George Schiffman, MD, FCCP
George Schiffman, MD, FCCP
Dr. Schiffman received his B.S. degree with High Honors in biology from Hobart College in 1976. He then moved to Chicago where he studied biochemistry at the University of Illinois, Chicago Circle. He attended Rush Medical College where he received his M.D. degree in 1982 and was elected to the Alpha Omega Alpha Medical Honor Society. He completed his Internal Medicine internship and residency at the University of California, Irvine.
Alan Szeftel, MD
Alan Szeftel, MD
Dr. Szeftel received his Medical Degree from the University of Cape Town Medical School in South Africa. His clinical training was at Groote Schuur Hospital. He completed his Internal Medicine residency at Brigham & Women's Hospital and Harvard University. He is board certified in Internal Medicine, Pulmonary Diseases, Critical Care and Allergy and Immunology.
William C. Shiel Jr., MD, FACP, FACR
William C. Shiel Jr., MD, FACP, FACR
Dr. Shiel received a Bachelor of Science degree with honors from the University of Notre Dame. There he was involved in research in radiation biology and received the Huisking Scholarship. After graduating from St. Louis University School of Medicine, he completed his Internal Medicine residency and Rheumatology fellowship at the University of California, Irvine. He is board-certified in Internal Medicine and Rheumatology.
In this Article
What medications are used in the treatment of asthma?
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Most asthma medications work by relaxing bronchospasm (bronchodilators) or reducing inflammation (corticosteroids). In the treatment of asthma, inhaled medications are generally preferred over tablet or liquid medicines, which are swallowed (oral medications). Inhaled medications act directly on the airway surface and airway muscles where the asthma problems initiate. Absorption of inhaled medications into the rest of the body is minimal. Therefore, adverse side effects are fewer as compared to oral medications. Inhaled medications include beta-2 agonists, anticholinergics, corticosteroids, and cromolyn sodium. Oral medications include aminophylline, leukotriene antagonists, beta-2 agonists, and corticosteroid tablets.
Historically, one of the first medications used for asthma was adrenaline (epinephrine). Adrenaline has a rapid onset of action in opening the airways (bronchodilation). It is still often used in emergency situations for asthma. Unfortunately, adrenaline has many side effects, including rapid heart rate, headache, nausea, vomiting, restlessness, and a sense of panic.
Medications chemically similar to adrenaline have been developed. These medications, called beta-2 agonists, have the bronchodilating benefits of adrenaline without many of its unwanted side effects. Beta-2 agonists are inhaled bronchodilators which are called "agonists" because they promote the action of the beta-2 receptor of bronchial wall muscle. This receptor acts to relax the muscular wall of the airways (bronchi), resulting in bronchodilation. The bronchodilator action of beta-2 agonists starts within minutes after inhalation and lasts for about four hours. Examples of these medications include albuterol (Ventolin HFA, Proventil HFA), levalbuterol (Xopenex), metaproterenol (Alupent), pirbuterol acetate (Maxair), and terbutaline sulfate (Brethaire). Recently, chlorofluorocarbons (CFCs) have been removed from all MDI inhalers because of the environmental effects on the ozone layer. These have been replaced by a new propellant, hydrofluoroalkane (HFA). Patients may notice that the jet they feel in the back of their throat is less intense when compared with the CFC inhaler. They should be instructed that they are still receiving the same amount of medication though it may feel different than their older inhaler. Another very important point that patients must be aware of is that "floating" these new inhalers does not help in determining the amount of medication left in the MDI. In the past, the CFC devices could be floated in a bowl of water. With more medicine in the inhaler, the canister would sink and gradually float as it emptied. This is not the case with the HFA inhalers, as floating will actually clog the inhaler. The number of actuations must be counted to determine if medication is still left in the inhaler. Shaking the inhaler is not an effective method of determining how much medication is left. Often propellant (HFA) will continue to come out of the inhaler even after the medication is used up. Ventolin HFA and Proventil HFA both come with a counter device. This group of inhalers are often referred to as rescue inhalers because they are used when symptoms are anticipated or occur.
The following medications are often referred to as maintenance medication because they are used routinely despite symptoms. Depending on the state of control of asthma, the number of medications and/or the dose can be adjusted up or down. This is referred to as step-up therapy and step-down therapy, respectively.
A new group of long-acting beta-2 agonists has been developed with a sustained duration of effect of 12 hours. These inhalers can be taken twice a day. Salmeterol xinafoate (Serevent) and formoterol (Foradil) are examples of this group of medications. The long-acting beta-2 agonists should not be used for acute attacks. Beta-2 agonists can have side effects, such as anxiety, tremor, palpitations or fast heart rate, and lowering of blood potassium. There is data to suggest that taking long-acting beta-2 agonists alone may be life-threatening and both of these agents come with an FDA-issued box warning. They are best taken along with inhaled corticosteroids (see below).
Just as beta-2 agonists can dilate the airways, beta blocker medications impair the relaxation of bronchial muscle by beta-2 receptors and can cause constriction of airways, aggravating asthma. Therefore, beta blockers, such as the blood pressure medications propranolol (Inderal) and atenolol (Tenormin), should be avoided by asthma patients if possible. Sometimes, however, the benefits of these agents outweigh the risks. Your physician's clinical judgement will take into account the balance of these conflicting properties.
The anticholinergic agents act on a different type of nerves than the beta-2 agonists to achieve a similar relaxation and opening of the airway passages. These two groups of bronchodilator inhalers when used together can produce an enhanced bronchodilation effect. An example of a commonly used anticholinergic agent is ipratropium bromide (Atrovent). Ipratropium takes longer to work as compared with the beta-2 agonists, with peak effectiveness occurring two hours after intake and lasting six hours. A long-acting anticholinergic, tiotropium (Spiriva), has recently be shown to be of benefit in treating asthma. When symptoms of asthma are difficult to control with beta-2 agonists, inhaled corticosteroids (cortisone) are often added. Corticosteroids can improve lung function and reduce airway obstruction over time. Examples of inhaled corticosteroids include beclomethasone dipropionate (Beclovent, Qvar, and Vanceril), triamcinolone acetonide (Azmacort), mometasone (Asthmanex), budesonide (Pulmocort), and flunisolide (Aerobid). The ideal dose of corticosteroids is still unknown. The side effects of inhaled corticosteroids include hoarseness, loss of voice, and oral yeast infections. Early use of inhaled corticosteroids may prevent irreversible damage to the airways.
To decrease the deposition of medications on the throat and increase the amount reaching the airways, spacers can be helpful. Spacers are tube-like chambers attached to the outlet of the MDI canister. Spacer devices can hold the released medications long enough for patients to inhale them slowly and deeply into the lungs. A spacing device placed between the mouth and the MDI can improve medication delivery and reduce the side effects on the mouth and throat. Rinsing out the mouth after use of a steroid inhaler also can decrease these side effects.
Combination inhaler therapy is now available for the treatment of asthma. These medications include Advair (fluticasone and salmeterol), Symbicort (budesonide and formoterol), and Dulera (mometasone and formoterol). Symbicort and Dulera use the standard MDI inhaler device with a dose counter. Advair has a unique powdered delivery system with a built-in counter.
Cromolyn sodium (Intal) prevents the release of certain chemicals in the lungs, such as histamine, which can cause asthma. Exactly how cromolyn works to prevent asthma needs further research. Cromolyn is not a corticosteroid and is usually not associated with significant side effects. Cromolyn is useful in preventing asthma but has limited effectiveness once acute asthma starts. Cromolyn can help prevent asthma triggered by exercise, cold air, and allergic substances, such as cat dander. Cromolyn may be used in children as well as adults.
Theophylline (Theo-Dur, Theolair, Slo-bid, Uniphyl, Theo-24) and aminophylline are examples of methylxanthines. Methylxanthines are administered orally or intravenously. Before the inhalers became popular, methylxanthines were the mainstay of treatment of asthma. Caffeine that is in common coffee and soft drinks is also a methylxanthine drug! Theophylline relaxes the muscles surrounding the air passages and prevents certain cells lining the bronchi (mast cells) from releasing chemicals, such as histamine, which can cause asthma. Theophylline can also act as a mild diuretic, causing an increase in urination. For asthma that is difficult to control, methylxanthines can still play an important role. Dosage levels of theophylline or aminophylline are closely monitored. Excessive levels can lead to nausea, vomiting, heart-rhythm problems, and even seizures. In certain medical conditions, such as heart failure or cirrhosis, dosages of methylxanthines are lowered to avoid excessive blood levels. Drug interactions with other medications, such as cimetidine (Tagamet), calcium channel blockers (Procardia), quinolones (Cipro), and allopurinol (Zyloprim) can further affect drug blood levels.
Corticosteroids are given orally for severe asthma unresponsive to other medications. Unfortunately, high doses of corticosteroids over long periods can have serious side effects, including osteoporosis, bone fractures, diabetes mellitus, high blood pressure, thinning of the skin and easy bruising, insomnia, emotional changes, and weight gain.
Expectorants help thin airway mucus, making it easier to clear the mucus by coughing. Potassium iodide is not commonly used and has the potential side effects of acne, increased salivation, hives, and thyroid problems. Guaifenesin (Entex, Humibid) can increase the production of fluid in the lungs and help to decrease the apparent thickness of the mucus but can also be an airway irritant for some people.
In addition to bronchodilator medications for those patients with atopic asthma, avoiding allergens or other irritants can be very important. In patients who cannot avoid the allergens, or in those whose symptoms cannot be controlled by medications, allergy shots are considered. The benefits of allergy shots (desensitization) in the prevention of asthma has not been firmly established. Some doctors are still concerned about the risk of anaphylaxis, which occurs in one in 2 million doses given. Allergy shots most commonly benefit children allergic to house dust mites. Other benefits can be seen with pollens and animal dander.
In some asthma patients, allergy antibodies of one form known as immunoglobulin E (IgE) may play a key role. If these substances are elevated in the blood, a new form of medication may be helpful for severe asthma. An antibody to IgE, known as omalizumab (Xolair) has been developed. This must be administered by injection in a doctor's office. This is extremely expensive. However, for patients with asthma that is difficult to manage, this option may be helpful.
In some asthma patients, avoidance of aspirin, or other NSAIDs (commonly used in treating arthritis inflammation) is important. In other patients, adequate treatment of backflow of stomach acid (esophageal reflux) prevents irritation of the airways. Measures to prevent esophageal reflux include medications, weight loss, dietary changes, and stopping cigarettes, coffee, and alcohol. Examples of medications used to reduce reflux include omeprazole (Prilosec) and ranitidine (Zantac). Patients with severe reflux problems causing lung problems may need surgery to strengthen the esophageal sphincter in order to prevent acid reflux (fundoplication surgery).
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