MEDICAL MATTERSWe would be wise to choose drugs based on the individual, not the affliction, writes Muiris Houston
JOHN, WHO had a coronary bypass operation 10 years ago, following a heart attack, came for a Heartwatch check recently.
This primary care programme is designed to help prevent further cardiac problems.
John has done well since his surgery. But there has been one significant challenge in managing his cardiac risk factors.
For the past couple of years, finding a cholesterol-lowering drug that he can tolerate has been a major challenge.
A statin, the drug of first choice in most patients, caused aches and pains in his arms and legs.
His cardiologist decided to stop the drug on the assumption that John was experiencing muscle inflammation, a known side effect in this class of drugs.
Next up was a trial of a fibrate, an alternative cholesterol-reducing agent. It caused diarrhoea and had to be stopped also. And when he arrived to see me last week, the latest drug combination was also causing side effects.
With his cholesterol climbing slowly towards 7.0 mmol/L (ideally he should have a fasting cholesterol of 4.5 mmol/L or less), doing nothing is simply not an option.
John mentioned that a sister of his had similar problems with statins. Despite experiencing muscle pains with two separate brands of the drug, a trial of a third formulation worked a treat. Is this something we could try, he asked?
Of course it was, as long as we both acknowledged that it would be a case of trial and error with a chance that the new drug could cause muscle problems also.
My choice of statin was further guided by John being able to tell me the exact name of the drug his sister had settled on.
All of which got me thinking about how helpful it would be if we were able to target drug treatments on a more individual basis.
Some experts maintain that the age of personalised medicine is not far away. Therapies will be tailored for people based on their genetic make-up and other factors. This should allow patients obtain drugs that are more likely to be effective for them and offer a lower risk of developing serious side effects.
Choosing a drug based on a person's genes is called pharmacogenetics.
Herceptin, the hugely successful breast cancer drug, is often quoted as an example. It is given to patients whose breast tumours have high levels of a protein called Her 2. But in the case of Herceptin, it is the tumour genes that are tested, rather than the patient's actual genes.
The likely target in the testing of an individual patient's genes will almost certainly be the enzymes we use to break down drugs. Some people have genetic differences that limit their ability to break down a drug, so that usual doses can quickly lead to dangerously high blood levels of the medication.
The opposite can also occur: fast drug metabolisers may need higher than normal doses for the drug to work. Enzyme testing would clearly be beneficial in both these scenarios.
The 2D6 and 2C19 enzyme systems contribute to the metabolism of almost one in four prescription drugs. By testing for variations in the genes that control these enzymes, it should be possible to tailor the dose of certain drugs to reflect the person's genetic make-up.
Warfarin, the blood-thinning drug used to prevent strokes and break up clots, is a notoriously fickle drug. A person who slowly metabolises warfarin could quickly develop dangerous blood levels of the drug, causing severe bleeding. Because of this, it is standard practice to check the blood's clotting ability on a regular basis in patients taking the drug.
The drug treatment of depression can also be a hit and miss affair.
We do not yet understand why a particular selective serotonin uptake inhibitor (SSRI) such as Prozac works really well in one patient but seems to have no more effect than taking Smarties in another. And because SSRIs take a couple of weeks to work anyway, it would be really helpful if a test emerged that could guide us in determining who might or might not benefit from a particular anti-depressant.
Advances in pharmacogenetics could even give a new lease of life to medicines previously blamed because of harmful side effects.
These drugs could then be reintroduced with a licence for use only in those people found to have genes for the specific enzymes needed to metabolise the drug in a predictable way.
Meanwhile, in the absence of an easily accessible pharmacogenetic test for John, I was glad to be able to choose a statin tolerated by a close relative. It will be interesting to see how he responds.
Dr Houston is pleased to hear from readers at mhouston@irish-times.ie but regrets he is unable to reply to individual medical queries
