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.

The role of pharmacotherapy in modifying the neurological status of patients with spinal and spinal cord injuries / O papel da farmacoterapia na modificação do estado neurológico de traumatizados vértebro-medulares

The aim here was to conduct a review of the literature on pharmacological therapies for modifying the neurological status of patients with spinal cord injuries. The PubMed database was searched for articles with the terms "spinal cord injury AND methylprednisolone/GM1/apoptosis inhibitor/calpain inhibitor/naloxone/tempol/tirilazad", in Portuguese or in English, published over the last five years. Older studies were included because of their historical importance. The pharmacological groups were divided according to their capacity to interfere with the physiopathological mechanisms of secondary injuries. Use of methylprednisolone needs to be carefully weighed up: other anti-inflammatory agents have shown benefits in humans or in animals. GM1 does not seem to have greater efficacy than methylprednisolone, but longer-term studies are needed. Many inhibitors of apoptosis have shown benefits inin vitro studies or in animals. Naloxone has not shown benefits. Tempol inhibits the main consequences of oxidation at the level of the spinal cord and other antioxidant drugs seem to have an effect superior to that of methylprednisolone. There is an urgent need to find new treatments that improve the neurological status of patients with spinal cord injuries. The benefits from treatment with methylprednisolone have been questioned, with concerns regarding its safety. Other drugs have been studied, and some of these may provide promising alternatives. Additional studies are needed in order to reach conclusions regarding the benefits of these agents in clinical practice.

O objetivo deste trabalho foi fazer uma revisão da literatura sobre a terapia farmacológica para a modificação do estado neurológico de traumatizados vértebro-medulares. Foi feita uma na base de dados Pubmed por artigos com os termos "spinal cord injury AND methylprednisolone/GM1/apoptosis inhibitor/calpain inhibitor/naloxone/tempol/tirilazad", em português ou em inglês, publicados nos últimos cinco anos. Trabalhos mais antigos foram incluídos pela sua importância histórica. Os grupos farmacológicos foram divididos em função da sua capacidade para interferir nos mecanismos fisiopatológicos da lesão secundária. O uso de metilprednisolona deve ser cuidadosamente ponderado. Outros anti-inflamatórios mostraram benefícios em humanos ou em animais. O GM1 não aparenta ter maior eficácia do que a MP, mas estudos em mais longo prazo são necessários. Muitos inibidores da apoptose têm mostrado benefício em estudos in vitro ou em animais. A naloxona não deu mostras de benefício. O tempol inibe as principais consequências da oxidação no nível da medula e outros fármacos antioxidantes aparentam ter um efeito superior ao da metilprednisolona. É urgente encontrar novos tratamentos que melhorem o estado neurológico dos traumatizados vértebro-medulares. Os benefícios do tratamento com metilprednisolona têm sido questionados, há preocupações em relação à sua segurança. Outros fármacos têm sido estudados, podem alguns deles ser opções promissoras. Estudos adicionais são necessários para tirar conclusões sobre o benefício desses agentes na prática clínica.

Avaliação do papel de opioides endógenos na analgesia do laser de baixa potência, 820 nm, em joelho de ratos Wistar / Role of endogenous opioids in 820 nm low power laser analgesia in the knees of Wistar rats

JUSTIFICATIVA E OBJETIVOS: A sensação de dor pode resultar em incapacidade, sendo associada à lesão estrutural. O laser de baixa potência mostra-se útil em terapias que objetivam a redução da dor articular e o reparo tecidual, mas ainda com algumas controvérsias. O objetivo deste estudo foi avaliar se a analgesia produzida pelo laser de baixa potência, 820 nm, sofre interferência pela aplicação de um inibidor de opioides endógenos. MÉTODO: Foram utilizados 24 ratos Wistar submetidos à hiperalgesia e divididos em quatro grupos: G1: não tratados; G2: tratados com laser 820 nm; G3: prévio a lesão, injeção de naloxona e não tratados; G4: naloxona e tratados com laser 820 nm. Para a produção de hiperalgesia foi administrado 100 µL de formalina a 5% no espaço articular tíbio-femoral direito. A avaliação da nocicepção ocorreu pelo tempo de elevação da pata (TEP), em cinco momentos, sendo AV1 (pré-lesão), AV2 (15 min/pós), AV3 (30 min/pós), AV4 (1 hora pós) e AV5 (2 horas pós). RESULTADOS: Todos os grupos apresentaram diferença significativa entre AV1 e AV2, mas, apenas G2 não apresentou diferença entre AV1 e AV3. Para os momentos seguintes não houve diferenças com relação à AV1. CONCLUSÃO: A analgesia oriunda do laser de baixa potência, 820 nm, sofre interferências com aplicação de naloxona.

BACKGROUND AND OBJECTIVES: Pain may result in incapacity when it is associated to structural injury. Low power laser is useful in therapies aiming at decreasing joint pain and at tissue repair, but it is still somewhat controversial. This study aimed at evaluating whether analgesia induced by 820 nm low power laser is affected by the application of an endogenous opioids inhibitor. METHOD: Twenty-four Wistar rats submitted to hyperalgesia were divided into four groups. G1: untreated; G2: treated with 820 nm laser; G3: naloxone injection before injury and untreated; G4: naloxone and treated with 820 nm laser. To induce hyperalgesia, 100 µL of 5% formalin were injected in the right tibiofemoral joint space. Nociception was evaluated by the time for flinching (TFF) in five moments: AV1 (pre-injury), AV2 (15 min/after), AV3 (30 min/after), AV4 (1 hour after) and AV5 (2 hours after). RESULTS: All groups showed significant difference between AV1 and AV2, but only G2 showed no difference between AV1 and AV3. There have been no differences for remaining moments as compared to AV1. CONCLUSION: Low power 820 nm laser analgesia is affected by naloxone.

Vértigo con nistagmo vertical por administración de morfina intratecal y reversión con naloxona / Vertigo and vertical nystagmus associated with intrathecal morphine administration and resolution by naloxone

La anestesia regional combinada es utilizada frecuentemente como herramienta para el tratamiento del dolor postoperatorio. Los efectos secundarios de los opioides utilizados por esta vía son similares a los que se presentan luego de la administración sistémica. La aparición de vértigo con nistagmo vertical es un efecto adverso muy pocas veces descripto con el uso de morfina por vía intratecal, epidural o endovenosa. Comunicamos el caso de un paciente que presentó esta complicación en el postoperatorio de una nefrectomía parcial, luego de la administración de morfina intratecal, con resolución completa mediante el uso de naloxona endovenosa.

Combined regional anesthesia is frequently used as a tool for management of postoperative pain. The profile of side effects of the opioids used via this route is similar to those occurring after systemic administration. The onset of vertigo with vertical nystagmus is an adverse effect rarely described after the use of intrathecal, epidural or intravenous morphine. We report the case of a patient who presented this complication in the postoperative period of a partial nephrectomy, after the administration of intrathecal morphine, with complete resolution by intravenous naloxone.

Eficacia de la naltrexona en el tratamiento de prurito severo / Effectiveness of naltrexone in the treatment of severe pruritus

Introducción. El prurito es una complicación frecuente de las patologías hepáticas, que puede llegar a ser de difícil manejo. El incremento en el tono opioide cerebral se ha postulado como mecanismo fisiopatológico causal del prurito. Es así como el antagonismo opioide causa mejoría y resolución sintomática en estos pacientes. Objetivo. Describir el manejo de prurito severo con antagonismo opioide en una paciente refractaria a manejo médico convencional, y hacer una revisión de la literatura. Metodología y resultados. Este es el caso de una paciente de 50 años de edad, con antecedente de hepatitis autoinmune, quien se presenta con historia de cinco años de prurito severo secundario a colestasis, manejada con antihistamínicos, esteroides, ácido ursodeoxicólico y colestiramina sin mejoría. Se decide manejo con antagonismo opioide; se inicia con naloxona infusión por 24 horas, con dosis ascendentes desde 0,002 mcg/ kg/min, hasta 0,2 mcg/kg/min, y posteriormente naltrexona, hasta dosis de 50 mg día. Se evalúo la respuesta terapéutica por medio de escala visual análoga (EVA). Desde el inicio de la infusión se obtiene disminución en la EVA hasta valores de 0/10 durante las primeras 24 horas, con mejoría clínica y sintomática.Conclusiones. En el enfoque de la paciente con prurito refractario debe considerarse el uso de antagonismo opioide como alternativa terapéutica.

Introduction. Pruritus is a frequent complication in liver disease and may be difficult to manage. Increased cerebral opiod tone has been proposed as the physiological mechanism that causes pruritus. Opiod antagonism, therefore, leads to an improvement and resolution of symptoms in these patients. Objective. Describe the management of severe pruritus using opiod antagonists in a patient who does not respond to conventional medical management, and conduct a review of the literature.Methodology and results. This is the case of a 50 year-old female patient with a history of autoimmune hepatitis with a five-year history of severe pruritus secondary to cholestasis whichdoes not improve after management with antihistamines, steroids, ursodeoxycholic acid and cholestyramine. It is decided to initiate management with opiod antagonists, starting with an infusion of naloxone for 24 hours with dose escalation from 0.002 μg/kg/min up to 0.2 μg/kg/min, followed by naltrexone up to a dose of 50 mg/day. The therapeutic response was assessed using the visual analog scale (VAS). Within 24 hours ofinitiating the infusion, there is a reduction in the VAS score down to 0/10, with clinical and symptomaticimprovement. Conclusions. The approach to patients with refractorypruritus should include the use of opioidantagonists as a therapeutic option.

Efecto de la Naloxona sobre la secreción pulsátil de la hormona luteinizante en vacas de doble propósito con doble ordeño y amamantamiento / Effect of Naloxone over the secretion of the Luteinizing Hormone on double purpose cows with double milking and suckling

Se examinó el efecto de cero, una y tres inyecciones de naloxona (NX; 500 mg) el día 30 posparto a intervalos de 1 h, sobre la liberación de la hormona luteinizante (LH), en vacas de doble propósito en anestro: ¾ Europeo x » Cebú (n = 18). Las vacas pastorearon en zacate Estrella de África (Cynodon plectostachyus) y gramas nativas (Axonopus y Paspalum spp.) con un consumo de 5 kg de alimento balaceado diariamente (16 % de PC). El ordeño fue mecánico dos veces al día y se realizó amamantamiento de las crías después del ordeño (30 min). Las vacas y las crías permanecieron separadas, excepto durante el amamantamiento. Se colectó una muestra de sangre cada 2 días desde el parto hasta el día 30 posparto y se cuantificó la progesterona (P) sérica por RIA. El anestro fue indicado por P < 1 ng/ml. El día 30 posparto se tomaron muestras de sangre cada 15 min durante 3 horas: una hora después de cada inyección de NX o solución salina fisiológica y se cuantificó la LH sérica por RIA. Las variables de respuesta fueron: concentración media (MLH) y basal (BLH), número (NP), amplitud (AP) y duración (DP) de pulsos de LH. Se usó un ANDEVA con parcelas divididas, parcela mayor = tratamiento y subparcela = período de muestreo. No hubo efectos (p >0.05) de tratamiento, período y sus interacciones en las variables de respuesta. En vacas de doble propósito con doble ordeño y amamantamiento, la naloxona no cambió la secreción de la LH en el día 30 posparto.

This study determined the effect of zero, one and three intramuscular injection of naloxone (NX, 500 mg) on 30 postpartum day for 1 hour intervals over the release of the luteinizing hormone in dual purpose cows in anestrous (¾ Europe x » Zebu) cows (n =18). The cows grazed on African Star grass (Cynodon plectostachyus) and native grass (Axonopus and Paspalum spp) and ate daily 5 kg of balanced food (16% crude protein). The cows were mechanically milked twice a day and after that their calves were allowed to suck for 30 minutes. A blood sample was collected every two days, from the delivery until 30 days postpartum for the quantification of progesterone (P) by RIA. In this blood anestrous was indicated by P< 1 ng/ml. On day 30 postpartum blood samples were drawn every 15 min during 3 hours: one hour after each naloxone injection or saline solution and Luteinising Hormone (LH) was measured by RIA. The response variables were mean (MLH) and basal concentration (BLH), number (PN), amplitude (PA) and pulse duration (PD) of LH. The statistic analysis was divided plot; principal plot was the treatment and secondary plot was the samples period. There were not effects (p>0.05) of treatment, samples period and its interactions on response variables. In double purpose cows with double milking and suckling naloxona did not affect the LH secretion at 30 day pospartum.