Leukotriene-Antagonists
Leukotriene-antagonists (also called anti-leukotrienes or leukotriene modifiers) are oral medications that block leukotrienes. Leukotrienes are powerful immune system factors that, in excess, produce a battery of damaging chemicals that can cause inflammation and spasms in the airways of people with asthma. As with other anti-inflammatory drugs, leukotrienes are used for prevention and not for treating acute asthma attacks.
Leukotriene-antagonists include zafirlukast (Accolate), montelukast (Singulair), zileuton (Ziflo), and pranlukast (Ultair, Onon). These drugs are proving to be effective for long-term prevention of asthma, including exercise-induced asthma and aspirin (or NSAID)-induced asthma. Most studies to date still report better success with inhaled corticosteroids than with the leukotriene-antagonists. Their anti-inflammatory actions are different from those of steroids, however, and combinations of the two drugs are being tried. A 2002 analysis of 13 studies, however, reported only modest benefits when anti-leukotrienes were added to corticosteroids. The combination did improve asthma control in some of the studies, but they did not reduce corticosteroid use. (In all but one of these studies the subjects were adults.)
Side Effects and Complications. Gastrointestinal distress is the most common side effect of leukotriene-antagonists. Very few other side effects have been reported. In general, these drugs appear to be safe and well tolerated.
Of some concern are reports of Churg-Strauss syndrome in a few people taking zafirlukast or montelukast. Churg-Strauss syndrome is very rare, but it causes blood vessel inflammation in the lungs and can be life threatening. Oral steroids quickly resolve the problem. Usually the syndrome has occurred in patients who were tapering off steroids and changing over to the leukotrienes-antagonists. Some experts believe that, in such cases, the steroids may simply have masked the presence of the disorder, which then developed when the steroid drugs were withdrawn. Symptoms include severe sinusitis, flu-like symptoms, rash, and numbness in the hands and feet.
Other concerns are indications of liver injury in patients taking zileuton and zafirlukast when taken at higher than standard doses. No adverse effects on the liver have been reported to date with montelukast.
Theophylline
Theophylline. Theophylline (Theo-Dur, Theolair, Slo-Phyllin, Slo-bid, Constant-T, Respbid) relaxes the muscles around the bronchioles and also stimulates breathing. One study reported that it may also have anti-inflammatory qualities even in low doses. Available in tablet, liquid, and injectable forms, some theophylline sustained-release tablets and capsules have a long duration of action and can, therefore, be taken once or twice a day with good results.
If theophylline is not taken exactly as prescribed, an overdose can easily occur. Toxicity can cause nausea, vomiting, headache, insomnia, and, in rare cases, disturbances in heart rhythm and convulsions. Contact a doctor immediately if any of these side effects occur.
The risks for these adverse effects are small if the drug is taken exactly as prescribed, but the following precautions should be noted:
- Chronic smokers metabolize theophylline much more quickly and require higher doses of the drug than nonsmokers; prolonged-release versions are helpful for such people.
- Too much caffeine can increase the concentration of this drug and the amount of time it stays in the body.
- Theophylline also interacts with many other drugs that are taken for other common medical conditions, including asthma. Exercise caution when using beta2-agonists and theophylline together.
- No one with a peptic ulcer should take theophylline. The elderly and anyone with heart disease, liver disease, hypertension, seizure disorders, or congestive heart failure, should take theophylline with caution. Of special note, people with heart conditions who take theophylline orally face an increased risk for sudden death from heart-related causes.
Omalizumab
Omalizumab (Xolair) is FDA-approved for patients age 12 and older who have moderate-to-severe persistent allergic asthma. The first drug of this type to be approved for asthma, omalizumab is a monoclonal antibody (MAb), a biologic drug designed to attack very specific targets.
Omalizumab prevents the antibody immunoglobulin E (IgE) from triggering the inflammatory events that lead to asthmatic attacks. Studies have shown the drug has excellent benefits, including a reduced need for corticosteroids, fewer hospitalizations, and significant symptomatic improvements. Because IgE may play an important role in causing childhood asthma, omalizumab may prove to be even more helpful for children than adults; further study is underway.
Omalizumab is given by injection every 2 to 4 weeks. Because of its high cost, the drug is reserved for patients whose symptoms are difficult to control even with corticosteroids. Experts predict that the applications of this therapy will likely expand in time, however, because it is a powerful modifier of severe seasonal and food allergies (in patients with or without asthma). A 2005 review of omalizumab clinical trials found that omalizumab reduced the rate of asthma worsening by 38% and reduced the rate of total emergency visits by 47%.
Previous Section
