/efectos adversos , Propiofenonas/farmacocinética , Triazolam/farmacocinéticaRESUMEN
The endemic fauna of New Zealand evolved in the absence of mammalian predators and their introduction has been responsible for many extinctions and declines. Introduced species including possums (Trichosurus vulpecula Kerr), ship rats (Rattus rattus L.) and stoats (Mustela erminea L.) are targeted to protect native birds. Control methodologies currently rely largely on labor-intensive trapping or the use of increasingly unpopular poisons, or poisons that are linked with low welfare standards. Hence, the development of safer humane predator toxins and delivery systems is highly desirable. Para-aminopropiophenone (PAPP) is being developed as a toxin for feral cats (Felis catus L.) and stoats. Carnivores appear to be much more susceptible to PAPP than birds, so it potentially has high target specificity, at least in New Zealand. Pen trials with 20 feral cats and 15 stoats have been undertaken using meat baits containing a proprietary formulation of PAPP. A PAPP dose of 20-34 mg kg(-1) was lethal for feral cats and 37-95 mg kg(-1) was lethal for stoats. Our assessments suggest that PAPP, for the control of feral cats and stoats, is a humane and effective toxin. PAPP causes methaemoglobinaemia, resulting in central nervous system anoxia, lethargy and death.
Asunto(s)
Bienestar del Animal , Gatos , Metahemoglobinemia/inducido químicamente , Metahemoglobinemia/mortalidad , Mustelidae , Control de Plagas/métodos , Plaguicidas/envenenamiento , Propiofenonas/envenenamiento , Animales , Nueva Zelanda , Control de Plagas/ética , Análisis de Regresión , Factores de TiempoAsunto(s)
Estimulantes del Sistema Nervioso Central/envenenamiento , Propiofenonas/envenenamiento , Adolescente , Estimulantes del Sistema Nervioso Central/química , Control de Medicamentos y Narcóticos , Resultado Fatal , Humanos , Internet , Propiofenonas/química , Factores de Riesgo , Trastornos Relacionados con Sustancias/etiologíaAsunto(s)
Cuerpo Estriado/efectos de los fármacos , Cuerpo Estriado/diagnóstico por imagen , Intoxicación por Manganeso/diagnóstico por imagen , Enfermedad de Parkinson Secundaria/inducido químicamente , Enfermedad de Parkinson Secundaria/diagnóstico por imagen , Propiofenonas/envenenamiento , Adulto , Antiparkinsonianos/uso terapéutico , Cuerpo Estriado/patología , Europa Oriental/epidemiología , Trastornos Neurológicos de la Marcha/inducido químicamente , Trastornos Neurológicos de la Marcha/fisiopatología , Humanos , Drogas Ilícitas/síntesis química , Drogas Ilícitas/envenenamiento , Imagen por Resonancia Magnética , Masculino , Intoxicación por Manganeso/patología , Intoxicación por Manganeso/fisiopatología , Vías Nerviosas/diagnóstico por imagen , Vías Nerviosas/efectos de los fármacos , Vías Nerviosas/patología , Pruebas Neuropsicológicas , Enfermedad de Parkinson Secundaria/patología , Terminales Presinápticos/efectos de los fármacos , Terminales Presinápticos/patología , Terminales Presinápticos/efectos de la radiación , Propiofenonas/síntesis química , Sustancia Negra/diagnóstico por imagen , Sustancia Negra/efectos de los fármacos , Sustancia Negra/patología , Tomografía Computarizada de Emisión de Fotón Único , Insuficiencia del TratamientoRESUMEN
A neurological syndrome characterized by levodopa unresponsive bradykinesia, retropulsion with falls backwards, dysarthria, gait disturbance, dystonia, and emotional lability was identified in 13 male opiate addicts following the prolonged intravenous use of ephedrone (methcathinone), a central nervous stimulant prepared from pseudoephedrine, potassium permanganate, and vinegar. The natural history, response to treatment, and clinical features has been studied, and MR and dopamine transporter SPECT brain imaging were carried out. Pubic hair was sampled for manganese. The clinical and radiological picture closely resembled previous reports of chronic manganese poisoning and increased mean manganese level in pubic hair observed for at least 1 year after cessation of ephedrone. Odor identification was intact. Cognitive assessment showed a mild executive dysfunction and a mild depression. DaTSCANs were all normal. The neurological syndrome bears some similarities to PSP but differs from Parkinson's disease. Delayed neurological progression despite discontinuation of ephedrone occurred in one-third of cases. Ephedrone poisoning should be considered as a possible cause of secondary Parkinsonism in young adults, particularly from Eastern Europe.