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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Having a Treatment Plan

The drop in peak flow to 50 percent of the patient’s best identifies a serious attack. The patient should repeat the maneuver to determine if it is reproducible. Each patient should have a plan of treatment that has been worked out with the physician. This will typically call for immediate use of rapidly acting bronchodilator medication delivered as an aerosol. The plan should contain instructions on the use of corticosteroids and notification of the patient’s physician.

The physician’s knowledge of the patient’s history will prove invaluable at this time. Patients who have required hospitalization and especially those who have required respirator support for treatment of asthmatic attacks in the past will be advised not to delay treatment decisions. This patient group may require emergency room treatment as will patients with severe attacks who do not rapidly increase their peak flows with bronchodilator medication administered as directed (and not overused).

In treatment of bronchial asthma it is necessary to be aggressive early in treatment of severe attacks, including the possible use of an emergency room. With early recognition of a severe attack and aggressive treatment at its onset, fatal or near-fatal episodes can be avoided.

In the patient group with severe attacks who respond promptly to treatment, the patient’s treatment plan may often be continued in the home. With severe attacks this will most certainly require corticosteroids. Communication with the physician is essential and will be more accurate with serial peak flow measurements. Increasing airflows will confirm the effectiveness of treatment and can be used to adjust medication dosage and frequency of administration.

Following a severe attack that has been successfully treated it is important for the physician and patient to reassess maintenance medication and the treatment plan. The diary of peak flows will be extremely helpful since it may identify a downward trend that began before a severe attack was recognized. Emphasis on earlier recognition may prove helpful in avoiding future attacks.

With each significant attack the physician will look for a “trigger” mechanism that might be prevented in the future. An example would be raking moldy leaves or dusting without a face mask. Avoiding allergens will be stressed in sensitive patients who suffer serious attacks on exposure to these substances. Often the trigger for an asthmatic attack is the common cold. Although this infection cannot be prevented, the patient should be alerted to the possible adverse effects that might result and be prepared to institute the treatment plan.

In many instances the trigger for a severe asthmatic attack cannot be identified. If attacks are frequent, a review of the medical evaluation should be made. Additional allergy tests may be indicated and another careful examination of the home and work environment made. The patient’s administration of medication should also be examined and the maintenance medication program reviewed.

What If Avoidance Doesn’t Work?

Despite measures to avoid asthma triggers, the patient may still experience asthmatic attacks. These attacks may be frequent and severe and at times require hospitalization. In a small number of patients these attacks may prove fatal.

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Since asthma has been defined as an illness characterized in part by airway obstruction it is essential for diagnosis to demonstrate this by using spirometry. The definition also includes the feature of reversibility; that is, that airflow can improve significantly. To demonstrate this feature spirometry is performed before and after inhaling bronchodilator medication. Th be significant, the physician looks for at least a 15 percent improvement in the spirometry parameters after the patient inhales bronchodilator medication.

Diseases such as emphysema, chronic bronchitis, cystic fibrosis, or bronchiectasis may demonstrate severe degrees of airflow obstruction without any improvement after bronchodilator use. However, it may be difficult to demonstrate reversibility in all asthmatics during a single laboratory session, possibly owing to severe degrees of bronchial narrowing or to inadequate inhalation of medication by the patient. Therefore, the absence of reversibility should never be taken as absolute proof that asthma is not present.

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