RESUMO
OBJETIVE: To describe the phenotype of DRESS syndrome induced by antituberculosis drugs. METHODS: Descriptive study, withdrawn from the review of the records of patients with DRESS syndrome, identified in the interconsultation of the Department of Research in Immunogenetics and Allergy, of the Insti-tuto Nacional de Enfermedades Respiratorias (INER) Ismael Cosío Villegas, among 2014 and 2020. Frequency analysis was performed. The associations between biomarkers and latency are calculated with the χ2 test and log-rank, and the evaluation of the change in the biomarkers with the Wilcoxon test. The value of p < 0.05 is considered statistically significant. For data analysis, the SPSS v.21 program was obtained. RESULTS: 15 patients were identified; represented by 0.02% of total cases treated in the Department for so-meimmuno-allergic condition (15/7052); the main symptomatology were: rash (100%), eosinophilia (93%), fe-ver (80%), adenomegaly (60%), kidney damage (40%), liver damage (33%), and latency of 21 days. Liver damage was associated with prolonged latency (p = 0.02). After treatment, the total levels of eosinophils (p < 0.001) and liver and kidney biomarkers (p < 0.04) decreased. DRESS syndrome induced by antituberculosis drugs is not associated with the number of drugs prescribed or with the pattern of resistance of Mycobacterium tuberculosis. CONCLUSIONS: DRESS syndrome induced by antituberculosis drugs is an atypical clinical reaction, similar to other types of DRESS syndrome that respond favorably to systemic corticosteroids.
OBJETIVO: Describir el fenotipo del síndrome de DRESS inducido por fármacos antituberculosos. MÉTODOS: Estudio descriptivo efectuado a partir de la revisión de los expedientes de pacientes con síndrome de DRESS, identificados en la interconsulta del Departamento de Investigación en Inmunogénetica y Alergia, del Instituto Nacional de Enfermedades Respiratorias (INER) Ismael Cosío Villegas, entre 2014 y 2020. Se realizó análisis de frecuencias. Las asociaciones entre biomarcadores y latencia se calcularon con la prueba de χ2 y log-rank, y la evaluación del cambio en los biomarcadores con la prueba de Wilcoxon. Se consideró esta-dísticamente significativo el valor de p < 0.05. Para el análisis de los datos se utilizó el programa SPSS v.21. RESULTADOS: Se identificaron 15 pacientes, que representaron el 0.2% de los casos atendidos en el Departa-mento por algún padecimiento inmuno-alérgico (15/7052); las principales manifestaciones fueron: exantema (100%), eosinofilia (93%), fiebre (80%), adenomegalia (60%), daño renal (40%), daño hepático (33%) y latencia de 21 días. El daño hepático se asoció con latencia prolongada (p = 0.02). Posterior al tratamiento disminu-yeron las concentraciones totales de eosinófilos (p < 0.001) y biomarcadores hepáticos y renales (p < 0.04). El síndrome de DRESS inducido por fármacos antituberculosos no se asoció con la cantidad de fármacos prescritos ni con el patrón de resistencia de Mycobacterium tuberculosis. CONCLUSIONES: El síndrome de DRESS inducido por fármacos antituberculosos es una reacción clínica atípica, similar a otros tipos de síndrome de DRESS que responden favorablemente a corticosteroides sisté-micos.
Assuntos
Antituberculosos , Síndrome de Hipersensibilidade a Medicamentos , Eosinofilia , Humanos , Corticosteroides/uso terapêutico , Antituberculosos/efeitos adversos , Síndrome de Hipersensibilidade a Medicamentos/etiologia , Eosinofilia/induzido quimicamente , EosinófilosRESUMO
ABSTRACT Isoniazid is a key component of tuberculosis treatment. Adequate exposure is a determinant for therapeutic success; however, considerable inter- and intraindividual variations in drug plasma levels can lead to unfavorable outcomes. While some predictors of isoniazid levels are well-known, others, such as sex, yield controversial results, requiring further investigation to optimize exposure. This study investigates whether the sex of patients influences the dose administered and the concentrations of isoniazid in plasma. Levels of isoniazid were associated with the N-acetyltransferase 2 phenotypes. A total of 76 male and 58 female patients were included. Isoniazid was measured by high-performance liquid chromatography, and N-acetyltransferase 2 phenotypes were assessed using molecular techniques. The results show that the dose administered, expressed in mg/kg, was higher in females, but the plasma levels were similar between both sexes. Among patients, 46.2%, 38.8%, and 15% were slow, intermediate, and fast acetylators, respectively. As expected, isoniazid levels were associated with the acetylation phenotypes, with higher concentrations in the slow acetylators. Thus, sex-related difference in isoniazid levels is due to the body weight of patients, and the optimized dose regimen based on patient weight and acetylator phenotypes can improve the treatment outcomes.
RESUMO
Tuberculosis is one of the most common infectious diseases around the world. With timely diagnosis and treatment, mortality in children is practically zero. It is usually associated with a diverse number of complications that can cause significant morbidity and mortality, such as deep and superficial vein thrombosis. This event has been associated with a procoagulant state caused by the systemic inflammatory response to infection. We report the case of a 14-year-old adolescent with pulmonary tuberculosis under the initial four-drug regimen. She presented two episodes of venous thromboembolism, the first in the kidneys and the second in the lungs. After ruling out diseases such as nephrotic and antiphospholipid antibody syndrome, chest and abdomen tomographies were performed as a fundamental tool for the diagnosis. Thereafter, treatment with low molecular weight heparin was initiated and the symptoms improved. Given the requirement for anticoagulation, further image studies could not be done. Thromboembolic complications in patients with no other risk factors, associated only with a previous pulmonary tuberculosis diagnosis, offer evidence to consider the procoagulant effect resulting from the systemic inflammatory response that, by itself, could be the cause of a serious complication, often underdiagnosed but also preventable. Therefore, it is recommended to consider the predisposition for venous thromboembolism in these patients and to establish strict surveillance so early anticoagulant therapy can be provided to prevent adverse outcomes.
La tuberculosis es una de las enfermedades infecciosas más comunes en el mundo. Aunque la mortalidad en niños es prácticamente nula cuando el diagnóstico y el tratamiento son oportunos, puede asociarse con complicaciones como la trombosis venosa profunda y la superficial a partir de la respuesta inflamatoria sistémica frente a la infección, lo que propicia la coagulación y ocasiona una significativa morbimortalidad. Se reporta el caso de una adolescente de 14 años con tuberculosis pulmonar en tratamiento combinado quien, de forma atípica, presentó dos episodios de tromboembolia venosa: el primero en el riñón y el segundo en los pulmones. Tras descartar el síndrome nefrótico y el antifosfolipídico, los estudios de tomografía de tórax y abdomen fueron una herramienta fundamental para su diagnóstico. Se inició tratamiento con heparina de bajo peso molecular con mejoría de los síntomas. Teniendo en cuenta las necesidades de anticoagulación no fue posible realizar estudios adicionales de ampliación. Las complicaciones tromboembólicas en pacientes con tuberculosis y sin otros factores de riesgo obligan a considerar el efecto coagulante que resulta de la reacción inflamatoria sistémica, la cual podría, por sí sola, ser la causa de una complicación significativa pero prevenible, aunque frecuentemente escapa al diagnóstico. En este sentido, se recomienda considerar la posibilidad de la tromboembolia venosa en estos pacientes y hacer un seguimiento estricto que permita aplicar el tratamiento anticoagulante tempranamente y prevenir, así, resultados adversos.
Assuntos
Rim/irrigação sanguínea , Pulmão/irrigação sanguínea , Tuberculose Pulmonar/complicações , Tromboembolia Venosa/etiologia , Adolescente , Anticoagulantes/uso terapêutico , Feminino , Heparina de Baixo Peso Molecular/uso terapêutico , Humanos , Pneumopatias , Veias Pulmonares/diagnóstico por imagem , Tromboembolia Venosa/diagnóstico por imagem , Tromboembolia Venosa/tratamento farmacológicoRESUMO
Resumen: La tuberculosis es una de las enfermedades infecciosas más comunes en el mundo. Aunque la mortalidad en niños es prácticamente nula cuando el diagnóstico y el tratamiento son oportunos, puede asociarse con complicaciones como la trombosis venosa profunda y la superficial a partir de la respuesta inflamatoria sistémica frente a la infección, lo que propicia la coagulación y ocasiona una significativa morbimortalidad. Se reporta el caso de una adolescente de 14 años con tuberculosis pulmonar en tratamiento combinado quien, de forma atípica, presentó dos episodios de tromboembolia venosa: el primero en el riñón y el segundo en los pulmones. Tras descartar el síndrome nefrótico y el antifosfolipídico, los estudios de tomografía de tórax y abdomen fueron una herramienta fundamental para su diagnóstico. Se inició tratamiento con heparina de bajo peso molecular con mejoría de los síntomas. Teniendo en cuenta las necesidades de anticoagulación no fue posible realizar estudios adicionales de ampliación. Las complicaciones tromboembólicas en pacientes con tuberculosis y sin otros factores de riesgo obligan a considerar el efecto coagulante que resulta de la reacción inflamatoria sistémica, la cual podría, por sí sola, ser la causa de una complicación significativa pero prevenible, aunque frecuentemente escapa al diagnóstico. En este sentido, se recomienda considerar la posibilidad de la tromboembolia venosa en estos pacientes y hacer un seguimiento estricto que permita aplicar el tratamiento anticoagulante tempranamente y prevenir, así, resultados adversos.
Abstract: Tuberculosis is one of the most common infectious diseases around the world. With timely diagnosis and treatment, mortality in children is practically zero. It is usually associated with a diverse number of complications that can cause significant morbidity and mortality, such as deep and superficial vein thrombosis. This event has been associated with a procoagulant state caused by the systemic inflammatory response to infection. We report the case of a 14-year-old adolescent with pulmonary tuberculosis under the initial four-drug regimen. She presented two episodes of venous thromboembolism, the first in the kidneys and the second in the lungs. After ruling out diseases such as nephrotic and antiphospholipid antibody syndrome, chest and abdomen tomographies were performed as a fundamental tool for the diagnosis. Thereafter, treatment with low molecular weight heparin was initiated and the symptoms improved. Given the requirement for anticoagulation, further image studies could not be done. Thromboembolic complications in patients with no other risk factors, associated only with a previous pulmonary tuberculosis diagnosis, offer evidence to consider the procoagulant effect resulting from the systemic inflammatory response that, by itself, could be the cause of a serious complication, often underdiagnosed but also preventable. Therefore, it is recommended to consider the predisposition for venous thromboembolism in these patients and to establish strict surveillance so early anticoagulant therapy can be provided to prevent adverse outcomes.
Assuntos
Tuberculose , Embolia Pulmonar , Adolescente , Trombose Venosa , Anticoagulantes , AntituberculososRESUMO
RESUMEN Con el objetivo de determinar las características de la enfermedad hepática inducida por el medicamento (DILI) se realizó un estudio de pacientes adultos con diagnóstico de tuberculosis y esquema de tratamiento antituberculoso con pirazinamida. El análisis de causa efecto de la DILI fue mediante el proceso de reexposición. Se encontraron 10 pacientes con DILI asociada a pirazinamida, la mediana de edad y de estancia hospitalaria fue de 40,5 años (rango 22-76) y 41 días (rango 11-130), respectivamente. La mediana de presentación del evento fue de 14 días (rango 3-46), 4 pacientes presentaron ictericia, 5 tuvieron patrón hepatocelular, 3 mixtas y 2 colestásicos. La presentación de la DILI fue leve en 6 casos (60%) y moderados en 3 (30%). En conclusión, la DILI asociada a la pirazinamida requiere estancia hospitalaria prolongada, se presenta con ictericia en un poco más de un tercio de los casos siendo el patrón predominante el hepatocelular.
ABSTRACT In order to determine the characteristics of drug-induced liver injury (DILI), adult patients diagnosed with tuberculosis and with an anti-tuberculosis treatment scheme including pyrazinamide were studied. The re-exposure process was used for the cause-effect analysis of the DILI. A total of 10 patients were found with pyrazinamide-associated DILI; the median age and hospital stay were 40.5 years (from 22 to 76 years) and 41 days (from 11 to 130 days), respectively. The median time in which the events appeared was 14 days (from 3 to 46 days); jaundice was observed in 4 patients and radiological patterns such as hepatocellular, mixed and cholestatic were found in 5, 3 and 2 patients, respectively. Mild presentation of DILI was observed in 6 cases (60%) and moderate in 3 (30%). In conclusion, pyrazinamide-associated DILI required prolonged hospital stay, presented jaundice in little more than a third of the cases, and radiologically, the hepatocellular pattern predominated.
Assuntos
Humanos , Masculino , Feminino , Pirazinamida , Tuberculose , Antituberculosos , Preparações Farmacêuticas , HipersensibilidadeRESUMO
BACKGROUND: Leprosy is a chronic granulomatous infection that affects skin and peripheral nerves. Its prevalence has declined, but is still observed mainly in poor rural areas. CASE REPORT: A male city dweller with photophobia and chronic dermatosis in the face: nodular and erythematous lesions, pustules, keratitis and entropion, partial eyebrows loss, and edema on eyelids, chin, and nose bridge. The rest of the body had no lesion or lymphadenopathy. Biopsy revealed Langhans giant cell proliferation in the superficial dermis without epidermal atrophy. BAAR staining for detection were positive, no Virschow cells were observed, and Fite-Franco staining (leprosy-specific) was negative. Cutaneous tuberculosis was diagnosed. Rifampicin/isoniazid/pyrazinamide and dialysate leukocyte extract were prescribed. A month later, the swelling had decreased significantly. Polymerase chain reaction (PCR) test was positive for Mycobacterium leprae. Flow cytometry showed CD4 count normalization. Long-term treatment with rifampicin, clofazimine, and dapsone was established. CONCLUSIONS: The host's immune response determines the clinical features of the disease: if response is bad there will be vacuolated macrophages filled with bacilli (lepromatous leprosy). Clinical and histopathological findings help typing.
Antecedentes: La lepra es una infección granulomatosa crónica que afecta piel y nervios periféricos. Aunque su prevalencia ha disminuido, se sigue observando principalmente en el medio rural pobre. Caso clínico: Hombre residente de una ciudad, con fotofobia y dermatosis crónica en la cara: lesiones nodulares y eritematosas, pústulas, queratitis y entropión, pérdida parcial de las cejas y edema de párpados, barbilla y puente nasal. El resto del cuerpo sin lesiones ni adenomegalias. La biopsia reveló proliferación de células gigantes de Langhans en la dermis superficial, sin atrofia epidérmica. Las tinciones para búsqueda de BAAR fueron positivas. No se observaron células de Virschow y la tinción de Fite-Franco (específica de lepra) fue negativa. Se diagnosticó tuberculosis cutánea. Se prescribió rifampicina-isoniazida-pirazinamida y extracto dializado de leucocitos. Un mes después, la inflamación había disminuido de forma importante. La reacción en cadena de la polimerasa fue positiva para Mycobacterium leprae. Con la citometría de flujo de seguimiento se observó normalización de la cuenta de CD4. Se estableció tratamiento a largo plazo con rifampicina, clofazimina y dapsona. Conclusiones: La respuesta inmune del huésped determina las características clínicas de la enfermedad: si la respuesta es mala habrá macrófagos vacuolados llenos de bacilos (lepromatosa). Los hallazgos clínicos e histopatológicos ayudan a la tipificación.
Assuntos
Hanseníase Virchowiana/imunologia , Humanos , Hanseníase Virchowiana/patologia , Masculino , Mycobacterium leprae/isolamento & purificação , Tuberculose Cutânea/diagnósticoRESUMO
In this study we evaluated the crystal violet decolorization assay (CVDA) for detection of minimum inhibitory concentration (MIC) of antituberculosis drugs. 53 isolates were tested in this study and 13 of them were multidrug resistant (MDR) isolates. The antibiotics concentrations were 2-0.06 mg/L for isoniazid (INH) and rifampicin (RIF) and were 16-0.25 mg/L for streptomycin (STM) and ethambutol (EMB). Crystal violet (CV-25 mg/L) was added into the microwells on the seventh day of incubation and incubation was continued until decolorization. Decolorization of CV was the predictor of bacterial growth. Overall agreements for four drugs were detected as 98.1%, and the average time was detected as 9.5 ± 0.89 day after inoculation. One isolate for INH and two isolates for STM were determined resistant in the reference method, but susceptible by the CVDA. One isolate was susceptible to EMB by the reference method, but resistant by the CVDA. All results were concordant for RIF. This study shows that CVDA is a rapid, reliable and suitable for determination of MIC values of Mycobacterium tuberculosis. And it can be used easily especially in countries with limited-sources.
Assuntos
Humanos , Antituberculosos/farmacologia , Mycobacterium tuberculosis/efeitos dos fármacos , Antituberculosos/administração & dosagem , Bioensaio , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Etambutol/administração & dosagem , Etambutol/farmacologia , Violeta Genciana/química , Indicadores e Reagentes/química , Isoniazida/administração & dosagem , Isoniazida/farmacologia , Testes de Sensibilidade Microbiana/métodos , Mycobacterium tuberculosis/crescimento & desenvolvimento , Rifampina/administração & dosagem , Rifampina/farmacologia , Estreptomicina/administração & dosagem , Estreptomicina/farmacologia , Tuberculose Resistente a Múltiplos Medicamentos/microbiologiaRESUMO
Introducción: el creciente hallazgo de cepas de Mycobacterium tuberculosis multidrogorresistentes extremadamente resistentes ratifica la importancia de ofrecer, de forma rápida, los resultados de susceptibilidad de M. tuberculosis a drogas de primera y segunda línea como única alternativa para evitar la transmisión. Objetivo: comparar el método de la nitrato reductasa y el de las proporciones para la detección de susceptibilidad a drogas antituberculosas de segunda línea en aislamientos clínicos de M. tuberculosis, recuperados de pacientes cubanos con tuberculosis multidrogorresistente. Métodos: se investigó, mediante el método de las proporciones en Löwenstein-Jensen y el de la nitrato reductasa, la susceptibilidad a la ofloxacina, la kanamicina y a la capreomicina en 34 aislamientos de M. tuberculosis multidrogorresistentes. Resultados: en tres aislamientos se evidenció un comportamiento extremadamente resistente por ambos métodos. Mediante el método de la nitrato reductasa los resultados estuvieron disponibles entre 7 y 14 días. La sensibilidad fue de 100 por ciento, 90,0 por ciento y 77,8 por ciento para la ofloxacina, la kanamicina y la capreomicina, respectivamente, mientras que la especificidad fue superior al 95,0 por ciento y el valor de kappa fue superior a 0,85 para las tres drogas. Conclusión: de acuerdo con los resultados alcanzados, consideramos que el método de la nitrato reductasa constituye una valiosa alternativa para la detección oportuna de tuberculosis extremadamente resistente en países con limitados recursos económicos(AU)
Introduction: the increase of multidrug resistant and extensively drug resistant tuberculosis underlines the urgent need to obtain early results of Mycobacterium tuberculosis susceptibility both to first and second line antituberculosis drugs in order to avoid dissemination of resistant isolates. Objective: the aim of this research was to compare the performance of the nitrate reductase assay and the proportion method for to detect the susceptibility to second line antituberculosis drugs in multidrug resistant clinical isolates of M. tuberculosis. Methods: the susceptibility to ofloxacin, kamamycin and capreomycin of 34 M. tuberculosis multidrug resistant isolates was investigated using the proportion method in Löwenstein-Jensen and the nitrate reductase assay. Results: three isolates were identified as extensively drug resistant by both methods. The results of the nitrate reductase assay were obtained between 7-14 days achieving 100 percent, 90.0 percent and 77.8 percent of sensitivity for ofloxacin, kamamycin and capreomycin, respectively while specificity was higher than 95.0 percent and kappa value was higher to 0,85 for all drugs. Conclusion: the nitrate reductase assay represents a useful tool for the rapid identification of extensively drug resistant tuberculosis in low resources setting(AU)
Assuntos
Humanos , Tuberculose/tratamento farmacológico , Resistência Microbiana a Medicamentos/efeitos dos fármacos , Nitrato Redutase/normas , Antituberculosos/uso terapêuticoRESUMO
In this study, a multisyringe chromatography system (MSC) using a C18 monolithic column was proposed for the on-line monitoring of the photocatalytic degradation of isoniazid (INH, 10 mg L(-1)) and pyrazinamide (PYRA, 5mgL(-1)) mixtures in aqueous solution using a small sample volume (200 µL) with an on-line filtration device in a fully automated approach. During the photocatalytic oxidation using TiO2 or ZnO semiconductor materials, total organic carbon (TOC) and the formed intermediates were analyzed off-line using ion chromatography, ion exclusion HPLC, and ESI-MS/MS. The results showed that TiO2 exhibits a better photocatalytic activity than ZnO under UV irradiation (365 nm) for the degradation of INH and PYRA mixtures, generating 97% and 92% degradation, respectively. The optimal oxidation conditions were identified as pH 7 and 1.0 g L(-1) of TiO2 as catalyst. The mineralization of the initial organic compounds was confirmed by the regular decrease in TOC, which indicated 63% mineralization, and the quantitative release of nitrate and nitrite ions, which represent 33% of the nitrogen in these compounds. The major intermediates of INH degradation included isonicotinamide, isonicotinic acid, and pyridine, while the ESI-MS/MS analysis of PYRA aqueous solution after photocatalytic treatment showed the formation of pyrazin-2-ylmethanol, pyrazin-2-ol, and pyrazine. Three low-molecular weight compounds, acetamide, acetic acid and formic acid, were detected during INH and PYRA decomposition. PYRA was more resistant to photocatalytic degradation due to the presence of the pyrazine ring, which provides greater stability against OH attack.
Assuntos
Antituberculosos/isolamento & purificação , Monitoramento Ambiental/métodos , Isoniazida/isolamento & purificação , Pirazinamida/isolamento & purificação , Poluentes Químicos da Água/isolamento & purificação , Purificação da Água/métodos , Antituberculosos/análise , Antituberculosos/efeitos da radiação , Catálise , Cromatografia Líquida de Alta Pressão , Monitoramento Ambiental/instrumentação , Desenho de Equipamento , Isoniazida/análise , Isoniazida/efeitos da radiação , Oxirredução , Processos Fotoquímicos , Pirazinamida/análise , Pirazinamida/efeitos da radiação , Espectrometria de Massas por Ionização por Electrospray , Espectrometria de Massas em Tandem , Titânio/química , Raios Ultravioleta , Poluentes Químicos da Água/análise , Poluentes Químicos da Água/efeitos da radiação , Purificação da Água/instrumentação , Óxido de Zinco/químicaRESUMO
INTRODUCTION: The prevalence and risk factors for rifampin, isoniazid and pyrazinamide hepatotoxicity were evaluated in HIV-infected subjects and controls. METHODS: Patients with tuberculosis (30 HIV positive and 132 HIV negative), aged between 18 and 80 years-old, admitted to hospital in Brazil, from 2005 to 2007, were selected for this investigation. Three definitions of hepatotoxicity were used: I) a 3-fold increase in the lower limit of normal for alanine-aminotransferase (ALT); II) a 3-fold increase in the upper limit of normal (ULN) for ALT, and III) a 3-fold increase in the ULN for ALT plus a 2-fold increase in the ULN of total bilirubin. RESULTS: In groups with and without HIV infection the frequency of hepatotoxicity I was 77 percent and 46 percent, respectively (p < 0.01). Using hepatotoxicity II and III definitions no difference was observed in the occurrence of antituberculosis drug-induced hepatitis. Of the 17 patients with hepatotoxicity by definition III, 3 presented no side effects and treatment was well tolerated. In 8 (36.4 percent) out of 22, symptoms emerged and treatment was suspended. Alcohol abuse was related to hepatotoxicity only for definition I. CONCLUSIONS: Depending on the definition of drug-induced hepatitis, HIV infection may or may not be associated with hepatotoxicity. The impact that minor alterations in the definition had on the results was impressive. No death was related to drug-induced hepatotoxicity. The emergence of new symptoms after initiating antituberculosis therapy could not be attributed to hepatotoxicity in over one third of the cases.
INTRODUÇÃO: Avaliou-se a prevalência e os fatores de risco para hepatotoxicidade aos tuberculostáticos em pacientes HIV positivos e controles. MÉTODOS: Selecionou-se 162 pacientes com tuberculose, tratados com rifampicina, isoniazida e pirazinamida, na faixa etária de 18 a 80 anos, internados em hospital público no Brasil, entre 2005 e 2007. Eles foram divididos em dois grupos: 30 infectados pelo HIV e 132 controles. Adotou-se três definições para hepatotoxicidade: I) aumento de três vezes no valor inferior normal da alanina-aminotransferase (ALT); II) aumento de três vezes no valor superior normal (VSN) da ALT; III) aumento de três vezes no VSN da ALT e duas vezes no VSN da bilirrubina total. RESULTADOS: Nos grupos com e sem infecção pelo HIV, a frequência de hepatotoxicidade I foi de 77 por cento e 46 por cento, respectivamente (p<0,01). Para as definições II e III a frequência de hepatotoxicidade não diferiu entre os grupos estudados. De 17 pacientes com hepatotoxicidade induzida por droga (definição III), três não apresentaram sintomas e o tratamento foi mantido sem intercorrências. Oito (36,4 por cento) de 22 indivíduos apresentaram efeitos colaterais e interromperam o tratamento, mas não apresentavam hepatotoxicidade pela definição III. O abuso de álcool associou-se à hepatotoxicidade apenas para a definição I. CONCLUSÕES: Na dependência da definição escolhida, a infecção pelo HIV pode ou não associar-se à hepatotoxicidade. Foi grande o impacto que pequenas alterações na definição de hepatotoxicidade tiveram nos resultados. Nenhuma morte associou-se ao uso de tuberculostáticos. O surgimento de sintomas não pôde ser atribuído aos tuberculostáticos em um terço dos casos.
Assuntos
Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Antituberculosos/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Infecções por HIV , Alanina Transaminase/sangue , Antituberculosos/uso terapêutico , Bilirrubina/sangue , Estudos de Casos e Controles , Infecções por HIV/complicações , Isoniazida/efeitos adversos , Pirazinamida/efeitos adversos , Fatores de Risco , Rifampina/efeitos adversos , Tuberculose/tratamento farmacológicoRESUMO
La tuberculosis (TB) es una enfermedad que afecta al mundo entero, sobretodo a países pobres. Durante mucho tiempo constituyó la primera causa de muerte por enfermedades infecciosas a nivel mundial, siendo después superada por la pandemia del VIH/SIDA.Ahora, nuevamente la tuberculosis ha tomado importancia por el surgimiento de cepas multidrogorresistentes en cuyo extremo de letalidad esta la tuberculosis extremadamente drogoresistente (TB XDR).
Tuberculosis (TB) is an illness that affects worldwide countries, mostly affecting poor countries. For a long time, tuberculosis was the first cause of death by infectious illness in the world, until the VIH/AIDS took that place. Lastly, tuberculosis isgettingthe same importance than before, because ofthe emergency of multidrug-resistantTB strains, with an extremely lethal form called extensively drug-resistantTB (XDRTB).
RESUMO
El fenómeno de la toxicidad hepática inducida por medicamentos cobró relevancia hace algunos años con el estudio de las reacciones adversas a medicamentos. El daño producido en el hígado por un xenobiótico que altera su función es lo que se conoce como toxicidad hepática. La importancia de reconocer y diagnosticar la toxicidad hepática por medicamentos estriba en su gravedad potencial; no en vano es la causa más frecuente por la que la industria farmacéutica retira medicamentos. La tuberculosis es una pandemia que afecta a gran parte de la población mundial y junto con el VIH es una enfermedad cada vez más frecuente en Colombia. Esta enfermedad se puede considerar como una situación especial porque para su tratamiento es preciso suministrar, por largos períodos, medicamentos con potencial tóxico para el hígado.El objetivo de este artículo es revisar algunos aspectos relacionados con la toxicidad hepática secundaria a medicamentos antituberculosos, tales como: epidemiología, factores de riesgo, mecanismos de toxicidad, manifestaciones clínicas, diagnóstico, tratamiento y seguimiento.
Hepatotoxicity is the alteration of liver structure and function induced by either drugs or other substances. The importance of its proper diagnosisrests on its potential severity. It is the most frequent reason by which the pharmaceutical industry withdraws its products. Tuberculosis is a pandemicinfection affecting a large proportion of the world population. Together with HIV infection it is becoming ever more frequent in Colombia. Tuberculosisposes a special challenge because itstreatment requires the administration, during long periods, of drugs with the potential of inducing liver injury. In this article some aspects of hepatotoxicity induced by antituberculosis drugs are reviewed, namely: epidemiology, risk factors, mechanisms, clinical manifestations, diagnosis, treatment and follow-up.
Assuntos
Antituberculosos/efeitos adversos , Antibióticos Antituberculose/toxicidadeRESUMO
The objective of this paper was to evaluate the hepatobiliary function of patients with pulmonary tuberculosis under triple treatment, using the technetium-99m-DISIDA (99mTc-DISIDA) hepatobiliary scintigraphy. Ten men and three women with pulmonary tuberculosis were subjected to hepatobiliary scintigraphy at the beginning of triple treatment (M1) and two months after it (M2). Patients were from the urban area, of low socioeconomic level, malnourished, and chronic alcohol and/or tobacco users. Ten normal individuals were evaluated as controls. Radiotracer images were acquired on a computerized gamma camera (Orbiter-Siemens) and T1/2 uptake and excretion values were calculated. Nutritional status and serum hepatic enzyme levels for each patient were evaluated at M1 and M2. None presented clinical or laboratory antecedent of hepatobiliary disease. At M1, there were no hepatic serum or kinetic alterations of the 99mTc-DISIDA. At M2, patients presented better nutritional conditions than at M1; there was increased serum aspartate aminotransferase (AST) and reduced excretion time for 99mTc-DISIDA, which was interpreted as a more adaptive than toxic phenomenon, yet not all alterations were significant and none manifested clinically. Apparently, triple treatment acted on the liver inducing the P450 cytochrome enzymatic system, accelerating radiotracer excretion, which follows the same path as the bilirubins.
RESUMO
The objective of this paper was to evaluate the hepatobiliary function of patients with pulmonary tuberculosis under triple treatment, using the technetium-99m-DISIDA (99mTc-DISIDA) hepatobiliary scintigraphy. Ten men and three women with pulmonary tuberculosis were subjected to hepatobiliary scintigraphy at the beginning of triple treatment (M1) and two months after it (M2). Patients were from the urban area, of low socioeconomic level, malnourished, and chronic alcohol and/or tobacco users. Ten normal individuals were evaluated as controls. Radiotracer images were acquired on a computerized gamma camera (Orbiter-Siemens) and T1/2 uptake and excretion values were calculated. Nutritional status and serum hepatic enzyme levels for each patient were evaluated at M1 and M2. None presented clinical or laboratory antecedent of hepatobiliary disease. At M1, there were no hepatic serum or kinetic alterations of the 99mTc-DISIDA. At M2, patients presented better nutritional conditions than at M1; there was increased serum aspartate aminotransferase (AST) and reduced excretion time for 99mTc-DISIDA, which was interpreted as a more adaptive than toxic phenomenon, yet not all alterations were significant and none manifested clinically. Apparently, triple treatment acted on the liver inducing the P450 cytochrome enzymatic system, accelerating radiotracer excretion, which follows the same path as the bilirubins.