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)

Acetaminophen-Induced Acute Liver Failure

Acetaminophen (AAP) is an antipyretic and analgesic agent, which is sold under many brand names including Tylenol. Although AAP rarely induces hepatotoxicity by an idiosyncratic mechanism, it is one of intrinsic hepatotoxins with a narrow therapeutic window. The overdose of AAP is the single most common cause of acute liver failure in the United States. In Korea, recent increase of working parents adds to the cause of overlooking children's AAP intoxication. Therapeutic dose of AAP is mostly converted to an inactive compound in the liver by conjugation with sulfate and glucuronide, with a small fraction (less than 5%) metabolized via the cytochrome P-450(CYP) system. The CYP enzymes oxidize AAP to produce a highly reactive metabolite: N-acetyl-p-benzoquinone imine (NAPQI), which is detoxified in the liver by conjugation with hepatic glutathione (GSH). In case of AAP overdose a large amount of NAPQI depletes hepatic glutathione. Then the excess NAPQI binds to hepatocellular proteins, initiating cell death. The toxicity of AAP may be enhanced by agents that either increase the production of NAPQI or reduce the supply of GSH. N-acetylcysteine(NAC) replenishes hepatic GSH, thereby detoxifying NAPQI. Early administration of NAC minimizes the hepatotoxicity. In general the survival rate from AAP-induced acute liver failure has been increased with the use of NAC and liver transplantation.