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NSAIDs: New and novel clinical patterns

Because people use NSAIDs so frequently, it’s important we know what they’re doing in the body.

San Francisco declares downtown emergency over drug deaths
US drug overdose deaths surged to more than 100,000 this year for the first time during the Covid-19 pandemic, exacerbated by a flood of fake online pills - Copyright AFP/File Patrick T. FALLON
US drug overdose deaths surged to more than 100,000 this year for the first time during the Covid-19 pandemic, exacerbated by a flood of fake online pills - Copyright AFP/File Patrick T. FALLON

No matter how long a drug substance is established for, there are opportunities for new developments often centred about the drug having previously unknown properties. Finding new applications for medicines is sometimes referred to a resupposing the drug.

An example is with non-steroidal anti-inflammatory drugs (NSAIDs) like ibuprofen and aspirin. These long-established medicines are widely used to treat pain and inflammation. Scientists are finding there are hitherto unknown effects on different diseases, such as heart disease and cancer.

At Yale University, one research stream has been looking at how NSAIDs affect the body. The data is challenging previously understood mechanisms, where NSAIDs were thought to solely function through the inhibition of enzymes.

This mechanism does not explain how NSAIDs have been linked to decreased incidence of colorectal cancer, or the way in which some NSAIDs affect asthma.

New mechanisms have been revealed through cell cultures and studies on rodents, Here, researchers have pinpointed distinct mechanism for how NSAIDs reduce inflammation.

The research has focused on the drugs indomethacin, which is used to treat arthritis and gout, and ibuprofen. These medications activate a protein called nuclear factor erythroid 2-related factor 2 (NRF2), which triggers anti-inflammatory processes in the body.

NRF2 controls many genes involved in a wide range of processes, including metabolism, immune response, and inflammation.

There is not only an issue in terms of positive effects. As lead researcher Anna Eisenstein points out: “Because people use NSAIDs so frequently, it’s important we know what they’re doing in the body.”

As an example of unintended effects, the researchers are also looking at the drugs’ dermatological effects such as leading to rashes, exacerbating hives, and worsening allergies.

Another area relates to clinical trials that are evaluating whether NRF2-activating drugs, and assessing if they are effective in treating inflammatory diseases like Alzheimer’s disease, asthma, and various cancers.

The research appears in the journal Immunity, titled: “Activation of the transcription factor NRF2 mediates the anti-inflammatory properties of a subset of over-the-counter and prescription NSAIDs.”

Written By

Dr. Tim Sandle is Digital Journal's Editor-at-Large for science news. Tim specializes in science, technology, environmental, and health journalism. He is additionally a practising microbiologist; and an author. He is also interested in history, politics and current affairs.

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