time to take your medicine?...

The way our bodies absorb and utilise drugs changes over the course of the day – here is a guide when to take what

Synchronising the timing and dosage of medicines with our internal body clocks makes them work better with fewer side effects. Doctors tell us to take pills before or after eating and at what intervals but rarely will they specify what time to take them.  If pressed they encourage us to link taking drugs to a daily routine such as cleaning our teeth. 

This is understandable since they want us to remember to take our treatments consistently.

Yet the severity of our symptoms and how our bodies absorb drugs fluctuate over 24 hours. “Indeed many drugs labelled ‘take one a day’ often work better at night,” says Michael Smolensky one of the world’s foremost authorities on chronotherapeutics.

As drug chronotherapy researchers discover the optimal times to take drugs the medical community is slowly revising its advice. In future when doctors prescribe medicines they may also routinely stipulate when to take them and possibly tell us to take unequal amounts at different times. Expect more smart drugs in the coming years that release medicine at intervals. This is some of the latest research but don’t change your regime without talking to your doctor as your case may be different.

High Blood Pressure
Taking at least one blood pressure-lowering medicine such as ACE inhibitors and ARBs at bedtime could give your arteries a much needed rest.  Blood pressure is usually 10-20% lower during sleep but many people with high blood pressure and especially those aged 55-plus don’t have a dip during the night. “Non-dipping” raises the risk of strokes, heart attacks and kidney disease. 

In a five year Spanish study of 2156 patients published in Chronobiology International in 2011 those taking one of their blood pressure medicines at night had a 33% lower risk of heart attack or stroke than those taking all their pills in the morning. In 2007 Dr Roberto Minutolo of the University of Naples told 32 “non-dippers” with kidney disease to take one drug at bedtime instead of in the morning. His study published in the American Journal of Kidney Diseases showed that nearly 90% of them had turned into “dippers” in two months.

Their night-time blood pressure dropped an average of seven points without side effects or increases in daytime readings. Lead researcher of the Spanish study Ramon Hermida of the University of Vigo advised patients to talk to their doctors before switching to evening doses, however.

High Cholsterol
The production in the liver of low-density lipoprotein or “bad” cholesterol which can lead to strokes and heart attacks is highest after midnight, perhaps because we have stopped eating. A 2003 trial at The University of Sunderland showed the common statin simvastatin (Inegy, Simvador, Zocor) worked better taken at night and in a 2008 study published in the International Journal of Clinical Practice found the same with atorvastatin (Lipitor).

Roda Plakogiannis and Henry Cohen, professors of pharmacy at Long Island University, New York, writing in the Annals of Pharmacotherapy in 2007 concluded there was “sufficient data” to recommend night-time statin use. The British Heart Foundation and online medical resource guide Patient.co.uk advises patients to take statins at night.

Conventional wisdom has been that proton-pump inhibitors which suppress acid production should be swallowed before the first meal of the day. 

However, studies including one in 2003 at the University of Kansas have found evening doses more effective against acid reflux especially for patients with night-time symptoms. More than 70% of patients taking the drugs in the afternoon or evening had relief from symptoms compared with 42% on a morning regime. This is probably because the drug acts when the stomach produces two to three times more acid between 10pm and 2am than at any other time and when heartburn is made worse by lying down. Some doctors now suggest taking half the daily dose in the morning and half in the evening.

Different people experience the pain, swelling and tenderness of osteoarthritis at different times of the day. Nonsteroidal anti-inflammatory drugs (NSAIDs) such as Ibuprofen are widely used to ease this condition. Convincing French research in 1985 found that the effectiveness of NSAIDs doubled when taken four to eight hours before the most intense pain.

That way the highest blood levels of the drug coincided with peak pain. “It was remarkable how much the time of day of taking the medicine mattered,” says the American Association of Medical Chronobiology and Chronotherapeutics. Take medicine for afternoon pain around mid-morning to noon, take it mid-afternoon for evening pain and for night-time pain take drugs with an evening meal.

Rheumatoid Arthritis (RA)
Stiffness, swelling and pain of RA, a chronic inflammatory autoimmune disorder, is characteristically worse in the morning. “Taking painkillers late evening may be the most effective way to prevent pain developing overnight,” advises The American Association of Medical Chronobiology and Chronotherapeutics.

Lung function undergoes circadian changes and reaches a low in the early morning. This dip is particularly pronounced in asthmatics who often suffer night-time attacks and debility and loss of sleep. Asthma authority Dr Richard Martin of the National Jewish Centre for Immunology and Respiratory Medicine in Denver says unless treatment improves night time asthma it is hard to improve its daytime manifestations. 

He says patients with severe asthma taking oral steroids should do so at 3pm. Those using steroid inhalers for milder asthma should use them between 3pm and 5.30pm. However, William E Berger, professor medicine at the University of California, says it is “unrealistic” to expect people who have to take medicines regularly to do so at inconvenient times, particularly if it is preventative and they feel fine.

Some chemotherapy treatments are being improved by chronotherapy. One example is 5-fluorouracil to treat colorectal cancer. It is now often given at night when these cancer cells are more vulnerable and normal cells are resting and least sensitive.

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