How Does Acetaminophen Work? All About Tylenol's Mechanism of Action
Key takeaways:
Acetaminophen is a common, effective option for mild-to-moderate pain and fever but doesn’t treat inflammation.
It works by affecting the brain’s pain and temperature regulation, though its exact mechanism is still not fully understood.
Using acetaminophen safely means sticking to the recommended dose and avoiding alcohol.
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Acetaminophen, commonly known by the brand name Tylenol, is a widely used over-the-counter (OTC) medication. It’s often a go-to treatment for headaches, muscle aches, and fever. But how does acetaminophen work? Here’s what we know about Tylenol’s mechanism of action.
What is acetaminophen?
Acetaminophen is an analgesic (pain reliever) and an antipyretic (fever reducer). People commonly take it for mild-to-moderate pain, such as headaches, menstrual cramps, and sore muscles. It’s also effective for reducing fevers caused by illnesses like a cold or the flu.
But acetaminophen is not a nonsteroidal anti-inflammatory drug (NSAID) like ibuprofen (Advil, Motrin) or naproxen (Aleve). More on that next.
Fun fact: Acetaminophen is typically referred to as paracetamol outside of the U.S. But there’s no difference between the two, other than the name. So if you’re traveling abroad and need some acetaminophen, you may need to keep an eye out for paracetamol on the OTC packaging instead.
How does acetaminophen work?
Even though acetaminophen has been used for decades, we still don’t know exactly how it works. But there are several theories, according to clinical studies.
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One theory suggests that acetaminophen blocks enzymes (proteins) called cyclooxygenase (COX) in the brain and spinal cord. COX enzymes help produce prostaglandins, which are chemicals that increase pain and raise body temperature. By reducing prostaglandin levels, acetaminophen lowers pain and fever.
NSAIDs also inhibit COX enzymes. But they work throughout the body, not just in the brain and spinal cord. So NSAIDs can reduce swelling and have blood-thinning effects, while acetaminophen doesn’t have these effects.
Another theory is that acetaminophen may reduce pain by increasing the pain threshold. This means it may help reduce your sensitivity to pain. Acetaminophen may also work on other pain and temperature-regulating pathways in the central nervous system, including those involving serotonin and cannabinoids.
Does acetaminophen increase blood pressure?
Yes, there’s some evidence that acetaminophen might raise blood pressure. It wasn’t linked to blood pressure changes in the past. But recent studies suggest acetaminophen may cause a small increase in blood pressure. The risk seems to be higher with frequent use or when taken in high doses.
The exact reason for this acetaminophen’s effect on blood pressure isn’t fully understood. But it’s thought to involve how acetaminophen affects blood vessels and fluid regulation in the body. NSAIDs, on the other hand, are strongly linked to increased blood pressure. Acetaminophen still appears to be safer than NSAIDs in this regard based on the information we have.
For most people, occasional use of acetaminophen is unlikely to cause significant blood pressure changes. You can reduce the risk by taking the lowest effective dose for the shortest time needed. But if you have a history of high blood pressure or cardiovascular disease, it’s best to check with your healthcare team before taking an OTC medication for pain or fever.
Is acetaminophen safe?
Acetaminophen is considered a safe medication when taken as directed. But taking too much Tylenol can lead to serious liver damage.
For adults, the maximum daily dose is typically 4,000 mg. But some experts recommend no more than 3,250 mg per day to add an extra margin of safety. Keep in mind that acetaminophen is a common ingredient in many OTC products, including cold and flu remedies. So it's crucial to check the product label of everything you're taking to ensure you aren’t doubling up on acetaminophen by mistake. Be aware that abbreviations for acetaminophen on packaging are common, such as APAP, AC, or acetam. So keep an eye out for those as well.
If you're taking other medications or have existing liver problems, talk to your healthcare team before taking acetaminophen. They can make sure it’s a safe option for you. It’s also best to avoid alcohol while taking acetaminophen, as the combination raises the risk of liver problems.
How much Tylenol is too much? Knowing the maximum dosage of Tylenol (acetaminophen) is important for avoiding Tylenol overdose or liver damage.
Tylenol side effects: Tylenol is usually well tolerated, but it does have some risks to know about.
Combining Tylenol with medications like Aleve or Advil: Typically, taking Tylenol along with Aleve (naproxen) or Advil (ibuprofen) is safe.
It’s also a good idea to talk to your prescriber if:
Your pain or fever lasts longer than a few days despite taking acetaminophen
You’re unsure about how much acetaminophen to take
You’re pregnant or breastfeeding
They can provide guidance on how much, if any, acetaminophen is safe for you.
The bottom line
Acetaminophen (Tylenol) is a trusted over-the-counter medication for pain and fever relief. Even though it’s been used for decades, we still aren’t exactly sure how acetaminophen works. But it seems to reduce the production of prostaglandins — chemicals that increase pain signaling and raise your body temperature. Acetaminophen may also affect other chemicals in the brain and spinal cord that regulate pain and fever.
Unlike nonsteroidal anti-inflammatory drugs (NSAIDs), acetaminophen doesn’t help with swelling. It also doesn’t have blood thinning effects. Acetaminophen may raise your blood pressure a small amount. But this is more common with frequent use and high doses. And acetaminophen is still considered a safer option than NSAIDs when it comes to its effects on the heart.
If you’re living with high blood pressure, heart disease, or liver problems, talk to your healthcare team before taking acetaminophen. They can help make sure it’s a safe option for you.
Why trust our experts?
References
American Chemical Society. (2014). Acetaminophen.
Aronoff, D. M., et al. (2006). New insights into the mechanism of action of acetaminophen: Its clinical pharmacologic characteristics reflect its inhibition of the two prostaglandin H2 synthases. Clinical Pharmacology & Therapeutics.
Ayoub, S. S. (2021). Paracetamol (Acetaminophen): A familiar drug with an unexplained mechanism of action. Temperature.
Dedier, J., et al. (2002). Nonnarcotic analgesic use and the risk of hypertension in US women. Hypertension.
Forman, J. P., et al. (2007). Frequency of analgesic use and risk of hypertension among men. JAMA Internal Medicine.
Freo, U., et al. (2021). Paracetamol: A review of guideline recommendations. Journal of Clinical Medicine.
Gerriets, V., et al. (2024). Acetaminophen. StatPearls.
Llamas, M. (2014). FDA sets acetaminophen dose limit, warns of liver damage. Drugwatch.
MacIntyre, I. M., et al. (2022). Regular acetaminophen use and blood pressure in people with hypertension: The PATH-BP trial. Circulation.
MedlinePlus. (2023). Acetaminophen.
Ohashi, N., et al. (2020). Analgesic effect of acetaminophen: A review of known and novel mechanisms of action. Frontiers in Pharmacology.
Ricciotti, E., et al. (2011). Prostaglandins and inflammation. Arteriosclerosis, Thrombosis, and Vascular Biology.
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