Asthma Medicines

Theophylline has been used for treating bronchial asthma for nearly sixty years but is a weaker bronchodilator than the B-adrenergic agonists. Although widely used as a bronchodilator, the mechanism of its action is unclear. The most recent theories suggest an anti-inflammatory effect that is supported by the inhibition of the late phase response. Due to the controversy over its mode of action, theophylline has fallen out of favor and is no longer regarded as a first-line asthma medication comparable to the B2adrenergic agonists. As more data is obtained that firmly establishes theophylline as an anti-inflammatory agent it is likely to be regarded again as a first-line agent.

At this time theophylline may still prove useful as a second-line drug. A recent study has demonstrated that theophylline may allow patients who require high doses of inhaled corticosteroids to reduce their steroid dosages. Patients with intolerance to B-agonist side effects may find they are better able to tolerate theophylline. Its availability as an oral medication in a sustained time release form may be preferred by some patients. Dosing is usually on a twice-a-day basis, with some patients able to achieve satisfactory results from once-a-day administration. This once-a-day dose is best given in the evening and may prove extremely helpful in treating nocturnal asthma.

Sustained-Release Preparations

Large numbers of sustained-release theophylline preparations are available by prescription, but they may vary in their rate of release of medication into the bloodstream. Once a certain preparation is prescribed, adjustment of the dosage will require follow-up and blood testing. After the proper dosage is established it is advisable not to substitute one preparation for another since the substitute may not achieve the same results. There is little use for short-acting theophylline preparations since they must be given several times a day.

Intravenous Form: Aminophylline

An intravenous form of theophylline known as aminophylline is available for emergencies. In view of the faster onset of action of the B2-adrenergic agonists intravenous aminophylline would also not be considered a first-line treatment in an emergency room. Although there is some controversy concerning its effectiveness in emergencies, aminophylline’s use as a second-line agent has been established.

Obtaining a Therapeutic level

One drawback to theophylline is that a certain amount must be present to achieve an effect. This has been termed a therapeutic level (10-20 mg of the drug per liter of blood). Some patients, however, may benefit from lower levels. To achieve the therapeutic level a certain dosage must be administered. Dosing is based on the patient’s body weight and when given by mouth may require several adjustments based on blood test results before the achievement of a patient’s daily maintenance dose. When theophylline is given by mouth an effect may be achieved in approximately one hour but it may require two to three days to achieve the desired maintenance level. With intravenous administration of aminophylline a “loading dose” is usually given over thirty minutes, followed by a constant infusion. Blood levels are again required to adjust the intravenous drip. Compared to the rapidly acting B-agonists, theophylline is both weaker and slower in producing bronchodilatation. Of note, however, when theophylline is given at the same time that the patient is receiving the B-agonist, the effect of the two drugs together may be greater than when given alone.

Adverse Effects of Theophylline

Besides the above considerations, theophylline may have significant side effects, often related to high blood levels, but some patients may experience adverse effects from small dosages, including stomach and bowel upset, rapid or irregular heart beat, insomnia, nervousness, urinary frequency, and headache. Some of these effects may be prevented or reduced by avoiding caffeine, which is structurally similar to theophylline; this explains why coffee has often been noted to relieve asthma. Patients should be advised to avoid or reduce caffeine in their diets while receiving theophylline.

Children and Theophylline

One disturbing but controversial side effect has been noted in children. A possible adverse effect on learning and behavior has been raised by some studies. There are conflicting results with additional studies that have not demonstrated these effects. At this time, theophylline should be used with caution in young children. Careful monitoring for changes in behavior patterns and learning must be performed.

Overdosage

In excessive or toxic dosages, theophylline may cause nausea, vomiting, irregular heart rhythms, and seizures. Theophylline should never be used without direction and supervision from the physician. Fatalities have been reported in asthmatics who have overused over-the-counter asthma medications that contain theophylline. These arc preparations should be withdrawn to avoid toxic reactions.

Drugs That Interact with Theophylline

Another important consideration when patients receive theophylline is the potential for drug interaction. This interaction may result in higher blood levels or toxicity from theophylline. One major group of drugs that can interact with theophylline are certain antibiotics, including erythromycin, clarithromycin, ciprofloxacin, levafloxacin, and olfloxacin. In addition, a widely prescribed stomach medication, cimetadine (Tagamet), may also interact with theophylline. One of the anti-leukotrienes, zileuton (Zyflo) has also been found to interact with theophylline. Fortunately, many other antibiotics and stomach medications, and anti-leukotrienes, are compatible with theophylline. In instances where one of the drugs that may interact with theophylline must be given, a reduction in the theophylline dosage may be made in order to avoid toxicity. A simple rule is to cut in half the total daily dose whenever receiving one of the above medications. It is vital to monitor blood levels in that situation.

Factors That Affect Theophylline Breakdown

Other factors may contribute to slower breakdown or clearance of theophylline, such as age, liver disease, and heart disease. Elderly patients have been found to clear theophylline more slowly. Patients with diseases of the liver as well as those with congestive heart failure have also been found to have slower metabolism of theophylline. In these groups, lower dosages of theophylline should be given.

Some drugs may accelerate clearance of theophylline from the body. Cigarette and marijuana smokers are often found to clear theophylline more rapidly than nonsmokers and may need their dosages increased. TWo medications used for epilepsy, phenytoin (Dilantin) and phenobarbital, may also increase breakdown of theophylline.

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