Recent reports have implicated paracetamol in a number of side effects. The medication is widely used in dentistry and other disciplines to control mild pain. What is the real story behind this drug? And compared to NSAIDS, which is safer and more accountable?
There are many indefinitely about the mechanism of action of paracetamol.It is commonly declared that, unlike the NSAIDs, it is a weak inhibitor of the synthesis of prostaglandins. However, in many cellular systems, paracetamol is an inhibitor of the synthesis of prostaglandins with IC50 ranging from approximately 4 µM to 200 µM. Paracetamol is not fixed significantly to plasma proteins.
According to the existing literature and clinical experience, paracetamol is the safest analgesic in short term to treat mild to moderate pain. In long term use or if taken more than 4 grams in 24 hours, it has been reported to be cytotoxic, even leading to necrosis of liver cells. There have been various mechanism described to support the hepatotoxicity of paracetamol. Formation of a reactive metabolite, N-acetyl-p-benzoquinone imine (NAPQI) by cytochrome P450 enzymes, is a well known pathway for necrosis of liver cells.
A systematic review of previous observational studies, published in 2015 and updated in 2016 in the Annals of the Rheumatic Diseases, found that long-term use of paracetamol was linked with a small increased risk of adverse events such as heart attacks, gastrointestinal bleeding and impaired kidney function. It is important to be aware that, as these were observational studies, there is the potential for various sources of bias and confounding factors. The studies were highly variable in their study populations. The authors had concluded that, "the dose-response seen for most endpoints suggests a considerable degree of paracetamol toxicity, especially at the upper end of standard analgesic doses". However, they also accepted that, "given the observational nature of the data, bias may have had an important impact".
Regarding this systematic review, British Newspapers have quoted Professor Nick Bateman, who specialises in clinical toxicology at the University of Edinburgh as: "Based on this study the risk is minimal. Paracetamol remains the safest analgesic available, and this study should not stop people taking it" and "Based on these results, the lowest effective dose for the shortest necessary period is advised, this is common sense for all medicines."
You may access the systematic review at following link:
http://ard.bmj.com/content/75/3/552
Thank you. Has there been any update on its safety during pregnancy?
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