Metaphedrone (3-Methylmethcathinone): Pharmacological, Clinical, and Toxicological Profile.

Introduction: Synthetic cathinones are a group of novel psychoactive substances used as an alternative to classical recreational drugs. As a result of legal prohibitions on older generations of these compounds, new formulations appeared on the drug market. One of them is metaphedrone (3-methylmethcathinone, 3-MMC), a structural isomer of 4-methylmethcathinone and a psychostimulant drug. Metaphedrone became popular in a large number of countries in a short period of time. The aim: The collection, analysis, and review of relevant research on the subject of metaphedrone in order to present information about the pharmacological, clinical, and toxicological profile of this compound. An assessment of the significance and role of metaphedrone in consumption patterns of novel psychoactive substances among recreational drug users. Methodology: By using search engines like Google Scholar and PubMed, the relevant literature on metaphedrone was looked for and analyzed. The search was not limited to a specific period of time. All information regarding the compound of interest was analyzed and presented. Key results and discussion: All novel psychoactive substances are abused due to their pronounced stimulatory, hallucinogenic, dissociative, and euphoric and/or relaxing characteristics. Users of 3-methylmethcathinone usually opt for this substance for recreational purposes and/or sexual stimulation. Metaphedrone has the potential to cause a psychological dependence to the users. It was determined in relevant studies that most users are from 17 to 50 years of age. Older users usually administer metaphedrone intravenously, while younger ones usually choose snorting and oral ingestion of the drug. In Serbia, metaphedrone is a legally controlled substance. The pharmacodynamic properties make metaphedrone similar to classical recreational drugs. The method of administration, mainly repeated administration in a single session, could be explained using the pharmacokinetic profile of the drug. The most reported symptoms of intoxication were those of a sympathomimetic nature, such as tachycardia, chest pain, hypertension, diaphoresis, and agitation. Most intoxications and fatal outcomes occurred to users who combined several psychoactive substances. The correlation between measured blood concentrations of the drug and outcomes of intoxication was not found. The mechanisms of metaphedrone's toxicity are not fully understood. Conclusions: There is an increasing trend of abuse of metaphedrone among recreational drugs users. Future studies should focus on pharmacological and toxicological effects of metaphedrone on animals and humans.

Cytogenotoxicity effects in addicts with multidrug consumption.

Drug abuse is considered a global health problem with serious social impact. In recent decades, changes in drug consumption patterns have shown a clear rising trend in the use of multiple drugs. Although the buccal micronucleus cytome (BMCyt) assay has evaluated cytotoxicity in drug abuse, there has not been an approach that takes into account this pattern of multiple drug use. Therefore, in this study, we evaluate for the first time the cytogenotoxic effects in multidrug users, and its correlation with the amount consumed and years of abuse. This study was conducted on 166 individuals by the BMCyt assay. A total of 83 individuals with a history of multiple licit (alcohol and tobacco) and at least one illicit drug abuse (marijuana, methamphetamines, cocaine, and/or inhalants), and 83 healthy individuals, non-drug abusers were analyzed. The results showed that drug abusers had higher frequencies of nuclear abnormalities nuclear buds, binucleated cells, pyknotic nuclei (PNs), karyorrhexis (KX), and abnormally condensed chromatin when compared with healthy controls. Moreover, results suggests that the use of licit and illicit drugs is related to cytogenotoxic damage, as was shown by an upward trend in the frequency of nuclear abnormalities identified in groups 1 (alcohol + tobacco + at least one illicit drug) and 2 (tobacco + at least one illicit drug). Furthermore, a positive correlation was found in the different groups, between the years and the amount of consumption of some drugs (alcohol, methamphetamine, and tobacco) with cytotoxicity markers such as KL, KX, and PNs.

Daphnia magna an emerging environmental model of neuro and cardiotoxicity of illicit drugs.

Cocaine, methamphetamine, ectasy (3,4-methylenedioxy amphetamine (MDMA)) and ketamine are among the most consumed drugs worldwide causing cognitive, oxidative stress and cardiovascular problems in humans. Residue levels of these drugs and their transformation products may still enter the aquatic environment, where concentrations up to hundreds of ng/L have been measured. In the present work we tested the hypothesis that psychotropic effects and the mode of action of these drugs in D. magna cognitive, oxidative stress and cardiovascular responses are equivalent to those reported in humans and other vertebrate models. Accordingly we expose D. magna juveniles to pharmacological and environmental relevant concentrations. The study was complemented with the measurement of the main neurotransmitters involved in the known mechanisms of action of these drugs in mammals and physiological relevant amino acids. Behavioural cognitive patters clearly differentiate the 3 psychostimulant drugs (methamphetamine, cocaine, MDMA) from the dissociative one ketamine. Psychostimulant drugs at pharmacological doses (10-200 µM), increased basal locomotion activities and responses to light, and decreased habituation to it. Ketamine only increased habituation to light. The four drugs enhanced the production of reactive oxygen species in a concentration related manner, and at moderate concentrations (10-60 µM) increased heartbeats, diminishing them at high doses (200 µM). In chronic exposures to environmental low concentrations (10-1000 ng/L) the four drugs did not affect any of the behavioural responses measured but methamphetamine and cocaine inhibited reproduction at 10 ng/L. Observed effects on neurotransmitters and related metabolites were in concern with reported responses in mammalian and other vertebrate models: cocaine and MDMA enhanced dopamine and serotonin levels, respectively, methamphetamine and MDMA decreased dopamine and octopamine, and all but MDMA decreased 3 MT levels. Drug effects on the concentration of up to 10 amino acids evidence disruptive effects on neurotransmitter synthesis, the urea cycle, lipid metabolism and cardiac function.

Epidemiología de las intoxicaciones agudas en el Servicio de Urgencias del Hospital Clínico Universitario de Santiago de Compostela / Epidemiology of acute poisonings in the Emergency Service of the Clinic University Hospital of Santiago de Compostela

Introducción y métodos: Las intoxicaciones agudas son un motivo frecuente de consulta urgente. Este estudio descriptivo observacional retrospectivo busca analizar la epidemiología de las intoxicaciones agudas atendidas en el Servicio de Urgencias entre junio y noviembre de 2019. Resultados: Las intoxicaciones agudas constituyeron el 1,2% de las consultas de Urgencias (edad media de 44 años, 64,9% hombres). Las drogas de abuso fueron el grupo más frecuente (sobre todo en el sexo masculino), siendo el etanol el principal agente; seguidas del policonsumo y los medicamentos (especialmente en el sexo femenino), destacando las benzodiacepinas. Las intoxicaciones fueron más habituales los fines de semana y durante la noche. La principal modalidad fue la voluntaria (principalmente en hombres), seguida de la autolítica (sobre todo en mujeres). El 26,5% de los pacientes acudieron en ambulancia. El 53,9% de los pacientes presentaba antecedentes toxicológicos (sobre todo hombres) y el 32,3% antecedentes psiquiátricos (principalmente en mujeres). La clínica más frecuente fue la neurológica. Se realizó tratamiento sintomático en la mayoría de los pacientes, empleándose tratamientos específicos en una pequeña proporción. El 84,4% de los pacientes fueron dados de alta desde Urgencias, necesitando atención de la Unidad de Cuidados Intensivos el 2,0%; los ancianos ingresaron más frecuentemente. Conclusiones: Las intoxicaciones agudas revisten poca gravedad en este medio. Hay diferencias en sus características según sexo y edad, así como en la modalidad en función del tóxico y los antecedentes personales. (AU)

Introduction and methods: Acute poisoning is a common reason for consultation in Emergency Services. This retrospective observational study looks for analysing the epidemiology of acute poisonings in the Emergency Service of the Clinic University Hospital of de Santiago de Compostela between June and November 2019. Results: Acute poisonings were 1,2% of Emergency Service consults (mean age 44 years, 64.9% men). Abuse drugs were the most usual group (specially in male sex), being ethanol the principal agent; followed by polycompsumption and medicines (specially in female sex), highlighting benzodiazepines. Poisonings were more frequent in weekends and during the night. The first modality was voluntary (principally in men), followed by suicidal (principally in women). 26.5% of patients came by ambulance. 53.9% of patients showed toxicological history (specially men) and 32.3% had psychiatric history (specially in women). The most common clinical manifestations were neurological. Most patients got symptomatic treatment, using specific treatment in a small proportion. 84.4% of patients were discharged from the Emergency Service, needing attention from the Intensive Care Unit 2.0%; the elderly patients were admitted more frequently. Conclusions: Acute poisonings have little gravity in this environment. There are differences in their features according to sex and age, as wells as in modality depending on the toxic agent and the personal history. (AU)

Intoxicaciones por drogas de abuso: características diferenciales en población VIH / Patients with drug-abuse poisoning with and without HIV infection: differential characteristics

Objetivo: La población VIH, consumidora de drogas de abuso (DA), tiene mayor morbimortalidad en relación con los no consumidores y no VIH. Se investiga si existen diferencias en las intoxicaciones agudas (IA) por DA, en pacientes VIH y no VIH atendidos en los servicios de urgencias hospitalarios (SUH), y se identifican factores independientes de mal pronóstico, definido por ingreso o fallecimiento. Método: Estudio bicéntrico y observacional de 1 de enero de 2017 al 31 de diciembre de 2021. Se incluyeron pacientes VIH y no VIH atendido en dos SUH por intoxicación por DA. Se recogieron variables demográficas y la sustancia consumida. La variable de resultado principal fue mal pronóstico, definido como ingreso o muerte a los 30 días. Resultados: Se recogieron 1.132 pacientes. La edad media de los pacientes VIH fue 39 ± 10 años, y 33 ± 10 años para los no VIH. En la población VIH predominaron los opiáceos 279 (85,3%) (ninguno de ellos estaba en tratamiento sustitutivo con metadona), la cocaína 226 (30,9%) y las anfetaminas 153 (69,1%), mientras que en la no VIH predominaron la cocaína 372 (47,2%) y el cannabis 238 (33,8%). El etanol se asoció con otras DA en 387 pacientes. El análisis multivariado mostró que las únicas variables independientes de mal pronóstico fueron el VIH [OR 2,19 (1,29-3,11), p < 0,003], la edad [OR 1,20 (1,01-1,05), p < 0,003], y la IA por benzodiacepinas (BDZ) [OR 3,48 (2,14-5,66), p < 0,001], con un área bajo la curva de la característica operativa del receptor de este modelo de 0,717. Conclusiones: Existen diferencias en las características de las IA en pacientes VIH. La infección VIH, la edad y el consumo de BZD son factores independientes de mal pronóstico en las IA. (AU)

Objective: Persons with HIV infection who use illicit drugs have higher morbidity and mortality rates than nonusers with or without HIV infection. The objetive were to detect differences between acute poisoning from illicit drugs in patients with and without HIV infection who are attended in hospital emergency departments, and to identify independent factors associated with a worse prognosis, defined by hospital admission or death. Methods: Observational study in 2 hospitals between January 2017 and 31 December 2021. Included were patients with acute illicit drug poisoning with and without HIV infection. Results: Information for 1132 patients was included. The mean (SD) ages of patients with and without HIV infection, respectively, were 38.9 (9.6) years and 32.6 (10.4) years. In patients with HIV, the main drugs used were opioids (279 [85.3%]), cocaine (226 [69.1%]), and amphetamines (153 [46.8%]. None in this group were on methadone substitution therapy for opioid addiction. In patients without HIV infection the main drugs were cocaine (372 [47.2%]) and cannabis (238 [33.8%]). Alcohol was used along with illicit drugs in 387 cases. Multivariate analysis showed that the only variables independently associated with a poor prognosis were HIV infection (odds ratio [OR], 2.19 [1.29-3.11], P < .003), age (OR, 1.20 [1.01-1.05], P < .003), and acute poisoning from benzodiazepines (OR, 3.48 [2.14-5.66], P < .001). The area under the receiver operating characteristic curve of the model was 0.717. Conclusion: Certain characteristics distinguish the illicit drug use of patients with HIV infection. HIV infection, age, and the use of benzodiazepines are independently associated with a poor prognosis in acute poisonings. (AU)

Acute, chronic, and post-mortem toxicity: a review focused on three different classes of new psychoactive substances.

PURPOSE: New psychoactive substances (NPS) are not controlled under the Single Convention on Narcotic Drugs of 1961 or the 1971 Convention, but they may pose a public health threat. Knowledge of the main properties and toxicological effects of these substances is lacking. According to the current Drugs Law (Law n. 11.343/2006), the Brazilian Surveillance Agency issues directives for forbidden substances in Brazil, and structural classes of synthetic cannabinoids, cathinones, and phenylethylamines are considered illicit drugs. Considering that data on these controlled substances are scattered, the main objective of this work was to collect and organize data to generate relevant information on the toxicological properties of NPS. METHODS: We carried out a literature review collecting information on the acute, chronic, and post-mortem toxicity of these classes of NSP. We searched info in five scientific databases considering works from 2017 to 2021 and performed a statistical evaluation of the data. RESULTS: Results have shown a general lack of studies in this field given that many NPS have not had their toxicity evaluated. We observed a significant difference in the volume of data concerning acute and chronic/post-mortem toxicity. Moreover, studies on the adverse effects of polydrug use are scarce. CONCLUSIONS: More in-depth information about the main threats involving NPS use are needed.

Accuracy of substance exposure history in patients attending emergency departments after substance misuse; a comparison with biological sample analysis.

CONTEXT: Acute toxicity caused by illicit substance use is a common reason for emergency department (ED) presentation. Knowledge of the substances involved is helpful for predicting and managing potential toxicity, but limited information is available about the accuracy of patient-reported substance exposure. This study assessed the accuracy of the history of exposure in those reporting use of a single substance by comparison with those identified by detailed toxicological analysis, focusing on synthetic cannabinoid receptor agonists (SCRA). METHODS: Adults (≥16 years) presenting between March 2015 and July 2021 to participating UK hospitals with toxicity after reporting use of a single illicit substance were included. Exposure details were documented from medical records and blood and/or urine samples analysed using high-resolution accurate mass liquid chromatography-mass spectrometry (HRAM LCMS). Sensitivity, specificity, and positive and negative predictive values of the exposure history were calculated by comparison with biological sample analysis ("gold standard"). RESULTS: Single substance exposure was reported for 474 (median age 33 years, IQR: 18 range 16-75, 80% males) patients. Analysis commonly identified multiple substances (Median 3, IQR 2-5). A history of exposure was documented for 121 of 151 patients where a SCRA or metabolite was detected on analysis (sensitivity 80.1%, 95% CI 72.9, 86.2%). Corresponding proportions were lower for 3,4-methylenedioxymethamphetamine (MDMA, 44/70, 62.9%., 95% CI 50.5%, 74.1%), heroin 41/108 (38.0% 95% CI 28.8-47.8%) and cocaine (22/56, 31.3%, 95% CI 20.9, 43.6%). CONCLUSIONS: Multiple undeclared substances were detected analytically in most patients reporting single substance use. Clinicians should be alert to the potential presence and toxicity of unreported substances when managing patients presenting after substance misuse.

The wire. Una iluminación profana / The wire. A profane illumination

Introducción: Considerada la mejor serie de televisión del siglo XXI, The wire pone en escena la ciudad de Baltimore, una de las más violentas del mundo, tomando como eje central la industria de las drogas baratas. Las dinámicas a las que da lugar esta economía ilegal sirve de matriz en la ficción para entender las instituciones de las ciudades contemporáneas y el actual contexto del lazo social. Metodología: Tomando como referencia los textos sociales de Sigmund Freud y la revisión crítica efectuada por Jacques-Alain Miller a partir de la obra de Jacques Lacan, el presente artículo aborda la función del tóxico en esta serie desde discusiones actuales del campo psicoanalítico. Resultados: Es posible corroborar que la cultura de las drogas a la que se refiere David Simon en diversas ocasiones implica un empuje a la obtención de un plus como principal horizonte de sus personajes e instituciones de las que forman parte. La lectura propuesta en el presente artículo plantea que esta mutación cultural puede ser analizada desde la noción de objeto plus de goce propuesto por Jacques Lacan. (AU)

Introduction: Considered the best television series of the 21st century, The Wire stages the city of Baltimore, one of the most violent in the world, taking the cheap drug industry as its central axis. The dynamics to which this illegal economy gives rise serves as a matrix in fiction to understand the institutions of contemporary cities and the current context of the social bond. Methodology: Taking as reference the social texts of Sigmund Freud and the critical review carried out by Jacques-Alain Miller based on the work of Jacques Lacan, this article addresses the function of the toxic in this series from current discussions in the psychoanalytic field. Results: It is possible to corroborate that the drug culture to which David Simon refers on several occasions implies a push to obtain a plus as the main horizon of his characters and institutions of which they are a part. The reading proposed in this article suggests that this cultural mutation can be analyzed from the notion of object plus jouissance proposed by Jacques Lacan. (AU)

The wire. A profane illumination / The wire. Una iluminación profana

Introduction: Considered the best television series of the 21st century, The Wire stages the city of Baltimore, one of the most violent in the world, taking the cheap drug industry as its central axis. The dynamics to which this illegal economy gives rise serves as a matrix in fiction to understand the institutions of contemporary cities and the current context of the social bond. Methodology: Taking as reference the social texts of Sigmund Freud and the critical review carried out by Jacques-Alain Miller based on the work of Jacques Lacan, this article addresses the function of the toxic in this series from current discussions in the psychoanalytic field. Results: It is possible to corroborate that the drug culture to which David Simon refers on several occasions implies a push to obtain a plus as the main horizon of his characters and institutions of which they are a part. The reading proposed in this article suggests that this cultural mutation can be analyzed from the notion of object plus jouissance proposed by Jacques Lacan. (AU)

Introducción: Considerada la mejor serie de televisión del siglo XXI, The wire pone en escena la ciudad de Baltimore, una de las más violentas del mundo, tomando como eje central la industria de las drogas baratas. Las dinámicas a las que da lugar esta economía ilegal sirve de matriz en la ficción para entender las instituciones de las ciudades contemporáneas y el actual contexto del lazo social. Metodología: Tomando como referencia los textos sociales de Sigmund Freud y la revisión crítica efectuada por Jacques-Alain Miller a partir de la obra de Jacques Lacan, el presente artículo aborda la función del tóxico en esta serie desde discusiones actuales del campo psicoanalítico. Resultados: Es posible corroborar que la cultura de las drogas a la que se refiere David Simon en diversas ocasiones implica un empuje a la obtención de un plus como principal horizonte de sus personajes e instituciones de las que forman parte. La lectura propuesta en el presente artículo plantea que esta mutación cultural puede ser analizada desde la noción de objeto plus de goce propuesto por Jacques Lacan. (AU)

Renal manifestations of recreational drugs: A narrative review of the literature.

Drug abuse has become a major problem of the modern world where drug-induced kidney injury can be caused by both prescribed drugs for clinical conditions and illegal (illicit) drugs or drugs of abuse. Heroin, cocaine, nicotine and alcohol are the most commonly abused drugs but with the emergence of various synthetic drugs, numerous novel descriptions of their nephrotoxic effects have been described. This review summarizes the key renal manifestations of recreational drugs as reported in case reports and case. A comprehensive review of published case reports and case series in English language of renal toxicity related to recreational drugs/drugs of abuse was conducted using search engines like PubMed/Medline. Publications which reported renal injury with raised creatinine levels, clinically symptomatic patients, those with oliguria and with renal biopsies are chosen. The medical literature on recreational drugs is full of claims of renal complications including different glomerular diseases, acute kidney injury, rhabdomyolysis, interstitial nephritis, and debilitating irreversible conditions like renal infarction and end stage renal disease, even though the pathogenesis of drug- related renal manifestations are not available for all the newer agents. The outcome of this review paper will help multidisciplinary physicians to understand the renal side effects of recreational drugs, their pathophysiology, and most importantly, the clinical presentations of renal dysfunction in relation each drug. Emphasizing these adverse effects will prevent future unfavorable outcomes.

Synthetical effect of microplastics and chiral drug amphetamine on a primary food source algae Chlorella pyrenoids.

The biological effects and fate of the chiral illicit drug amphetamine in the presence and absence of microplastics on freshwater algae (Chlorella pyrenoids), including acute toxicity, growth inhibition, photosynthetic pigment content, oxidative stress, lipid peroxidation, and enantioselective fate were assessed. An agglomeration and the shading effects of microplastics in algae suspension were also determined. Microplastics were observed to increase the toxicity of amphetamine to algae and reduce algae cell growth. Exposed Chlorella pyrenoids exhibited a reduced algae cell counts in an agglomeration test, wherein algae cells decreased between 18% and 56% among treatment groups exposed to 5-50 mg L-1 of microplastics. The agglomeration test suggested that microplastics might significantly increase the adverse effect on algae. Furthermore, our experiments demonstrated enantioselective degradation of amphetamine in algae, and demonstrated that the S-enantiomer was preferably degraded by algae cells. Adding microplastics to the algae suspension significantly reduced the enantioselectivity, with an EF value of 0.41 compared with amphetamine-alone group (0.34) after 21 d exposure. These results demonstrated the first evidence of microplastics acting as a vehicle to enhance amphetamine toxicity to Chlorella pyrenoids, as well as provided new insights into the co-effect of microplastics and organic contaminants on food source.

Induction of CYP450 by illicit drugs: Studies using an in vitro 3D spheroidal model in comparison to animals.

Information regarding the metabolism of illicit drugs is under urgent need for toxicological assessment. Its development, however, is limited by the currently available animal models. To this end, we proposed three-dimensional (3D) HepaRG spheroids as an in vitro model to study the effects of illicit drugs on hepatic cytochrome P450 (CYP450) enzymes and potential drug-drug interactions (DDIs). By comparing the results from animal and cell experiments, we confirmed the significant impact of heroin, morphine, tetrahydrocannabinol, and fentanyl on CYP450 enzymes, and the 3D spheroids results were in good agreement with the animal results for 2B6, 2C19, 2D6. Using 3D HepaRG spheroids, we demonstrated DDIs between heroin as a 2B6 perpetrator and clinical medicine for cancer, depression, and illicit drug withdrawal. Specifically, the clearance rate of 5.4 µM bupropion was increased by 214 % under DDI with 5 µM heroin, highlighting the importance of DDI pre-screening and individualized medication guidance for illicit drug users. This research contributes to the growing body of evidence regarding the metabolic toxicity of illicit drugs and suggests 3D HepaRG spheroids as a high-throughput and cost-efficient platform for DDI analysis.

Nitrous oxide abuse induced subacute combined degeneration despite patient initiated B12 supplementation.

INTRODUCTION: Nitrous oxide (N2O) is a commonly used inhaled anesthetic that is legal to purchase as a food additive and is popular as a recreational euphoric drug. Abuse causes a functional B12 deficiency, leading to clinical features and imaging consistent with subacute combined spinal cord degeneration (SCD). CASES: Poison Center medical records from four patients are reviewed in this series. Four patients presented with lower extremity weakness, paresthesias and gait abnormalities in the setting of chronic N2O abuse. Each reported using 50-150 N2O cartridges ("whippets") almost daily for months to years, and reported supplementing with oral B12 at the recommendation of other users and online forums. None reported prior B12 deficiency or dietary restrictions, and none exhibited hematologic abnormalities. RESULTS: All patients had clinical signs of neurotoxicity including weakness and ataxia. Additionally, all had elevated methylmalonic acid and homocysteine concentrations with normal B12 indicating a functional B12 deficiency. Three had imaging consistent with SCD despite home supplementation The MRI in the fourth case was inconclusive due to movement artifact. CONCLUSION: We report four cases of subacute combined degeneration induced by recreational nitrous oxide abuse despite self-administered vitamin B12 supplementation.

Toxicokinetics of U-47700, tramadol, and their main metabolites in pigs following intravenous administration: is a multiple species allometric scaling approach useful for the extrapolation of toxicokinetic parameters to humans?

New synthetic opioids (NSOs) pose a public health concern since their emergence on the illicit drug market and are gaining increasing importance in forensic toxicology. Like many other new psychoactive substances, NSOs are consumed without any preclinical safety data or any knowledge on toxicokinetic (TK) data. Due to ethical reasons, controlled human TK studies cannot be performed for the assessment of these relevant data. As an alternative animal experimental approach, six pigs per drug received a single intravenous dose of 100 µg/kg body weight (BW) of U-47700 or 1000 µg/kg BW of tramadol to evaluate whether this species is suitable to assess the TK of NSOs. The drugs were determined in serum and whole blood using a fully validated method based on solid-phase extraction and LC-MS/MS. The concentration-time profiles and a population (pop) TK analysis revealed that a three-compartment model best described the TK data of both opioids. Central volumes of distribution were 0.94 L/kg for U-47700 and 1.25 L/kg for tramadol and central (metabolic) clearances were estimated at 1.57 L/h/kg and 1.85 L/h/kg for U-47700 and tramadol, respectively. The final popTK model parameters for pigs were upscaled via allometric scaling techniques. In comparison to published human data, concentration-time profiles for tramadol could successfully be predicted with single species allometric scaling. Furthermore, possible profiles for U-47700 in humans were simulated. The findings of this study indicate that unlike a multiple species scaling approach, pigs in conjunction with TK modeling are a suitable tool for the assessment of TK data of NSOs and the prediction of human TK data.

Caracterización del estilo de vida en la etapa de recuperación de adolescentes adictos a drogas ilegales / Characterization of the lifestyle in the recovery stage of adolescents addicted to illegal drugs

Introducción: El consumo de drogas ilegales por los adolescentes se considera en la actualidad, como un problema de salud pública a nivel mundial. Cuba no está exenta de esta problemática. Una vez instaurada la adicción, el estilo de vida que desarrolle cada individuo es determinante para el proceso de recuperación. Objetivo: Caracterizar el estilo de vida de adolescentes adictos a drogas ilegales en la etapa de recuperación. Métodos: La investigación se basó en un diseño mixto y consistió en el estudio de los 26 adolescentes adictos a drogas ilegales que fueron atendidos en el Departamento de Salud Mental del municipio Playa, La Habana, Cuba, durante el primer trimestre de 2018. Se aplicó el Cuestionario de Estilo de Vida Promotor de Salud y se realizaron cuatro grupos focales. Resultados: Los 26 sujetos evaluados presentaron una conducta irresponsable ante la salud y el cuidado de sí mismo. No obstante, el soporte interpersonal fue adecuado en 76,9 por ciento de los casos estudiados, y 46,15 por ciento de ellos presentó habilidades para manejo adecuado del estrés. Fue identificada la carencia de hábitos adecuados de ejercitación física (73,1 por ciento) y de comportamientos nutricionales y de autoactualización (69,2 por ciento). Conclusiones: Las adicciones constituyen un trastorno crónico y el tratamiento para la recuperación tiene entre sus pilares principales la modificación del estilo de vida. El apoyo interpersonal y las habilidades para manejar el estrés que logre desarrollar el paciente adicto pueden ayudarlo asumir su estilo de vida, y su salud con más responsabilidad. Para que el proceso de recuperación concluya satisfactoriamente y se eviten recaídas desmoralizantes, debe procurarse la adecuación de la autoestima, el compromiso con proyectos de vida realistas y la satisfacción con su situación personal(AU)

Introduction: The use of illegal drugs by adolescents is nowadays considered as a global public health problem. Cuba is not an exception of this problem. Once the addiction is established, the lifestyle developed by each individual is determinant for the recovery process. Objective: Characterize the lifestyle of adolescents addicted to illegal drugs in the recovery stage. Methods: The research was based in mixed design and consisted in the study of 26 adolescents addicted to illegal drugs whom were attended in the Mental Health Service of Playa municipality, Havana, Cuba during the first quarter of 2018. It was applied the Questionnaire of Lifestyle - Health Promoter and four focus groups were formed. Results: The 26 patients assessed showed an irresponsible behaviour towards health and self-care. However, the interpersonal support was adequate in 76,9percent of the studied cases, and 46,15percent of them presented skills for an adequate management of stress. It was identified lack of adequate habits of physical activity (73,1percent) and of nutritional behaviours and auto-updating (69,2percent). Conclusions: Addictions are a chronic disorder and the treatment for recovery has among its pillars the modification of lifestyle. Interpersonal support and skills to manage stress that the addict patient is able to develop would help to assume his-her lifestyle and health with more responsibility. In order that the recovery process ends up satisfactorily and to avoid that demoralizing relapses occur, it must be seek the adequacy of self-steem, the commitment with realistic life projects and satisfaction with the personal situation(AU)

Clinical Pharmacology, Toxicity, and Abuse Potential of Opioids.

Opioids were the most common drug class resulting in overdose deaths in the United States in 2019. Widespread clinical use of prescription opioids for moderate to severe pain contributed to the ongoing opioid epidemic with the subsequent emergence of fentanyl-laced heroin. More potent analogues of fentanyl and structurally diverse opioid receptor agonists such as AH-7921 and MT-45 are fueling an increasingly diverse illicit opioid supply. Overdose from synthetic opioids with high binding affinities may not respond to a typical naloxone dose, thereby rendering autoinjectors less effective, requiring higher antagonist doses or resulting in a confusing clinical picture for health care providers. Nonscheduled opioid drugs such as loperamide and dextromethorphan are associated with dependence and risk of overdose as easier access makes them attractive to opioid users. Despite a common opioid-mediated pathway, several opioids present with unique pharmacodynamic properties leading to acute toxicity and dependence development. Pharmacokinetic considerations involve half-life of the parent opioid and its metabolites as well as resulting toxicity, as is established for tramadol, codeine, and oxycodone. Pharmacokinetic considerations, toxicities, and treatment approaches for notable opioids are reviewed.

Canvis en les característiques de les intoxicacions en menors de 18 anys. Revisió de casos en un servei d’urgències (2011-2018) / Cambios en las características de las intoxicaciones en menores de 18 años. Revisión de casos en un servicio de urgencias (2011-2018) / Changes in the pattern of poisonings in patients under 18 years. A review of cases in an emergency department (2011–2018)

Fonament. Les intoxicacions han sofert canvis al llarg deltemps en relació amb l’etiologia, el maneig i les complicacions. Conèixer-ne l’epidemiologia ajuda a generar mesurespreventives.Objectiu. Analitzar les característiques epidemiològiques iclíniques, el pronòstic i la mortalitat de les intoxicacions enun servei d’urgències pediàtriques.Mètode. Estudi descriptiu, retrospectiu, observacional. Període: vuit anys. Es van incloure menors de divuit anys ambsospita d’intoxicació atesos a urgències que van requeriringrés hospitalari o observació. Anàlisi feta mitjançant elprograma SPSS.Resultats. Es van incloure cinquanta-dos pacients, delsquals trenta-tres van ser menors de sis anys (63,5%) i dinou majors de dotze anys (36,5%). Tots els successos enels menors de sis anys van ser involuntaris. El 94,7% deles intoxicacions en els majors de dotze anys van ser intencionades, de les quals el 72,2% tenien intenció suïcida.Els tòxics més freqüents van ser els medicaments (63,4%),seguits de les drogues il·lícites (15,4%). El 50% del totald’intoxicacions va presentar alteració del nivell de consciència i el 28,8% va requerir suport respiratori. Enl’11,5% es va fer rentat gàstric i en el 30% es va administrar carbó activat. L’alteració del nivell de consciència vaser l’únic factor significatiu (p<0,05) associat a l’ingrés ala Unitat de Cures Intensives Pediàtriques (UCIP).Conclusions. Les intoxicacions predominaren en els menors de sis anys. Del total d’intoxicacions, la medicamentosa va ser la causa més freqüent, seguida de les drogues il·lícites.El factor clínic més relacionat amb l’ingrés a la UCIP va serl’alteració de la consciència. (AU)

Fundamento. Las intoxicaciones han sufrido cambios a lo largo del tiempo en etiología, manejo y complicaciones. Conocer su epidemiología ayuda a generar medidas preventivas. Objetivo. Analizar las características epidemiológicas y clínicas, el pronóstico y la mortalidad de las intoxicaciones en un servicio de urgencias pediátricas. Método. Estudio descriptivo, retrospectivo, observacional. Periodo:8 años. Se incluyó a los menores de 18 años con sospecha de intoxicación atendidos en urgencias que requirieron ingreso u observación. Análisis realizado mediante el programa SPSS. Resultados. Se incluyeron 52 pacientes, de los cuales 33 fueron menores de 6 años (63,5%) y 19 mayores de 12 años (36,5%).Todos los eventos en los menores de 6 años fueron involuntarios. El 94,7% de las intoxicaciones en los mayores de 12 años fueron intencionadas, de las cuales el 72,2% tenían intención suicida. La causa medicamentosa (63,4%) fue la más frecuente, seguida por las drogas ilícitas (15,4%). El 50% del total de intoxicaciones presentaron alteración del nivel de consciencia y el 28,8% precisó soporte respiratorio. En el 11,5% se realizó lavado gástrico y en el30% se administró carbón activado. La alteración del nivel de consciencia fue el único factor significativo (p<0,05) asociado con el ingreso en la unidad de cuidados intensivos pediátricos (UCIP).Conclusiones. Las intoxicaciones predominaron en los menores de6 años. Del total de intoxicaciones, la medicamentosa fue la causa más frecuente, seguida por las drogas ilícitas. El factor clínico más relacionado con el ingreso a UCIP fue la alteración del nivel de consciencia. (AU)

Background. Poisonings in pediatrics have undergone changes overtime in terms of etiology, management, and complications. It is important to know the epidemiology to generate preventive measures. Objective. To analyze the epidemiology, clinical characteristics,prognosis, and mortality of poisonings in pediatric patients caredfor in the emergency department.Method. This is a descriptive, retrospective and observationalstudy. Period: 8 years. Patients under 18 with suspected poisoningadmitted in the emergency department were included. The statistical analysis was performed using the SPSS program.Results. 52 patients were selected, 33 under 6 years of age (63.5%)and 19 over 12 years (36.5%). All events in children under 6 wereunintentional. 94.7% of poisonings in patients over 12 years of agewere intentional, of which 72.2% had a suicidal intention. Pharmacologic agents (63.4%) were the most frequently identified ingestedsubstance, followed by illicit drugs (15.4%). 50% of all cases hadaltered level of consciousness and 28.8% required respiratory support. Gastric lavage was performed in 11.5% and activated charcoalwas administered in 30%. Altered level of consciousness was theonly significant factor (p<0.05) associated with admission to thepediatric intensive care unit (PICU).Conclusions. Poisoning cases were more frequent in children under6 years. Pharmacologic agents were the most frequently identifiedpoisoning substances, followed by illicit drugs. Decreased consciousness was the most significant clinical factor leading to admission to the PICU. (AU)

Uso de club drugs entre estudantes de graduação: prevalência, características associadas e a influência dos pares / Club drugs use among undergraduate students: prevalence, associated characteristics and peer influence

OBJETIVO: Medir a prevalência do uso na vida, no último ano e no último mês de duas club drugs ­ o ecstasy e o LSD ­, bem como as características associadas ao uso dessas substâncias, no último mês, entre estudantes de graduação de uma universidade no Sul do Brasil. MÉTODOS: Trata-se de um estudo transversal conduzido no ano de 2015 com amostragem aleatória sistemática por conglomerados. Participaram 1.423 estudantes de graduação. Foi utilizado um modelo de análise multivariável em três níveis hierárquicos por meio da regressão de Poisson com ajuste robusto da variância. RESULTADOS: As prevalências de uso na vida, no último ano e no último mês de club drugs foram de 12,7%, 7,8% e 3,8%, respectivamente. Indivíduos do sexo masculino, com orientação sexual homossexual ou bissexual, mais jovens, que moravam com seus pares, solteiros, e que relataram uso no último mês de tabaco e maconha apresentaram maior probabilidade de ter feito uso no último mês de alguma club drug. Entretanto, a variável mais fortemente associada a esse desfecho foi ter algum amigo que já fez uso de alguma droga ilícita na vida (RP = 19,54). CONCLUSÕES: O ambiente universitário parece ser um terreno fértil para a difusão do uso de club drugs. O fortalecimento de uma rede de apoio institucional da universidade, capaz de propor atividades de prevenção, bem como de identificar, acolher e encaminhar casos em que haja abuso e dependência dessas substâncias, pode ser uma estratégia importante para lidar com essa problemática.

OBJECTIVE: To measure the prevalence of lifetime, last-year, and last-month use of two club drugs ­ ecstasy and LSD ­, as well as the characteristics associated with the last-month use of these substances among undergraduate students at a university in southern Brazil. METHODS: This was a cross-sectional study conducted in 2015 with a clustered systematic sampling strategy. Overall, 1,423 undergraduate students participated. A three-level hierarchical multivariate analysis model was used through Poisson regression with robust adjustment of variance. RESULTS: Prevalence of lifetime, last-year, and lastmonth use of club drugs were 12.7%, 7.8% and 3.8%, respectively. Male participants, with homosexual or bisexual sexual orientation, younger, who lived with their peers, who were single, and who reported last-month use of tobacco and marijuana had higher probability of last-month use club drugs. However, the variable most strongly associated with this outcome was having a friend with lifetime use of illicit drugs (PR = 19.54). CONCLUSIONS: University environment seems to be a fertile ground for the spread of the use of club drugs. The strengthening of the university's institutional assistance network, capable of proposing prevention activities, as well as identifying, supporting and referring cases where there is abuse and dependence on these substances can be an important strategy to deal with this problem.