As Dr. Laura James held her left palm up off of her desk, the silver thread in her blue multishade sweater glinted under the fluorescent lights. She then swiftly raised her right hand, palm down high above her head.
"This is the normal distance between a drug's normal dosage and when it reaches toxic levels," James said before lowering her right hand to within 5 inches of her left palm.
"This is the difference from safe to dangerous levels of acetaminophen," she said grimly. "It's much easier to overdose on acetaminophen than any other over-the-counter drug out there."
James has led a research team at the Arkansas Children's Hospital Research Institute for the past nine years in the development of the nation's only test that rapidly detects acetaminophen through protein compounds called cysteine adducts in blood.
James -- also a pediatrics professor at the University of Arkansas for Medical Sciences -- said the daily adult recommended dosage of acetaminophen is 4 grams, or eight 500 mg tablets. She recommends no more than six 500 mg pills in a 24-hour period. An overdose can occur at just 7 grams, or 14 of the 500 mg tablets.
Acetaminophen -- the most common drug ingredient in the United States -- is used in more than 600 different over-the-counter and prescription medications. It has been linked to about 980 deaths per year, according to statistics from the U.S. Food and Drug Administration.
Beyond the widely used over-the-counter drug, Tylenol, acetaminophen is also found in frequently prescribed pain relievers such as Percocet, Tramadol, Tylenol with Codeine and Vicodin.
A lethal overdose manifests initially in severe abdominal pain and nausea and can quickly lead to liver and renal injury, said Howell Foster, the director of the Arkansas Poison and Drug Information Center. Death can occur within hours of an overdose, or even sooner depending on the circumstances, he added.
Long-term, consistent use of the drug can also have the same effects. In fact, acetaminophen use is the nation's leading cause of acute liver failure, according to the National Institutes for Health.
The state's poison hotline receives about three calls per day concerning acetaminophen overdose in adults and children, Foster said. The center received about 1,063 acetaminophen-related calls in 2014.
"There were 337 suicide attempts or suicidal gestures in those 1,063 cases. We deal with an acetaminophen-associated suicide almost daily," Foster said.
The new test to rapidly detect acetaminophen, called AcetaSTAT, can be lifesaving, said Dr. William Lee, a disease specialist and professor of internal medicine at the University of Texas Southwestern Medical Center in Dallas, who has consulted with James since the study's inception.
"We think this is a very robust invention with a lot of promise. It will likely be taken up by every emergency room in the country once it makes it to market," Lee said.
Working with UAMS BioVentures, James and UAMS faculty members Dean Roberts and Jack Hinson formed the company Acetaminophen Toxicity Diagnostics LLC to develop and eventually market the test. The 2006 startup has received more than $2.2 million in grants from the National Institutes of Health for study and development of the innovative product.
The application of the test was primarily to determine if liver damage in patients was caused by acetaminophen overuse, as opposed to other common causes, such as alcohol use.
There is treatment for acetaminophen liver injury, and knowing that the damage is from the painkiller instead of other causes brightens the long-term prognosis, James said.
"Research has shown that [patients with] severe cases of acetaminophen liver injury are more likely to survive than other cases of liver injury. So it is possible that in the future the test could be used to help make decisions about liver transplants in the individual patient," James said.
"Knowing that a patient has acetaminophen liver injury is actually good news compared to what we know about survival from other cases of acute liver injury."
Lee said the test also has more immediate implications because it can save lives in emergency rooms when patients arrive exhibiting overdose symptoms, especially if they are unconscious.
"They are comatose. They can't tell you which drugs they took," Lee said."Within 20 minutes, we can know definitively that it was acetaminophen and can administer the antidote. It cannot reverse damage, but it can stop further injury or death."
There is a test that will produce the same results, but it is administered by highly skilled technicians in a hospital laboratory with complicated, expensive equipment, and it typically takes at least 48 hours to get results.
The diagnosis of acetaminophen-related liver injury is currently based on an elevated level of the drug in the blood and a patient history of overuse of the drug.
The new test works much like an at-home pregnancy test, using a patient's blood sample on a disposable dipstick, James said. It takes only a matter of minutes to get results.
Acetaminophen stays in the bloodstream for about 24 hours, but James' test measures cysteine adducts that form with the drug's overuse. The protein marker stays in the blood for up to nine days, making it possible to diagnose acetaminophen poisoning after the drug has already left the bloodstream.
Denise Robertson, a pharmacist and the prescription monitoring program administrator for the Arkansas Department of Health, said education and increasing awareness about the drug's potentially deadly and debilitating side effects are crucial.
"People just don't realize how close they can come to overuse," Robertson said. "It's very easy to overdose."
Single father Kevin Baxter of Des Arc said he was not aware of the damage that acetaminophen could cause or the amount it would take for an overdose. It has been his pain reliever of choice for his 9-year-old daughter, Callie, when she is running a fever or has a headache.
Acetaminophen is the only pain reliever Baxter can take because he has hemophilia factor 9 disorder, meaning his liver does not produce enough of the enzyme to make his blood clot.
Robertson said it is important for consumers, especially parents, to closely read bottle labels.
"The children's products can vary as to the concentration. Read the instructions and don't change up your measuring devices. One might be a little cup and another might be a little dropper. They measure differently," Robertson said.
She added that patients should communicate with their pharmacists to determine if any prescribed medication contains acetaminophen.
"Be sure you are only taking one medication at a time that contains acetaminophen so that you don't double up on the dose," Robertson said.
J.R. Thrift of Macon said acetaminophen is the strongest medication he can take for pain from a previous leg and neck injury. He realizes the danger of the drug, he said, and had a "clear" liver test three years ago.
"I have a non-narcotic doctor, and I prefer it that way," Thrift said. "I only take them when I'm hurting too bad, when I get to the point that I'm bawling. Otherwise, I get out of the house and work on my property to try to take my mind off the pain."
The new test is in the final stages of development and review by federal authorities, but it could take a couple more years to be approved for market by the federal Food and Drug Administration.
"This has been a passion of mine for 10 years. As an early faculty member, we had three kids die one year from acetaminophen overdose. I have teenagers of my own now," James said. "I was frustrated with the lack of diagnostic tools. I just felt that as a medical community we could do better."
State Desk on 03/22/2015