___________________________________________________________ Asthma: Diagnosis and Management
Inhaled beta 2 agonist medications are associated with fewer major side effects than orally administered preparations. However, patients who use inhalers may report problems as well. The most common complaint is shakiness; other notice- able side effects may include tachycardia, heart palpitations, headache, dizziness, and increased serum glucose [35]. These side effects tend to diminish over time. Patients using oral beta 2 agonists have reported tremors, nervousness, tachycardia, muscle cramps, and sleeplessness [9; 11]. There are several beta 2 agonists approved by the U.S. Food and Drug Administration (FDA) for use as bronchodilators. Beta 2 agonists come in every administration form, which can assist in individualizing treatment. Injections may work quickly in case of emergency, although the effect lasts only about 20 minutes. Two to four puffs of an inhaled beta 2 agonist taken before exercise or travel in cold air can block wheezing for up to four hours [11; 35]. Long-acting beta 2 agonists are usually taken twice a day and last up to 12 hours. Their longer action can help prevent interruptions from night-time symptoms and/or allow patients to engage in activities that they would otherwise be advised to avoid. However, even longer-acting beta 2 agonists cannot control unstable asthma. These medications are unable to reverse the chronic airway inflammation found in patients with asthma, necessitating the additional use of an anti-inflammatory drug to prevent symptoms in the long-term. And, as discussed, overuse of these medications can lead to poor asthma control, possible desensitization, and even death. FDA analyses of clinical tri- als have shown that use of long-acting beta 2 agonists without concurrent use of an inhaled corticosteroid is associated with an increased risk of severe worsening of asthma symptoms, leading to hospitalization and death in some patients with asthma, including children [9; 36; 37]. Theophylline Derivatives Before inhalers became widely available, methylxanthines were the leading asthma medications. They could be administered intravenously or orally. Theophylline was formerly the most widely prescribed bronchodilator in the methylxanthine cat- egory and a keystone of asthma treatment in the United States. Theophylline reduces airway responsiveness to histamine, adenosine, methacholine, and allergens, and also relaxes air- way muscles and pulmonary blood vessels, allowing the tubes to open and airflow to continue [35]. However, controversies over the medication’s benefits and action, and higher efficacy of newer drugs have led to a decline in use [11; 35]. Theophylline provides both a short- and a long-term alterna- tive for patients who cannot tolerate beta 2 agonists. The drug reduces mucus buildup and blocks night-time symptoms in mild-to-moderate asthma. Its long-term benefits for preventing symptoms are well documented for up to 12 hours, although theophylline is generally less effective than beta 2 agonists. It should be noted that caffeine is considered a methylxanthine drug, so patients should be advised to monitor coffee, tea, and chocolate intake while using this medication. Many factors may
affect the metabolism or serum concentration of theophylline, including diet, viral infections, hypoxia, age, some antibiotics, and smoking [11; 35]. In addition, studies have shown that theophylline for asthma management is not as effective in patients with obesity [20]. Anticholinergics Anticholinergics such as ipratropium bromide, atropine, and tiotropium are shown to be effective in relieving breathing disorders, including asthma. When used for asthma, these medications are not usually the first line of defense but rather are used to supplement beta 2 agonists. Anticholinergics act on different nerves than beta 2 agonists, although both block nerve pathways to the lung and alter muscle tone in the bronchial wall. Anticholinergics affect specific lung nervous system receptors, or cholinergics, in the vagus nerve; this nerve branches into the smooth muscles responsible for airway opening and the mucous glands that discharge thick secretions. The result is reduced inflammation and relaxed bronchial muscles. Throughout the respiratory tract, the drug stimulates nerve activity in other reac- tive cells to decrease mouth and lung secretions [9; 11]. Anti-Inflammatory Medications In 2007, a panel of experts, under the guidance of the NAEPP, noted that the critical role of airway inflammation in asthma has been further substantiated since the 1990s, when this inflammatory role was first acknowledged and treatment was shifted away from calming acute flare-ups to engaging in preven- tative measures. The NAEPP also noted that bronchodilators work best for acute asthma situations and for preventative treatment before exertion or exercise, but it emphasized anti- inflammatory medications as the foundation for long-term treatment of asthma; this was reaffirmed in the NAEPP 2020 Focused Updates to the Asthma Management Guidelines and in the 2024 GINA guidelines. This approach relies on daily medication to maintain healthy lungs. Patients who require regularly administered bronchodilators should switch to longer- acting drugs designed to reduce airway inflammation [8; 9; 10]. Anti-inflammatory medications block production of substances from cells involved in inflammation, such as mast cells; this action reduces or reverses the swelling that causes asthma symptoms. Equally important, these medications lessen airway sensitivity, which prevents edema. If asthma symptoms appear more than once or twice a week and less powerful options can- not control them, anti-inflammatory medication is indicated. Before newer drugs were developed, the only anti-inflammatory asthma medication available was an oral corticosteroid, such as prednisone. Long-term treatment with oral corticosteroids is associated with serious side effects, including stunted growth in children, hyperlipidemia, thinning skin, and immune system impairment, making patient compliance difficult. As a result, several inhaled anti-inflammatory drugs were developed, which greatly reduced negative reactions. The four primary types of anti-inflammatory drugs are corticosteroids, mast cell stabiliz- ers, antiallergic medications, and antileukotriene medications [9; 11; 13].
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