Paracetamol e asma: evidências atuais
Paracetamol and asthma: current evidence
Geórgia Véras de Araújo; Bruno Acatauassú Paes Barreto; Emanuel Sávio Cavalcanti Sarinho; Germana Pimentel Stefani; Herberto José Chong Neto; Joseane Chiabai; Dirceu Solé
Resumo
Há vários mecanismos possíveis para explicar o nexo de causalidade entre o paracetamol e a asma. A hipótese mais abordada está relacionada com o desequilíbrio entre o balanço oxidante/ antioxidante, principalmente no epitélio pulmonar. A produção de um metabólito altamente reativo, o N-acetil-p-benzoquinonaimina (NAPQI), derivado do metabolismo do paracetamol, promove depleção no pool de glutationa intracelular, resultando em danos oxidativos, inflamação e broncoespasmo, destacados na asma. A diminuição dos níveis de glutationa pode alterar a apresentação antigênica e favorecer uma resposta imune polarizada para Th2. Existem evidências fisiopatológicas e epidemiológicas consistentes na literatura para considerar a forte relação de causalidade do paracetamol no desencadeamento da asma e outras desordens alérgicas, como rinoconjuntivite e eczema, em diferentes populações no mundo. Descrições em consensos e diretrizes devem enfatizar esta associação e orientar o uso somente de forma esporádica, evitando doses altas deste fármaco em grávidas. Estudos randomizados controlados seriam úteis em dirimir possíveis dúvidas quanto ao não uso em crianças e adultos com asma ou em risco de asma. Esta revisão narrativa pretende ressaltar o conhecimento científico atual sobre a relação causal do paracetamol (acetaminofeno), durante exposição intrauterina, infância, adolescência e na fase adulta, e as desordens alérgicas, em especial a asma. Para tanto, foram selecionados os principais artigos abordando o tema de interesse, em inglês e espanhol, a partir da pesquisa nos bancos de dados MEDLINE, SCOPUS e Web of Science publicados entre março de 1983 a março de 2014, e livros-textos selecionados sobre o assunto.
Palavras-chave
Abstract
There are several possible mechanisms to explain the causal relationship between asthma and the use of paracetamol (or acetaminophen). The hypothesis most commonly referred to is related to an imbalance in the oxidant/antioxidant status, particularly in lung epithelium. The production of a highly reactive metabolite, namely, N-acetyl-p-benzoquinone imine (NAPQI), derived from the metabolism of acetaminophen, promotes depletion of the intracellular glutathione pool, resulting in oxidative damage, inflammation, and bronchospasm – all features of asthma. Decreased levels of glutathione may alter antigen presentation and favor a polarized Th2 immune response. There is consistent pathophysiological and epidemiological evidence in the literature to support a strong role of acetaminophen in triggering asthma and other allergic disorders, such as rhinoconjunctivitis and eczema, in different populations worldwide. Consensus documents and guidelines should emphasize this association and recommend the use of acetaminophen only sporadically, avoiding high doses of this drug in pregnant women. Randomized controlled studies would be useful to solve possible doubts regarding its use or not in children and adults with asthma or at risk for asthma. The present narrative review intends to describe the scientific knowledge currently available on the causal relationship between exposure to acetaminophen in the prenatal period, during childhood, adolescence, and in adulthood, and allergic disorders, especially asthma. In order to do that, major articles addressing the topic of interest were selected and reviewed after searching the MEDLINE, SCOPUS and Web of Science databases for articles published in English or Spanish between March 1983 and March 2014, in addition to textbooks on the subject.
Keywords
Referências
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Submetido em:
12/09/2013
Aceito em:
02/07/2014
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