Take meds at the right time and get the greatest benefit with lowest risk of unpleasant side effects.

The instructions on the pill bottle simply say "take once a day." Yet the specific time of day you take your medications may make an important difference.

Inside each of us ticks a finely tuned master clock driven by a tiny region in the brain that keeps us in sync with Earth's cycle of light and dark. This master clock also directs a host of peripheral clocks found in organs, tissue and cells, says Michael Smolensky, adjunct professor of biomedical engineering at the University of Texas, Austin. "The body doesn't respond to medications in the same way at different times of the day," he says. "Some drugs are not as effective or as well tolerated if they're taken at the wrong biological time. It's not that they're not effective at all, but they're certainly much less effective."

In fact, drugs labeled "take one a day" often work better when taken at night. Modifying the timing of drugs to achieve the greatest benefit with the lowest risk of unpleasant side effects is called drug chronotherapy.

There have been tremendous advances in timing treatments for hypertension and rheumatoid arthritis, for example, according to Smolensky. And even some cancer treatments can be improved through chronotherapy. A drug called 5-fluorouracil (5-FU), used to treat colorectal cancer, is now given at night when these cancer cells are more vulnerable and normal cells are resting and least sensitive.

Although chronotherapy is a hot topic these days, your doctor or pharmacist may not be aware of it.

"Unfortunately, there's a disconnect between what's taught to doctors and what we know from chronotherapy research," says circadian biologist Georgios Paschos of the University of Pennsylvania School of Medicine. "Except for a few conditions, clinical medicine hasn't yet caught up with our findings," he says. But, he predicts, this will change in the next decade or two.

Here is what researchers have discovered about the best time to take your medicine. (Note: Never change the timing of your drugs without first discussing it with your doctor or pharmacist.)

High cholesterol

Buildup in the arteries of LDL, or "bad cholesterol," can lead to stroke, heart attack and other problems. Statin drugs are used together with diet and exercise to reduce LDL levels.

When to take medicine: Take statins at bedtime, advises the British Heart Foundation.

Here's why: Cholesterol production in the liver is highest after midnight and lowest during the morning and early afternoon, so statins are most effective when taken just before bedtime.

High blood pressure

Blood pressure shows a 24-hour rhythm, higher during the day and lower during nighttime sleep. However, especially after age 55, many people with high blood pressure don't exhibit this nighttime dip, a condition called non-dipping.

When to take medicine: Take at least one blood pressure-lowering medication at bedtime. Drugs called ACE inhibitors and ARBs are the most effective when taken at this time.

Here's why: Non-dipping is a major risk factor for stroke, heart attack and kidney disease. Taking one or more of the prescribed medications just before bedtime normalizes daily blood pressure rhythm and significantly decreases the risk, studies have found.

Osteoarthritis

The gradual deterioration of cartilage covering bone ends within joints causes pain, tenderness and swelling around the joint. People experience pain at different times of the day.

When to take medicine: NSAIDs, such as naproxen and ibuprofen, are the most widely used medications for osteoarthritis. According to French researchers, it's best to take them four to six hours before the pain is at its worst, so that they'll kick in at the appropriate time. For afternoon pain, for example, take meds around mid-morning to noon; for evening pain, schedule them for midafternoon; and for nighttime pain, take them with your evening meal.

Here's why: Timing NSAIDs so that the highest blood levels of the drug coincide with peak pain will offer the most relief.

Heartburn

This distressing condition is caused by a backup of stomach contents into the esophagus, also called the gullet, where gastric acids produce a burning sensation and discomfort. The stomach produces two to three times more acid between 10 p.m. and 2 a.m. than at any other time of day.

When to take medicine: If you have recurring bouts of nighttime heartburn, you may be using an acid-reducing H-2 medication for relief. These drugs have a chemical name that ends in "tidine" (cimetidine (Tagamet), famotidine (Pepcid), ranitidine (Zantac), nizatidine (Axid)). Take them 30 minutes before your evening meal.

Here's why: Taking an H-2 blocker before the evening meal controls the secretion of stomach acid both after the meal and during the critical overnight period when secretion reaches its peak, making stomach juices less likely to irritate the esophagus, says Smolensky.

Asthma

Asthma attacks occur 50 to 100 times more often between 4 and 6 a.m. than during the day. Four in 10 people with asthma wake up every night with trouble breathing.

When to take medicine: Take in midafternoon if it's an oral medication, or late afternoon if it's an inhaled steroid.

Here's why: Medications to reduce inflammation and relax airways will take effect when asthma attacks are most likely to strike. For example, a single dose of inhaled steroid in the afternoon helps prevent asthma trouble that night, researchers found. The same dose taken in the morning or at night does not significantly reduce the number of attacks.

Rheumatoid arthritis

The immune system component that normally attacks foreign bacteria and viruses mistakenly attacks cells lining the joints, causing swelling, stiffness and pain. Symptoms tend to be at their worst in the morning.

When to take medicine: Take RA medicines in the evening or at night.

Here's why: Taking aspirin and other NSAIDs with dinner or before bed produces better relief than taking the same meds in the morning. A new low-dose modified-relief corticosteroid is meant to be taken at bedtime, so the highest concentration, midway through sleep, effectively inhibits production of substances called cytokines, which trigger morning symptoms.

Hay fever

An overreaction of the immune system triggers the watery and itchy eyes, sneezing, coughing and stuffy nose of hay fever. Blame histamine, a chemical released by the immune system after exposure to pollen.

When to take medicine: Antihistamines, which block the action of histamine, are the most common remedy for hay fever. Take once-a-day antihistamines in the evening. Take twice-a-day antihistamines morning and evening. Otherwise follow label directions, taking at least one dose in the evening.

Here's why: Hay fever typically worsens at night and is most severe in the morning, when histamine levels are highest. Once-daily antihistamines reach their peak 12 hours after taking them, so evening use produces better control of morning symptoms.

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