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Asthma Drugs

Asthma drugs come in two main varieties: short-acting or quick-relief medications (also called "rescue" drugs) and long-term control drugs. Most asthma medications are taken through an inhaler.

Inhalers aren't just for short-acting drugs; many long-term control drugs are also delivered that way. To treat an occasional asthma attack, you'll use a short-acting drug. If you only have symptoms every once in awhile, this may be the only type of medication you need. People with moderate to severe asthma need to keep a quick-relief drug handy in case of an attack.

Long-acting drugs are used to control and prevent symptoms in people with persistent asthma (who have symptoms more than twice a week). The recommended dose may change over time, depending on how severe your asthma is. These drugs are usually anti-inflammatory, working to prevent the immune reactions that cause asthma symptoms in the first place.

Short-acting drugs for quick relief

Quick-relief drugs are bronchodilators -- they usually work on the nervous system's autonomic (involuntary) nerve pathways, causing them to relax the muscles in the airways. They work by mimicking other chemicals that would normally act on these types of nerves; specifically, they bind to a nerve receptor to either intensify a natural reaction or block it. (A receptor is a type of gateway or "docking station" that only certain chemicals can fit into).

Beta-2 agonists: These are the most common quick-relief asthma medicines. An agonist is something that "turns on" a reaction when it lands in the right place -- it's the opposite of an antagonist. Beta-2 agonists are a class of chemicals that include adrenaline, which controls your body's responses to stress. Beta-2 agonists bind in the tissues around your airways, and this sets off a reaction that relaxes the muscles in your bronchial tubes and helps you breathe easier.

Short-acting inhaled beta-2 agonists start to work within 5 minutes and the effects can last up to 3-8 hours. You can use it as symptoms appear, and about 20 minutes before exercising to prevent exercise-induced asthma symptoms. (There are also longer-acting forms used for long-term control.)

Side effects of inhaled beta-2 agonists are usually milder than the oral form used for long-term control. Common side effects of the inhaled form include shakiness (tremors), faster heart rate, restlessness, anxiety, sleeplessness, headache, and muscle cramps. Different drugs have slightly different sets of side effects.

Cautions: If you overuse this type of drug, you don't have good control of your asthma. Ask your doctor if you need more controller medication. Be sure to let your doctors know if you have a history of angina, heart disease, high blood pressure, stroke or seizure, diabetes, thyroid disease, or glaucoma.

Interactions: Other drugs may increase the effects of oral beta-2 agonists, including certain antidepressants, thyroid drugs and, other bronchodilators (oral or inhaled). If you're also taking methylxanthines for long-term control, you may feel more of the effects on your heart. Beta blockers, used to treat heart disease, can decrease the effect of these drugs. Oral beta-2 agonists, in turn, can interfere with drugs that reduce blood pressure and with digitalis drugs, used to treat congestive heart failure and very rapid heartbeat.

Anticholinergics: These drugs work by blocking a type of acetylcholine receptor in the tissues of the lungs, which causes bronchial muscles to relax and reduces the amount of mucous produced.

Anticholinergics work through the cholinergic branch of the involuntary nervous system, which in conjunction with the autonomic nervous system, controls your heartbeat, breathing, and other core "housekeeping" activities.

This type of asthma medication comes in an inhaler and is usually used in conjunction with other medicines for moderate or severe asthma attacks because it takes longer to act. It can be used as the primary reliever medication for some patients with chronic obstructive pulmonary disease (COPD) like emphysema, or for those who do not respond well to short-acting beta agonists. It is also beneficial in combination with a short-acting beta agonist for a patient having a severe, acute asthma attack. A nasal formulation is used to treat rhinitis associated with the common cold or allergies.

Side effects are uncommon and usually mild. The most common ones include dry mouth, abnormal bitter taste in mouth, and nasal congestion.

Cautions and interactions: This medication has no known drug interactions.

Oral corticosteroids: While they don't provide quick relief, oral corticosteroids (a class of anti-inflammatory drugs) are sometimes used to stabilize symptoms when an asthma attack strikes. Corticosteroids interfere with inflammation, which is often the immune system's natural response to an irritant or invader. For this reason, a course of corticosteroid pills is often recommended to fight inflammation.

Common side effects of short-acting drugs

Inhaled short-acting beta2-agonists include Ventolin HFA, Proventil HFA(albuterol), and Breathaire (terbutaline). They serve to relax the airway muscles, making it easier to breathe. Side effects include shakiness (tremors), faster heart rate, cough, dry or sore throat, restlessness, anxiety, sleeplessness, and headache. The side effects of inhaled anti-cholinergics such as Atrovent (ipratroprium bromide, include relaxing the airway muscles, decreasing mucus in nasal passages, dry mouth, nervousness, dizziness, headache, nausea, upset stomach, and throat or mouth irritation, and cough.

Long-term asthma controller drugs: Asthma is now understood to be a chronic inflammatory disorder of the airways in which many types of cells play a role. Controller drugs are usually anti-inflammatory -- they help to control the immune reactions that cause asthma attacks, thus reducing the frequency of attacks and sometimes preventing them from happening at all. Some long-acting bronchodilators are also used for long-term control.

Beta-2 agonists, long-acting: These drugs work the same way as the short-acting beta-2 agonists, and are often used together with a corticosteroid to provide long-term control. The long-acting beta-2 agonists start working in 3 to 30 minutes depending on the specific drug and last anywhere from 10-12 hours after a single dose.

Side effects: Common side effects of long-acting beta-2 agonists include: cough, rapid heart rate, shakiness (tremors), dizziness, throat irritation, and headache. Different drugs have slightly different sets of side effects -- although the Food and Drug Administration warns that all of these medications may increase the chance of a severe asthma episode, possibly leading to death.

Cautions: Do not take more than the prescribed amount of long- acting beta-2-agonists. They should also not be used alone for long-term asthma control. These agents are not designed for "as needed" use and over-use could result in an over-dose. A safety study of the drug Serevent (salmeterol) involving more than 25,000 subjects found that the drug may be associated with a very slight increase in serious asthma episodes and deaths, particularly in African Americans. The increase was not statistically significant, and the Food and Drug Administration strongly advises patients on the medication not to stop taking it without talking to their doctors.

However, the FDA has issued its strongest caution, a "black box" warning, for long-acting beta-2 agonists like Serevent (salmeterol), Advair Diskus (salmeterol/fluticasone), and Foradil (formoterol). Further investigation of possible risks is planned.

Inhaled corticosteroids: These are anti-inflammatory medications that interfere in a broad way with the immune system and are used to control many types of inflammation, which is simply the immune system's response to an irritation or invader. In asthma treatment, corticosteroids reduce the immune system's response to triggers in the airways and prevent the resulting inflammation. That accounts for the reduction in inflammation symptoms, such as airway hypersensitivity, swelling inside the airway muscles, and mucus and secretions in the lungs.

Side effects: Inhalers -- Corticosteroids come in inhalers and pills. Common side effects of the inhaled form include dry mouth, throat irritation, hoarseness, and thrush (yeast infection in the mouth). They can be used in short bursts, in oral form to get symptoms under control after an attack, or as long-term prevention (usually in the inhaled form, but sometimes oral as well in severe asthma) for people with persistent asthma.

Pills: The most common side effect of short-term pill dosages is an upset stomach, which can lead to or aggravate an ulcer of the esophagus. Other common ones include change in appetite, emotional instability, water retention, muscle weakness, potassium loss (tiredness, weakness, muscle cramps), slower wound healing, increased blood sugar, sweating, itchiness, headache, dizziness, and convulsions.

Because corticosteroids act by interfering with the immune system, it's easier to catch infections while taking them and harder to recover from new or existing infections. For the same reason, don't get any vaccines without consulting your doctor first. The effects of long-term use, especially on high doses of pills, can include adrenal suppression, osteoporosis, caratacts, glaucoma, esophageal ulcers, thinned skin, hair loss, "moon face," menstrual irregularities, and "steroid psychosis" -- symptoms can include mood swings, sleeplessness, personality changes, and depression. There are many other side effects from long-term use, so if you notice any unusual symptoms please ask your doctor about them. If you're on long-term corticosteroid treatment, it's very important for your current dosage to be tapered down slowly (even if you're switching to a different form of the medicine) to avoid serious complications such as adrenal insufficiency.

Cautions: Oral corticosteroids should be used with caution in some people, including anyone who's had a recent heart attack and people with osteoporosis, antibiotic-resistant infections (viral and fungal especially), and cancer.

Interactions: Many drugs, including oral contraceptives, can either increase or decrease the effects (and side effects) of corticosteroids, so it's especially important to tell your doctor about all the drugs you're taking, including over-the-counter medicines, and herbs. Corticosteroids may also affect some lab tests.

Mast cell stabilizers: Mast cells are a type of immune cell that carry different chemicals, including histamines, which mediate and aggravate allergic responses. Mast cells tend to spill their contents when there's trouble, and mast cell stabilizers keep that from happening. They're also useful in preventing exercise-induced asthma.

Side effects and cautions:Side effects are uncommon. Cough and throat irritation are the most common side effects from the inhaled mast cell stabilizers. Sometimes people who are lactose intolerant will have gastrointestinal side effects because the medication contains lactose.. In rare cases, it may cause a severe allergic reaction.

Interactions: This medication has no known drug interactions.

Leukotriene modifiers: Leukotrienes are one type of chemical released by mast calls and other immune cells, and they cause airways to constrict. They also stimulate mucus secretion and fluid buildup, making the airways even narrower. Leukotriene modifiers are designed to prevent leukotrienes from wreaking their havoc.

Side effects and cautions: Leukotriene receptor antagonists -- The most common side effect of these drugs is headaches, and other common side effects include nausea, diarrhea, and infections.

5 Lipoxygenase inhibitors: The most common side effect is headache, followed by general throat and upper abdominal pain, nausea, upset stomach, and more rarely liver inflammation. People with active liver disease should avoid it altogether, and if you're taking it, you'll need periodic blood tests to check how your liver and blood counts are doing.

Interactions: Both types of leukotriene modifiers enhance the blood levels of many other drugs, so be sure to tell your doctor about all the medications you're on.

Immunomodulators: These medications, such as Xolair (omalizumab), help reduce your body's sensitivity to allergens. Omalizumab is used in the treatment of patients 12 years of age and older who have severe persistent asthma in conjunction with allergies. The drug is delivered by shot every two to four weeks.

Side effects and cautions: The most common side effects are pain and bruising at the injection site. Hives are reported less commonly.

Anaphylaxis -- a severe, potentially life-threatening allergic reaction -- has happened frequently enough to elicit an FDA alert. Clinicians administering the drug should be prepared to treat anaphylaxis should it occur.

Interactions: There are no known drug interactions.

Methylxanthines (Xanthine bronchodilators): This class of drugs includes theophylline, a stimulant similar to caffeine but far more powerful. Theophylline relaxes the muscles around the airways, but we don't know exactly how. Because these drugs cause many side effects, they're less often a first choice for long-term asthma control.

Theophylline and related drugs come in pill and syrup form. They're also available as sustained or timed-release pills so you can take fewer doses in a day. If you have this type of pill, it's important not to chew or crush the pills, or take them with hot food or drinks, because that will release too much of the drug too quickly into the body and cause potentially dangerous side effects. The medication may be taken with or without food but must be consistently taken the same way so that your body always absorbs the same amount.

Side effectsThe most common side effects are dose related and occur mostly when blood levels are high. They include nausea, vomiting, stomachache, diarrhea, restlessness, irritability, headache, trouble sleeping, and faster heartbeat. These drugs can cause or worsen abnormal heart rhythms.

Cautions: You should avoid methylxanthines if you have seizure disorders, and use them with caution if you have a stomach ulcer, heart disease, high blood pressure, or liver disease. If you're on a methylxanthine, you'll need periodic blood tests to monitor your dosage and minimize the side effects from these drugs.

Interactions: Caffeine is a methylxanthine too, so try to minimize the amount of tea, coffee, chocolate, and caffeinated soft drinks you consume to keep your dosage within safe limits. Smoking decreases the effects of methylxanthines. Many different drugs can interact with theophylline and related drugs, either increasing or decreasing levels in the blood, so it's especially important to tell your doctor about all the drugs you're taking, including oral contraceptives, over-the-counter medicines, and herbs. Methylxanthines themselves can interfere with other drugs, including sedatives and anesthetics. People with thyroid disorders may need their dose adjusted.

Anticholinergics: These drugs are sometimes used for long-term control. For more information, see the listing under short-term medicines, above, and the entry in the table below.

Common side effects of long-acting drugs

Long-acting inhaled TBeta-2 agonists include Serevent (salmeterol), Foradil (formeterol), and Advair (salmeterol/fluticasone). These combination long-acting B2 agonist and inhaled corticosteroids relaxe airway muscles and keep them open by acting directly on the nerves in the lungs. Side effects include shakiness (tremors), increased heart rate, sleeplessness, weakness, dizziness, headache, sweating, nausea, vomiting, and muscle cramps. These act longer than the beta-2 agonists used for quick relief, although overuse can worsen asthma symptoms.

Inhaled corticosteroidsThese include Qvar (beclomethasone dipropionate), Pulmicort (budesonide), Aerospan HFA (flunisolide hemihydrate), Kenalog (triamcinolone), Flovent (fluticasone propionate), and Asmanex (mometasone furoate). Oral corticosteroids Omnipred (prednisolone acetate), Millipred (prednisolone) and Econopred (prednisolone acetate), Prelone (prednisolone), and Deltasone (prednisone). They block the body's immune response to allergens or irritants, which prevents and reduces inflammation of the airways. Side effects of the inhaled variety include dry mouth, throat irritation, hoarseness, and thrush (yeast infection in the mouth). Side effects of the pills may include upset stomach, water retention, muscle weakness, potassium loss (tiredness, weakness, muscle cramps), slower wound healing, sweating, itchiness, headache, dizziness, increased blood sugar, and convulsions. (The effects of long-term use listed above.)

For best results with inhaled corticosteroids, rinse your mouth and gargle with water after each use to prevent thrush and dry mouth. In addition, don't switch brands without consulting your doctor. If you are using the pill variety, don't stop taking them suddenly -- they need to be tapered down to a safe dosage, or serious side effects can occur.

Inhaled mast cell stabilizers include Intal (cromolyn sodium) These block the release of histamines from mast cells, which interrupts the immune response to allergens or irritants. Side effects include dry cough and throat irritation, though they're rare. Some people think they taste bad.

Leukotriene modifiers (oral tablets) include LTRAs, Singulair (monteleukast) and Accolate (zafirlukast); leukotriene synthesis inhibitors include Zyflo CR (Zileuton CR). These drugs block the action of leukotrienes, which interrupts the immune response to allergens or irritants. Side effects include headache, nausea, diarrhea, upset stomach, and infections. You'll need periodic blood tests to monitor your dosage with some of these.

Immunomodulators (injected) include Xolair (omalizumab). This reduces immune system reaction to allergens by preventing mast cell and basophil receptors from binding with IgE (a blood protein that activates allergic reactions). Side effects include pain and bruising at the injection site and anaphylaxis. Clinicians should monitor their patients following an injection and be prepared to provide treatment for anaphylaxis. The shot should be administered every two to four weeks.

Xanthine bronchodilators (methylxanthines), in the form of oral tablets and capsules, include Theo-24 and Uniphyl (theophylline). These relax the airway muscles and keep them open through an unknown mechanism. They may also help decrease reaction to asthma triggers. Side effects include nausea, vomiting, stomach pain, diarrhea, restlessness, irritability, headache, trouble sleeping, and faster heartbeat. They are no longer a common first choice for long-term control because side effects are common.

It is crucial not to chew or crush the sustained-release tablets or take them with hot food or drinks because you may get a dangerously high dose. You'll also need periodic blood tests to monitor your dosage.

Other drugs that may be used by people with asthma:

Antihistamines: This type of allergy medicine works by blocking histamine, which is released by mast cells. They fight itchiness, redness, and swelling, but they may or may not help your asthma.

Decongestants: These drugs reduce congestion by constricting the blood vessels in the nose, which decreases swelling, and mucus. The most common decongestant is pseudoephedrine. It's the synthetic form of ephedrine, the active ingredient in the herb ephedra (known as ma huang in Chinese medicine). Decongestants are stimulants, and the side effects of your other asthma medications (brochodilators) may be magnified if you take them.

Mucolytic agents: These drugs help dissolve excess mucous in the airways, but it's unclear how useful they are in improving asthma symptoms; they may also be irritating to the airway. Available drugs include N-acetylcysteine (Mucomyst).

The FDA has also approved a therapy for people with severe asthma that isn't responding well to drugs. It's called bronchial thermoplasty, and it works by reducing some of the smooth muscle that can block the lungs during an asthma attack. Some patients who have understand the treatment are able to cut back on medication and get their asthma under control.

References

Mayo Clinic, 2016, Asthma: Treatments and Drugs http://www.mayoclinic.org/diseases-conditions/asthma/basics/treatment/con-20026992

What's New in Asthma Management. US News and World Report, Sept, 4, 2014.

National Heart, Lung, and Blood Institute and National Asthma Education and Prevention Program. Expert Panel Report 3: Guidelines for the Diagnosis and Management of Asthma. http://www.nhlbi.nih.gov/guidelines/asthma/asthgdln.pdf

Drug Digest. Xolair Solution for Injection.

Mayo Clinic. Anaphylaxis. http://www.mayoclinic.com/health/anaphylaxis/DS00009

Mayo Clinic. Asthma. http://www.mayoclinic.com/health/asthma/DS00021

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