Painkiller overdose unravelled

    Press/Media: Research


    More light has been shed on the devastating effects of taking an overdose of paracetamol.

    Scientists believe that the presence of a particular body chemical hinders the body's attempts to deal with the poisons produced by taking large quantities of the painkiller.

    This could eventually help doctors come up with the most effective treatments for paracetamol poisoning, although this is only a small step towards this.


    Overdose with paracetamol is an horrendous way to die
    Professor John Henry

    There are an estimated 70,000 cases of intentional paracetamol overdose in the UK each year, and more than 350 deaths.

    If taken in sufficient quantities, and medical attention is delayed, then irreversible liver damage can be caused.

    Far from proving a swift and painless method of suicide, dying from paracetamol poisoning can take as much as two weeks, and involve intense pain and discomfort.

    The scientists, from the Imperial Cancer Research Fund's Molecular Pharmacology Unit in Dundee, identified a body chemical, or enzyme, called GST Pi, which appears to have an effect on the way the body deals with the toxic by-products of paracetamol.

    If taken in normal quantities, then paracetamol is broken down harmlessly by the body, but if enough of the drug is taken, a substance called NAPQI is produced, which can prove highly toxic to cells.

    A chemical called glutathione can help by binding with NAPQI, and rendering it harmless. The more glutathione there is, the less damage there will be to liver cells.

    Genetically-altered mice

    Professors Roland Wolf and Colin Henderson from the unit wanted to examine exactly what role GST Pi has on paracetamol toxicity.

    They compared mice genetically engineered not to produce the enzyme with normal mice.

    The mice without any GST Pi appeared to suffer far less cell damage than ordinary mice.

    They believe that the enzyme may get in the way of a natural defence which protects a cell from damage by toxic compounds like NAPQI.

    Professor Wolf said: "Therefore, a lack of GST Pi would mean a cell would be less sensitive to toxic attack while the presence of GST Pi interferes with a cell's defence, making it more susceptible to paracetamol toxicity."

    The research may eventually even have applications in the fight against cancer, helping scientists find ways of either making tumours more vulnerable to chemotherapy, or protecting healthy tissue from its effects.

    Dr Colin Henderson said: "This study doesn't just have implications for paracetamol overdoses, because GST Pi is found in nearly all normal cells and cancer cells, it looks like an important factor in cell sensitivity to toxic chemicals in general."

    'Unlikely to alter treatment'

    Professor John Henry, a toxicologist from Imperial College London and St Mary's Hospital, Paddington, said that the research represented a step forward, although it was unlikely to influence the immediate treatment of paracetamol overdoses in accident and emergency.

    He said doctors already treated overdoses with drugs which convert to glutathione in the body to mop up paracetamol's toxic by-products.

    He said: "Overdose with paracetamol is an horrendous way to die.

    "You get people who have changed their minds about suicide, but the damage has already been done.

    "It is important to get medical help as soon as possible.

    "Once you get beyond 20 hours, there are not many treatments that will make a difference."

    The research was published in the Proceedings of the National Academy of Sciences.

    Period6 Nov 2000

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