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Toxicological Property of Acetaminophen: The Dark Side of a Safe Antipyretic/Analgesic Drug?

Ishitsuka, Yoichi ; Kondo, Yuki ; Kadowaki, Daisuke

Biological and Pharmaceutical Bulletin, 2020/02/01, Vol.43(2), pp.195-206 [Periódico revisado por pares]

Japan: The Pharmaceutical Society of Japan

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Título:
Toxicological Property of Acetaminophen: The Dark Side of a Safe Antipyretic/Analgesic Drug?
Autor: Ishitsuka, Yoichi ; Kondo, Yuki ; Kadowaki, Daisuke
Assuntos: Acetaminophen ; acetaminophen (APAP) ; Acetylcysteine ; Analgesics ; Asthma ; Bronchospasm ; c-Jun protein ; Drug overdose ; drug-induced asthma ; ductus arteriosus ; Endoplasmic reticulum ; endoplasmic reticulum stress ; Epidemiology ; Geriatrics ; Hepatitis ; Hepatotoxicity ; Inflammation ; JNK protein ; Liver diseases ; Mitochondria ; Molecular modelling ; Nonsteroidal anti-inflammatory drugs ; Oxidative stress ; p-Aminophenol ; Paracetamol ; Renal function ; Risk groups ; Transcription factors
É parte de: Biological and Pharmaceutical Bulletin, 2020/02/01, Vol.43(2), pp.195-206
Notas: ObjectType-Article-2
SourceType-Scholarly Journals-1
ObjectType-Feature-3
content type line 23
ObjectType-Review-1
Descrição: Acetaminophen (paracetamol, N-acetyl-p-aminophenol; APAP) is the most popular analgesic/antipyretic agent in the world. APAP has been regarded as a safer drug compared with non-steroidal anti-inflammatory drugs (NSAIDs) particularly in terms of lower risks of renal dysfunction, gastrointestinal injury, and asthma/bronchospasm induction, even in high-risk patients such as the elderly, children, and pregnant women. On the other hand, the recent increasing use of APAP has raised concerns about its toxicity. In this article, we review recent pharmacological and toxicological findings about APAP from basic, clinical, and epidemiological studies, including spontaneous drug adverse events reporting system, especially focusing on drug-induced asthma and pre-and post-natal closure of ductus arteriosus. Hepatotoxicity is the greatest fault of APAP and the most frequent cause of drug-induced acute liver failure in Western countries. However, its precise mechanism remains unclear and no effective cure beyond N-acetylcysteine has been developed. Recent animal and cellular studies have demonstrated that some cellular events, such as c-jun N-terminal kinase (JNK) pathway activation, endoplasmic reticulum (ER) stress, and mitochondrial oxidative stress may play important roles in the development of hepatitis. Herein, the molecular mechanisms of APAP hepatotoxicity are summarized. We also discuss the not-so-familiar “dark side” of APAP as an otherwise safe analgesic/antipyretic drug.
Editor: Japan: The Pharmaceutical Society of Japan
Idioma: Inglês;Japonês

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Toxicological Property of Acetaminophen: The Dark Side of a Safe Antipyretic/Analgesic Drug?

Ishitsuka, Yoichi ; Kondo, Yuki ; Kadowaki, Daisuke

Japan: The Pharmaceutical Society of Japan

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