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Paracetamol vs. Ibuprofen: What is the Difference?


Paracetamol, otherwise known as acetaminophen, and ibuprofen are the most widely used medications worldwide. Both available as prescription and over-the-counter, they address aches, pains, and fever, and are found in many medicine cabinets. While both alleviate pain and fever, the two drugs are quite different. Curious as to what those differences are? This article will highlight how each drug works, when you should take them, and other noticeable differences.

How they work

Acetaminophen belongs to a class of drugs called analgesics and antipyretics (pain relievers and fever reducers, respectively). Ibuprofen is a non-steroidal anti-inflammatory drug (NSAID). All NSAIDs, including ibuprofen, work by blocking enzymes called cyclooxygenases (or COX). Cyclooxygenases produce substances known as prostaglandins. There are two main types of cyclooxygenases, cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2).

COX-1 generates prostaglandins that:

  • Stimulate blood cells called platelets involved in forming a blood clot to cease bleeding.
  • Protect your stomach lining from the harmful effects of acid.
  • Contribute to pain, fever, and inflammation.

COX-1 also generates another chemical, which narrows your blood vessels and causes the platelets to clump together, forming a blood clot. Hence, any factor or drug that hinders the actions of Cox-1 will promote bleeding and unwanted effects on your stomach. But it will also ease pain, fever, and inflammation simultaneously.

COX-2 produces prostaglandins that:

  • More strongly mediate pain, fever, and inflammation.
  • Dilate (widen up) your blood vessels, including those supplying blood to your heart, kidneys, and brain.

Thus, any factor or medicine that blocks the actions of Cox-2 will reduce pain, fever, and inflammation. It is also important to note that blocking COX-2 without COX-1 will prevent the prostaglandins from keeping your blood vessels open, thus narrowing them.

Most NSAIDs, including ibuprofen, are non-selective, meaning they inhibit both COX-1 and COX-2. Thus, ibuprofen eases pain, fever, and inflammation. But on the downside, they also induce stomach ulcers and secondary bleeding, since COX1 can no longer protect your stomach lining or cease bleeding.

Acetaminophen, on the other hand, works by various mechanisms. Surprisingly though, how this drug acts is still a mystery. Nonetheless, there are a few evolving hypotheses.

One of the most widely accepted notions is that acetaminophen may also block the COX enzymes. However, it doesn’t inhibit these enzymes to a similar degree as ibuprofen. It may weakly inhibit COX-1 but selectively block COX-2 in tissues with mild-to-moderate inflammation.

Some experts also claim that paracetamol targets a unique COX-1 variant, dubbed COX-3, that mainly resides in the brain. Thus, it may minimize pain signals in the brain rather than at the site itself of pain. However, many experts refuted this hypothesis because they failed to find Cox 3 in human brains.

Another novel theory is that your brain metabolizes acetaminophen into a chemical that provides pain relief by acting on specialized pain receptors, such as cannabinoid receptors.

Acetaminophen targets fever

Though acetaminophen and ibuprofen are equally effective at reducing fever, doctors prefer paracetamol over ibuprofen as it's safer.

Another technique for fever is alternating acetaminophen and ibuprofen, which lowers your body temperature at a faster rate than using any of the drugs alone. However, one should be mindful of the maximum doses used in 24 hours while managing fever at home.

Clinical evidence also shows that acetaminophen, when used sparingly, is safe to use for treating fever in children of all ages. In contrast, the US Food and Drug Administration (FDA) recommends avoiding the use of ibuprofen in kids less than six months unless advised by the doctor.

Ibuprofen helps inflammation

Acetaminophen has a very weak anti-inflammatory activity. It appears to be active at low levels of arachidonic acid and peroxides (inflammatory molecules). Low levels of arachidonic acid lead to low peroxide levels, such as in milder cases of inflammation.

As a result, acetaminophen can lessen milder cases of inflammation as seen in tooth extraction. However, it fails to dampen the severe inflammation of arthritis and acute gout. In comparison, ibuprofen is a much more powerful anti-inflammatory agent.

Ibuprofen kills pain

Both acetaminophen and ibuprofen suppress pain. However, ibuprofen seems to be more effective at minimizing pain, especially that caused by inflammation.

A clinical trial on patients with tooth extraction showed that ibuprofen offered better pain relief than paracetamol at 200 milligrams to 512 milligrams and 600 milligrams to 1000 milligrams, respectively.

And a combination of ibuprofen and acetaminophen seems to be more effective at relieving acute pain, as revealed in this Cochrane review. With that said, experts consider paracetamol as a suitable first choice for addressing mild to moderate pain in people with stomach ulcers, asthma, or liver, since acetaminophen causes liver damage and kidney disease.

Acetaminophen is gentler on the stomach

Since it weakly inhibits COX1, paracetamol does not affect the protective functions of COX-1 on the stomach lining. Unlike ibuprofen, it is gentle on the stomach when taken within the recommended doses. Doctors prefer paracetamol over ibuprofen in patients with stomach ulcers or those at increased risk of bleeding from the digestive tract. To be on the safer side, physicians prescribe antacids or other meds along with NSAIDs like ibuprofen to counter the stomach irritation caused by them.

Acetaminophen is safer

When used at appropriate doses, acetaminophen does not affect platelet function or promote bleeding like ibuprofen. Therefore, it is a suitable choice for patients with bleeding disorders. However, be careful while using paracetamol with blood thinners like Warfarin. Also, be wary of higher doses of paracetamol that come with the potential risk of liver damage.

Ibuprofen is better for the liver

Ibuprofen is metabolized by the kidneys, making it safer for your liver. Alternatively, your body processes paracetamol in the liver. Therefore, if taken at doses greater than 4 grams per day, paracetamol carries a higher risk of liver damage. Be mindful of accidentally taking more than one medicine containing paracetamol at the same time when you have a fever due to a cold.

The conclusion: Acetaminophen is safer

NSAIDs, including ibuprofen, induce kidney injury by several mechanisms. First, as mentioned above, NSAIDs block prostaglandins that dilate blood vessels supplying your kidneys. Reduced prostaglandins can narrow those blood vessels, depriving your kidneys of oxygen and blood flow. This culminates in acute kidney injury.

While acetaminophen also blocks PGs that keep your blood vessels open, this drug is primarily processed in your liver as opposed to ibuprofen which exits your body through your kidneys. Thus, paracetamol doesn’t cause kidney damage when used within the recommended dose.

Prolonged use of ibuprofen at higher doses also poses a risk of chronic kidney disease and even kidney failure.

For similar reasons, the National Kidney Foundation recommends acetaminophen as the pain reliever of choice for patients with existing kidney disease.

Key take-aways

  • Both acetaminophen and ibuprofen block enzymes called cyclooxygenases, but they do so differently. This variation accounts for most of the differences seen between the two drugs.
  • Paracetamol is safer than ibuprofen, but if you have inflammation with your pain, ibuprofen will be more effective.
  • Due to its safety profile, acetaminophen is the first-line agent for treating fever and pain.
  • Acetaminophen is preferred over ibuprofen in people with stomach ulcers, bleeding from the digestive tract, or bleeding disorders like hemophilia.
  • The biggest abuse of paracetamol is on the liver, whereas that of ibuprofen is on the stomach and kidneys.
  • Before taking any medicine, be sure to check with your doctor.

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