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Acetaminophen or Paracetamol: Method of Action and Precautions

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 can help a headache, but it needs to be used carefully.

Acetaminophen can help a headache, but it needs to be used carefully.

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 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, ibuprofen, and naproxen, which not only relieve pain and fever but also reduce inflammation.

Aspirin, ibuprofen, and naproxen 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 NSAIDS, though. At recommended doses, it 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. Unfortunately, acetaminophen has the potential to cause liver damage.

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

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.

Four main theories concerning the mechanism of action of acetaminophen exist. 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 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.

Prostaglandin Inhibition

Like NSAIDs, 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 NSAIDs. 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

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 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 particular 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.

The Endocannabinoid System and AM404

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.

Tylenol Safety Recommendations From the Manufacturer

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.

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.

Anyone with questions about acetaminophen safety in their life or in the life of a family member should consult their doctor.

Acetaminophen Dosage Dangers

Your Favorite Medication For Pain Relief

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 maximum dose that is safe should be noted.

In July 2011, the maximum daily dose of Tylenol for adults was lowered from 4 grams or 4000 milligrams to 3 grams or 3000 milligrams to reduce the chance of an accidental overdose. This meant that no more than six extra strength Tylenol (each containing 500 milligrams of acetaminophen) could be swallowed in a twenty-four hour period, or one tablet every four hours. As of 2020, this maximum dose is still in effect according to Tylenol's United States website.

Some researchers think that extra strength acetaminophen shouldn't be available without a prescription because of the potential harm that it can cause. If someone finds that they need to use the maximum dose continually or frequently, it's time to get medical help.

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. The amount needs to be included in the maximum daily allowance of the substance. The School of Medicine at the University of California, San Diego recommends that we don't use a combination product to treat a problem, as does the doctor in the Tylenol video above. If we have a runny nose, for example, we should use a product that contains a single medicinal chemical to relieve the symptom and make us feel better instead of a product containing multiple chemicals.

The dose of any medication should be monitored carefully.

The dose of any medication should be monitored carefully.

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

This content is accurate and true to the best of the author’s knowledge and does not substitute for diagnosis, prognosis, treatment, prescription, and/or dietary advice from a licensed health professional. Drugs, supplements, and natural remedies may have dangerous side effects. If pregnant or nursing, consult with a qualified provider on an individual basis. Seek immediate help if you are experiencing a medical emergency.

© 2013 Linda Crampton

Comments

Linda Crampton (author) from British Columbia, Canada on November 06, 2013:

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

Devika Primić from Dubrovnik, Croatia on November 06, 2013:

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

Linda Crampton (author) from British Columbia, Canada on January 28, 2013:

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

drbj and sherry from south Florida on January 28, 2013:

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

Linda Crampton (author) from British Columbia, Canada on January 25, 2013:

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

Dianna Mendez on January 25, 2013:

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.

Linda Crampton (author) from British Columbia, Canada on January 25, 2013:

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

prasetio30 from malang-indonesia on January 25, 2013:

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

Linda Crampton (author) from British Columbia, Canada on January 24, 2013:

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

Deb Hirt from Stillwater, OK on January 24, 2013:

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

Linda Crampton (author) from British Columbia, Canada on January 23, 2013:

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.

Shining Irish Eyes from Upstate, New York on January 23, 2013:

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.

Linda Crampton (author) from British Columbia, Canada on January 23, 2013:

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

Kathi from Saugatuck Michigan on January 23, 2013:

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!

Linda Crampton (author) from British Columbia, Canada on January 23, 2013:

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

Linda Crampton (author) from British Columbia, Canada on January 23, 2013:

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

Bill Holland from Olympia, WA on January 23, 2013:

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

Wilbart26 on January 23, 2013:

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! :)