Adverse drug reactions

A drug is a substance used specifically, to cure, treat or prevent disease. All drugs have potential side-effects but the benefits usually outweigh any side effects or harmful outcomes, as tested through clinical trials.

Studies have shown that at any one time in the UK over 5,000 beds are occupied by patients admitted with adverse drug reactions.

An adverse drug reaction is when a medication given as instructed and at a normal dose has an unwanted or harmful effect on a patient.

Adverse drug reactions are now considered a significant healthcare issue.

Adverse drug reactions are still surprisingly common. Studies have shown that at any one time in the UK over 5,000 beds are occupied by patients admitted with adverse drug reactions. The biggest cause of adverse drug reaction-related hospital admissions is aspirin, which in some patients can cause bleeding in the gut.

Adverse drug reactions are now considered a significant healthcare issue. As a result, huge efforts are being made to push forward with pharmacogenomics research to reduce the number of patients receiving drugs that may have a harmful effect.

Why do we respond differently to drugs?

To understand why we all respond differently to drugs we need to consider the problem from the genetic level. What are the key genetic factors that are linked to drug effects and what effect do these genetic differences have on the functional proteins that these genes code for?

There are two main ways in which a pharmacogenetic effect may occur:

• hrough the action of enzymes, particularly those in the liver, that are responsible for processing drugs
• variation in the molecule that the drug targets and binds to.

Codeine, a drug that we might take to treat a headache, is converted into morphine by liver enzymes.

Enzymes in our liver play a key role in processing the drugs that we take. For example, codeine, a drug that we might take to treat a headache, is converted into morphine by liver enzymes. The morphine then provides pain relief by binding to particular chemical receptors in the brain.

However, variations can occur in these enzymes that affect how efficiently they process the drug. So, in the case of codeine, some people may not be able to convert the codeine into enough morphine to reduce their headache, whereas some may convert the codeine into so much morphine that it reduces their headache but also reaches toxic levels in their body.

About one in 10 Caucasians are poor at converting codeine into morphine. This is because they have a genetic variant in the gene that results in an inefficient enzyme. A small percentage of people have multiple copies of the gene causing them to become ‘supermetabolisers’ and at risk of morphine poisoning.

The key liver enzymes involved in our response to drugs are called cytochrome P450 enzymes. However, there are lots of different types of cytochrome P450 enzymes and lots of variation in how they process different drugs in different people.