The granddaddy of NSAIDs is aspirin (acetylsalicylic acid), made from a compound found in willow bark and introduced into modern medicine in 1899. Ibuprofen, a non-aspirin analgesic, was introduced in 1974 and is best known as Advil or Motrin. Naproxen was first marketed in 1976, and is best known as Aleve.
The COX-2 inhibitors
In the 1990s drugs were developed to solve the NSAIDs stomach problem. Known as COX-2 inhibitors, they primarily disable the COX-2 enzyme, leaving the COX-1 to do its job protecting the stomach. Vioxx, Celebrex, and Bextra were widely marketed, and became hugely popular prescription-only painkillers. However, in 2004 studies showed that Vioxx can increase the risk of heart attack and stroke, and its maker, Merck, yanked it from the market. More than a dozen cases went to court, and although Merck won many of them, some cases resulted in huge damages against the company. In November 2007 Merck agreed to a massive payout of $4.85 billion to settle thousands of additional cases. In 2005 Bextra was also removed. Celebrex remains on the market.
Acetaminophen, best known as Tylenol, isn't an NSAID. Its exact painkilling mechanism is not fully understood, and it doesn't reduce inflammation. Nor does acetaminophen have many side effectsexcept one whopper: It can damage the liver, sometimes fatally, if taken in large doses or by someone with liver disease (sometimes caused by long-term, regular use of alcohol).