Do not give Tylenol to infants under 12 weeks of age without talking to your healthcare provider or pediatrician.The research was supported by grants from the National Science Foundation (EF-1038593, DMS-0943760) and the National Institutes of Health (R01 ES019876). “NAC has been the standard antidote for acetaminophen overdose for decades, and we are excited at the chance of improving it,” the authors said. To test the model, the researchers plan to treat overdosed mice with different relative concentrations of NAC and glutamine - which the liver converts to glutamate - to see which dosing combinations maximize their survival. Usually the glutathione precursor in shortest supply is cysteine, which is also found in NAC.īut the researchers discovered that after an overdose, liver cells turn on a gene that shuttles desperately-needed cysteine into the cell but pumps glutamate out, until eventually glutamate levels start to run low, too. Most of what the body needs to make glutathione comes from three amino acid precursors - glycine, glutamate and cysteine. The standard antidote for acetaminophen overdose is a drug called N-acetylcysteine, or NAC, which helps restore glutathione levels to normal by adding the glutathione precursor that is usually in shortest supply.īut by modeling the dozens of biochemical reactions involved in synthesizing, transporting and breaking down glutathione in the body, the researchers found that the rarest ingredient changes over time. Trouble starts when the recommended dose of acetaminophen is exceeded, and the body’s natural detox process requires more glutathione than the liver can make. To find out if tweaking current overdose protocols could prevent fatal liver damage, Duke mathematicians Lydia Bilinsky and Mike Reed and Duke biologist Fred Nijhout developed a mathematical model of acetaminophen metabolism, based on previous studies of lab rats given high doses of the drug.Īcetaminophen is broken down in the body into several byproducts, one of which can be toxic to the liver.Īt normal doses, the liver is able to clean this toxin from the body with the help of a naturally-occurring protective molecule called glutathione. Many cases involve children or infants whose parents accidentally measure the wrong dose in the middle of the night, or combine different medicines without realizing that they all contain the same ingredient - for example, Tylenol for a fever and then a second medicine for a cough. each year as a result of acetaminophen overdose.
More than 44,000 people end up in the emergency room and four hundred people die in the U.S. In extreme cases patients die unless they get a liver transplant.
But taking more than the maximum recommended dose of four grams per day can damage the liver. in 2009 alone, making it the most widely-used over-the-counter or prescription drug in the country.Īvailable without a prescription for more than 50 years, the drug is safe when used as directed. More than 27 billion doses of acetaminophen-containing products were sold in the U.S. take at least one acetaminophen-containing product a week. Known for relieving minor aches and pains without upsetting the stomach like some other pain medicines, acetaminophen is a major ingredient in Tylenol and more than 600 other store brand pain relievers, fever reducers, cold remedies and allergy medicines, as well as prescription painkillers like Percocet and Vicodin. The results appear online and are scheduled to be published in the July 2015 issue of the Journal of Theoretical Biology. The findings suggest that giving patients glutamine - a common amino acid in the body - alongside the standard antidote for acetaminophen overdose could prevent liver damage and boost the body’s ability to recover. Researchers at Duke University have developed a mathematical model of acetaminophen metabolism based on data from lab rats. New research could help reverse deadly side effects caused by excessive doses of the drug acetaminophen, the major ingredient in Tylenol and many other over-the-counter and prescription medicines.
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