Authors Sher Mohammad and others discuss one of the most frequently used medicines around the world
Brief History of Paracetamol/Acetaminophen
In the 1880s, two young doctors at the University of Strasburg, to eradicate worms, by mistake dispensed acetanilide to a patient instead of naphthalene. They noticed that the drug had a small impact on intestinal parasites, however, it significantly decreased high temperature. Young doctors, Arnold Cahn and Paul Heppa, quickly published their discovery and acetanilide was introduced into medical practice in 1886 under the name antifebrin. Soon it appeared that although the production of the drug was very cheap, acetanilide could not be used as an antipyretic medicament due to its high toxicity, the most alarming was met-hemoglobinemia. A few years later, paracetamol was found to be a metabolite of acetanilide. This discovery was largely ignored.
Phenacetin was introduced as antipyretic in 1887. Six years later, paracetamol was discovered in the urine of individuals who had taken phenacetin, and was concentrated into a white, crystalline compound with a bitter taste. So, a major portion of a dose of phenacetin would be rapidly metabolised to paracetamol, it seemed possible that phenacetin owed some of its antipyretic activity to its main metabolite, paracetamol, whereas its most troublesome side effect (methemoglobinemia) was due to another metabolite-phenetidine. So, phenacetin was discontinued as antipyretic.
It was obvious that paracetamol could be derived from the above-mentioned chemicals, but by this time, paracetamol had already been synthesized by Harmon Northrop Morse [1] via the reduction of p-nitrophenol with Tin in glacial acetic acid.
p-nitrophenol + acetic acid Sn N-acetyl-p-aminophenol
While this synthesis was first performed in 1873, paracetamol was not used medically for another two decades. N-acetyl-p-aminophenol appeared to be the most satisfying compound, which was introduced for limited use in 1893, and for wide unrestricted use after 1950s.
Both paracetamol and acetaminophen are contractions of the chemical names for the compound. The word” paracetamol” is a shortened form of para-acetyl-aminophenol, and was coined by Frederick Stearns & Co in 1956. While the word” acetaminophen” is a shortened form of N-acetyl-p-aminophenol (APAP), and was coined and first marketed by McNeil Laboratories in 1955.The initialism APAP is used by dispensing pharmacists in the United States. So, there is no difference between acetaminophen and paracetamol, they are both generic names for a chemical substance known as N-acetyl-p-amino-phenol.
Paracetamol is the British and Australian Approved Name as well as the international non-proprietary name used by WHO and in many other countries; acetaminophen is the US adopted name and Japanese accepted name, and the name generally used in Canada, Venezuela, Colombia and Iran.
Paracetamol is one of the most frequently used medicine around the world. Today, paracetamol is used by patients of practically all ages and for indications and is available over the counter. Such wide utilization is primarily due to its proven antipyretic and analgesic actions.
Pharmacology of ACETAMINOPHEN
Paracetamol is well absorbed from the gut and readily inactivated in the liver by conjugation to its glucuronide and (to a lesser degree) sulphate. Any fraction that is not conjugated, then undergoes CYP 450 metabolic pathway being converted to cytotoxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI).
Table-1: Pharmacology of ACETAMINOPHEN
Risk factors for paracetamol toxicity
Paracetamol poisoning can occur accidentally or as an attempt