Acetaminophen (also known as paracetamol) is a p-aminophenol derivative with analgesic, antipyretic, and mild anti-inflammatory effects.1 Although its mechanism of action is not fully understood, it is believed that the drug’s effects are primarily the result of its inhibition of the cyclooxygenase (COX) enzymes in the central nervous system. By blocking the peroxidase function of these enzymes, acetaminophen prevents the synthesis of prostaglandins that mediate pain, fever, and possibly inflammation. Acetaminophen is believed to be slightly selective for COX-2, but it also acts on COX-1 and possibly COX-3 in neural tissues.2 The analgesic effects of acetaminophen may also result from its inhibition of the nitric oxide pathway or its activation of descending serotonergic pathways.3
Acetaminophen has few side effects. Patients should contact a doctor immediately if they experience signs of an allergic reaction to acetaminophen including hives, difficulty breathing, or swelling of the face, lips, tongue, or throat. Patients should also seek medical attention if they experience rare but serious side effects such as nausea, upper abdominal pain, dark urine, clay-colored stools, or jaundice. High doses of acetaminophen can lead to liver damage, especially in patients who also consume large amounts of alcohol.6 Long-term use can also cause renal, hematological, or gastrointestinal tract damage. In rare cases, the drug can lead to serious skin reactions such as Stevens-Johnson Syndrome and toxic epidermal necrolysis.7
Acetaminophen has few major drug interactions, but it is more likely to cause liver damage when taken in conjunction with alcohol. It may also increase the anticoagulant effects of blood thinners such as warfarin.8 The analgesic effects of acetaminophen may be enhanced when it is taken alongside NSAIDs, opioid painkillers, or caffeine.9
Acetaminophen was first synthesized by American chemist Harmon Northrop Morse at Johns Hopkins University in 1877, but it was not tested on patients until 1887. The drug was widely ignored in the following decades because of a claim that it could cause methemoglobinemia, a blood disorder. This claim was discredited in the late 1940’s and acetaminophen was approved for prescription use in the United States in 1953. The drug was marketed as Tylenol starting in 1955 and it was approved for over-the-counter use in 1959.10 Today, acetaminophen is the most commonly used over-the-counter drug for pain relief and fever reduction in both the United States and Europe. It is also on the WHO Model List of Essential Medicines.
Research studies continue to probe acetaminophen’s mechanism of action and the chemical pathways involved in its hepatotoxicity11, as well as the specific consequences of acetaminophen-induced liver damage.12 Some researchers are also seeking prevention strategies: one recent study suggests that taking N-acetylcysteine after an acetaminophen overdose can block liver damage.13
There are also many studies on the efficacy of acetaminophen in combination with other drugs for treating different types of pain. Recent examples include a study on an acetaminophen/opioid combination for treating post-cesarean pain14 and a study on an acetaminophen/N-palmitoylethanolamide combination for treating neuropathic diabetes pain.15
Many compound pharmacists prefer NSAIDs such as Diclofenac Sodium, Flurbiprofen, Ketoprofen, Meloxicam, and Piroxicam, which can treat more severe pain and have stronger anti-inflammatory effects than acetaminophen. Please find more information about our Bulk APIs here.