Using drugs to block drug side effects

Side effects are a common problem associated with prescription drugs, but now a new technique can help to find other drugs that can prevent them from happening.

It's a fact that some of the most successful drugs for controlling certain conditions can be rendered redundant owing to poor side effect profiles.

An example of this is the diabetes drug rosiglitazone, which works by sensitising fat cells to the effects of the blood sugar-lowering hormone insulin.

Yet all that glitters isn't gold, because rosiglitazone, despite being highly effective as a diabetic medication, has also been linked to a significantly elevated risk of having a heart attack, leading to a decline in its use.

But is there a way to mitigate the heart attack risk by combining rosiglitazone with another drug?

To find out, Ravi Iyengar and his colleagues from the Icahn School of Medicine in New York, writing in Science Translational Medicine, delved into the US FAERS - "FDA Adverse Event Reporting System" - a freely available database recording adverse outcomes associated with prescription drugs.

What they were looking for were any instances where heart attacks associated with taking rosiglitazone were reported less frequently if another drug was also being taken at the same time by the patient.

One agent, called exenatide, and is also used to treat diabetes fitted the bill perfectly. Patients who were taking this as well as rosiglitazone featured in just 2% of MI reports, compared with 34% for patients taking just rosiglitazone alone.

To discover how this might be happening, the researchers then drew up a chart resembling a wiring diagram of the known biochemical impacts of the two drugs - rosiglitazone and exenatide - in cells.

The two drugs were converged, they found, on the blood's clotting system, with rosiglitazone triggering an increase in blood stickiness, while exenatide seems to stop this happening. Tests on diabetic mice confirmed this.

But the findings are not confined to diabetes drugs. Their analysis of the FAERS data revealed over 19,000 other potentially beneficial drug interactions, including a way to prevent muscle breakdown in patients taking cholesterol-lowering statin drugs: a dose of the blood pressure agent lisinopril - and a way to reduce suicide risk amongst patients taking the SSRI class of antidepressants: an antihistamine antacid treatment.

"This type of crowdsourced approach," say the New York team, "using databases like FAERS, can help to identify drugs that could potentially be repurposed for mitigation of serious adverse events."