Pharmacological and toxicological effects of paracetamol: current knowledge and a review

Paracetamol, commonly referred to as acetaminophen, is a widely used pain reliever and fever reducer. It is effective in treating mild to moderate pain and fever. The drug's mechanism of action involves inhibition of prostaglandin synthesis in the central nervous system, which reduces pain and fever. Paracetamol is generally well-tolerated at therapeutic doses, with minimal gastrointestinal side effects compared to nonsteroidal anti-inflammatory drugs (NSAIDs). However, paracetamol toxicity is a significant concern, particularly in cases of overdose. The primary site of toxicity is the liver, where excessive doses lead to the accumulation of a toxic metabolite, N-acetyl-p-benzoquinone imine (NAPQI). This metabolite depletes glutathione and causes oxidative stress, resulting in hepatocellular damage and potentially acute liver failure. Renal impairment and pancreatitis are also associated with paracetamol toxicity, though less commonly. Risk factors for toxicity include chronic alcohol use, fasting, and concurrent use of enzyme-inducing drugs.