Link between the drug-metabolizing enzyme UGT2B17 and the severe side effects associated with diclofenac

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Diclofenac is a non-steroidal anti-inflammatory drug (NSAID) used to relieve pain and inflammation in various conditions such as arthritis, menstrual cramps, and postoperative pain. However, this drug has been associated with severe side effects such as liver damage, gastrointestinal bleeding, and cardiovascular events.

In a recent study, scientists have discovered a significant link between the drug-metabolizing enzyme UGT2B17 and the severe side effects associated with diclofenac. This groundbreaking discovery has the potential to pave the way for the development of personalized medicine and safer drug therapies.

Background:

NSAIDs are among the most commonly used drugs worldwide, with diclofenac being one of the most frequently prescribed. NSAIDs work by blocking the activity of cyclooxygenase (COX) enzymes, which are responsible for producing prostaglandins, a group of substances involved in inflammation and pain. By inhibiting COX enzymes, NSAIDs reduce inflammation and pain.

However, the use of NSAIDs has been associated with various adverse effects, particularly in the liver and gastrointestinal tract. Long-term use of diclofenac can lead to liver damage and even liver failure. Additionally, diclofenac has been linked to an increased risk of gastrointestinal bleeding and perforation. Cardiovascular events such as heart attacks and strokes have also been reported in some patients taking diclofenac.

UGT2B17 is a gene that encodes for the UGT2B17 enzyme, which plays a crucial role in the metabolism and elimination of a variety of drugs and xenobiotics from the body. Studies have shown that UGT2B17 is one of the most deleted genes in humans, with the gene deletion frequency ranging from ~20% in the White population to 90% in the Japanese population. This genetic variation has been shown to have significant implications for drug metabolism, particularly in the case of the commonly prescribed non-steroidal anti-inflammatory drug (NSAID) diclofenac.

UGT2B17 and Drug Metabolism:

Drug metabolism is the process by which drugs are converted into less harmful substances that can be eliminated from the body. This process involves various enzymes, including UGT2B17, which is responsible for metabolizing diclofenac.

UGT2B17 is a poorly understood enzyme that is known to metabolize various drugs, including steroid hormones and xenobiotics. However, its role in drug metabolism and its variability among individuals are not well understood.

Health Problems Associated with Diclofenac:

Diclofenac is a widely prescribed NSAID due to its effectiveness in relieving pain and inflammation. However, this drug has been associated with various adverse effects, particularly in the liver and gastrointestinal tract. Long-term use of diclofenac can lead to liver damage and even liver failure.

Additionally, diclofenac has been linked to an increased risk of gastrointestinal bleeding and perforation. Cardiovascular events such as heart attacks and strokes have also been reported in some patients taking diclofenac.

Link between UGT2B17 and Diclofenac Side Effects:

In a groundbreaking study published in the journal Clinical Pharmacology and Therapeutics, scientists have discovered a significant link between the poorly understood drug-metabolizing enzyme UGT2B17 and the severe side effects associated with diclofenac.

This enzyme is responsible for metabolizing diclofenac and converting it into a less harmful form that can be excreted from the body.

The study found that individuals with a genetic variation that leads to reduced UGT2B17 activity are at a higher risk of experiencing severe side effects when taking diclofenac. Specifically, these individuals were found to have higher levels of diclofenac in their blood, which could explain the increased risk of adverse effects.

Implications of the Study:

This groundbreaking discovery has significant implications for personalized medicine and drug therapy. The identification of the genetic variation that affects UGT2B17 activity can enable healthcare providers to identify patients who are at a higher risk of experiencing severe side effects when taking diclofenac. This information can then be used to adjust the dosage or prescribe alternative medications that are safer for these patients.

Furthermore, this study highlights the importance of understanding the role of drug-metabolizing enzymes in drug therapy. The variability in drug metabolism among individuals can have a significant impact on the safety and efficacy of drug therapy. Therefore, a better understanding of the genetic and environmental factors that affect drug metabolism is essential for the development of personalized medicine and safer drug therapies.


reference link :

https://ascpt.onlinelibrary.wiley.com/doi/abs/10.1002/cpt.2907

https://pubmed.ncbi.nlm.nih.gov/37042794/

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