President Trump’s unhinged, ill-informed and potentially dangerous diatribe aimed at Tylenol is a demonstration of his scientific illiteracy soaring to record heights. Many others have, and will dissect the distressing drivel he spouted, but I’ll take his vilification of Tylenol as an opportunity to discuss the history of this medication.
Trump’s tirade is not the first time that Tylenol has made the headlines. In 1982, thirty-one million bottles were recalled because some wretched soul, who was never caught, had managed to open capsules and insert potassium cyanide before placing the bottles with their poisoned contents on pharmacy shelves to be purchased by unfortunate customers seven of whom died.
This tragic episode had nothing to do with the pain-killer’s active ingredient, acetylaminophenol, which also gives rise to the drug’s trade name, aceTYLaminophENOL. That ingredient is also known as acetaminophen in North America and paracetamol elsewhere. Given that acetaminophen can be found in some 600 products, it was grossly unfair for the President to single out Tylenol in his mind-rupturing rant. But that simplified the harangue for him because as we witnessed, he was unable to pronounce “acetaminophen.”Â
Now for a little history lesson. Back in 1884, two young German physicians, Arnold Cahn and Paul Hepp, made a serendipitous discovery when treating a patient who was infested with worms and was running a fever. On the advice of their mentor, Professor Adolf Kussmaul, the two doctors tried administering naphthalene, believed at the time to be effective against worms. It did nothing for the worms, but did reduce the patient’s fever, an effect that had not previously been described. Â
Intrigued, Cahn and Hepp wondered whether the naphthalene they purchased may have contained some other substance as well. Tracking down the source, they discovered that the pharmacy had made a mistake and had provided acetanilide instead of naphthalene. In those days pharmacies dispensed not only drugs, but also stocked chemicals used in research laboratories. One of these was acetanilide, a derivative of aniline, a compound that had recently been isolated from coal tar and used in the production of the novel synthetic dyes that were all the rage. It now occurred to Cahn and Hepp that acetanilide might be a useful fever reducer. As luck would have it, Hepp’s brother worked as a chemist at the Kalle pharmaceutical firm which was willing to investigate the compound. Finding that it did indeed reduce fever, acetanilide was put on the market as “Antifebrin.”
Unfortunately, it wasn’t long before a problem cropped up. Users complained of “blueish skin,” a sign soon identified as methemoglobinemia, a condition in which oxygen transport by hemoglobin is impaired. This stimulated a search for safer alternatives. As is still common today, such a search involves making alterations in the molecular structure of a compound, hoping to eliminate side effects while maintaining its therapeutic potential. In 1887, the German company Bayer modified acetanilide to produce phenacetin which did not cause methemoglobinemia. The same year, physician Joseph von Mering tried another derivative of acetanilide that had been synthesized by Harmon Morse at Johns Hopkins university. This was acetaminophen, which worked well as a pain reliver and fever reducer, but von Mering claimed that unlike phenacetin, it had a potential to produce methemoglobinemia. For this reason, acetaminophen languished on laboratory shelves until 1947 when researchers discovered that both acetanilide and phenacetin were converted into acetaminophen in the body and the latter was the actual active agent! Furthermore, von Mering had been wrong, even large doses of acetaminophen did not cause methemoglobinemia in rats. Â
In the meantime, phenacetin had been linked with kidney problems, and its competitor, aspirin, with stomach irritation and Reye’s syndrome, a rare children’s disease. This set the stage for the promotion of acetaminophen as a safer drug and led to its mass marketing as Tylenol in 1955. Acetaminophen turned out to be a popular pain reliever and fever reducer, safe when taken in the proper dose, which for an adult is a maximum of eight 500 mg pills a day. Exceeding this dose can lead to serious problems due to a metabolite of the drug being toxic to the liver. (N-acetyl-p-benzoquinone imine, if you must know). Just 20 pills of acetaminophen taken over a short period can be lethal!
Normally, the toxic metabolite is mopped up by glutathione, one of the body’s prime detoxicating agents, but it cannot handle an overdose. Indeed, acetaminophen overdose is the predominant cause of acute liver failure in industrialized countries and is the prime reason for liver transplants. Luckily, the vast majority of the 60,000 emergency room visits a year in North America due to acetaminophen toxicity do not have such dire consequences thanks to emergency rooms stocking an antidote, N-acetylcysteine (NAC), which can help replenish glutathione. Â
Today, the global annual acetaminophen market is an astounding nine and a half billion dollars, fueled by heavy promotion that emphasizes the lack of gastrointestinal side effects associated with aspirin and other non-steroidal anti-inflammatory drugs (NSAIDS). While the concern about liver toxicity has to be recognized, there is no worry about cyanide-tainted Tylenol. A consequence of the 1982 poisoning case was the development of tamper-proof packaging that features a plastic seal, an aluminum foil cover, and a pop-up cap. If you have an ordinary headache, the struggle is worth it. But no amount of acetaminophen will cure the headache caused by listening to Trump’s disjointed pseudoscientific rampage about the evils of Tylenol during pregnancy. “Just grin and bear the pain and fever” is just drastically dangerously dumb.
