Antidotes to reverse drug effects

A delicate balance is required during surgery

Scientists believe they have found a way to safely turn on and off the effects of drugs.

They are developing a class of drugs for which they believe they can also create an antidote that could neutralise, or counteract, the effects of the initial drug when needed.

An antidote would be used in caes when patients experience complications from a drug, or when doctors think a change is needed in the course of a treatment and they cannot wait for the effects of the drug to wear off naturally.

Within 10 minutes you can totally reverse the activity of that anticoagulant

Dr Bruce Sullenger

The researchers, from Duke University Medical Center in North Carolina, targetted their efforts on blood thinning drugs after being told by doctors that this would be the most useful area for their research.

Blood thinning drugs are given to prevent the formation of blood clots, which can clog up the blood vessels and lead to heart attack or stroke.

The researchers specifically examined the drug heparin, a particularly potent anti-clotting drug often given to patients about to undergo heart surgery, and sometimes to people who have had a sudden heart attack.

Haemorrhage risk

The drug has been proven to be a lifesaver, but during and after surgical procedures use of blood thinners can put a patient at risk of haemorrhaging, other complications and sometimes death.

Bruce Sullenger led the research

Having the ability to control the medication with an antidote would give surgeons more control over bleeding in patients during and after surgical procedures.

There is a drug called protamine that is used as an antidote, but it was not specifically designed as such, is difficult to administer and can cause complications itself.

To develop drugs and matching antidotes, researchers concentrated on a class of drugs called aptamers.

By manipulating the tiny nucleic acids that make up the drugs they were able both to create a blood thinning, anti-coagulant version, and an antidote version that had the opposite effect.

Using plasma samples from six patients who cannot tolerate heparin, researchers showed the newly created anticoagulant worked and that the antidote could reverse the blood-thinning effect of heparin.

Fast action

Lead researcher Dr Bruce Sullenger said: "Our study shows that once you've administered the blood thinner and then add an antidote, within 10 minutes you can totally reverse the activity of that anticoagulant."

Duke researchers plan to test the drug-antidote combination on animals, and to move to clinical trials within the next several years.

They hope the same principle could eventually be applied to other areas such as chemotherapy.

Professor Neil Poulter, an expert in cardiology at University College Hospital London, told BBC News Online that it could be difficult for heart surgeons to strike the right balance between clotting and bleeding.

He said: "An antidote is not something that would have to be used every day, but it would be a very useful addendum to the therapeutic armoury."

The research is published in the journal Nature.