Drug Interactions: Know the Ingredients (cont.)

During the ensuing 24 hours John's jaundiced increased, and he became more lethargic. While neither the internist nor I had a clear explanation for his liver damage, both of us were impressed by the rapidity of his deterioration and realized that unless liver transplantation could be arranged quickly, he would die of liver failure.

Luckily, the medical director of a near-by liver transplantation unit transferred John to his unit as soon as we contacted him. In fact, John lapsed into a coma within minutes of arriving at the unit. (Coma in the setting of rapidly deteriorating liver damage usually progresses rapidly to death.) The transplantation team had to perform emergency liver transplantation using a non-immunologically matched liver. Ordinarily, liver transplant recipients have to wait weeks to months for a liver from a donor who immunologically, is similar to (matches) the recipient to avoid rejection of the organ. In John's case, the non-matched liver kept him alive just long enough until a matched liver became available, and a second transplant could be performed. Today, John is alive and well, and, by my calculation, his children should be graduating from high school soon.

Several months later, I called the transplant director to thank him and the transplant team on behalf of John. The transplant director told me that they were still uncertain of the cause for the liver failure, but examination of John's liver under the microscope suggested drug toxicity-most likely acetaminophen.

Acetaminophen is the pain-reliever in Tylenol. Acetaminophen also is in many prescription and OTC pain relievers and cold/flu remedies. For example, each tablespoon of the common nighttime cold remedy, NyQuil, contains acetaminophen. Similarly, each tablet of hydrocodone/acetaminophen (Vicodin), a popular narcotic painkiller also contains acetaminophen in some of its formulations.

For the average healthy adult, the maximum recommended dose of acetaminophen over a 24 hour period is four grams (4000 mg) or eight extra-strength pills. (Each extra-strength pill contains 500 mg and each regular strength pill contains 325 mg of acetaminophen.). In recommended doses, acetaminophen is quite safe to use for minor headaches, fever, aches and pains. Acetaminophen usually is toxic to the liver only in high doses; a single dose of 7 to 10 grams of acetaminophen (14 to 20 extra-strength tablets) can cause liver damage in the average healthy adult. The most common cause of acetaminophen induced liver damage is suicidal overdose.

Can acetaminophen cause liver damage in lower doses?

The answer is yes. It seems that certain individuals are more prone than others to develop acetaminophen-induced liver damage; doses as low as 3 to 4 grams in a single dose or 4 to 6 grams over 24 hours have been reported to cause severe liver injury, sometimes even resulting in death. People who drink alcohol regularly appear to be especially susceptible to acetaminophen-induced liver damage. Therefore, a person who drinks more than two alcoholic beverages per day should not take more than two grams of acetaminophen (equivalent to four extra strength tablets) over 24 hours.

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