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1.
J Med Toxicol ; 5(4): 183-90, 2009 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19876849

RESUMO

INTRODUCTION: The use of less than the traditional 72-hour course of oral N-acetylcysteine has been an alternative treatment option following potentially toxic acute and chronic acetaminophen ingestions felt to be at low risk of developing hepatotoxicity. While clinical experience with shortened treatment duration is extensive, there are few studies evaluating the effectiveness and extent to which these regimens may be used. METHODS: A large statewide poison center database was reviewed for all acetaminophen exposures involving potentially toxic acute and chronic ingestions, in addition to those taking place at unknown times. Patients were identified who met laboratory criteria for early N-acetylcysteine (NAC) discontinuation (APAP>10 micro/mL, INR

Assuntos
Acetaminofen/intoxicação , Acetilcisteína/administração & dosagem , Analgésicos não Narcóticos/intoxicação , Antídotos/administração & dosagem , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Administração Oral , Adolescente , Adulto , Idoso , California , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Esquema de Medicação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Centros de Controle de Intoxicações , Intoxicação/tratamento farmacológico , Guias de Prática Clínica como Assunto , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
2.
Ann Emerg Med ; 50(3): 282-8, 2007 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-17559970

RESUMO

STUDY OBJECTIVE: The foraging of wild mushrooms can be complicated by toxicity from several mushroom types. Amatoxin, a peptide contained in several mushroom species, accounts for the majority of severe mushroom poisonings by binding to RNA polymerase II irreversibly, leading to severe hepatonecrosis. There is no effective antidote for severe amatoxin poisoning. We compare the effectiveness of 5 potential antidotal therapies in limiting the degree of hepatonecrosis in a randomized, controlled, murine model of amatoxin-induced hepatotoxicity. METHODS: One hundred eighty male Institute of Cancer Research mice were randomized into 6 equal groups. Within each group, 21 mice were intraperitoneally injected with 0.6 mg/kg of alpha-amanitin (amatoxin); the remaining 9 were injected with 0.9% normal saline solution. Four hours postinjection, each group of 30 mice was randomized to 1 of 5 intraperitoneal treatments (N-acetylcysteine, benzylpenicillin, cimetidine, thioctic acid, or silybin) or normal saline solution. Repeated dosing was administered intraperitoneally every 4 to 6 hours for 48 hours. After 48 hours of treatment, each subject was killed, cardiac blood was aspirated for hepatic aminotransferase measurements (alanine transaminase and aspartate transaminase), and liver specimens were harvested to evaluate the extent of hepatonecrosis. The degree of hepatonecrosis was determined by a pathologist blinded to the treatment group and divided into 5 categories according to percentage of hepatonecrosis. RESULTS: Amanitin significantly increased aspartate transaminase in treated mice compared with normal saline solution-treated controls (mean [SD] 2,441 [2,818] IU/L versus 310 [252]; P=.03). None of the antidotal therapies were found to significantly decrease the increase in aminotransferases compared with controls. Further, none of the antidotal therapies demonstrated an important decrease in hepatonecrosis compared with controls when a histologic grading scale was used. CONCLUSION: In this murine model, N-acetylcysteine, benzylpenicillin, cimetidine, thioctic acid, and silybin were not effective in limiting hepatic injury after alpha-amanitin poisoning. Increases of aminotransferases and degrees of histologic hepatonecrosis were not attenuated by these antidotal therapies.


Assuntos
Amanitinas/intoxicação , Antídotos/farmacologia , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Intoxicação Alimentar por Cogumelos/tratamento farmacológico , Acetilcisteína/administração & dosagem , Acetilcisteína/farmacologia , Alanina Transaminase/sangue , Animais , Antídotos/administração & dosagem , Aspartato Aminotransferases/sangue , Cimetidina/administração & dosagem , Cimetidina/farmacologia , Modelos Animais de Doenças , Masculino , Camundongos , Penicilina G/administração & dosagem , Penicilina G/farmacologia , Distribuição Aleatória , Silibina , Silimarina/administração & dosagem , Silimarina/farmacologia , Ácido Tióctico/administração & dosagem , Ácido Tióctico/farmacologia
3.
Ann Emerg Med ; 50(3): 272-9, 2007 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-17210206

RESUMO

STUDY OBJECTIVE: Treatment with a shortened duration of oral N-acetylcysteine (20 to 48 hours) after acute acetaminophen poisoning is effective in the prevention of subsequent hepatic failure and death when administered to individuals meeting appropriate laboratory criteria. METHODS: Individuals with a potentially toxic acetaminophen ingestion according to serum acetaminophen levels were identified prospectively using a large statewide poison control system database throughout a 12-month period. N-acetylcysteine was administered for a minimum of 6 doses (20 hours), after which laboratory studies were obtained. Discontinuation of N-acetylcysteine was recommended by the poison center when 2 criteria were met: serum acetaminophen was undetectable (<10 microg/mL) and liver test results were normal (serum aminotransferase, international normalized ratio). A follow-up questionnaire was administered to individuals treated with N-acetylcysteine for 48 hours or less to ascertain the presence of symptoms consistent with progressive hepatotoxicity. RESULTS: Of 205 acutely poisoned individuals treated with N-acetylcysteine for 48 hours or less, 195 were successfully contacted after discharge, and 187 of 195 (95.9%) reported no symptoms consistent with hepatic failure. Eight individuals (4.1%) reported abdominal pain or vomiting; however, none received further N-acetylcysteine treatment or additional hospitalization. CONCLUSION: A shortened duration of treatment with N-acetylcysteine (20 to 48 hours) may be an effective treatment option in individuals considered to be at no further risk of developing liver toxicity according to the fulfillment of appropriate laboratory criteria before N-acetylcysteine discontinuation.


Assuntos
Acetaminofen/intoxicação , Acetilcisteína/uso terapêutico , Analgésicos não Narcóticos/intoxicação , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Acetilcisteína/administração & dosagem , Administração Oral , Adolescente , Adulto , California/epidemiologia , Doença Hepática Induzida por Substâncias e Drogas/mortalidade , Criança , Pré-Escolar , Intervalos de Confiança , Overdose de Drogas/tratamento farmacológico , Feminino , Humanos , Lactente , Testes de Função Hepática , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Medição de Risco , Inquéritos e Questionários , Resultado do Tratamento
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