Paracetamol: The drug we know, the uses we don’t



  • History of Paracetamol
  • Chemical Properties
  • Mechanism of Paracetamol
  • Medical Uses
  • Adverse Effects
  • Conclusion



Fast paced life in today’s time is inclusive of dead-lines for numerous targets, increasing traffic and competitiveness, even a small thought of these problems is enough for giving you headache. Speaking of headaches, the first word which comes in mind immediately is ‘Paracetamol’. The work horse painkiller has been part of our lives and medical kit since decades. It is in fact most trusted drugs of many families across the globe and yet majority of them are not aware of its various uses and benefits.


History of Paracetamol


It takes us back to ancient and medieval times, when the people existing in that era knew about antipyretic agents were actually the compounds contained in white willow bark of a tree majorly found in Central Asia and Europe, which is in fact family of chemicals ‘Salicin’, which similarly also leads to development of another famous drug ‘Aspirin’ and also about compounds contained in South American native tree called cinchona. Later cinchona bark was also used to create the anti-malaria drug ‘quinine’. Like white willow bark, even quinine also has antipyretic effects. Various researches and programs were undertaken in mid and late nineteenth century in order to refine and isolate salicin and salicylic acid and was accomplished by Bayer chemist Felix Hoffmann.

Too much cutting down of cinchona tree led to its scarcity in the year 1880 and this led to people finding a replacement for it. Alternative antipyretic agents by the name of acetanilide and phenacetin were discovered in year 1886 and 1887 respectively. Finally an American chemist named as Harmon Northrop Morse was the man, who invented paracetamol as he synthesized paracetamol via the reduction of p-nitrophenol with tin in glacial acetic acid in the year 1878 itself, but wasn’t used for almost 15 years. In 1893, urine samples of individuals who consumed phenacetin were tested and as result paracetamol was found in them, this was then concentrated into a white, bitter tasting crystalline compound. 1899, was remarkable year of medical science, when paracetamol was discovered as metabolite of acetanilide.

Decades later in the year 1946, New York City Department of Health was awarded a grant by Institute for the Study of Analgesic and Sedative Drugs in order to find out the problems associated with analgesic agents. Two researchers were assigned task of investigating the reason behind association of non-aspirin with the development of methemoglobinemia, a condition that decreases the oxygen-carrying capacity of blood and is incredibly lethal. Subsequently in year 1948, Brodie and Axelrod made a conclusion that use of acetanilide with methemoglobinemia and metabolite paracetamol was the reason behind analgesic effect of acetanilide. They also stated that paracetamol should be used as it has no toxic elements.

McNeil Laboratories was the first company to sell paracetamol product as a pain and fever reliever for kids, by the brand name Tylenol Children’s Elixir in the year 1955. Later it started gaining popularity in UK and other countries by the name of ‘Panadol’, which was produced by Frederick Stearns and Co.




Chemical Properties

Paracetamol is made of a benzene ring core, which is substituted by one hydroxyl group and the nitrogen atom of an amide group in para pattern. This amide group is acetamide, which means solid crystalline form of acetic acid and is musty in odour. It is densely conjugated system, reason being the lone pair on the hydroxyl oxygen, the benzene pi cloud, the nitrogen lone pair, the p orbital on the carbonyl carbon, and resulted pair on the carbonyl oxygen are all conjugated. The presence of two activating groups result in making the benzene ring highly reactive towards electrophilic aromatic substitution. While the substituents are ortho, para-directing and para with respect to each other, meaning all positions on the ring are more or less equally activated. Conjugation which was formed also resulted in greatly reducing the basicity of the oxygens and the nitrogen, in parallel making the hydroxyl acidic through delocalisation of charge developed on the phenoxide anion.

Paracetamol is not a Non-steroidal Anti-inflammatory Drugs (NSAID), despite having similarity with NSAIDs because of pharmacological activity and this is why it can be used regularly.


How Paracetamol works

Paracetamol generally works against pain or reduces fever by cutting down the production of prostaglandins, pro-inflammatory chemicals which are sometimes inhibited by aspirin, but on contrary to aspirin, paracetamol has low anti-inflammatory action. As aspirin inhibits the production of the pro-clotting chemicals thromboxanes, paracetamol refrains from doing so. Aspirin is also known to inhibit the cyclooxygenase (COX) family of enzymes and paracetamol also has similarity with aspirin’s this action, it was found that paracetamol works in dual ways when it comes to releasing of COX enzymes.

Speaking of COX, these family of enzymes is responsible for the metabolism of arachidonic acid to prostaglandin H2, which is an unstable molecule that is converted to numerous other pro-inflammatory compounds as other conventional NSAIDs block this process. This activity of the COX enzyme relies on whether the enzyme is in oxidized form or not. It has been shown that paracetamol is instrumental in reducing the oxidized form of the COX enzyme thus preventing it from forming pro-inflammatory chemicals.

Metabolism of paracetamol takes place in the liver, where the process includes inactive sulfate and glucuronide conjugates as they part of excreted contents from kidneys. Very small amount is metabolised with the help of hepatic cytochrome P450 enzyme system, which is responsible for the toxic effects of paracetamol due to a minor alkylating metabolite (N-acetyl-p-benzo-quinone imine, abbreviated as NAPQI). Various study states that there is great deal of polymorphism in the P450 gene, and genetic polymorphisms in CYP2D6. Metabolism of paracetamol also depends on metabolic capabilities of individual, hence resulting that toxic nature of paracetamol is not because of itself, but the metabolite NAPQI.

Annually there are cases of over 100,000 Paracetamol overdose as results in more calls to poison control centers in the US than overdose of any other pharmacological substance, which accounts to almost 56,000 emergency room visits, along with 2600 hospitalizations and 458 deaths due to acute liver failure per year. During the period of November 2000 and October 2004, a study was conducted by Centers for Disease Control and Prevention (U.S) towards cases of acute liver failure and found significant amount of data related to effects of paracetamol on adults and kids

The toxic metabolite NAPQI at specific doses was quickly detoxified by combining irreversibly with the sulfhydryl groups of glutathione or administration of a sulfhydryl compound such as N-acetylcysteine, to produce a non-toxic conjugate that is eventually excreted by the kidneys. Also, methionine has been recommended in some cases, although recent studies show that N-acetylcysteine is a more effective antidote to paracetamol overdose





Paracetamol is available in almost every part of the globe, but with different names. In areas like Europe, Africa, Asia, Central America and Australia, this drug is marketed by the name of ‘Panadol’. With the trade name of Tylenol, it is sold in most generic form in the region of North America.

In the United States and Canada, it is again sold under the name of Tylenol with variety of content of paracetamol. While the paracetamol is available only by prescription in U.S, and over-the-counter in Canada, and, in other countries, other strengths may be available over the counter. There are numerous generics also available. In countries like U.K, this combination of paracetamol is sold under the names of Tylex CD and Panadeine, while other names include Captin, Disprol, Dymadon, Fensum, Hedex, Mexalen, Nofedol, Paralen, Pediapirin, Perfalgan, and Solpadeine. In some countries, paracetamol is also combined with other opioids such as dihydrocodeine and codeine, referred to as co-dydramol oxycodone or hydrocodone and co-codamol respectively, while sold in the U.S. as Percocet and Vicodin, respectively. Another most commonly used analgesic combination of paracetamol is with propoxyphene napsylate, sold under the brand name Darvocet, also combination of paracetamol, codeine, and the calmative doxylamine succinate is marketed as Syndol or Mersyndol. Paracetamol is generally used in multi-ingredient preparations for migraine or tension headaches, usually inclusive of butalbital and paracetamol with or without caffeine, and sometimes containing codeine.

The forms in which paracetamol is commonly available are tablet, liquid suspension, suppository, intravenous, or intramuscular.




Medical Uses


Headaches: The most common purpose of paracetamol is to cure headaches. Various researchers from countries like Austria, Germany and Switzerland have jointly stated that consumption of paracetamol along with caffeine is one of the best remedies for headaches caused by migraine and tension. These claims were made after carrying tests on numerous people with similar headaches.


Fever: Second in line is fever, paracetamol is instrumental in reducing fever of people from different age group, depending on amount of dosage. In case of children, it is only advised to be consumed after they have temperature higher than 38.5 degree C. as per stated by World Health Organisation (WHO). Paracetamol also don’t have any anti-inflammatory effects and compared with ibuprofen, it is less effective in kids.


Osteoarthritis: People with arthritis pain are very common around the world, as every one of them is suffering with pain of at least one body parts like hip, hand or knee and that cannot be treated with general exercise and diet. A study say paracetamol is partially effective in osteoarthritis as it has very less anti-inflammatory properties compared with its other analgesic contemporaries as ibuprofen and aspirin. Paracetamol is effective in mild osteoarthritis but have no effectiveness against swelling and redness of joint.


Pain: People have been using paracetamol in moderate body pains and there are conclusive evidences showing it efficiency in countering body as it reduces the production of prostaglandins in the brain and spine. Production of prostaglandins is due to response to injury and various diseases and reduction in prostaglandins will stop the feeling of pain.

Lower Back: People mostly working in IT companies and travelling for chunk time in a day are prone to back aches, especially in lower backs. Paracetamol has found to deliver soothing effect in lower back ache as per few studies.




Adverse effects of Paracetamol

Like every other drug, even paracetamol has its list of adverse effects. The adverse effects are as follows


  • Liver Damage
  • Skin reactions
  • Asthma
  • Mild gastrointestinal effects


The reason of all these adversities are related to dosage of these drug. Paracetamol abuse can lead to all the above said ailments. So they are recommended to consume as per the dose prescribed by Doctor or any practicing medical physician.



Like every other scientific or medical invention, the drug paracetamol was invented in order to treat human ailments and provide some form of relief.  The instant relieving and harmless part of paracetamol makes it a mandatory part of your life and this is also the same reason to use in advised proportions. Invention of paracetamol has proved path breaking in the world of medical science and has successfully served its purpose till date. Along with humans, these drug has also played an important role in treating few ailments in animals like Cat and Dogs. Paracetamol is definitely the drug we trust but we should also be aware of every aspect of it.