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Acetaminofeno e hepatotoxicidade
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Resumo(s)
O consumo de medicamentos tem aumentado muito nos últimos anos. Com o surgimento de patologias sazonais a tendência para a automedicação tende a aumentar.
O Paracetamol (ou Acetaminofeno) é um dos medicamentos mais vendidos a nível mundial. A sobredosagem com este fármaco pode provocar danos hepáticos graves como a necrose hepática centrilobular. No entanto, estes danos podem não ser evidentes nas primeiras horas, o que pode provocar atraso no tratamento da intoxicação. Crê-se que o metabolismo hepático do Paracetamol ocorra por intermédio de enzimas do Citocromo P450 para formar a N-acetil-p-benzoquinona-imina (NAPQI). Após uma dose terapêutica, a NAPQI é eficientemente destoxificada pela Glutationa (GSH). Em sobredosagem, a NAPQI leva à depleção da GSH hepática e à formação de ligações com proteínas celulares hepáticas para formar aductos. Pensa-se que este efeito pode gerar stress oxidativo potencialmente responsável pela destabilização mitocondrial que possui repercussões ao nível do núcleo da célula. Uma revisão de outras hipóteses de mecanismos fisiopatológicos associados à intoxicação com o Paracetamol será apresentada ao longo deste trabalho.
O tratamento mais comum baseia-se na administração de N-Acetilcisteína. Este aminoácido é eficaz se administrado nas primeiras horas após intoxicação.
Como tal, torna-se importante prevenir contra os erros de medicação associados à toma deste fármaco bem como adoptar estilos de vida correctos que diminuam as complicações inerentes.
Drug use has increased greatly in recent years. With the emergence of seasonal diseases the tendency for self-medication tends to increase. Paracetamol (or Acetaminophen) is one of the best-selling drugs worldwide. A potencial overdose with this drug can cause severe liver damage producing a centrilobular hepatic necrosis. This damage may not be evident in the first few hours which may cause a delay in treatment of intoxication. Toxicity is believed to occur by initial hepatic metabolism by cytochrome P450 enzymes to form N-acetyl-p-benzoquinone-imine (NAPQI). After a therapeutic dose NAPQI is efficiently detoxified by GSH. When taken in overdose NAPQI leads to depletion of hepatic GSH levels and covalent binding to hepatic cellular proteins to form adducts. It is believed that this effect may generate an oxidative stress which is responsible for mitochondrial destabilization that has repercussions on the cell nucleus. An overview on other mechanistic hypotheses underlying the hepatotoxicity of Paracetamol will be presented in this work. The most common treatment is based on the administration of N-acetylcysteine. This amino acid is effective if administered within the first hours after intoxication. As such, it is important to prevent medication errors associated with the therapy with this drug as well as the adoption of healthy lifestyle that can reduce the associated complications.
Drug use has increased greatly in recent years. With the emergence of seasonal diseases the tendency for self-medication tends to increase. Paracetamol (or Acetaminophen) is one of the best-selling drugs worldwide. A potencial overdose with this drug can cause severe liver damage producing a centrilobular hepatic necrosis. This damage may not be evident in the first few hours which may cause a delay in treatment of intoxication. Toxicity is believed to occur by initial hepatic metabolism by cytochrome P450 enzymes to form N-acetyl-p-benzoquinone-imine (NAPQI). After a therapeutic dose NAPQI is efficiently detoxified by GSH. When taken in overdose NAPQI leads to depletion of hepatic GSH levels and covalent binding to hepatic cellular proteins to form adducts. It is believed that this effect may generate an oxidative stress which is responsible for mitochondrial destabilization that has repercussions on the cell nucleus. An overview on other mechanistic hypotheses underlying the hepatotoxicity of Paracetamol will be presented in this work. The most common treatment is based on the administration of N-acetylcysteine. This amino acid is effective if administered within the first hours after intoxication. As such, it is important to prevent medication errors associated with the therapy with this drug as well as the adoption of healthy lifestyle that can reduce the associated complications.
Descrição
Trabalho Final de Mestrado Integrado, Ciências Farmacêuticas, Universidade de Lisboa, Faculdade de Farmácia, 2013
Palavras-chave
Mestrado Integrado - 2013