The need for opioid in the postoperative analgesia of dogs undergoing hemilaminectomy due to intervertebral disc extrusion

ABSTRACT: The aim of this study was to evaluate the postoperative analgesic effect of protocols with and without the opioid methadone in dogs with intervertebral disc extrusion undergoing decompressive surgery. Sixteen paraplegic dogs with preserved nociception underwent hemilaminectomy/disc fenestration and were randomly assigned to two groups. The analgesic protocol consisted of methadone, meloxicam and dipyrone in Group I (G1), and meloxicam and dipyrone in Group II (G2). The animals were blindly assessed by two observers, using the visual analogue scale (VAS) and the short-form Glasgow Composite Measure Pain Scale (CMPS-SF). Assessments occurred every 2 hours during first 24 hours post-surgery, and every 4 hours afterwards. There was no statistical difference among groups regarding pain scores or analgesic rescues. Both analgesic protocols provided analgesia in the initial 48 hours postoperatively, demonstrating that opioids are not necessary in the postoperative period of dogs undergoing hemilaminectomy and disc fenestration.

RESUMO: O objetivo deste estudo foi avaliar a analgesia pós-operatória de protocolos com e sem o opioide metadona em cães com extrusão de disco intervertebral submetidos à descompressão cirúrgica. Dezesseis cães paraplégicos com presença de nocicepção foram submetidos à hemilaminectomia/fenestração de disco e distribuídos aleatoriamente em dois grupos. No Grupo I (G1), o protocolo analgésico consistiu em metadona, meloxicam e dipirona e, no Grupo II (G2), por meloxicam e dipirona. Os pacientes foram avaliados de maneira cega por dois avaliadores, com base na escala visual analógica (EVA) e na escala simplificada composta de dor de Glasgow (CMPS-SF). As avaliações ocorreram a cada 2 horas durante as primeiras 24 horas de pós-operatório e, por mais 24 horas, a cada 4 horas. Não houve diferença estatística entre os grupos avaliados em relação à escores de dor e nem a necessidade de resgate analgésico. Ambos os protocolos promoveram analgesia nas 48 horas iniciais de pós-operatório, demonstrando não haver a necessidade do uso de opioide em cães submetidos à hemilaminectomia e fenestração de disco.

Revisión de metadona intraoperatoria para el manejo de dolor posquirúrgico / Intraoperative methadone for the management of postsurgical pain a review

Pain management associated with surgery is a constant concern of the health team as well as the patient. Multiple proposals for analgesia have been made in the perioperative context. The use of opioids with rapid effect and easy titration in the intraoperative period are currently frequent; to then perform a postoperative analgesic control with drugs with a longer half-life, usually achieving adequate pain management. However, sometimes the standard analgesic scheme is not enough. The problems associated with this situation have led to the need for high doses of opioids in the postoperative period, with the requirement for monitoring, health personnel, and the adverse effects that these involve. Methadone is a long-acting, rapid-onset opioid, the latter secondary to its long elimination half-life. It is presumed that these characteristics have led patients to report adequate pain management, which has been related to a decrease in the need and dose of rescue opioids, in addition to delaying the requirement of these if necessary during the postoperative. These properties allow methadone to be a potential solution to perioperative pain management.

El manejo del dolor asociado a la cirugía es una preocupación constante del equipo de salud al igual que del paciente. Se han planteado múltiples propuestas de analgesia en el contexto perioperatorio, siendo actualmente frecuente el uso de opioides de rápido efecto y fácil titulación en el intraoperatorio; para luego realizar un control analgésico postoperatorio con fármacos de mayor vida media, logrando habitualmente un manejo adecuado del dolor. Sin embargo, a veces el esquema analgésico estándar no es suficiente. La problemática asociada a esta situación ha llevado a la necesidad de altas dosis de opioides en el posoperatorio, con el requerimiento de monitorización, personal de salud y efectos adversos que estos involucran. La metadona es un opioide de inicio de acción rápido y larga duración, este último secundario a su vida media de eliminación prolongada. Se presume que estas características han logrado que los pacientes reporten un adecuado manejo de su dolor, lo que se ha relacionado a una disminución en la necesidad y dosis de opioides de rescate, además de retrasar el requerimiento de éstos en el caso de ser necesarios durante el postoperatorio. Estas propiedades permiten que la metadona pueda ser una potencial solución al manejo del dolor perioperatorio.

The need for opioid in the postoperative analgesia of dogs undergoing hemilaminectomy due to intervertebral disc extrusion / A necessidade de opioide na analgesia pós-operatória de cães submetidos à hemilaminectomia devido à extrusão do disco intervertebral

The aim of this study was to evaluate the postoperative analgesic effect of protocols with and without the opioid methadone in dogs with intervertebral disc extrusion undergoing decompressive surgery. Sixteen paraplegic dogs with preserved nociception underwent hemilaminectomy/disc fenestration and were randomly assigned to two groups. The analgesic protocol consisted of methadone, meloxicam and dipyrone in Group I (G1), and meloxicam and dipyrone in Group II (G2). The animals were blindly assessed by two observers, using the visual analogue scale (VAS) and the short-form Glasgow Composite Measure Pain Scale (CMPS-SF). Assessments occurred every 2 hours during first 24 hours post-surgery, and every 4 hours afterwards. There was no statistical difference among groups regarding pain scores or analgesic rescues. Both analgesic protocols provided analgesia in the initial 48 hours postoperatively, demonstrating that opioids are not necessary in the postoperative period of dogs undergoing hemilaminectomy and disc fenestration.(AU)

O objetivo deste estudo foi avaliar a analgesia pós-operatória de protocolos com e sem o opioide metadona em cães com extrusão de disco intervertebral submetidos à descompressão cirúrgica. Dezesseis cães paraplégicos com presença de nocicepção foram submetidos à hemilaminectomia/fenestração de disco e distribuídos aleatoriamente em dois grupos. No Grupo I (G1), o protocolo analgésico consistiu em metadona, meloxicam e dipirona e, no Grupo II (G2), por meloxicam e dipirona. Os pacientes foram avaliados de maneira cega por dois avaliadores, com base na escala visual analógica (EVA) e na escala simplificada composta de dor de Glasgow (CMPS-SF). As avaliações ocorreram a cada 2 horas durante as primeiras 24 horas de pós-operatório e, por mais 24 horas, a cada 4 horas. Não houve diferença estatística entre os grupos avaliados em relação à escores de dor e nem a necessidade de resgate analgésico. Ambos os protocolos promoveram analgesia nas 48 horas iniciais de pós-operatório, demonstrando não haver a necessidade do uso de opioide em cães submetidos à hemilaminectomia e fenestração de disco.(AU)

Psychosocial reintegration process in patients who receive maintenance treatment with methadone: A qualitative analysis / Proceso de reintegración psicosocial en pacientes que reciben tratamiento de mantenimiento con metadona: un análisis cualitativo

Abstract Introduction The evaluation of methadone maintenance programs reports generally positive outcomes. Objective To explore the psychosocial factors that contribute to achieve treatment goals even when patients live in conditions of precariousness and exclusion. Method Qualitative study of multiple cases, with a sample of 12 interviews with patients participating in a maintenance and detoxification program with methadone; a thematic and discursive-narrative analysis was undertaken. Results We identified the predominance of a typical discursive scheme composed of clearly differentiated narrative segments: previous conditions, establishment of a relationship with the therapeutic system, process of adjustment as a part of treatment and social reintegration. Two main themes were also identified: addiction and dealing with substances, and the problem of normative integration; there was also an experience of acceptance and recognition that constitutes a central factor for treatment. Discussion and conclusion These findings are discussed in light of the disaffiliated conditions of people using injected heroin and the need to consider psychosocial and normative adjustment as a relevant factor for treatment and social reintegration, which leads to the suggestion to include psychotherapeutic interventions to accompany and reinforce the process.

Resumen Introducción La evaluación de los programas de mantenimiento con metadona reporta, en general, resultados positivos. Objetivo Explorar factores psicosociales que contribuyan al logro de los objetivos del tratamiento, incluso cuando los pacientes se encuentran en condiciones de precariedad y exclusión. Método Estudio cualitativo de casos múltiples, con una muestra de 12 entrevistas con pacientes participantes en un programa de mantenimiento y deshabituación con metadona; se realizó un análisis discursivo-narrativo y temático. Resultados Identificamos el predominio de un esquema discursivo típico compuesto de segmentos narrativos claramente diferenciados: condiciones previas, vinculación con el sistema terapéutico, proceso de ajuste al interior del tratamiento y proceso de reintegración social. También se identificaron dos ejes de articulación temática: la adicción y el manejo de sustancias, y el problema de la integración normativa; hubo además una experiencia de aceptación y reconocimiento que constituye un factor central en el tratamiento. Discusión y conclusión Estos hallazgos se discuten a la luz de las condiciones de desafiliación del usuario de heroína y de la necesidad de considerar el ajuste psicosocial y normativo como un factor relevante para el tratamiento y la reintegración social, lo que lleva a sugerir que los programas incluyan componentes psicoterapéuticos con el objeto de acompañar y reforzar efectivamente el proceso.

Enfrentando el problema emergente de consumo de heroína en Colombia: los nuevos programas de tratamiento asistido con metadona / Facing the Growing Heroin Problem in Colombia: The New Methadone-assisted Treatment Programs

RESUMEN Objetivo: Colombia está enfrentado una epidemia emergente del consumo endovenoso de heroína. Un conocimiento de los programas existentes que ofrecen tratamiento asistido con metadona en el país es necesario para que se puedan proponer estrategias de mejoría. Métodos: Se encuestaron 13 programas de regiones prioritarias. Se evaluaron las caracte rísticas demográficas y clínicas de los usuarios, así como los servicios ofrecidos por estos programas, sus protocolos de tratamiento con metadona y las diferencias en las barreras al tratamiento y las causas de abandono del tratamiento. Resultados: Se analizaron 12/13 cuestionarios, con un total de 538 pacientes activos. La mayo ría de los pacientes eran varones (85,5%) de 18 a 34 arios (70%). El 40% eran usuarios de drogas intravenosas y el 25% admitió compartir agujas. Entre las comorbilidades asociadas con el consumo de heroína se encontró la enfermedad mental (48%), la hepatitis C (8,7%) y la infección por el VIH (2%). La comorbilidad psiquiátrica se asocia más con los pacientes que acuden al sector privado (el 69,8 frente al 29,7%; p < 0,03). La media de la dosis inicial de metadona es 25,3 ± 8,9mg/día y las dosis de mantenimiento van de 41 a 80 mg/día. La falta de articulación con atención primaria fue una barrera más sentida que los problemas con la cobertura del seguro médico y los prejuicios del tratamiento con metadona (p < 0,05). También, los problemas administrativos y de la aseguradora (p < 0,003), la falta de sumi nistro de metadona (p < 0,018) y la recaída en el consumo (p < 0,014) son las razones más significativas de abandono del tratamiento. Conclusiones: Estos programas tienen diferentes niveles de desarrollo e implementación en los protocolos de tratamiento. Algunas de las barreras de acceso y de las causas de abandono del tratamiento pueden mitigarse mejorando la administración de salud.

ABSTRACT Objective: Colombia is facing a rising epidemic of intravenous heroin use. Knowledge of the methadone-assisted treatment programs in the country is crucial in order to propose improvement strategies. Methods: 13 programmes from priority regions were surveyed. The demographic and clinical characteristics of the patients attending the programs, a description of the services offered, their methadone treatment protocols, the various barriers to treatment and the causes of treatment abandonment were reviewed. Results: 12/13 questionnaires were analysed with a total of 538 active patients. Most of the patients attending these programs were men (85.5%) between 18 and 34 years-old (70%). Forty percent (40%) were intravenous drug users and 25% admitted sharing needles. The comorbidities associated with heroin use were mental illness (48%), hepatitis C (8.7%) and HIV (2%). Psychiatric comorbidity was more likely in patients attending the private sec tor (69.8% vs 29.7%; p < 0.03). The initial average dose of methadone administered was 25.3 ± 8.9mg/day, with a maintenance dose ranging from 41 to 80mg/day. Lack of align ment with primary care was perceived to be the most serious barrier to access, ahead of problems with insurance and prejudice towards treatment with methadone (p < 0.05). Health Administration and insurance problems (p < 0.003), together with the lack of availa bility of methadone (p < 0.018) and relapse (p < 0.014) were the most important reasons for abandonment of treatment. Conclusions: The treatment protocols of these programmes offer different levels of develop ment and implementation. Some of the barriers to access and reasons for abandonment of treatment with methadone can be mitigated with better health administration.

Efeitos adversos da morfina, metadona e tramadol no pós-operatório de cães submetidos à cirurgia da coluna vertebral: 180 casos (2011-2016) / Adverse effects of morphine, methadone and tramadol in the postoperative period of dogs undergone vertebral surgery: 180 cases (2011-2016)

A dor pós-operatória em cães que são submetidos a cirurgias da coluna vertebral é considerada severa e seu manejo inadequado pode influenciar no tempo de recuperação do paciente, na qualidade de vida e no resultado cirúrgico. Dentre os analgésicos indicados para uso no pós-operatório dessas cirurgias tem-se os opioides, que podem apresentar inúmeros efeitos adversos que requerem atenção. Devido à escassez de estudos clínicos acerca desse assunto em se tratando do pós-operatório de cães, objetivou-se com o presente estudo retrospectivo apresentar os efeitos adversos da morfina, metadona e tramadol utilizados no pós-operatório de cirurgias da coluna vertebral. Foram revisadas e avaliadas as fichas de 180 cães e anotadas as alterações observadas no pós-operatório e decorrentes do uso de opioides. Os principais efeitos adversos observados foram anorexia, hiporexia, vômito, salivação, vocalização, bradicardia, hipotermia, ofegação e sedação. Também foi observada persistência da dor em alguns cães mesmo com o uso de analgésicos. Houve diferença na ocorrência de anorexia nos cães tratados com morfina e nos tratados com metadona em relação aos tratados com tramadol. Ocorreu diferença também entre a observação de dor dos grupos morfina e tramadol. A associação de dipirona com morfina e com metadona não revelou diferença com relação à ocorrência de efeitos adversos, bem como a variação de doses. Conclui-se que a morfina, a metadona e o tramadol apresentam efeitos adversos quando empregados para tratamento da dor pós-operatória em cães submetidos à cirurgia da coluna vertebral; a anorexia, a hiporexia e o vômito foram os efeitos adversos frequentes com o uso de morfina e de metadona e, mesmo que o tramadol apresente menor ocorrência desses efeitos, seu uso, na dose estudada, pode não ser vantajoso quando se leva em consideração o grau de dor para cirurgias da coluna vertebral.(AU)

Postoperative pain in dogs undergone vertebral surgery is classified as severe and it's important an adequate approach to it, because it can influence recovery time, quality of life and surgery outcome. Opioids are indicated for postoperative pain treatment in these surgeries. Opioids may have adverse effects that may require attention. There are few clinical studies that present the adverse effects of these analgesics in canine postoperative period. The aim of this retrospective study was to present the adverse effects of morphine, methadone and tramadol in canine vertebral surgery postoperative period. There were revised the postoperative records of 180 dogs and the changes resulted from the opioids use were noted. The adverse effects observed were anorexia, hyporexia, vomiting, vocalization, bradycardia, hypothermia, panting, sedation. Pain was also observed in some dogs. A significant difference was found in anorexia between dogs treated with morphine and tramadol and methadone and tramadol. Significant difference was also found in pain between dogs treated with morphine and tramadol. The association of metamizole and morphine or metamizole and methadone was not different in relation to the adverse effects. There was also no difference with the dosage variation and the adverse effects. In conclusion, morphine, methadone and tramadol have adverse effects when used for pain control in the postoperative period of dogs submitted to vertebral surgery. Anorexia, hypophagia and emesis were frequent the adverse effects observed with morphine and methadone and, despite tramadol presented less adverse effects, its use may be not beneficial in the studied doses when we consider the degree of pain, however more controlled studies with clinical situation are needed to confirm this.(AU)

Tratamiento opioide del dolor mixto en pacientes pediátricos asistidos por el equipo de Cuidados Paliativos: Cinco años de experiencia / Opioid treatment for mixed pain in pediatric patients assisted by the Palliative Care team: Five years of experience

Introducción: El dolor se define como una experiencia sensorial y emocional desagradable, relacionada con daño tisular actual o potencial. Según su mecanismo fisiopatológico, se clasifica en dolor nociceptivo, neuropático y mixto. Cuando su intensidad es de moderada a grave, se debe administrar un opioide potente, y la morfina es el fármaco de elección. Si resulta ineficaz o aparecen efectos adversos intolerables, se recomienda la rotación de opioide. Nuestro objetivo fue describir el tratamiento farmacológico del dolor mixto en los pacientes asistidos por el equipo de Cuidados Paliativos del Hospital General de Niños Pedro de Elizalde entre agosto de 2011 y septiembre de 2015. Se incluyeron 72 pacientes, con edad media de 10,1 años y la enfermedad de base más frecuente fue patología oncológica. El opioide de inicio fue morfina en 57 casos; 48 recibieron fármacos adyuvantes. La rotación de opioides ocurrió en la mitad de los casos y la más frecuente fue de morfina a metadona.

Pain is defined as an unpleasant sensory and emotional experience associated with actual or potential tissue damage. Depending on its pathophysiological mechanism, it may be classified into nociceptive, neuropathic, and mixed pain. If pain is moderate to severe, a strong opioid should be administered and, when this is the case, morphine is the drug of choice. If morphine is ineffective or causes intolerable adverse effects, opioid rotation is recommended. Our objective was to describe the drug management for mixed pain used in patients assisted by the Palliative Care team of Hospital General de Niños Pedro de Elizalde between August 2011 and September 2015. A total of 72 patients were included. Their mean age was 10.1 years, and the most common underlying disease was cancer. The initial opioid was morphine in 57 cases; 48 patients received adjuvant drugs. Opioid rotation was indicated in half of cases, and the most common switch was from morphine to methadone.

Patrones de prescripción de metadona entre médicos colombianos especialistas en manejo del dolor / Methadone Prescription Patterns among Pain Physicians in Colombia

Introducción: el dolor crónico es una enfermedad con graves consecuencias para personas, médicos y sistemas de salud. Una de las estrategias de manejo es el uso prolongado de opioides, y dentro de los disponibles en Colombia se encuentra la metadona, con características farmacológicas únicas y asociación con aumento de mortalidad por sobredosis y complicaciones cardiovasculares. La adecuada prescripción y seguimiento de metadona se relaciona con complicaciones similares al manejo con otros opioides. Objetivo: describir los patrones de prescripción de metadona entre médicos colombianos especialistas en manejo de dolor y comparar estos patrones de prescripción con las recomendaciones mayormente aceptadas por la comunidad científica internacional. Materiales y métodos: se utilizó una encuesta electrónica estructurada aplicada entre médicos especialistas en dolor identificados a través de las principales agremiaciones y programas de formación nacionales. Resultados: los encuestados que respondieron son mayoritariamente experimentados anestesiólogos, con entrenamiento universitario clínico y que trabajan en hospitales universitarios. La mayoría de ellos percibe como efectivo el manejo a largo plazo con opioides para el control analgésico y la mejoría funcional, a pesar de la falta de respaldo empírico. La mayoría no aplica las herramientas recomendadas por guías de práctica clínica, aunque las conocen. Conclusiones: se debe mejorar la educación de prescriptores de metadona para mejorar la seguridad de los pacientes. Se infiere pobre aplicabilidad de herramientas recomendadas por guías de práctica clínica en el medio colombiano. Los resultados de la presente encuesta no son fácilmente generalizables.

Background: Chronic pain is a disease with serious consequences for people, physicians, and health care systems. Chronic opioid usage is one of this therapy strategy. Methadone is among the available opioids in Colombia and it is characterized by unique pharmacological properties and increased mortality reports because of overdose and cardiovascular complications. Appropriate monitoring and prescribing patterns of methadone are associated with complications similar to chronic management with other opioids. Aim: To describe methadone prescribing patterns among Colombian pain physicians and compare them to the accepted recommendations by the international scientific community. Materials and Methods: An electronic structured survey was applied to pain specialist physicians identified through major pain study associations and national training programs. Results: Respondents of the survey are mostly experienced university certified physicians and anesthesiologists with clinical training working at university hospitals. Most of them perceive chronic opioid therapy as an effective strategy for pain relief and functional outcomes despite the lack of empirical support. Most of them know clinical practice guidelines but are not applying them despite this matter. Conclusions: We must enhance education for prescribers in order to improve patient safety. The recommended clinical practice guidelines are poorly applied by Colombian doctors. The results of this study must be cautiously assessed.

Caracterización del uso de metadona en pacientes paliativos en el Instituto Nacional del Cáncer, Santiago de Chile / Characterization of methadone use in palliative patients at the National Cancer Institute, Santiago, Chile

OBJETIVOS: realizar un estudio de tipo descriptivo y retrospectivo para caracterizar el uso y efecto de metadona en una población de pacientes de la unidad de cuidados paliativos del Instituto Nacional del Cáncer. MATERIALES Y MÉTODOS: los datos analizados se obtuvieron desde los registros de la farmacia y las fichas clínicas de los pacientes de la unidad de cuidados paliativos del Instituto Nacional del Cáncer que estaban siendo tratados con metadona durante el mes de agosto de 2013. las variables cuantificadas fueron edad, sexo, diagnóstico oncológico, tipo de dolor, motivo de indicación de metadona, duración del tratamiento, dosis utilizadas, respuesta analgésica y uso concomitante con analgésicos no opioides. RESULTADOS: la población de pacientes bajo control mensual en la unidad de cuidados paliativos al mes de agosto fue de 445 pacientes. en el estudio se incluyeron a 31 pacientes que estaban en ese periodo tratados con metadona, lo que representa un 7% del total de pacientes. la indicación, según tipo de dolor, fue en un 80,6% por dolor de tipo neuropático o mixto. la indicación de metadona se debió, en un 68%, a una rotación de opioides y solo en un 3% fue por indicación primaria. la dosis promedio diaria fluctuó entre 16,7 mg, al inicio del tratamiento; y 26,1 mg, al momento del estudio o periodo de observación. la mediana de uso fue de 211 días. la intensidad del dolor, medida por la escala numérica verbal, fue de 8,3 ± 0,3 mg al inicio del tratamiento y 5,4 ± 0,6 mg durante el control de agosto de 2013, lo que significa una disminución promedio de 34,9%. DISCUSIÓN: el uso de metadona en la unidad de cuidados paliativos del Instituto Nacional del Cáncer está en concordancia con las propuestas internacionales, indicándose principalmente como rotación de opioides y en el tratamiento del dolor neuropático. el análisis de las fichas mostró utilización de dosis bajas de metadona (menores de 30 mg), con pequeños incrementos de dosis durante el período de tratamiento, obteniéndose como resultado una reducción significativa del dolor.

OBJETIVES: to carry out a descriptive and retrospective study to characterize the use and effect of methadone in a group of patients of the Palliative Care Unit of the National Cancer Institute. MATERIALS AND METHODS: the information was obtained from the patient pharmacy and clinical records at the palliative care unit of the National Cancer Institute who were being treated with methadone during the month of august, 2013. the variables assessed were age, sex, oncology diagnosis, type of pain, reason for methadone prescription, treatment duration, dosage, pain response and associated use of non- opioid analgesics. RESULTS: the patient group under monthly monitoring at the palliative care unit in august was made up of 445 people. the study included 31 patients who at that time were being treated with methadone, 7% of the total. the indication according to the type of pain was in an 80.6% caused by a neuropathic or mixed pain. a 68% of the methadone indication was caused by an opioid rotation and only a 3% by a primary indication. the average daily dose went from 16.7 mg at the beginning to 26.1 mg at the moment the study or observation period was carried out. the use average was of 211 days. The pain intensity, using a numeric scale, was of 8.3 ± 0.3 mg at the beginning of the treatment and a 5.4 ± 0.6 mg during the august 2013 control, which means an average decrease of 34,9 %. DISCUSSION: the use of methadone at the palliative care unit of the National Cancer Institute is in accordance with the international proposals, being indicated mostly as opioid rotation and in the neuropathic pain treatment. the record analysis showed a low dose use of methadone (lower than 30 mg), with small dose increase during the treatment period, getting a significant pain decrease as a result

Efectividad del cambio de tratamiento desde Metadona a Buprenorfina/Naloxona en dependientes a opiáceos, Bilbao - España / Effectiveness of treatment change from methadone to Buprenorphine / Naloxone in opiate dependents, Bilbao - Spain

A nivel mundial la dependencia a opiáceos es un problema vigente, y los pacientes afectados por esta condición requieren programas de tratamiento sustitutivo farmacológico, que utilizan tradicionalmente Metadona. Actualmente, existe debate sobre el hecho de que la Buprenorfina/Naloxona podria ser utilizada como un reemplazo adecuado del fármaco tradicional. Las investigaciones aún no son totalmente concluyentes, faltando estudios que prueben los resultados en la práctica clínica. Objetivos: Determinar la efectividad del tratamiento con Buprenorfina/Naloxona como reemplazo de la metadona en pacientes dependientes de opiáceos tratados en un Módulo de Asistencia Psicosocial en la ciudad de Bilbao, España. Métodos: Se realizó un estudio cuasiexperimental, cuantitativo, longitudinal, prospectivo, con 21 pacientes dependientes de opiáceos que formaban parte del Programa de mantenimiento con Metadona con dosis inferiores o iguales a 40 mg/día, en quienes se sustituyó ese tratamiento por el de Buprenorfina/Naloxona (8mg/2mg) siguiendo para esto los criterios de la Guía para el tratamiento de la adicción a opiáceos con Buprenorfina/Naloxona de la Sociedad Científica Española de estudios sobre alcohol, el alcoholismo y otras toxicomanías del 2010. Resultados: Después de tres meses de cambio de terapéutica a Buprenorfina/Naloxona se evidencio una reducción estadísticamente significativa en el consumo de opiáceos ilegales, medido a través de los controles de substancias en orina desde un promedio de 2,67 controles positivos con metadona, a 2,24 controles con Buprenorfina/Naloxona. La adherencia, se mantuvo similar a la previa, presentando además una retención del 100% de los pacientes. La calidad de vida, medida con el Test TECVASP, presento una mejora estadísticamente significativa, desde una puntuación de 76,76 cuando recibían Metadona (DE 6,41) hasta 90,33 (DE 5,77 ) con la nueva terapéutica. Conclusiones: Cambiar la terapia de mantenimiento con Metadona, en pacientes dependientes de opioides, por buprenorfina/naloxona es una buena opción, ya que tiene una efectividad similar en términos de adherencia y retención, y produce una mayor reducción en el uso de opiáceos ilegales, al tiempo que mejora la calidad de vida del paciente.

At the global level, opioid dependence is an ongoing problem, and patients with this condition require pharmacological substitution treatment programs, which traditionally use methadone. Currently there is debate over whether Buprenorphine / Naloxone could be used as a suitable replacement for the traditional drug. The investigations are not yet totally conclusive, lacking studies that prove the results in the clinical practice. Objectives: To determine the effectiveness of treatment with Buprenorphine / Naloxone as a replacement for Methadone in opioid dependent patients treated in a Psychosocial Assistance Module in the city of Bilbao, Spain. Methods: A quasi-experimental, quantitative, longitudinal, prospective study was conducted with 21 opioid-dependent patients that were part of the maintenance program with Methadone at doses lower than or equal to 40 mg / day, in which treatment was replaced by that of Buprenorphine / Naloxone (8 mg/2 mg) following for this the criteria of the Guide for the treatment of the addiction to opiates with Buprenorphine / Naloxone of the Spanish Scientific Society of studies on alcohol, alcoholism and other drug addictions of 2010. Results: After a three-month change in therapy to Buprenorphine / Naloxone, a statistically significant reduction in illegal opioid use was observed, measured through urine substance controls from an average of 2.67 methadone-positive controls 2.24 controls with Buprenorphine / Naloxone. The Adherence remained similar to the previous one, presenting a retention of 100% of the patients. Quality of life, measured with the TECVASP test, showed a statistically significant improvement, from a score of 76.76 when receiving Methadone (DE 6.41) to 90.33 (DE 5.77) with the new therapy. Conclusions: Changing maintenance therapy with methadone, in opioid-dependent patients, by buprenorphine/naloxone is a good option, because it has a similar effectiveness in terms of adherence and retention, and produces a greater reduction in the use of illegal opiates, and the same time improves the quality of life of the patient.

Neuropsychological functioning in methadone maintenance patients with HIV / Función neuropsicológica en el tratamiento de mantenimiento con metadona en pacientes con VIH

Although highly active antiretroviral therapy (HAART) has improved survival rates of HIV patients, HIV-associated neurocognitive disorders (HAND) still exist in a highly prevalent group of persons with this disease. In this study we seek to evaluate the influence of drug use in the neuropsychological performance of seropositive drug users. We carried out an extensive neuropsychological evaluation and compared the performance of seropositive drug users (n = 90) with that of a control group of seronegative drug users (n = 48). The results reveal that methadone maintenance programmes can make the seropositive subject neuropsychologically vulnerable. Likewise, we found that giving up drugs have a protective effect in the presence of neuropsychological alterations associated with HIV. These findings lead us to suggest that seropositivity is not sufficient to explain the neuropsychological alterations of seropositive drug users, noting that these alterations are multifactorial.

Aunque la terapia antirretroviral de gran actividad (TARGA) ha mejorado los índices de supervivencia de los pacientes infectados por el VIH, los trastornos neurocognitivos asociados con el VIH (TNAV) todavía existen en un grupo de personas altamente prevalente a esta enfermedad. En este estudio buscamos evaluar la influencia del consumo de drogas en el rendimiento neuropsicológico de los usuarios de drogas seropositivos. Llevamos a cabo una amplia evaluación neuropsicológica, y el rendimiento de los usuarios de drogas seropositivos (n = 90) se comparó con la de un grupo control de usuarios de drogas seronegativos (n = 48). Los resultados demuestran que los programas de tratamiento de mantenimiento con metadona pueden convertir en vulnerable a nivel neuropsicológico al individuo seropositivo. Asimismo, descubrimos que abandonar las drogas provoca un efecto protector frente a la existencia de alteraciones neuropsicológicas asociadas con el VIH. Estos resultados nos llevan a sugerir que la seropositividad no basta para explicar las alteraciones neuropsicológicas de los usuarios de drogas seropositivos, ya que estas alteraciones al parecer son multifactoriales.

Electrocardiographic, echocardiographic, and indirect blood pressure evaluation in dogs subjected to different sedation protocols / Avaliação eletrocardiográfica, ecocardiográfica e de pressão arterial não invasiva de cães submetidos a diferentes protocolos de sedação

ABSTRACT: The present study aimed to evaluate the effects of different sedation protocols on blood pressure and echocardiographic and electrocardiographic parameters in dogs. In total, 24 male mixed-breed dogs with a mean weight of 9.87±3.0kg were used.Animals were randomly divided into four groups (n=6), which were subjected to sedation using the following protocols: acepromazine (0.05mgkg-1) and butorphanol (0.3mgkg-1) (AB); acepromazine (0.05mgkg-1)and methadone (0.5mgkg-1) (AM); acepromazine (0.03mgkg-1), methadone (0.5mgkg-1), and midazolam (0.3mgkg-1)(MAM); and methadone only (0.5mgkg-1) (M). Indirect blood pressure (BP) measurements and computerized electrocardiography (ECG) and echocardiography (ECO) were performed immediately before the application of the sedation protocol (baseline), and the same evaluations were repeated after 15 minutes. BP decreased in groups AB, MAM, and AM compared to baseline values. Electrocardiographic measurements showed decreased heart rates (HRs) after sedation in all groups, and bradycardia was observed after sedation in two dogs from group M and one animal from group AM. The P-wave duration increased after sedation in groups AM and M. After sedation, no changes in cardiac dimensions were revealed byECO.Fractional shortening (FS) decreased after sedation in the AM group, and dogs from group AB exhibited a smaller decrease in FS compared with the other groups. The cardiac index (CI) was lower in groups AM and M than in the other groups. Animals from group AB were less resistant to examination and exhibited the most favorable sedation scores. It was concluded that the combination of acepromazine and butorphanol was the best sedation protocol for performing echocardiogram measurementsbecause dogs were less resistant to examinations and echocardiographic parameters of FS and CI remained stable.

RESUMO: O objetivo deste estudo foi avaliar os efeitos de diferentes protocolos de sedação sobre a pressão arterial, parâmetros ecocardiográficos e eletrocardiográficos em cães. Foram utilizados 24 cães, machos, SRD, com peso médio de 9,87±3,0kg, os quais foram alocados aleatoriamente em quatro grupos (n=6), que foram submetidos à sedação com os protocolos acepromazina (0,05mgkg-1) e butorfanol (0,3mgkg-1) (AB), acepromazina (0,05mgkg-1) e metadona (0,5mgkg-1) (AM), acepromazina (0,03mgkg-1), metadona (0,5mgkg-1) e midazolam (0,3mgkg-1) (MAM) e metadona isolada (0,5mgkg-1) (M). Foi realizada avaliação da pressão arterial sistólica (PAS) não invasiva, eletrocardiografia computadorizada e ecocardiografia imediatamente antes da aplicação do protocolo de sedação (basal) e repetindo-se as mesmas avaliações, 15 minutos após. Observou-se redução na PAS nos grupos AB, MAM, AM, em relação ao basal. Na eletrocardiografia, houve redução da FC após sedação em todos grupos, sendo observada bradicardia após sedação em dois cães do grupo M e um animal do grupo AM. A duração da onda P aumentou após sedação nos grupos AM e M. Não foram observadas alterações nas dimensões cardíacas, avaliadas pela ecocardiografia, após sedação. A fração de encurtamento (FS) reduziu após sedação no AM e os cães do AB apresentaram menor queda da FS, diferindo dos demais grupos. O índice cardíaco (IC) foi menor no AM e M em relação aos demais. Os animais do grupo AB foram menos resistentes à execução dos exames, apresentando melhores escores de sedação. Concluiu-se que a associação acepromazina e butorfanol foi o melhor protocolo de sedação para realização do ecocardiograma, sendo os cães menos resistentes à execução do exame, mantendo estáveis os parâmetros ecocardiográficos de fração de encurtamento e índice cardíaco.

Cartografía de heterotopías psicoactivas: una mirada a los discursos médicos, jurídicos y sociales sobre los usos de drogas / Cartography of psychoactive heterotopias: a look at the medical, legal and social discourses regarding drug use

Este artículo traza un mapa del control social de las drogas a partir de las políticas del espacio, de acuerdo al concepto foucaultiano de heterotopía. En primer lugar, se describe una breve genealogía de los usos de sustancias psicotrópicas en los diversos tiempos y culturas hasta la llegada del paradigma prohibicionista, atendiendo al modo en que el poder ha señalado, separado y encerrado determinados rituales y usos del placer en emplazamientos físicos y simbólicos. Este itinerario se centra en el contexto español para establecer un diálogo entre las distintas políticas del espacio que se han sucedido y superpuesto en la construcción y gestión de un problema que deviene objeto de la mirada, la mecánica y los discursos médicos, jurídicos y sociales. Así, se analizan las intersecciones de los emplazamientos liminares de consumo con el paradigma de la reducción de daños, así como las estrategias terapéuticas con prescripción farmacológica, desde los programas de metadona hasta los más recientes de heroína.

This article traces a map of the social control of drugs through the politics of space, according to the Foucaultian concept of "heterotopia." Firstly, a brief genealogy of the use of psychotropic substances in different times and cultures is described, up to the introduction of the prohibitionist paradigm. Attention is paid to the way in which power has marked, separated and enclosed certain rituals and uses of pleasure in physical and symbolic sites. The itinerary is focused on the Spanish context to establish a dialogue between the various policies of space that have come into being and have overlapped in the construction and management of a problem which has been rendered an object to the gazes, mechanics and discourses of the medical, legal, and social fields. In this way, the intersections between the liminal spaces of drug use and the harm reduction paradigm are analyzed, including therapeutic strategies with prescribed drugs, from methadone programs to the new heroin programs.

Avaliação da analgesia pós-operatória da metadona, da cetamina ou da sua associação em gatas submetidas a ovariossalpingo-histerectomia / Evaluation of postoperative analgesia of methadone, ketamine or their associations in cats undergoing ovariohysterectomy

A prevenção e o controle da dor são componentes básicos para um procedimento anestésico adequado. Objetivou-se com este estudo avaliar a analgesia pós-operatória da cetamina, em dose subanestésica, da metadona e da associação de ambas pela via intramuscular em felinos. Foram utilizadas 24 gatas, hígidas, submetidas à ovariossalpingo-histerectomia eletiva. No dia anterior ao início do estudo, os animais foram anestesiados para colocação de cateter na veia jugular, para posterior coleta de sangue para mensuração da concentração sérica do cortisol. No dia do experimento, os animais foram alocados aleatoriamente em três grupos (n=oito), os quais receberam cetamina (GC), na dose de 0,5mg/kg; ou metadona (GM), na dose de 0,3mg/kg; ou cetamina e metadona (GCM), nas doses de 0,5mg/kg e 0,3mg/kg, respectivamente, todos pela via intramuscular. Todos os grupos receberam os fármacos 20 minutos antes da indução anestésica, a qual foi realizada com propofol, e a manutenção com isoflurano. Os parâmetros avaliados foram a mensuração do cortisol nos momentos M0 (basal - antes da cirurgia), M1(transoperatório), M2, M3, M4, M8, M12 e M24 (duas, três, quatro, oito, 12 e 24 horas após o término da cirurgia),e a do escore de dor por meio da escala multidimensional de dor aguda em felinos nos momentos M0, M2, M3, M4, M8, M12 e M24. Os valores de cortisol foram maiores no GC em comparação ao GM e ao GCM em M2 e M3. Os escores de dor foram maiores no GC nos momentos M2 e M3 em comparação ao GM e ao GCM, respectivamente. No somatório de pontos, no M2, o GC apresentou valores maiores que o GM e o GCM, e, no M4, o GC obteve valores maiores que o GCM. Em relação ao número de resgates no pós-operatório no GC, 8/8 dos animais necessitaram de resgate, no GM 5/8 e no GCM 3/8. Conclui-se que a associação de metadona e cetamina em gatas submetidas à OSH eletiva promove analgesia pós-operatória adequada e, assim, reduz o requerimento de analgésicos no período pós-operatório.(AU)

The prevention and control of pain are basic components to have an adequate anesthesia. The aim of this study was to investigate the postoperative analgesia of ketamine in subanestesica dose, of methadone and the association of both intramuscularly in cats. A total of 24 cats proven healthy were referred for elective ovariossalpingohisterectomia. The day before the beginning of the experiment animals were anesthetized for placing a catheter in the jugular vein for subsequent blood sampling for measurement of serum concentration of cortisol. The next day, animals were randomly allocated to three groups (n = 8), which received ketamine (GC) at a dose of 0.5mg/kg; methadone (GM) at a dose of 0.3mg/kg; methadone and ketamine (GCM) at doses of 0.5mg/kg and 0.3mg/kg, respectively, all in the intramuscular route. All groups received the drug 20 minutes before induction of anesthesia, which was performed with propofol and maintained with isoflurane. The parameters evaluated were the measurement of cortisol in moments M0 (baseline-before surgery), M1(intraoperative), M2, M3, M4, M8, M12 and M24 (2,3,4,8,12 and 24 hours after the end of surgery) and evaluation of pain score by multidimensional scale of acute pain in cats in the moments M0, M2, M3, M4, M8, M12 and M24. The cortisol levels were higher in GC compared to GM and GCM in M2 and M3. Pain scores were higher in GC in moments M2 and M3 compared to GM and GCM, respectively. In summation of points in M2, GC showed higher values than GM and GCM, and M4, GC obtained values greater than GCM. Comparing the number of rescues postoperatively in GC 8/8 of animals required rescue, in GM /8 and in GCM 3/8. It was concluded that the combination of methadone and ketamine in cats undergoing elective OSH provides adequate postoperative analgesia, reducing the requirement for analgesics in the postoperative period.(AU)

Meperidine: opioid not indicated for analgesia / Meperidina: opioide não indicado para analgesia

BACKGROUND AND OBJECTIVES: Pain evaluation and the choice of the analgesic best providing its control are extremely important for patients’ quality of life. This study aimed at describing the characteristics which make meperidine unfeasible for pain management, at calling the attention to the incidence of its prescriptions and to the need of a multidisciplinary educative action aiming at decreasing its use, in addition to presenting two opioids as options for analgesia. CONTENTS: National or international scientific and governmental publications between the years 1997 and 2013 used in this study report that meperidine is not indicated for pain management, primarily due to its short action time, presence of neurotoxic metabolite (normeperidine) and possibility of rapidly developing tolerance. CONCLUSION: According to analyzed data, meperidine was the most widely used opioid for analgesic or was among the most prescribed analgesics. This fact shows the real need for an educative multidisciplinary action to promote awareness of meperidine risks and to decrease its prescription. According to searched literature, morphine and methadone have longer action time and higher analgesic potency, with metabolites which are less toxic and noxious for patients as compared to meperidine. .

JUSTIFICATIVA E OBJETIVOS: A avaliação da dor e a escolha do analgésico que mais bem provenha o seu controle são de extrema importância para a qualidade de vida do paciente. O objetivo deste estudo foi elucidar as características que inviabilizam a administração da meperidina para o tratamento da dor, atentar para a incidência de sua prescrição e a necessidade de uma ação educativa multidisciplinar visando à redução do seu uso e apresentar dois opioides como opções de escolha para a analgesia. CONTEÚDO: As publicações científicas e governamentais de âmbito nacional ou internacional entre os anos de 1997 e 2013 utilizadas neste artigo relatam que a meperidina não é indicada para o tratamento da dor devido, principalmente, ao seu curto tempo de ação, presença de metabólito neurotóxico (normeperidina), e a possibilidade de desenvolver tolerância rapidamente. CONCLUSÃO: Segundo os dados das pesquisas analisadas, a meperidina foi o opioide mais utilizado para analgesia ou estava entre os analgésicos mais prescritos. Esse fato relata a real necessidade de uma ação multidisciplinar educativa em prol da conscientização sobre os riscos presentes no tratamento com a meperidina e da diminuição da sua prescrição. De acordo com a literatura consultada, a morfina e a metadona apresentam maior tempo de ação e potência analgésica com metabólitos menos tóxicos e prejudiciais ao paciente que a meperidina. .

Revisiting methadone: pharmacokinetics, pharmacodynamics and clinical indication / Revisitando a metadona: farmacocinética, farmacodinâmica e uso clínico

BACKGROUND AND OBJECTIVES: Methadone is a synthetic long-duration opioid with pharmacological properties qualitatively similar to morphine for its action on µ-opioid receptor. It is primarily used to treat cancer pain refractory to morphine. This study aimed at presenting a review of this drug with focus on pharmacokinetic and pharmacodynamic aspects, in addition to its clinical indication. CONTENTS: Articles available in Medline, Scielo, Cochrane library and Pubmed platforms until July 2014 were reviewed using the following descriptors: Methadone; Acute Pain; Chronic Pain; Cancer Pain; and Opioids. CONCLUSION: Its pharmacological properties make methadone a unique opioid analgesic, since it is less susceptible to tolerance, prevents hyperalgesia, is less conducive to abusive consumption and has a possible better action on neuropathic pain. However, risks of accidental death due to overdose, of arrhythmias and of pharmacological interactions should not be overlooked. In addition, there is lack of conclusive clinical trials comparing methadone to other analgesics with regard to risks and benefits. .

JUSTIFICATIVA E OBJETIVOS: Metadona é um opioide sintético de longa duração com propriedades farmacológicas qualitativamente semelhantes às da morfina por ação sobre o receptor µ-opioide. É utilizada principalmente no tratamento de dor oncológica refratária à morfina. O objetivo deste estudo foi apresentar uma revisão desse fármaco com foco nos aspectos farmacocinéticos e farmacodinâmicos, além de seu uso clínico. CONTEÚDO: Foi realizada uma revisão dos artigos disponíveis nas plataformas Medline, Scielo, biblioteca Cochrane e Pubmed até julho de 2014, por meio dos seguintes descritores: Metadona; Dor Aguda; Dor Crônica; Dor Oncológica; e Opioides. CONCLUSÃO: Foi realizada uma revisão dos artigos disponíveis nas plataformas Medline, Scielo, biblioteca Cochrane e Pubmed até julho de 2014, por meio dos seguintes descritores: Metadona; Dor Aguda; Dor Crônica; Dor Oncológica; e Opioides. .

Clinical pharmacology of methadone in neonates and in their mothers. A review / Farmacologia clínica da metadona em neonatos e suas mães: revisão

The outstanding properties of methadone are its analgesic activity, its efficacy by oral route, its extended duration of action in suppressing of withdrawal symptoms in physically dependent individuals, and its tendency to show persistent effects with repeated administration. The analgesic activity of methadone, a racemate, is almost entirely the result of its R-methadone content. Respiratory depression is the chief hazard associated with methadone, and its peak respiratory depressant effects typically occur later, and persist for longer than its peak analgesic effect, particularly in the early dosing period. Methadone undergoes extensive metabolism in the liver and the major metabolic pathway is N-demethylation by CYP3A4 and CYP2B6. There is a remarkable interindividual variability in the rate of methadone metabolism. Mothers with opioid addiction are often placed on methadone before delivery in an attempt to reduce illicit opioid usage. Methadone is useful because it can be taken orally, only requires one or two daily doses and has a long-lasting effect. Weaning should not be attempted during pregnancy and, because of increased clearance, the dose of methadone may need to be increased in the last 3 months of pregnancy. Significant positive correlations were found for umbilical cord methadone concentrations, methadone mean daily dose, mean dose during the third trimester, and methadone cumulative daily dose. In conclusion, umbilical cord methadone concentrations were correlated to methadone dose. A total of 55-94% of infants born to opioid-dependent mothers in US show signs of opioid withdrawal. Methadone is useful to avoid use of opioid illicit drugs.

As mais importantes propriedades da metadona são sua atividade analgésica, a sua eficácia por via oral, a sua prolongada acão supressora de sintomas de abstinência em indivíduos fisicamente dependentes e a persistência de seus efeitos com administração repetida. A actividade analgésica de metadona, um racemato, é quase inteiramente o resultado do seu teor de R-metadona. A depressão respiratória é o principal risco associado a seu uso, e o pico de depressão respiratória normalmente ocorre tardiamente e persiste após o fim de seu efeito analgésico especialmente durante as fases iniciais de seu uso terapêutico. A metadona é metabolizada no fígado e a principal via metabólica é a N-desmetilação por CYP3A4 e CYP2B6. Há uma variabilidade interindividual notável em relação à sua taxa de metabolisacão. Mães com dependência de opiáceos são frequentemente colocadas em terapêutica com metadona antes do parto, na tentativa de reduzir o uso de opiáceos ilícitos. A metadona é útil porque pode ser tomada por via oral, só precisa de uma ou duas doses diárias e tem efeito de longa duração. O desmame não deve ser executado durante a gravidez; por causa do aumento da depuração, a dose de metadona pode precisar ser aumentada nos últimos três meses de gravidez. Correlações positivas significativas foram encontradas para a metadona entre os seguintes parâmetros: concentrações no cordão umbilical, dose média diria, dose durante o terceiro trimestre, e dose diária média cumulativa. Em conclusão, as concentrações de cordão umbilical de metadona foram correlacionados com a dose de metadona. Entre 55% e 94% dos recém-nascidos de mães dependentes de opiáceos nos Estados Unidos mostram sinais de abstinência a opiáceos. A metadona é útil para evitar o uso de drogas ilícitas opióides.

Evaluación del programa de mantenimiento con metadona del Hospital Mental de Risaralda / Evaluation of the Methadone Maintenance Program of the Risaralda Mental Hospital

Introducción: La atención psicosocial y el tratamiento de mantenimiento con metadona (TMM) son las estrategias preferidas para el manejo de adictos a heroína, pero los resultados siguen siendo insatisfactorios, lo que justifica la búsqueda e intervención sobre los factores que influyen en la respuesta al tratamiento. Métodos: Con el propósito de determinar la contribución de una serie de variables demográficas, clínicas y genéticas en las concentraciones séricas y la respuesta a la metadona, estudiamos a pacientes del TMM que estuvieran recibiendo metadona con supervisión y sin cambios en las dosis por lo menos durante las últimas 2 semanas. Se les registró edad, sexo, índice de masa corporal (IMC), tiempo de abuso de heroína, adicción a otras drogas, antecedentes delictivos, dosis diaria actual de metadona, tiempo de permanencia en el TMM, comorbilidad y comedicación. Se les tomaron muestras de sangre para determinar concentraciones séricas de metadona racémica y sus enantiómeros R-y S-, y para la tipificación de alelos candidatos de los genes POR, CYP2B6, ABCB1, GRIN1, OPRM1, SLC6A3, DßH y ARRB2, todos ellos asociados con el metabolismo, la distribución tisular y el mecanismo de acción de la metadona. La cuantificación de metadona se hizo mediante HPLC-DAD y la detección de los marcadores genéticos por los métodos de PCR en tiempo real y VNTR. Resultados: Se incluyó a 80 personas de 23,5 ± 5a ˜nos (el 86% varones), todos policonsumidores de sustancias adictivas, el 60% con antecedentes delictivos, con 5,1 ± 2,9 años de consumo de heroína y 5,3 ± 4 meses de ingreso al TMM, con 41 ± 12 mg/día de meta-dona tomada con supervisión. Las concentraciones valle de RS-, R-y S-metadona fueron, respectivamente, 168 ± 77, 84 ± 40 y 84 ± 42 ng/ml. Todos los genotipos estuvieron en equilibrio de Hardy-Weinberg. Las dos pruebas de orina fueron negativas para heroína en el 61,3% (49/80) de los voluntarios; el descenso en el consumo de cocaína/basuco fue del 83%; el de marihuana, del 30% y el de otros psicoactivos (inhalantes, benzodiacepinas, anfetaminas) bajó a cero, mientras el consumo de tabaco permaneció en el 93,5% (75/80). Las concentraciones de metadona racémica y sus enantiómeros se correlacionaron significativamente con las dosis diaria del fármaco, pero ninguna de las demás variables demográficas, clínicas o genéticas incidió en la concentración sérica de metadona. En cuanto a los resultados del TMM, los no consumidores y los consumidores ocasionales de heroína, así como los que abandonaron el consumo de otros psicoactivos y los que no, tuvieron características similares con respecto a las variables demográficas, genéticas y clínicas, incluidas las concentraciones sanguíneas de metadona, con excepción de los individuos que no disminuyeron el consumo de otros psicoactivos distintos de heroína, quienes tuvieron significativamente (p = 0,03) mayores concentraciones sanguíneas de S-metadona que quienes sí abandonaron el consumo. Conclusiones: Hubo importante reducción en los consumos de heroína y otros psicoactivos y reinserción social de los pacientes; sin embargo, la amplia superposición entre las dosis efectivas e inefectivas de metadona apunta a la presencia de variables personales y sociales que trascienden el simple manejo farmacológico y probablemente deban ser abordadas con más éxito desde lo psicosocial, particularmente en lo que tiene que ver con la identificación y superación de las experiencias detonantes de recaídas y con ciertos rasgos del paciente, tales como su nivel de estrés psicológico o sus trastornos psiquiátricos.

Background: Psychosocial care and methadone maintenance treatment (MMT) are the preferred strategies for the management of heroin addicts, but the results are still unsa-tisfactory, justifying the search and intervention of the factors influencing the response to treatment. Methodology: In order to determine the contribution of demographic, clinical and genetic variables on serum concentrations and response to methadone, we investigated patients on MMT, who were receiving methadone in supervised and unchanged doses at least during the previous two weeks. The age, gender, body mass index (BMI), duration of heroin abuse, addiction to other drugs, criminal background, current daily methadone doses, time spent in the TMM, comorbidity and concomitant medication were recorded. Blood samples were taken for the determination of serum levels of racemic methadone and its R and S-enantiomers, and for typing of candidate alleles of POR, CYP2B6, ABCB1, GRIN1, OPRM1, SLC6A3, DßH and ARRB2 genes, all associated with the metabolism, tissue distribution and mechanism of action of methadone. Methadone quantification was by HPLC-DAD, and the detection of genetic markers by Real Time PCR and VNTR methods. Results: A total of 80 subject volunteers were enrolled, with a mean age of 23.5 (5) years (86% male), all of them were addicts of multiple drugs, 60% with a criminal background, 5.1 (2.9) years taking heroin, and 5.3 (4) months on MMT, and taking a supervised dose of 41 (12) mg/day methadone. The (R), (S) and (R, S) methadone enantiomer trough plasma levels were, 84 (40), 84 (42), and 168 (77) ng/mL, respectively. All genotypes were in Hardy-Weinberg equilibrium. The two urine tests were negative for heroin in 61.3% (49/80) of the volunteers, the decline in cocaine/crack use was 83%, 30% of marijuana, and other psychoactives (inhalants, benzodiazepines, amphetamines) decreased to zero, while the consumption of snuff remained at 93.5% (75/80). Blood concentrations of racemic methadone and its enantiomers were significantly associated with the dose/day of the medication, but none of the other demographic, clinical or genetic variables impacted on serum levels of methadone. As for the results of the MMT, non-users and occasional users of heroin, as well as those who stopped taking other psychoactive drugs, and the ones who did not, were similar as regards the demographic, genetic and clinical variables. This included the blood metahdone concentrations, except for individuals who did not reduce their consumption of other psychoactives other than heroin, who had significantly (P = .03) higher blood levels of S-methadone, compared with those who did stop taking them. Conclusions: There was a significant reduction in the consumption of heroin and other psychoactives, and social rehabilitation of patients. However, the extensive overlap between effective and ineffective doses of methadone suggests the presence of personal and social variables that transcend the simple pharmacological management. These probably need to be addressed more successfully from the psychosocial features, particularly as regards to identifying and overcoming relapse-trigger experiences, as well as certain features of the patient, such as their psychological distress level or their psychiatric disorders.

QT interval prolongation associated with azithromycin/methadone combination / Prolongación del intervalo QT asociada con combinación de azitromicina/metadona

This report documents the occurrence of QT prolongation in a 57-year old man, on methadone replacement therapy, treated with azithromycin for community acquired pneumonia. This case highlights a hitherto unknown drug interaction. In light of ever-increasing use of azithromycin, it is imperative that azithromycin be used with caution in patients who are already on drugs that are known to cause QT prolongation or that cause torsades de pointes.

Este reporte documenta la ocurrencia de la prolongación del intervalo QT en un hombre de 57 años, en la terapia de reemplazo con metadona, tratado con azitromicina por pulmonía adquirida en la comunidad. Este caso destaca una interacción de medicamentos desconocida hasta ahora. En vista del uso cada vez mayor de la azitromicina, resulta absolutamente necesario usarla con precaución en pacientes que ya están bajo tratamiento con medicamentos de los cuales se sabe que causan prolongación del intervalo QT o que causan torsades de pointes.