Treatment of Asthma - Part II

by Warren P. Silberstein, M.D.
06/23/97
updated 09/10/98
updated 04/07/01

Maintenance Medications

Maintenance medications include anti-inflammatory medications which relieve the inflammation that provokes bronchospasm and causes increased mucus, and long acting bronchodilators which keep the airways open for prolonged periods. Anti-inflammatory medications include steroids and non-steroidal anti-inflammatory medications. The non-steroidal anti-inflammatory medications used for asthma are not related to the non-steroidal anti-inflammatory drugs (NSAIDs) used for arthritis such as ibuprofen. The steroids used to treat asthma are corticosteroids which are not anabolic steroids and have nothing to do with those illegal drugs used by some unscrupulous athletes. Maintenance medications are not to be taken for treatment of an acute asthma attack. Attacks are treated with rescue medications. In fact, if a patient is wheezing when he is due to take a dose of an inhaled maintenance medication, he should take his rescue medication first to control the wheezing so that the maintenance medication can be delivered to the entire bronchial tree.

• Cromolyn (Intal) - available as a spray and nebulizer solution. Cromolyn is an anti-inflammatory medication which is relatively free of side effects. It may cause some throat irritation and, as with all inhalation medications, may provoke cough or wheezing. Initially treatment with cromolyn is generally taken 4 times daily. After 2 to 4 weeks there is usually an improvement in symptoms including a decreased need for rescue medications. After a period of good control of symptoms the dose of cromolyn can be decreased to 3 times daily and eventually to a maintenance of twice daily. The medication should not be discontinued without the advice of a physician since the absence of symptoms may be the result of taking the medication. Cromolyn and most of the other anti-inflammatory medications are not useful when taken intermittently or just when symptoms begin. Cromolyn can be used to prevent exercise induced asthma if taken prior to sports or exercise even if it is not taken regularly.
• Nedocromil (Tilade) - available as a spray. This medication is very similar to cromolyn. It is a more potent anti-inflammatory than cromolyn. It is relatively side effect free. The main side effects are headache and nausea. Bad taste has also been listed as a cause for discontinuing therapy.
• Zafirlukast (Accolate) - available as a tablet. Accolate is one of the newest asthma medications. It is a completely different type of anti-inflammatory known as a leukotriene inhibitor. Leukotrienes are involved in the inflammatory response that provokes asthma. Adverse reactions include headaches, infections, nausea, and diarrhea. This medication is a mid-potency anti-inflammatory whose main advantage is that it can be used by patients who can't or prefer not to use sprays. It is not recommended for young children.
• Montelukast (Singulair) - available as a tablet and chewable tablet. Singulair is the newest leukotriene antagonist, and is similar to Accolate. Its advantages are that it is approved for children 6 years old and older, and it is taken only once daily. Its use can decrease or even avoid the use of steroids. Like Accolate, it is also useful for patients who prefer tablets over sprays or children who have not yet mastered the use of sprays. Reactions to the medication may include diarrhea, laryngitis, pharyngitis, nausea, otitis, sinusitis, and viral infection.
• Inhaled Steroids - available as sprays. Steroids are used for their potent anti-inflammatory effect. There are many brands available, all of which are good medications. They are difficult to compare with regard to potency because 1 mg of one type of steroid is not equivalent to 1 mg of another. Current recommendations and guidelines form the U.S. Federal Government are to use high potency inhaled steroids for treating severe asthma, but until recently, there was no high potency spray available in the U.S. Higher doses can be given by increasing the number of sprays given, however, in my experience, the more sprays a patient has to take at a time, the less effectively he takes them. Some of the major brands include:
  • Beclomethasone (Beclovent, Vanceril, Becloforte) - Becloforte is a high potency spray which is available from Canada. Each spray delivers almost six times the amount of medicine as one spray of the other two brands. If your physician feels you would benefit from Becloforte he can order it from Clayman's Pharmacy in Quebec at 514-735-5243. They will ship it to you if you provide them with credit card information. I'm sure there are other Canadian pharmacies that would do the same, but I provide this information because I have dealt with them and have their telephone number. Given the other high potency inhaled steroids now available in the USA, that should not be necessary.
  • Flunisolide (Aerobid, Aerobid-M)
  • Triamcinolone (Azmacort) - comes with a built in spacer.
  • Fluticasone (Flovent) - Flovent comes in three strengths including the highest potency inhaled steroid currently available in the United States.
  • Budesonide (Pulmicort) - comes as a turbohaler which is activated by breathing in. It's delivery mechanism makes it easier for children to use. It is approved for children over 6 years. Pulmicort Respules come in two strengths for use in the nebulizer once or twice daily. It is approved for children 1 year old and up. It is the only nebulized steroid available in the USA.

  All inhaled steroids have essentially the same side effects which include thrush (a yeast infection in the mouth), hoarseness, dry throat, irritated throat, and dry mouth. The risk of thrush can be minimized by using a spacer which increases the amount of medication deposited in the lungs and decreases the amount deposited in the mouth and throat. Rinsing the mouth after each use can also decrease the risk of thrush.

  Inhaled steroids are the most potent available anti-inflammatory drugs available for the treatment of asthma besides oral steroids. They are excellent medications for the long term management and control of moderate to severe asthma. In general they do not cause the side effects of systemic (oral, intravenous, or injected) steroids, but they are absorbed to some extent, and in high enough doses, can suppress the normal production of steroids by the body. Because of the possibility of systemic absorption of inhaled steroids, patients treated with these drugs should be observed carefully for any evidence of systemic steroid effects including suppression of growth in children. The degree to which inhaled steroids suppress gowth, if at all, is currently under study. Steroids also blunt the immune response. While there are no reports of serious problems with infection in children on the sprays, caution is advised if susceptible children on these sprays are exposed to chicken pox or measles. Because of all these cautions, inhaled steroids are generally not first line drugs. They are reserved for more severe asthma. Generally, cromolyn or nedocromil should be tried first. Inhaled steroids are much preferred over systemic steroids for management of asthma, so in situations where children end up taking oral steroids frequently for management of asthma, using the steroid spray to maintain control after discontinuing the oral steroid is an excellent idea.

  Steroids are serious medicine, but asthma can be a serious disease. When steroids are needed, they are excellent medicines. My daughter has been using an inhaled steroid for 12 years.

• Systemic Steroids - Systemic means taken into the body rather than put directly into the lungs as with a spray or nebulizer. Children who are sick enough to be hospitalized for asthma generally get steroids intravenously. Some physicians will give an injection of Decadron, Depomedrol , or another steroid to patients in their office for acute asthma attacks. Most commonly, patients take steroids by mouth for severe exacerbations of their asthma.. There are many brands - pills such as Prednisone, Medrol, Decadron, Aristocort, and liquids like Pediapred, or Prelone.

  Systemic steroids have a much more potent anti-inflammatory effect on the inflamed airways than inhaled steroids, and they have a much more rapid onset of action than inhaled steroids. They also have a much greater risk of side effects. Initial side effects such as stomach irritation and mood changes are dose related. The most serious side effects are related to prolonged use. Prolonged use of steroids can cause growth retardation, osteoporosis, cataracts, a rounded face, increased body fat, fluid retention, muscle weakness, peptic ulcer, menstrual irregularities, aggravation of diabetes mellitus, impaired wound healing, and decreased immunity. In addition, systemic steroids taken for more than two weeks causes sufficient suppression of normal adrenal gland function that the steroids must be tapered rather than abruptly withdrawn. For these reasons, the use of systemic steroids is reserved for treatment of severe or persistent asthma symptoms or increasing symptoms not adequately controlled by treatment. Courses of systemic steroids should be kept as short as possible to minimize side effects, but generally a minimum of three days is required to achieve an adequate anti-inflammatory response. In spite of potential side effects, it is not desirable to stop steroids prematurely since that will most likely result in a return of symptoms necessitating reinstitution of the steroids. Therefore, patients must be monitored closely to determine the optimal duration of treatment.

  Steroids are potent medicines, but in short courses they are generally well tolerated. Asthma can be a serious disease. Even though the use of steroids should not be taken lightly, with appropriate monitoring, there should be no hesitation about using steroids to control asthma symptoms.

• Albuterol (Proventil Repetabs, Volmax) - available as tablets. The two brands listed are long acting preparations of albuterol which can be taken by mouth to provide prolonged bronchodilation. Side effects include hyperactivity, shakiness, rapid heart rate, and are the same as the shorter acting albuterol.
• Salmeterol (Serevent) - available as a spray. Salmeterol is a 12 hour bronchodilator. It is meant to be taken every 12 hours to control recurrent wheezing. Long acting bronchodilators are especially useful for patients who are awakened by wheezing. The 12 hour duration helps them to stay wheeze free through a night of sleep. Salmeterol is similar to the rescue medicine albuterol, but its duration of action is longer and its onset of action is slower. Salmeterol should not be taken to control the acute onset of wheezing. It is not a rescue medicine. If a patient is wheezing when it is time to take his Salmeterol he should first take his rescue medicine to control the wheeze. Side effects are similar to albuterol although sprays generally have fewer systemic side effects than medicines taken by mouth.
• Ipratropium bromide (Atrovent) - available as a spray. Useful for prevention of bronchospasm. Unlike other bronchodilators, Ipratropium bromide blocks the reflexes that cause bronchospasm. Its onset of action is not rapid enough to use as a rescue medication. It can be used in combination with the bronchodilators that cause bronchial relaxation to achieve better control. Ipratropium bromide is used more commonly for chronic bronchitis and emphysema than for asthma. The most common side effects are dry mouth and cough.
• Methylxanthines include aminophylline and theophyllines (Elixophylline, Slo-bid, Theo-Dur, Quibron, and many others). These drugs are stimulants similar to caffeine which act as bronchodilators. When I first became a pediatrician, prior to the development of drugs like albuterol and metaproterenol, theophyllines were the first line drugs for treating asthma. Only the intravenous aminophylline and theophylline elixir (Elixophylline) have relatively rapid onset of action. The others are long acting medications primarily useful for chronic management. Aside from being stimulants, theophyllines taste terrible and tend to upset the stomach. Their use requires monitoring of the blood level of theophylline. Most pediatricians today use these medicines only for additional control of wheezing in children already on the other medications.

Combination Medications

These include combinations of ephedrine and theophylline such as Marax and Tedral. I mention them only for historical perspective in case you hear of patients on these medications. They are generally not used anymore. Even though both theophylline and ephedrine are bronchodilators, their use in combination increases their side effects more than it increases their therapeutic benefits.

Next article in series: Equipment Used in the Management of Asthma (Nebulizers, Spacers, Peak Flow Meters, Sprays)

To review rescue medications check Treatment of Asthma - Part I

Check the following important news articles about asthma maintenance medicines:

11/8/96 - ACCOLATE, New Asthma Drug, Now Available Nationwide

6/9/97 - Physicians Under-Prescribing Important Asthma Therapy - inhaled corticosteroids

Read Ask Dr. Warren Column