How to use antipyretic and analgesic drugs Tylenol and ibuprofen correctly?

Recently, many places across the country have relaxed their epidemic prevention policies and advocated that "everyone is the first person responsible for their own health", which means that everyone should be prepared to deal with the virus and protect themselves. If you are unfortunately infected with the Omicron strain, one of the most likely symptoms is fever, and the first item on the "medicine list" circulating on the Internet is also antipyretics. So, how should antipyretics be used? Which is better, ibuprofen or Tylenol?

This article by drug development expert Shi Jun answers common questions about the use of ibuprofen and Tylenol.

Written by | Shi Jun

Flu and the common cold

Before explaining antipyretic and analgesic drugs, let us first understand the difference between the common cold and flu.

The common cold and flu are both respiratory diseases, but they are caused by different viruses. Most common colds are caused by respiratory viruses (there are more than 200 kinds), and a small number of diseases are caused by other viruses or even bacteria. Because of the similar symptoms, they are also classified as colds; while flu is caused by specific influenza viruses (such as the famous avian influenza H5N1).

Generally speaking, flu symptoms are more severe than the common cold. People with a cold may have a runny or stuffy nose, but they usually do not lead to serious health problems such as pneumonia, myocarditis, or hospitalization, while flu can cause very serious complications. Because the two types of illness have similar symptoms, it is often difficult to distinguish them based on symptoms alone. Usually, special tests must be done within the first few days of illness to determine whether you have the flu.

Differences between Flu and Common Cold

Flu can be effectively prevented by getting a flu shot. However, we often hear people ask, "I got a flu shot, why am I still sick?"

First, you may not have the flu, so the flu vaccine is useless. Second, the annual flu vaccine only targets 3-4 flu viruses that are predicted to be prevalent, and the virus you are infected with may not be targeted by this year's vaccine. Finally, some people may still be infected with the flu virus covered by the vaccine despite being vaccinated, because the protection provided by the vaccine varies greatly from person to person and is related to a person's health status and age. In general, vaccines work best in healthy young people and older children. The elderly and people with certain chronic diseases have weaker immunity and do not respond well to vaccines.

Flu vaccines are not perfect, but they are still the best way to prevent the flu. Some studies have shown that flu vaccination can reduce the severity of illness. Studies have shown that flu vaccination can reduce mortality, intensive care unit (ICU) admissions, ICU length of stay, and hospital stay in patients hospitalized with flu [1] . Other studies have shown that adults who received the flu vaccine were 59% less likely to be admitted to an intensive care unit than those who did not receive the vaccine [2] .

Commonly used antipyretic and analgesic drugs: ibuprofen and Tylenol

Flu is usually accompanied by high fever and muscle aches, which may require painkillers to relieve severe cases. The two most common over-the-counter antipyretic and analgesic drugs on the market: ibuprofen and Tylenol, can both be used to reduce fever and relieve pain. This pain is not just muscle aches caused by flu, but can also be caused by other things, such as toothaches, joint pains, etc.

Ibuprofen : The main ingredient in Advil, Motrin, and Nuprin. It is a nonsteroidal anti-inflammatory drug (NSAID). Other NSAIDs include aspirin, which is well known to everyone.

Acetaminophen: The main ingredient in Tylenol. Many drugs in the pharmacy contain these ingredients. There is no need to stick to a specific commercial brand. Just look for the ingredients and dosage when choosing.

However, the problem of overdose is very common and serious .

In the United States, about 15% of patients taking ibuprofen or other nonsteroidal anti-inflammatory drugs exceed the maximum recommended daily dose, which results in a significantly increased risk of internal bleeding and heart attack[3]. I think this proportion is not low in China either. Tylenol is the leading cause of acute liver failure. In the United States, overdose of Tylenol leads to 50,000 emergency room visits and 25,000 hospitalizations each year. A study by the National Institutes of Health found that about 450 people die each year from overdose of Tylenol.

So why do patients overdose? There are two reasons:

Active reasons : Generally speaking, it takes at least 45 minutes for the medication to start working and 90 minutes for pain relief to be felt. Many people expect the medication to work quickly after taking it, and if it still doesn’t work after what they consider to be a “long” amount of time (because it’s really hard to bear!), they often take another pill, leading to an overdose.

Passive cause : Many common cold and sinus medicines include Tylenol, which leads people to overdose without realizing it.

I often hear friends say that if it is an over-the-counter drug, it means it is safe. If the recommended dose does not work, just take a little more and you will save yourself the trouble of going to the doctor. Is this really the case? Absolutely not!

Next, we will analyze it from the aspects of efficacy and side effects, and tell you whether to choose Tylenol or ibuprofen, and how to take it for more effective results.

Tylenol vs Ibuprofen, which one works better?

Fever

A 2004 review summarized the results of 17 clinical trials and found that ibuprofen was more effective than Tylenol in reducing fever in children under 18 years old [4] . However, many articles subsequently pointed out that the analysis method of this review was flawed and the conclusions needed to be confirmed by clinical trials with larger samples [5, 6].

For most people, both drugs work about the same in reducing fever. Some people may be more sensitive to one drug than the other.

For me, Ibuprofen usually works, but during my recent illness, it didn't work at all. After taking it twice, my temperature didn't go down at all, but instead went up from 38ºC to 39.7ºC. The pain all over my body was unbearable, so I had to take Tylenol to get better.

Pain relief

In most cases, ibuprofen is more effective in relieving pain. A 2015 BMJ paper summarizing 13 clinical trials found that Tylenol was not effective in treating low back pain and had little effect on patients with osteoarthritis [7] .

This is because ibuprofen and Tylenol work in different ways. Ibuprofen (and other NSAIDs) inhibit the synthesis of prostaglandins and prostacyclins. Prostaglandins and prostacyclins are chemicals that cause inflammation and pain. The mechanism by which Tylenol works is not well understood. It is generally believed that it works on the central nervous system, blocking pain receptors in the brain, so Tylenol can reduce fever and pain, but not inflammation. Since inflammation is the root cause of many pains, Tylenol is not as effective as ibuprofen for pain caused by inflammation.

Tylenol vs. Ibuprofen, which one has fewer side effects?

In the process of drug development, there is a data that is often mentioned:

The larger the TI, the greater the gap between the beneficial dose and the toxic dose, and the safer the drug. Drugs with a TI of more than 10 are generally considered safer. For example, cocaine is not only a drug, it can also be used as a stimulant and local anesthetic, and its TI is about 15.

Do you know what the TI of Tylenol is?

Tylenol is a narrow therapeutic index (NTI) drug, and its TI is very small, about 3. This means that the beneficial dose is close to the toxic dose, and it is easy to overdose and cause damage to the body, partly because Tylenol is almost entirely broken down by the liver. Because alcohol is also metabolized in the liver, if you take Tylenol and drink a lot of alcohol at the same time, it will put a great burden on the liver.

If not treated promptly, Tylenol overdose can lead to liver failure and death within a few days. A well-nourished person who does not drink alcohol may suffer serious liver damage if he or she takes a single dose of more than 10 grams of Tylenol or takes more than 5 grams per day for a long time, or a person who drinks alcohol may suffer serious liver damage if he or she takes more than 4 grams of Tylenol per day for a long time.

A 2017 epidemiological correlation study found that women who took Tylenol for 22-28 days during pregnancy were six times more likely to give birth to babies with attention deficit hyperactivity disorder (ADHD) than women who did not take the drug at all during pregnancy.[8] However, short-term use did not increase the risk of ADHD. Therefore, long-term or excessive use of Tylenol should be avoided.

So is ibuprofen absolutely safe? Not really.

Unlike Tylenol, ibuprofen is mainly broken down by the kidneys and has little effect on the liver. Ibuprofen can inhibit the synthesis of prostaglandins and prostacyclins, thereby irritating the stomach and esophagus, and can also cause dilation of blood vessels leading to the kidneys. This is why long-term use of ibuprofen can lead to gastritis, gastric ulcers, and acute kidney injury.

In vitro studies have found that ibuprofen is highly toxic to the ovarian development of three-month-old female embryos[9] and also inhibits the endocrine capacity of adult testicular explants, thereby causing compensatory hypogonadism [10]. However, both of the above experiments were conducted on tissues cultured in vitro, and it is not clear whether similar effects exist in humans.

Aspirin, another nonsteroidal anti-inflammatory drug, is also not recommended for children because it has been linked to Reye's syndrome, which can cause swelling of the brain and liver.

Precautions for correct medication use

Tylenol and ibuprofen have different mechanisms of action and are cleared by different organs. Tylenol can increase the burden on the liver, and ibuprofen may put some pressure on the stomach and kidneys. However, if used correctly and in safe doses, the damage to the body caused by these two drugs is negligible. Here are the precautions for taking these two drugs:

NSAIDs such as ibuprofen (especially aspirin) can help relieve gastrointestinal discomfort when taken with food. Drink at least 118 ml of water while taking the medication.

Many people at high risk for cardiovascular disease or stroke take low-dose aspirin daily because it acts as a blood thinner. However, people who take aspirin daily should use Tylenol instead of ibuprofen because ibuprofen can interfere with the effectiveness of aspirin.

Tylenol is metabolized in the liver. People with liver disease or alcohol abuse should avoid taking it. Drinking alcohol while taking the drug can lead to incomplete metabolism of the drug and increase the risk of liver toxicity.

Infants under six months of age and pregnant women should avoid ibuprofen and take only Tylenol. To reduce the risk, the lowest dose and for the shortest duration should be used.

Older people, or those with a history of gastrointestinal and kidney problems, ulcers, or inflammatory bowel disease, may be better off with Tylenol, which provides effective pain relief without many risks.

In general, the dosage and duration of medication should be minimized. Overdose is a serious concern. If you need to take Tylenol for more than 10-14 days or ibuprofen for more than 10 days, you should consult your doctor.

Since different manufacturers have different recommended doses for different people and different symptoms, you should read the label carefully before taking it. For example, Johnson & Johnson has reduced the maximum daily dose of their Extra-strength Tylenol from 4 grams to 3 grams, and the dosing interval has also been changed from two tablets every 4-6 hours to two tablets every 6 hours.

Can I use two drugs at the same time/alternately?

Sometimes, if you use only one drug to reduce fever and relieve pain, and the fever and pain occur again before the next dose, some doctors will recommend using ibuprofen and Tylenol at the same time or alternately. Using drugs at the same time/alternately is a very controversial topic. If you use Google to search now, all the results that pop up are recommended not to use drugs at the same time/alternately. But this is not a one-size-fits-all issue, and it only represents the views of some doctors .

In fact, taking these two drugs together can provide more pain relief than taking them alone. Studies have shown that taking ibuprofen and Tylenol together can provide good pain relief with few side effects .[11, 12] Even for extreme dental pain, the combination of these two drugs is more effective and has fewer side effects than many opioid painkillers (such as Vicodin) .[13]

In the United States, about 50% of doctors still recommend using ibuprofen and Tylenol together/alternatingly, rather than increasing the dose of one, but only if symptoms cannot be controlled with a single drug and the patient can tolerate both drugs.

Many parents are concerned about whether their children can take medications simultaneously or alternately. In this regard, a review study [14] summarized multiple clinical trials and its analysis results showed that this issue is still controversial. Generally speaking, it is recommended that children take medications alternately rather than simultaneously. In addition, parents need to carefully control the dosage to avoid overdose .

It should be emphasized here that fever is a reaction of the human body against disease. If the fever is not very high, there is no need to take medicine. This is because antipyretics only help relieve symptoms and make patients feel less uncomfortable, but cannot kill the virus fundamentally. If the body temperature is high (usually considered to be 38.8 degrees, but everyone's basal body temperature is different, and this value is not absolute), the person is very uncomfortable and cannot rest well, you can take medicine to help cool down.

Most patients will respond to one antipyretic medication, but if the temperature does not drop 1-2 hours after taking the medication, a different medication can be taken to help lower the temperature, provided both medications are tolerated. This can be lifesaving in some cases. Why wait 1-2 hours before taking medication? Because it usually takes 45-90 minutes for the medication to take effect. This can avoid unnecessary extra medication.

When taking medications simultaneously/alternatingly, the two drugs should still follow the recommended medication interval. Tylenol is recommended to be taken every 6 hours, and ibuprofen every 6-8 hours. It is recommended to use a pen and paper to write down the time of each medication to avoid forgetting .

From a pharmacokinetic perspective, as long as the drug is not overdosed, the human body can generally fully metabolize and excrete the drug without causing toxicity. For example, after taking a single oral dose of 200 mg of ibuprofen, the serum concentration reaches its highest level in 1 hour, and is already very low after 6 hours [15]. The pharmacokinetic profile of Tylenol is similar, and there are many pharmacokinetic profiles of different formulations.

Because Tylenol and ibuprofen have different metabolic pathways, I personally think that if both drugs are tolerated, the risk of simultaneous/alternating use is far less than excessive accumulation of a single drug in the body. In short, the efficacy of these two drugs varies among different groups of people. In order to achieve the purpose of relieving symptoms, take the least dose of the drug as possible, which is also the most basic standard for medication.

Shi Jun, pen name "Cat with Free Will", currently lives in Boston, USA. He graduated from the Department of Biological Sciences and Technology of Tsinghua University with a bachelor's degree. After obtaining a doctorate in the United States, he joined a well-known multinational pharmaceutical company to engage in drug research and development. For more than ten years, he led the team to fight against diabetes, muscular dystrophy, etc. In recent years, he has focused on the research and development of anti-aging drugs. His personal WeChat public account "Yi Ran Sui Xin" will chat with you about medical care.

Shi Jun

References

[1] C. Arriola et al., Influenza Vaccination Modifies Disease Severity Among Community-dwelling Adults Hospitalized With Influenza. Clin Infect Dis 65, 1289-1297 (2017).

[2] MG Thompson et al., Influenza vaccine effectiveness in preventing influenza-associated intensive care admissions and attenuating severe disease among adults in New Zealand 2012-2015. Vaccine 36, 5916-5925 (2018).

[3] DW Kaufman et al., Exceeding the daily dosing limit of nonsteroidal anti-inflammatory drugs among ibuprofen users. Pharmacoepidemiol Drug Saf, (2018).

[4] DA Perrott, T. Piira, B. Goodenough, GD Champion, Efficacy and safety of acetaminophen vs ibuprofen for treating children's pain or fever: a meta-analysis. Arch Pediatr Adolesc Med 158, 521-526 (2004).

[5] RD Goldman, Efficacy and safety of acetaminophen versus ibuprofen for treating children's pain or fever: a meta-analysis. J Pediatr 146, 142-143 (2005).

[6] Review: no evidence exists that paracetamol and ibuprofen differ for short term pain relief or safety in children, but ibuprofen more effectively reduces fever. Evidence Based Nursing 8, 10-10 (2005).

[7] GC Machado et al., Efficacy and safety of paracetamol for spinal pain and osteoarthritis: systematic review and meta-analysis of randomized placebo controlled trials. BMJ 350, h1225 (2015).

[8] E. Ystrom et al., Prenatal Exposure to Acetaminophen and Risk of ADHD. Pediatrics 140, (2017).

[9] S. Leverrier-Penna et al., Ibuprofen is deleterious for the development of first trimester human fetal ovary ex vivo. Hum Reprod, (2018).

[10] DM Kristensen et al., Ibuprofen alters human testicular physiology to produce a state of compensated hypogonadism. Proc Natl Acad Sci USA 115, E715-E724 (2018).

[11] AF Merry et al., Combined acetaminophen and ibuprofen for pain relief after oral surgery in adults: a randomized controlled trial. British journal of anaesthesia 104, 80-88 (2010).

[12] CK Ong, RA Seymour, P. Lirk, AF Merry, Combining paracetamol (acetaminophen) with nonsteroidal antiinflammatory drugs: a qualitative systematic review of analgesic efficacy for acute postoperative pain. Anesth Analg 110, 1170-1179 (2010).

[13] PA Moore et al., Benefits and harms associated with analgesic medications used in the management of acute dental pain: An overview of systematic reviews. J Am Dent Assoc 149, 256-265 e253 (2018).

[14] L. Shortridge, V. Harris, Alternating acetaminophen and ibuprofen. Paediatr Child Health 12, 127-128 (2007).

[15] P. Kale, Pharmacokinetics and bioavailability of single dose ibuprofen and pseudoephedrine alone or in combination: a randomized three-period, cross-over trial in healthy Indian volunteers. Front Pharmacol 5, 98 (2014).

Produced by: Science Popularization China

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