Chapter 28 - Adverse events associated with analgesics: A focus on paracetamol use

Abstract

Acetaminophen is one of the most commonly used analgesics worldwide. It can induce toxic liver injury and hypersensitivity reactions. Toxicity may occur after an acute or chronic overdose. The mechanism is mainly associated—in contrast to nonsteroidal antiinflammatory drugs—with the presence of a toxic metabolite. N-Acetyl-p-benzoquinone imine is a product of acetaminophen oxidation via cytochromes and it is directly responsible for hepatotoxicity. Excessive production of this toxic agent, with reduced ability to neutralize it with glutathione, leads to clinically significant liver damage. First line treatment for acetaminophen toxicity is N-acetylcysteine. The criteria for this antidote treatment are based on Rumack-Matthew nomogram, the dose of paracetamol taken and symptoms of liver injury. Early administration of N-acetylcysteine significantly reduces risk of hepatoxicity. Hypersensitivity to paracetamol involve immediate reactions such as urticaria, bronchospasm, anaphylaxis and delayed reactions, including the most the most severe one—SJS/TEN. The majority of patients hypersensitive to NSAIDs tolerate paracetamol up to 500mg. Management of paracetamol hypersensitivity is based on long-term drug avoidance and finding a safe alternative antipyretics.