Efectos tóxicos de la mezcla cocaína-levamisol en modelos farmacológicos
nº36 [Agosto 11 - Noviembre 11] Retel04/08/2011
1María Luisa Di Bernardo, 2Yasmin Morales, 3ONA-OVD, 4Rosa de Jesús, 4Mileyna Gudiño, 4Andrés Osorio.
1GITAEF: Grupo de Investigaciones en Toxicología Analítica y Estudios Farmacológicos. Facultad de Farmacia y Bioanálisis. Universidad de Los Andes-Mérida, Venezuela.2CICPC: Laboratorio de Toxicología. Cuerpo de Investigaciones Científicas, Penales y Criminalística. Delegación Mérida-Venezuela.3ONA-OVD: Oficina Nacional Antidrogas-Observatorio Venezolano de Drogas. Caracas, Venezuela.4BIOULA: Bioterío de la Universidad de Los Andes-Mérida, Venezuela.
Correspondencia de autor: Dra. María Luisa Di Bernardo, correo: girard@ula.ve, marydi32@gmail.com . y/o Dra. Yasmin Morales, correo: dancar2men@gmail.com
Correspondencia de autor: Dra. María Luisa Di Bernardo, correo: girard@ula.ve, marydi32@gmail.com . y/o Dra. Yasmin Morales, correo: dancar2men@gmail.com
Resumen
Se estudian efectos tóxicos de la mezcla de cocaína con levamisol, en 120 ratones NMRI machos en etapa adulto-joven, como modelos farmacológicos con conversión aproximada a 26 años de un humano. El levamisol es un fármaco con actividad antihelmíntica e inmunomoduladora utilizado en medicina veterinaria y actualmente registrado en “corte” (adulterante) de cocaína en EEUU y otros países. El estudio se realizó en seis grupos de 20 modelos cada uno (cocaína sola, levamisol sólo, tres concentraciones de la mezcla y control de suero fisiológico) e incluyó valoraciones hematológicas, bioquímicas, clínicas y conductuales antes, durante y al final de la experiencia, y hallazgos anatomopatológicos. Mediante los perfiles de transaminasas y creatinina, se evidencian daños severos a nivel hepático y renal. Los cambios en la formula hematológica son indicativos de daño a nivel del sistema inmunológico, corroborado por el hallazgo anatomopatológico de un bazo hipertrofiado. Entre los cambios conductuales se observa aumento en tiempo-efecto de la actividad psicomotora, conductas agresivas, ingesta excesiva de agua, baja ingesta de alimentos y marcado daño a nivel de piel, llegando a putrefacción de la misma en la semana 4 y 5 del estudio. El estudio permitió además observar que la mezcla tiene un efecto sinérgico, potenciando los efectos de la cocaína a nivel del sistema nervioso central. Para confirmar esta presunción se tomaron muestras de regiones cerebrales para estudios ulteriores de neurotransmisores aminoacidicos inhibitorios, excitatorios y dopaminérgicos. De igual forma se encuentran actualmente en curso en nuestra unidad de investigación estudios toxicogenéticos. Son necesarios otros estudios para aseverar que esta asociación prolonga la vida media de la cocaína, como se presume por algunas pruebas rápidas realizadas. Estos primeros resultados permiten concluir que el corte de cocaína con levamisol produce daños severos a nivel hepático, renal, inmunológico, siendo lo más relevante el daño dérmico (necrosis). Esto sirve para alertar al personal de salud, de centros de tratamientos y organismos de seguridad, sobre esta patología que no debe confundirse con vasculitis ni infecciones dérmicas y por ende, administrar medicamentos que puedan exacerbar el cuadro clínico o potenciar el efecto de la mezcla.
Palabras claves: cocaína, levamisol, ratones NMRI, hematología, piel.
Descargar Archivo PDF (379 KB)
Palabras claves: cocaína, levamisol, ratones NMRI, hematología, piel.
Descargar Archivo PDF (379 KB)
Abstract
Toxic effect of cocaine- levamisole in pharmacological models
We study the toxic effects of mixing cocaine with levamisole in 120 male NMRI mice, young adult stage, as pharmacological models with approximate conversion to 26 years in a human. Levamisole is a drug with immunomodulating activity and anthelmintic used in veterinary medicine and currently enrolled in a "cut" (adulterant) of cocaine in the U.S. and other countries. The study was conducted in six groups of 20 models each (cocaine alone, levamisole alone, three concentrations of the mixture and saline control) and included hematologic values, biochemical, clinical and behavioral before, during and after the experience, and pathological findings, with three concentrations of the mixture and controls. Through profiles of transaminases and creatinine are evident severe damage to the liver and kidneys. Changes in hematologic formula are indicative of damage to the immune system level, confirmed by the pathological finding of an enlarged spleen. Among the behavioral changes observed time-effect increased psychomotor activity, aggressive behavior, excessive water intake, low food intake and marked damage to skin level, leading to putrefaction of the same in Week 4 and 5 of the study. The study also allowed to observe that the mixture has a synergistic effect, enhancing the effects of cocaine on central nervous system. To confirm this assumption was sampled brain regions for further study inhibitory amino acid neurotransmitters, excitatory and dopaminergic receptors. Likewise are currently underway in our research unit Toxicogenetics studies. Further studies are needed to assert that this association extends the half-life of cocaine, as assumed by some rapid tests performed.These early results suggest that cutting cocaine with levamisole produces severe damage to the liver, renal, immune, the most relevant of the skin damage (necrosis). This serves to alert personnel of health, treatment centers, and security of this pathology should not be confused with vasculitis or skin infections and therefore, medications that may exacerbate the clinical or enhance the effect of the mixture.
Keywords: cocaine, levamisole, NMRI mice, hematology, skin.
Download PDF (379 KB)
We study the toxic effects of mixing cocaine with levamisole in 120 male NMRI mice, young adult stage, as pharmacological models with approximate conversion to 26 years in a human. Levamisole is a drug with immunomodulating activity and anthelmintic used in veterinary medicine and currently enrolled in a "cut" (adulterant) of cocaine in the U.S. and other countries. The study was conducted in six groups of 20 models each (cocaine alone, levamisole alone, three concentrations of the mixture and saline control) and included hematologic values, biochemical, clinical and behavioral before, during and after the experience, and pathological findings, with three concentrations of the mixture and controls. Through profiles of transaminases and creatinine are evident severe damage to the liver and kidneys. Changes in hematologic formula are indicative of damage to the immune system level, confirmed by the pathological finding of an enlarged spleen. Among the behavioral changes observed time-effect increased psychomotor activity, aggressive behavior, excessive water intake, low food intake and marked damage to skin level, leading to putrefaction of the same in Week 4 and 5 of the study. The study also allowed to observe that the mixture has a synergistic effect, enhancing the effects of cocaine on central nervous system. To confirm this assumption was sampled brain regions for further study inhibitory amino acid neurotransmitters, excitatory and dopaminergic receptors. Likewise are currently underway in our research unit Toxicogenetics studies. Further studies are needed to assert that this association extends the half-life of cocaine, as assumed by some rapid tests performed.These early results suggest that cutting cocaine with levamisole produces severe damage to the liver, renal, immune, the most relevant of the skin damage (necrosis). This serves to alert personnel of health, treatment centers, and security of this pathology should not be confused with vasculitis or skin infections and therefore, medications that may exacerbate the clinical or enhance the effect of the mixture.
Keywords: cocaine, levamisole, NMRI mice, hematology, skin.
Download PDF (379 KB)