Australasian Science: Australia's authority on science since 1938

Paracetamol Overdose Explained

By Stephen Luntz

The association between paracetamol overdose and liver failure has been explained, accompanied by prospects for resolving the problem.

“Paracetamol is the most frequently used over-the-counter pain medication,” says Dr Grigori Rychkov of Adelaide University’s School of Medical Sciences. “Overdose of paracetamol is the most common cause of acute liver failure and the leading cause of liver damage requiring transplantation in developed countries. The precise mechanisms of liver toxicity due to paracetamol overdose, however, have remained unclear.”

Paracetamol overdose leads to toxic quantities of calcium in the liver, and Rychkov has now revealed that the transient receptor potential melanostatine-2 (TRPM2) channel is responsible, overloading cells with calcium when triggered by excessive paracetamol doses. “We now have a potential drug target for treating paracetamol overdose and possibly some other liver-damaging poisonings,” Rychkov says.

Drugs that block the TRPM2 channel exist, but Rychkov describes them as “laboratory drugs not suitable for humans”. Nevertheless the potential exists to develop TRPM2-blockers with clinical applications.

Currently paracetamol overdoses can be treated within around 18 hours. However, after this point damage to the liver is so severe that it is unable to recover. “Once less than 30% of liver function remains, complete failure can occur, at which point the only option is a transplant,” Rychkov says.

The normal function of the TRPM2 channel is unknown, but Rychkov thinks it may induce cell death in damaged cells to prevent them from becoming cancerous.

Paracetamol overdose is one of the most common forms of poisoning, and can also lead to acute kidney failure. “It is possible the same mechanism is responsible,” Rychkov says. “The same channels exist there, but no one has investigated if they are involved.”

There is some evidence that long-term medium-level use of paracetamol can also contribute to liver damage, but Rychov says “there are not a lot of studies of this”.