A History of Painkillers
In the 1960s, a new class of drugs was developed to help relieve some of the symptoms of rheumatoid arthritis, osteoarthritis, and gout. Called nonsteroidal anti-inflammatory drugs (NSAIDS), the first of these was ibuprofen which was approved by the Food and Drug Administration (FDA) for over-the-counter sale in a reduced strength version. Its usage has grown to the point where it has now surpassed aspirin as the second best-selling nonprescription pain-reliever. Acetaminophen (Tylenol) continues to be the most popular.
Like most drugs, however, ibuprofen can have some undesirable side effects such as stomach pain and bleeding from ulcers and gastritis. Although the probability of occurrence is relatively small—about one to two percent—it cannot be predicted who will have trouble or when. With the release of a study showing that, in some cases, acetaminophen provided the same relieve as ibuprofen for nonflare, intermittent, mild-to-moderate pain from osteoarthritis—without the gastrointestinal risk—many physicians began to recommend that osteoarthritis patients with chronic discomfort and acute swelling reduce their intake of ibuprofen by taking acetaminophen during the day.
Two studies, however, have raised issues concerning possible hazards associated with acetaminophen ingestion. The first, by Thomas Perneger, Paul Whelton, and Michael Klag and published in the New England Journal of Medicine, questions the safety of prolonged usage of acetaminophen (more than 1,000 mg per day and more than 500 g in a lifetime) in terms of increased risk of end-stage renal disease (ESRD). They recommended that people requiring large quantities of analgesic medicine and those at high risk of renal failure use aspirin for pain control.
The second study, by David Whitcomb and Geoffrey Block and published in the Journal of the American Medicine Association (JAMA), suggests that chronic ethanol (alcohol) abuse and fasting may pre-dispose some people to hepatoxicity when taking acetaminophen in higher than recommended dose (4,000 mg per day). Whitcomb and Block recommended future studies on the effects of alcohol and fasting on the metabolic pathways of acetaminophen.
In an editorial response to the first study, Pierro Ronco and Antoine Flahault, writing in the New England Journal of Medicine, noted that:
“…the advertisement and sale of analgesic drugs correlates better with the geographic distribution of analgesic-associated nephropathy than do any other factors, with high rates of both in Switzerland, Belgium, Austria, and the South Eastern United States. On the other hand, the incidence of analgesic nephropathy has been dramatically reduced in Sweden and Australia, mainly because the over-the-counter sale of combination analgesics has been prohibited.”
In the United States, no oral painkiller that contains more than one analgesic compound is available over-the-counter. Ronco and Flahault cautioned, however, that taking large amounts of acetaminophen should be discouraged and care should be exercised. Brian Strom, in an editorial response in JAMA, also commented on the Whitcomb and Block study. Strom suggested that suitable precautions should be taken to preclude ingesting more than the recommended dose, and also called for the implantation of a suitable manufacturers’ warning about the use of acetaminophen by alchoholics.
Thus, the stage was set for debate on acetaminophen use and product safety that continues today.
