RESUMO
Antecedentes: Las intoxicaciones en pediatría asociadas a medicamentos representan una importante carga para los sistemas de salud pública. Objetivo: Caracterizar al paciente pediátrico con intoxicación por medicamentos, Servicio de Emergencia de Pediatría, Hospital Escuela, Tegucigalpa, 2019- 2021. Métodos: Estudio observacional descriptivo. Se revisaron expedientes clínicos de pacientes pediátricos atendidos por intoxicación por medicamentos. Los resultados se presentan como cuadros y figuras de frecuencias y porcentajes de las variables estudiadas. La información personal de manejó confidencialmente. Resultados: La proporción hospitalaria de pacientes pediátricos atendidos por intoxicación por medicamentos durante el período del estudio fue 0.08%. La media de la edad 12.6 años (DS+/-5.0). El sexo femenino 77.6% (59/76), procedencia Francisco Morazán 84.2% (64/76); y del ambiente urbano marginal 55.3% (42/76). El nivel de escolaridad fue secundaria incompleta 67.1% (51/76). Además del diagnóstico de intoxicación por medicamentos, se identificaron los diagnósticos de intento suicida y trastorno depresivo 76.3% (58/76), cada uno. La intoxicación fue aguda 97.4% (74/76), intencional 76.3% (58/76). La procedencia del fármaco fue medicación del paciente 44.7% (34/76). El lugar donde ocurrió el evento fue en casa/domicilio del paciente 96.1% (73/76). Se utilizó clonazepam en 30.3% (23), fármaco perteneciente al grupo de las benzodiacepinas. No hubo muertes. Discusión: El paciente pediátrico atendido en el Hospital Escuela por intoxicación por medicamentos se caracterizó como adolescente del sexo femenino, con acceso a medicamentos tipo benzodiacepina en el domicilio, relacionado a depresión e intento suicida. Se recomienda realizar estudios para la identificación de factores de riesgo. Es necesaria la creación de políticas públicas que contribuyan a implementar un abordaje integral de la niñez, adolescencia y la familia...(AU)
Assuntos
Humanos , Masculino , Feminino , Pré-Escolar , Criança , Adolescente , Intoxicação/complicações , Tentativa de Suicídio/psicologia , Benzodiazepinas/toxicidade , EmergênciasRESUMO
El diazepam (DZ) es un tranquilizante menor sintético, utilizado en pacientes con trastornos psicológicos y psiquiátricos. Es sedante, miorrelajante, anticonvulsionante y antipsicótico. El DZ atraviesa la barrera placentaria humana y la del ratón. Mujeres jóvenes que son adictas al fármaco, si se embarazan y continúan utilizándolo, sobre todo durante el primer trimestre, exponen a sus hijos a presentar alteraciones psicomotoras. El propósito de este trabajo fue investigar si el DZ administrado durante la gestación,induce alteraciones ultraestructurales del miocardio fetal de ratón. El grupo (DZ) de hembras gestantes deratón de la cepa CD-1 fue tratado con dosis únicas diarias de 1,0 mg/kg/pc/sc del día 6 al 17 y un grupo (C)que recibió solución salina. El día 18 las hembras de ambos grupos se anestesiaron, los fetos se perfundieron por vía intracardiaca con paraformaldehído al 1 % y glutaraldehido al 2,5 %, se les extrajo el corazón, se disecó el atrio, se fijó en OsO4 al 1 % y se incluyó en resina epóxica. Los cortes finos se contrastaron conacetato de uranilo y citrato de plomo y se observaron en un microscopio electrónico de transmisión. En los miocitos de los fetos del grupo DZ las sarcómeras del miocardio compacto tenían menor longitud que las del grupo C. Se observaron zonas con miofibrillas desorganizadas. El retículo sarcoplásmico de algunos miocitos presentaba cisternas distendidas y fragmentadas, mitocondrias alteradas y se observaron abundantes polirribosomas. Los cambios podrían deberse al efecto del DZ sobre la síntesis de actina y miosina pesada y sobre los organelos citoplásmicos, mediados por receptores benzodiazepínicos periféricos presentes en la membrana externa de las mitocondrias y asociados a canales de calcio dependientes de voltaje. Las alteraciones ultraestructurales del miocardio atrial de fetos de ratones expuestos in utero a DZ podrían tener efectos posnatales.
Diazepam (DZ) is a syntheticminor tranquilizer, used in patients with psychologicaland psychiatric disorders. It is a relaxing sedative,anticonvulsant and antipsychotic. DZ crosses thehuman placental barrier in mouse. Young women who are addicted to the drug, if they become pregnantand continue to use it, particularly during the firsttrimester, expose their children to psychomotor disorders. The purpose of this study was to investigate whether DZ administered during pregnancy induces ultrastructural alterations of fetal mouse myocardium.The group (DZ) of pregnant female mice of the CD-1strain was treated with a single daily dose of 1.0 mg/ kg / pc / sc of day 6 to 17 and a group (C) that received saline solution. On day 18 females of bothgroups were anesthetized, the fetuses were perfusedby intracardiac route with 1 % paraformaldehyde and 2.5 % glutaraldehyde, the heart was removed, theatrium was dissected, fixed in 1 % OsO4, it wasimmersed in epoxy resin. The fine sections werecontrasted with uranyl acetate and lead citrate and observed in a transmission electron microscope. Inthe myocytes of the fetuses of the DZ group, the sarcomers of the compact myocardium were shorter than those of the C group. Areas with disorganized myofibrils were observed. The sarcoplasmic reticulumof some myocytes had distended and fragmented 996cisterns, altered mitochondria, and abundant polyribosomes were observed. The changes may bedue to the effect of DZ on the synthesis of actin and heavy myosin and on cytoplasmic organelles mediatedby peripheral benzodiazepine receptors present onthe outer membrane of the mitochondria and associated with voltage-dependent calcium channels.Ultrastructural alterations of the atrial myocardium of fetuses of mice exposed to DZ in utero may have postnatal effects.
Assuntos
Animais , Gravidez , Camundongos , Diazepam/toxicidade , Coração Fetal/efeitos dos fármacos , Retículo Sarcoplasmático/efeitos dos fármacos , Retículo Sarcoplasmático/ultraestrutura , Benzodiazepinas/toxicidade , Coração Fetal/ultraestruturaRESUMO
OBJETIVO: Delirium é uma condição frequente em idosos com doenças agudas, associado à alta morbimortalidade e ao prolongamento do período de internação. Diversos fármacos estão relacionados ao risco de desencadeá-lo ou agravá-lo. O objetivo do estudo foi identificar medicamentos potencialmente causadores de delirium em pacientes idosos portadores desta síndrome e seu risco para mortalidade durante a hospitalização. MÉTODOS: Realizou-se estudo transversal, com 51 idosos internados que preenchiam critérios de diagnóstico para delirium pelo Confusion Assesment Method. Os fármacos potencialmente inapropriados foram os relacionados segundos os critérios de Beers. As variáveis avaliadas foram: idade, gênero, causas do delirium, fármacos em uso regular, período de internação e óbitos. RESULTADOS: 30 pacientes (58,82%) faziam uso de fármacos de risco para delirium, sendo que 39,2% utilizavam medicamentos considerados de alto risco e 13,7% usavam concomitantemente três fármacos. Dentre as medicações de alto risco, os benzodiazepínicos foram empregados em 23,5% dos pacientes. O tempo médio de internação foi de 24±18 (1-86) dias e 25 (49%) pacientes evoluíram para o óbito. CONCLUSÃO:Observou-se longa permanência hospitalar e frequente uso de medicamentos com potencial de agravar ou desencadear o estado de delirium, sendo os benzodiazepínicos, os mais frequentemente utilizados. Apesar da alta mortalidade, não foi possível associar este fato ao uso dos fármacos. Tais resultados ratificam que o delirium é uma síndrome pouco reconhecida pelos clínicos em um hospital geral.
OBJECTIVE: The aim of the study was to identify the medications potentially causing or exacerbating delirium in elderly patients, and review the risk of mortality associated with the use of these medications during hospitalization. METHODS: Cross-sectional study with 51 elderly inpatients who met diagnostic criteria for delirium. The pharmaceuticals considered inappropriate were related according to the Beers criteria. The variables were: age, gender, cause for delirium, pharmaceuticals in regular use, hospitalization time and deaths. RESULTS: 30 patients (58,82%) were using pharmaceuticals that presented a risk of delirium. 39.2% of these used medications of high risk, 23.5% being benzodiazepines. 25 (49%) patients died during hospitalization. CONCLUSION: It was noted frequent use of potentially inappropriate drugs, benzodiazepines being the most frequently used. However, this fact was not linked to the high mortality. These results confirm that delirium is a syndrome that is poorly recognized by clinicians in a general hospital.
Assuntos
Humanos , Masculino , Feminino , Idoso , Idoso de 80 Anos ou mais , Benzodiazepinas , Benzodiazepinas/toxicidade , Prescrições de Medicamentos , Delírio/mortalidade , Pacientes InternadosRESUMO
OBJECTIVES: The aim of this study was to investigate the effects of oral administration of a novel benzodiazepine derivative, JM-20, on the neurological behavior of different rodent models, focusing on the GABAergic effect. We have also investigated the acute toxicity of oral administration of JM-20 in mice. METHODS: Mice or rats received oral administration of JM-20 at 2, 4, 8, and 10 mg/kg to evaluate the sedative/hypnotic, anxiolytic, and anticonvulsant effects, as well as the influence on the stereotyped behavior induced by amphetamine. Diazepam (DZP) was used as a positive control. In addition, the mice received a single oral JM-20 dose of 2000 mg/kg to evaluate the acute toxicity. RESULTS: In a dose-dependent manner, JM-20 (i) increased the number of crossings and decreased the number of rearings in the open-field test; (ii) decreased the aggressive behavior of socially-isolated mice; and (iii) increased the latency period for tonic seizure's onset and the percentage of survival of animals with seizures. Moreover, JM-20 increased the sleeping time induced by barbiturates and the time spent and the number of entries in the open arms of the elevated plus-maze test. In the JM-20 toxicity test, no mortality was observed and only minor signs of toxicity associated with sedation were detected. CONCLUSIONS: These results indicate that JM-20 has an anxiolytic profile similar to DZP and its dihydropyridine moiety did not appear to interfere with the GABAergic activity associated with benzodiazepine. Furthermore, JM-20 did not show significant acute toxic effects in mice.
Assuntos
Ansiolíticos/farmacologia , Comportamento Animal/efeitos dos fármacos , Benzodiazepinas/química , Di-Hidropiridinas/química , Hipnóticos e Sedativos/farmacologia , Niacina/análogos & derivados , Administração Oral , Animais , Ansiolíticos/administração & dosagem , Ansiolíticos/efeitos adversos , Ansiolíticos/toxicidade , Anticonvulsivantes/administração & dosagem , Anticonvulsivantes/efeitos adversos , Anticonvulsivantes/farmacologia , Anticonvulsivantes/toxicidade , Benzodiazepinas/síntese química , Benzodiazepinas/farmacologia , Benzodiazepinas/toxicidade , Diazepam/farmacologia , Relação Dose-Resposta a Droga , Avaliação Pré-Clínica de Medicamentos , Interações Medicamentosas , Feminino , Hipnóticos e Sedativos/administração & dosagem , Hipnóticos e Sedativos/efeitos adversos , Hipnóticos e Sedativos/toxicidade , Masculino , Camundongos , Niacina/síntese química , Niacina/química , Niacina/farmacologia , Niacina/toxicidade , RatosRESUMO
Although some studies have investigated the influence of kindling model of epilepsy on the glutamatergic neurotransmission, the relation between glutamatergic receptors and seizure susceptibility remains unclear. The present study sought to determine if rats with high (HTR) and low (LTR) thresholds to clonic convulsions induced by the benzodiazepine inverse agonist DMCM differed in the [(3)H]-L-glutamate binding to membranes from discrete brain regions. Compared to the HTR subgroup, the LTR subgroup presented a lower binding of [(3)H]-L-glutamate in the hippocampus, frontal cortex and amygdala plus limbic cortex, suggesting that glutamatergic receptors in these brain regions may underlie the susceptibility to DMCM-induced convulsions.
Assuntos
Benzodiazepinas/toxicidade , Encéfalo/efeitos dos fármacos , Convulsivantes/toxicidade , Ácido Glutâmico/farmacocinética , Convulsões/induzido quimicamente , Convulsões/patologia , Animais , Encéfalo/metabolismo , Encéfalo/patologia , Carbolinas/farmacologia , Modelos Animais de Doenças , Masculino , Ligação Proteica/efeitos dos fármacos , Ratos , Ratos Wistar , Trítio/farmacocinéticaRESUMO
Olanzapine is an atypical antipsychotic drug that has been increasingly used in acute treatment of, and therapeutic support for, schizophrenia, bipolar disorder and other psychoses. Considering that olanzapine acts on the dopaminergic receptor and this receptor is detected in germ cells, the present study aims to investigate the effects of treatment with different doses of olanzapine on spermatogenesis, plasma testosterone and weight of androgen-dependent organs in rats. Results showed reduced plasma testosterone levels, and reduced testis, epididymis and prostate weights. Histopathologic and histomorphometric analysis of spermatogenesis indicated testicular degeneration. Furthermore, germ cell desquamation, syncytial multinucleated cells, Sertoli cell vacuolization and presence of necrotic and apoptotic germ cells wwew observed. Olanzapine treatment in rats promoted endocrinological changes and lesions in the testis, leading to a disturbance in spermatogenesis.
Assuntos
Antipsicóticos/toxicidade , Benzodiazepinas/toxicidade , Doenças dos Genitais Masculinos/induzido quimicamente , Espermatogênese/efeitos dos fármacos , Testículo/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Contagem de Células , Epididimo/efeitos dos fármacos , Epididimo/patologia , Doenças dos Genitais Masculinos/sangue , Doenças dos Genitais Masculinos/patologia , Letargia/induzido quimicamente , Masculino , Necrose/induzido quimicamente , Necrose/patologia , Olanzapina , Tamanho do Órgão/efeitos dos fármacos , Próstata/efeitos dos fármacos , Próstata/patologia , Ratos , Ratos Wistar , Células de Sertoli/efeitos dos fármacos , Células de Sertoli/patologia , Espermatócitos/efeitos dos fármacos , Espermatócitos/patologia , Testículo/patologia , Testosterona/sangueRESUMO
Typical and atypical antipsychotic drugs have been shown to have different clinical and behavioral profiles. Haloperidol (HAL) is a typical neuroleptic that acts primarily as a D(2) dopamine receptor antagonist. It has been proposed that reactive oxygen species play a causative role in neurotoxic effects induced by HAL. We evaluated oxidative damage in rat brain induced by chronic (28 days) HAL, clozapine (CLO), olanzapine (OLZ) or aripiprazole (ARI) administration. Adult male Wistar rats received daily injections of HAL (1.5 mg/kg), CLO (25 mg/kg), OLZ (2.5, 5 or 10 mg/kg) or ARI (2, 10 or 20 mg/kg); control animals received vehicle (Tween 1% solution). Thiobarbituric acid reactive substances (TBARS) and protein carbonylation were measured in the prefrontal cortex, hippocampus, striatum and cerebral cortex. The results showed that TBARS were increased in the striatum after HAL treatment. On the other hand, TBARS were diminished in the prefrontal cortex by OLZ and ARI. Our results also showed that all drugs tested in this work decreased TBARS levels in the cerebral cortex. In hippocampus, TBARS levels were not altered by any drug. Protein carbonyl content after HAL and CLO treatment was increased in the hippocampus. Moreover, OLZ and ARI did not alter protein carbonyl content when compared to control group. ARI chronic administration (20 mg/kg) also increased mitochondrial superoxide in the prefrontal cortex and striatum. ARI did not alter mitochondrial superoxide in the hippocampus and cerebral cortex. Moreover, HAL, OLZ and CLO did not cause significant alterations in mitochondrial superoxide in rat brain. Our findings demonstrate that OLZ and ARI do not induce oxidative damage in rat brain as observed after HAL and CLO treatment.
Assuntos
Antipsicóticos/toxicidade , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Haloperidol/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Animais , Aripiprazol , Benzodiazepinas/toxicidade , Clozapina/toxicidade , Corpo Estriado/efeitos dos fármacos , Corpo Estriado/metabolismo , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Masculino , Olanzapina , Piperazinas/toxicidade , Córtex Pré-Frontal/efeitos dos fármacos , Córtex Pré-Frontal/metabolismo , Quinolonas/toxicidade , Ratos , Ratos Wistar , Superóxidos/metabolismo , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismoRESUMO
A series of 1-alkylsulfonylaryl-1,4-benzodiazepine derivatives were synthesized and assayed for their pharmacological profile. All the compounds tested exhibited a competitive antagonism of 3H-diazepam binding in cerebellum, cerebrum and submaxillary gland. Compound II (rec. INN tolufazepam) had a Ki of 12.7 nM in cerebrum and 400 nM in the submaxillary gland. It was very potent in preventing convulsions elicited by pentylenetetrazol (ED50 p.o.: 16.5 and ED50 i.v.: 20 mg/kg). This anticonvulsant action was suppressed by previous administration of Ro 15-1788. Compound II was also active in inhibiting suppressive behaviour in the test of Vogel. This compound has a relative low hypnogenic activity as well as a low potency to produce motor incoordination. Our results show that tolufazepam has a potential clinical usefulness.