Indicación de N-acetilcisteína en distintas formas de toxicidad por paracetamol / Indication of n-acetylcysteine in differents forms of paracetamol toxicity

Introducción: la hepatotoxicidad por paracetamol está relacionada con la formación del metabolito N-acetil-parabenzoquinoneimina (NAPQI) y su falta de detoxificación a través del glutatión, cuyas reservas se deplecionan en el contexto de una sobredosis. La administración de N-acetilcisteína (NAC) como sustancia dadora de grupos tioles (-SH) contribuye a la prevención del daño hepático que puede desarrollarse con dosis terapéuticas o tóxicas. Métodos: se comentan 5 casos de exposición a paracetamol en los cuales se administró NAC por alteración de la función hepática. La gravedad de los cuadros varió en función de las dosis y del tiempo de latencia hasta la consulta. Resultados: cuatro pacientes ingirieron una única dosis tóxica y una paciente recibió la dosis diaria máxima de paracetamol de 4000 mg/día durante 5 días. La paciente que consultó dentro de las 4 horas posteriores a la ingesta no presentó elevación de transaminasas. Todas las pacientes recibieron NAC y sus valores de enzimas hepáticas se normalizaron al momento del alta. Conclusión: la administración temprana de NAC puede ser útil para prevenir daño hepático tanto en ingestas de dosis tóxicas, como en casos de utilización de dosis terapéuticas máximas durante varios días. (AU)

Introduction: paracetamol hepatotoxicity is related to the formation of the metabolite N-acetyl-parabenzoquinoneimine (NAPQI) and its lack of detoxification through glutathione, whose reserves are depleted in paracetamol overdose. The administration of N-acetylcysteine (NAC) as a donor of sulfhydryl groups (-SH) can prevent liver damage that could even occur with therapeutic or toxic doses. Methods: 5 cases of exposure to paracetamol are discussed, in which NAC was administered due to impaired liver function. These manifestations presented different severity depending on the drug doses and the time until medical consultation. Results: four patients ingested single toxic doses and one patient received the maximum daily dose of paracetamol of 4000 mg/day for 5 days. The patient who consulted within 4 hours after ingestion did not present elevation of transaminases. All patients received NAC, with normal liver enzymes at discharge. Conclusion: the early administration of NAC may be useful to prevent liver damage both in toxic dose intakes and in cases of use of maximum therapeutic doses for several days. (AU)

Consultorio de Salud Ambiental en un Hospital Privado de Comunidad de la Ciudad de Buenos Aires / Environmental Health consulting office in a Private Community Hospital of the Buenos Aires City

En los últimos años surge el concepto de Una Sola Salud que reconoce la interdependencia sistémica al observar que los cambios en la salud humana se expresan de manera sincrónica e indivisible de la salud del ambiente. Nuevas enfermedades y daños crónicos inespecíficos ocurren a la par de la pérdida de biodiversidad y vitalidad. En las últimas décadas venimos observando el surgimiento de "adaptaciones sistémicas" que requieren un abordaje desde la clínica y la toxicología a nivel individual y desde la epidemiología de la complejidad a nivel poblacional. Luego de un largo recorrido de investigaciones, el Hospital Italiano formalizó el consultorio de Salud Ambiental con la intención de brindar respuesta a la demanda de pacientes que atribuyen síntomas y signos a la polución ambiental. (AU)

In recent years, the concept of One Health has emerged, recognizing the systemic interdependence and the changes in human health that are expressed synchronously and indivisible from the environment. New diseases and nonspecific chronic damage are occuring in parallel with the loss of biodiversity and vitality.In recent decades we have observed the appearance of "systemic adaptations" that require a clinical and toxicological approach at the individual level, and address the population level from an epidemiological and complexity science paradigm. After many years of research, the Hospital Italiano de Buenos Aires formalized the Environmental Health consulting office and the measurement of glyphosate levels, giving answer to the demand of patients who associate their signs and symptoms to environmental pollution. (AU)

Validation of a Reversed-Phase Ultra-High-Performance Liquid Chromatographic Method With Photodiode Array Detection for the Determination of Voriconazole in Human Serum and Its Application to Therapeutic Drug Monitoring.

BACKGROUND: Voriconazole is a broad-spectrum triazole antifungal agent. It is widely used in the treatment of invasive fungal infections in immunocompromised patients. Because the pharmacokinetics of voriconazole demonstrates considerable variability, monitoring its serum levels plays an important role in optimizing therapies against many clinically relevant fungal pathogens. The aim of this study was to validate a simple and rapid U-HPLC-PDA method with minimal sample preparation for routine therapeutic drug monitoring (TDM) of voriconazole. METHODS: After protein precipitation with the internal standard solution (posaconazole 5.0 mg/L in acetonitrile), chromatographic separation was performed in 4 minutes using water and acetonitrile as mobile phases and an Acquity UPLC BEH HSS C18 column (2.1 × 100 mm, 1.7 µm). The temperature was set at 45°C and the flow rate was 0.4 mL/min. Photodiode array detection at 256 nm was used as detection system. The method was validated according international guidelines for linearity, accuracy, precision, selectivity, lower limit of quantitation, carry over, and stability under different conditions. RESULTS: All performance parameters were within acceptance criteria, demonstrating that the validated method is fit for purpose. After assay validation, 115 serum samples collected from 41 patients were analyzed to report the experience of the laboratory in TDM of voriconazole. Results showed a large variability in voriconazole trough levels, suggesting that this drug should be frequently measured in patients under treatment to enhance therapies efficacy and improve safety. CONCLUSIONS: In this study, a reproducible U-HPLC-PDA assay with a short analysis time, requiring only a small amount of serum, good accuracy and reproducibility was validated, which is suitable for routine TDM of voriconazole in serum.