Acetaminophen or Paracetamol: Pain Relief and Precautions

Updated on August 1, 2017
AliciaC profile image

Linda Crampton is a writer and teacher with a first class honors degree in biology. She often writes about the scientific basis of disease.

Acetaminophen is a good medication for a headache, provided the dosage recommendations are followed carefully.
Acetaminophen is a good medication for a headache, provided the dosage recommendations are followed carefully. | Source

Acetaminophen or Paracetamol

Acetaminophen is a very popular pain reliever and is an over-the-counter drug in many stores. It's often the medication of choice for people who have a headache, toothache, muscle ache, or other relatively minor pain. It's also used to reduce fever. The medication is known as acetaminophen in North America and Asia, but in other parts of the world it's called paracetamol.

Acetaminophen is recommended by doctors, dentists, and pharmacists and is a staple product in many people's medicine cabinets. The method by which it relieves pain or reduces fever isn't well understood, however. It's thought to work in a different way from aspirin and ibuprofen, which not only relieve pain and fever but also reduce inflammation.

Aspirin and ibuprofen belong to a class of medications known as nonsteroidal anti-inflammatory drugs, or NSAIDs. Acetaminophen has only a weak ability to suppress inflammation and isn't classified as an NSAID. It does have some important advantages compared to aspirin and ibuprofen, though. At recommended doses, acetaminophen doesn't cause stomach irritation or bleeding. In addition, unlike aspirin it doesn't increase the risk of Reye's syndrome in children. This syndrome is a potentially fatal condition.

This is a ball-and-stick model of an acetaminophen or paracetamol molecule. Black balls = carbon atoms, grey balls = hydrogen atoms, blue ball - nitrogen atom, red balls = oxygen atoms.
This is a ball-and-stick model of an acetaminophen or paracetamol molecule. Black balls = carbon atoms, grey balls = hydrogen atoms, blue ball - nitrogen atom, red balls = oxygen atoms. | Source

An Intriguing Chemical

Acetaminophen is an analgesic (a pain reliever) and an antipyretic (a fever reducer). Its chemical name is N-acetyl-p-aminophenol and its formula is C8H9NO2. It's a white, crystalline substance. Tylenol is a common brand of acetaminophen in North America.

Acetaminophen is produced by chemical reactions in laboratories. It's also made inside the human body from a medication called phenacetin. Phenacetin is obtained from coal tar and was once commonly used as an analgesic and an antipyretic. It's rarely used today because scientists have discovered that it can cause cancer and kidney failure. Acetaminophen is not known to cause cancer and at normal doses doesn't damage the kidneys.

Acetaminophen was first used by the U.S. public in 1955, yet sixty years later its mechanism of action is still unconfirmed. It's believed to work in several different ways. It seems to act mainly on the central nervous system—the brain and the spinal cord—and only slightly on the peripheral nervous system, which consists of nerves extending from the central nervous system to the rest of the body.

Acetaminophen reduces fever, perhaps by preventing prostaglandins from stimulating the hypothalamus in the brain. The hypothalamus regulates body temperature.
Acetaminophen reduces fever, perhaps by preventing prostaglandins from stimulating the hypothalamus in the brain. The hypothalamus regulates body temperature. | Source

How Does Acetaminophen Work?

There are four main theories concerning the mechanism of action of acetaminophen. The drug may influence the action of chemicals called prostaglandins, a membrane protein called TRPA1, a neurotransmitter called serotonin, or a part of the nervous system known as the endocannabinoid system.

Prostaglandins

It's thought that one way in which acetaminophen works is by inhibiting the production of chemicals called prostaglandins. There are many kinds of prostaglandins in the body and they have many different functions. Some prostaglandins are beneficial, while others cause pain, fever, and inflammation.

Even the prostaglandins that cause unpleasant symptoms may be helpful. Pain lets us know that something is wrong with our body and that we need to help it. The increased temperature of a fever speeds up the action of the immune system and helps it to destroy the pathogen (microbe) that is causing the disease. The inflammatory response sends blood, cells, and chemicals to an infected or damaged area to help eliminate pathogens and heal the injury.

Although pain, fever, and inflammation are natural body responses to an infection or injury, prolonged or intense symptoms may be very uncomfortable and even dangerous. This is why medications that stop the production of prostaglandins can be helpful.

Inflammation and chilblains: unlike aspirin and ibuprofen, acetaminophen doesn't reduce inflammation
Inflammation and chilblains: unlike aspirin and ibuprofen, acetaminophen doesn't reduce inflammation | Source

Prostaglandin Inhibition

Like aspirin and ibuprofen, acetaminophen may inhibit a type of enzyme in the body known as cyclooxygenase, or COX. COX activates the reaction that converts the arachidonic acid in our cell membranes into prostaglandins. The ability to block the the production of prostaglandins that cause pain and fever can make a person feel better when they are ill or injured.

Although acetaminophen may interfere with prostaglandins, some researchers think that it blocks the production of the chemicals (or their action) in a different way from aspirin and ibuprofen. There are three types of COX enzymes. NSAIDs influence the level of COX-1 and COX-2. The inhibition of COX-2 produces the benefits of NSAIDs and the inhibition of COX-1 produces their side effects. It was once proposed that acetaminophen works by influencing COX-3. This is considered unlikely today because it's doubtful that COX-3 exists in humans.

A diagrammatic representation of the cell membrane
A diagrammatic representation of the cell membrane | Source

Activation of the TRPA1 Protein

TRPA1 is a protein in the cell membrane of sensory neurons (nerve cells). It acts as a channel that allows substances to pass through the membrane. Researchers at Kings College in London, England, have discovered that mice require functioning TRPA1 proteins in order to experience pain relief from acetaminophen. If the proteins are inactivated, acetaminophen doesn't work. Humans also have TRPA1 proteins, so the results of the experiment may apply to us as well.

Inside the spinal cord of a mouse, acetaminophen is converted to a substance called NAPQI (N-acetyl-p-benzoquinone imine). This substance activates the TRPA1 protein and apparently interferes with the nerve impulses that travel from pain-sensing receptors and nerves to the brain. The process is thought to be responsible for the prevention of pain. Unfortunately, NAPQI is also produced from acetaminophen in the liver of both mice and humans, where it's a toxic substance. The scientists hope to find other substances that activate the TRPA1 protein and are safer than NAPQI.

A synapse and neurotransmission
A synapse and neurotransmission | Source

Neurotransmission

A synapse is the region where one neuron ends and another begins. When the nerve impulse reaches the end of the first neuron, a chemical called a neurotransmitter travels across the tiny gap between the two neurons. Excitatory neurotransmitters bind to receptors on the second neuron and trigger a new nerve impulse.

Effects on the Serotonin Pathway

Serotonin is an important neurotransmitter that has many effects in the brain. One type of serotonin receptor is known as the 5-HT3 receptor. A receptor is a cell membrane protein that binds to certain substances. When the union occurs, a specific process takes place.

Researchers have discovered than when the 5-HT3 receptor is blocked, acetaminophen's ability to relieve pain is reduced. This suggests that acetaminophen works at least in part by causing stimulation of the receptor.

AM404 and Influence on the Endocannabinoid System

The endocannabinoid system consists of cell membrane receptors in the central nervous system and specific lipids that affect the body when they join to the receptors. The system seems to be involved in many body processes, including pain, mood, memory, and glucose metabolism.

The processing of acetaminophen in the body produces a substance known as AM404. This substance inhibits the removal of a chemical that stimulates the endocannabinoid receptors. As a result, the stimulation of the receptors continues to occur. This may be yet another way in which acetaminophen relieves pain.

Safety Precautions for Tylenol

Potential Dangers of Acetaminophen Use

Acetaminophen taken at the recommended dose appears to be safe for most people. Exceeding the dose may be very dangerous, however, and may even be fatal.

When normal doses of acetaminophen are taken, the liver is able to break down the toxic NAPQI that is produced from the acetaminophen by a reaction between NAPQI and glutathione. However, this isn't possible when too much acetaminophen is ingested and not enough glutathione is left in the liver. In addition, even normal amounts of acetaminophen may be toxic for some individuals, such as alcoholics or people with certain enzyme deficiencies in their liver.

The usual treatment for acetaminophen poisoning is the administration of acetylcysteine, which is converted to glutathione inside the liver. However, if the liver damage is severe, the only treatment that may work is a liver transplant. The sooner an affected individual reaches a hospital the more likely he or she is to recover from acetaminophen poisoning.

Acetaminophen Dosage Dangers

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Dose and Safety

Acetaminophen is a very useful pain reliever, but like other medicines it must be treated with respect and kept safely out of the reach of children (and pets). The instructions for maximum doses should be followed very carefully.

In July 2011, the maximum daily dose of Tylenol for adults was lowered from 4 grams (4000 milligrams) to 3 grams (3000 milligrams) to reduce the chance of an accidental overdose. This means that no more than six extra strength Tylenol (each containing 500 milligrams of acetaminophen) should be swallowed in a twenty-four hour period—one tablet every four hours. Some researchers think that extra strength acetaminophen shouldn't be available without a prescription because of the potential harm that it can cause.

It's important to read all medication labels carefully because some products that contain a mix of substances have acetaminophen as one of their ingredients. This acetaminophen needs to be included in the maximum daily allowance of the substance.

The dose of any medication should be monitored carefully.
The dose of any medication should be monitored carefully. | Source

Dealing with the Medication

Some people who find acetaminophen helpful may not care about how it works. The only thing that may matter to them is that their pain disappears. Understanding the medication's mechanism of action is important, however. The drug may have subtle and undesirable effects on the body as well as beneficial ones, even at normal doses.

For now, acetaminophen is a useful addition to a home medicine cabinet, provided the dosage instructions on the medication label are followed. It's advisable to write down the time and dose of each tablet that is ingested in case a person can't remember when they last swallowed a tablet and is tempted to take another one at the wrong time. In addition, if the maximum dose of acetaminophen isn't enough to relieve pain, a doctor's or dentist's advice should be sought to find an alternative treatment.

References

King's College London. (2011, December 14). First study to reveal how paracetamol works could lead to less harmful pain relief medicines. ScienceDaily. Retrieved August 1, 2017 from www.sciencedaily.com/releases/2011/11/111122113205.htm

Acetaminophen Action from the American Chemical Society

Paracetamol Information from Oxford Journals

Questions & Answers

    © 2013 Linda Crampton

    Comments

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      • AliciaC profile imageAUTHOR

        Linda Crampton 

        4 years ago from British Columbia, Canada

        Thank you for the comment, DDE. I'm glad you found the article helpful.

      • DDE profile image

        Devika Primić 

        4 years ago from Dubrovnik, Croatia

        What is Acetaminophen and How Does it Relieve Pain? most helpful and a well informed hub on Acetaminophen I am now enlightened about his tablet

      • AliciaC profile imageAUTHOR

        Linda Crampton 

        5 years ago from British Columbia, Canada

        Thank you very much, drbj. I agree - acetaminophen is an awkward name! Tylenol is much simpler.

      • drbj profile image

        drbj and sherry 

        5 years ago from south Florida

        Thank you, Alicia, for this very thorough examination of acitamin ... acetoming ... acetomin ... Tylenol! Much appreciated. But then your scientific, clear-cut explanations always are. :)

      • AliciaC profile imageAUTHOR

        Linda Crampton 

        5 years ago from British Columbia, Canada

        Thank you very much for the comment, Dianna. I appreciate your visit!

      • teaches12345 profile image

        Dianna Mendez 

        5 years ago

        I thought acetaminophen was just another form of aspirin, but now I know from reading your article that it is completely different as a pain reliever. Interesting and another wonderful hub post.

      • AliciaC profile imageAUTHOR

        Linda Crampton 

        5 years ago from British Columbia, Canada

        Thanks for the comment and the vote, Prasetio. It is confusing that acetaminophen has two different names!

      • prasetio30 profile image

        prasetio30 

        5 years ago from malang-indonesia

        Very informative hub. I had never heard about Acetaminophen, but I am familiar with paracetamol. I learn something new here. Good job, Alicia. Thanks for share with us. Voted up!

        Prasetio

      • AliciaC profile imageAUTHOR

        Linda Crampton 

        5 years ago from British Columbia, Canada

        Thank you very much for the comment, Deb. I appreciate it.

      • aviannovice profile image

        Deb Hirt 

        5 years ago from Stillwater, OK

        This is great information with good reasons to restrict dosages. Everything was so well explained, too.

      • AliciaC profile imageAUTHOR

        Linda Crampton 

        5 years ago from British Columbia, Canada

        I'm sorry that you experience migraines, shiningirisheyes. My sister does too, so I know how debilitating they can be. Acetaminophen helps her only occasionally. Thanks for the visit and the comment.

      • shiningirisheyes profile image

        Shining Irish Eyes 

        5 years ago from Upstate, New York

        Very informative article on this increasingly popular over the counter drug. I have tried taking it for my migraines but it doesn't appear to do much good.

      • AliciaC profile imageAUTHOR

        Linda Crampton 

        5 years ago from British Columbia, Canada

        Thanks for the interesting comment about acetaminophen, Kathi. I'm glad that the other two medications work for you!

      • Fossillady profile image

        Kathi 

        5 years ago from Saugatuck Michigan

        Very useful information Alicia. I usually stay away from acetaminophen cause it makes me feel nauseated. I take ibuprofen or aspirin instead and they both seem to work wonders!

      • AliciaC profile imageAUTHOR

        Linda Crampton 

        5 years ago from British Columbia, Canada

        Thank you, Bill. I appreciate your comment! It's strange that acetaminophen is such a common medication yet is understood so poorly.

      • AliciaC profile imageAUTHOR

        Linda Crampton 

        5 years ago from British Columbia, Canada

        Thanks for the comment, the vote and the share, Wilbart26. It's very nice to meet you!

      • billybuc profile image

        Bill Holland 

        5 years ago from Olympia, WA

        Great information, Alicia! Heard of it, obviously, and used it often, but really knew nothing about it. Thanks for the info.

      • profile image

        Wilbart26 

        5 years ago

        Very informative hub, can't wait to see more of your hubs in the future, in the meanwhile, I will be looking into your profile and gonna read some stuffs, I think your a great writer and hope to be with you here in the writing world for longer time. Happy hubbing, voted up! And shared! :)

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