Extrahepatic toxicity of acetaminophen: critical evaluation of the evidence and proposed mechanisms
Journal Title: Journal of Clinical and Translational Research - Year 2017, Vol 3, Issue 3
Abstract
Research on acetaminophen (APAP) toxicity over the last several decades has focused on the pathophysiology of liver injury, but increasingly attention is paid to other known and possible adverse effects. It has been known for decades that APAP causes acute kidney injury, but confusion exists regarding prevalence, and the mechanisms have not been well investigated. More recently, evidence for pulmonary, endocrine, neurological, and neurodevelopmental toxicity has been reported in a number of published experimental, clinical, and epidemiological studies, but the quality of those studies has varied. It is important to view those data critically due to implications for regulation and clinical practice. Here, we review evidence and proposed mechanisms for extrahepatic adverse effects of APAP and weigh weaknesses and strengths in the available data. Relevance for patients: APAP is one of the most commonly used drugs in the West. Although it is generally considered safe when used according to manufacturer recommendations, it has been known for decades that overdose can cause liver injury. Recent studies have suggested that APAP can damage cells in other organs as well, leading to calls for more and stricter regulations, which would limit use of this otherwise effective drug. It is especially important to view claims of developmental effects of antenatal APAP exposure with a critical eye because APAP is currently the only over-the-counter medication recommended for pregnant women to self-treat pain and fever.
Authors and Affiliations
Stefanie Kennon-McGill, Mitchell R. McGill
Cardiac vagal activity and daily clinical practice
During most of the day heart rate (HR) is dominated by cardiac vagal (parasympathetic) activity – a fact taught in physiology classes and duly repeated at the appropriate exams. Only later in medical practice does one b...
Layer-by-layer heparinization of decellularized liver matrices to reduce thrombogenicity of tissue engineered grafts
Background: Tissue–engineered liver grafts may offer a viable alternative to orthotopic liver transplantation and help overcome the donor organ shortage. Decellularized liver matrices (DLM) have a preserved vasculature a...
Connexin-based signaling and drug-induced hepatotoxicity
Being critical mediators of liver homeostasis, connexins and their channels are frequently involved in liver toxicity. In the current paper, specific attention is paid to actions of hepatotoxic drugs on these communicati...
Primary headache syndromes in the elderly: epidemiology, diagnosis and treatment
Although secondary headaches due to e.g. temporal arteritis or a brain tumor are common among the elderly, primary headache disorders also occur in this age group, albeit less frequently than in younger individuals. A di...
Novel circulating- and imaging-based biomarkers to enhance the mechanistic understanding of human drug-induced liver injury
Liver safety biomarkers in current clinical practice are recognized to have certain shortcomings including their representation of general cell death and thus lacking in indicating the specific underlying mechanisms of i...