MEDICAL MATTERS: Prescribing medicine remains a relatively simple affair. Most drugs are now taken once or twice daily. Some older preparations follow a six or eight-hourly regime. Occasionally, you will be asked to take the drug before or after meals. But, in general, the timing of drug administration avoids complexity.
There are two principal reasons for this. One is to ensure a high level of compliance. As anyone who has tried to remember to take even a week's supply of antibiotics at regular intervals will testify, it is actually quite difficult to take medication exactly on time. Hence, the drug industry's drive towards once-daily preparations. The second reason is the desire to produce a steady level of the drug in the bloodstream and, by extension, at its site of action, throughout a 24-hour period. This is done partly to avoid dangerous peaks in drug levels that could be toxic to the body, and partly because a steady level of active drug is the best way to tackle disease.
It all seems a perfectly reasonable, safe and logical way to prescribe and take medication. But is it? Some recent reading on the topic of "chronobiology" has made me wonder.
Readers will be familiar with the concept of a circadian rhythm. It describes the normal 24-hour variations in various bodily activities such as blood pressure, heart rate and the release of hormones. Not surprisingly, the presence of such rhythms has an impact on disease patterns. The risk of a heart attack from 6 a.m. to noon is some 30-40 per cent higher than would be expected if all heart attacks occurred randomly throughout a 24-hour period. And there is a similar rise in the risk of stroke.
Blood pressure is at its lowest during the night and rises by 10-25 per cent between 6 a.m. and noon. This rise in blood pressure places additional stress on the wall of the coronary arteries: if there is an unstable plaque present, then there is an increased likelihood of it being dislodged, blocking the artery and causing a heart attack.
Given that this is the most dangerous time of the day, it would make sense if blood pressure drugs were at their most active in the morning. Night-time dosing would allow blood pressure medication to reach peak concentrations just as the morning circadian peak appeared.
Stephen Glassen, professor of epidemiology at the University of Minnesota School of Public Health, claims this is not the case: "Traditionally antihypertensive medications are not designed - and are clearly not being administered - in a way that adequately addresses increased morning risks. To maximise the many advantages of once-daily dosing, physicians must ensure that peak concentrations are in effect when patients need them most. Given the prevalence of morning administration, most patients enter the 'a.m. surge' with the lowest concentrations of the day."
Other illnesses also show a definite diurnal pattern. Asthma symptoms occur most frequently around 4 a.m., yet most asthma medication is not timed to take effect when the inflammation in the airways is at its peak.
Rheumatoid arthritis and osteoarthritis are two other diseases which have definite circadian rhythms in the intensity of their symptoms. Morning stiffness and pain are characteristic of rheumatoid arthritis, whereas symptoms tend to be worse in the afternoon and evening with osteoarthritis (wear and tear arthritis).
Doctors will try to prescribe anti-inflammatory drugs to take this into account, with rheumatoid arthritis benefiting more from an evening dosage (allowing time for the drug to build up in the joints for the next day) while osteoarthritis patients do best by taking medication in the morning.
Chronotherapy - the name given to the timing of medication - could be most important in cancer patients. Almost 20 years ago, Dr Bill Hrushesky, an oncologist at the University of South Carolina, published a paper describing an experiment in which he switched the timing of chemotherapy in 31 women who had ovarian cancer. He divided the women into two groups, with each receiving two standard cancer drugs, adriamycin and cisplatin. One group received the adriamycin at 6 a.m. and the cisplatin at 6 p.m., while the daily schedule was reversed for the second group.
The first group of women suffered approximately half the side effects, with less hair loss and less kidney damage. More recently, French doctors, treating colon cancer patients with an oscillating level of medication, reported a three-fold increase in the proportion of tumours that shrank by half or more compared with more standard dose scheduling.
Is it time doctors and the pharmaceutical industry took a closer look at the whole area of when patients take their medications? I think so.
• Dr Muiris Houston is pleased to hear from readers at mhouston@irish-times.ie but regrets he cannot answer individual queries.