Chapter 55: Drugs Acting on the Lower Respiratory Tract

Drugs Acting on the Lower Respiratory Tract agents are primarily used to treat pulmonary obstructive diseases such as asthma and Chronic Obstructive Pulmonary Disease (COPD), the latter comprising emphysema and chronic bronchitis, disorders often caused by inflammation and muscular constriction. Treatment strategies focus on two major goals: promoting muscular bronchodilation to open conducting airways or decreasing the severe effects of inflammation. Bronchodilators include three main classes. Xanthines, such as theophylline, directly relax the smooth muscles of the respiratory tract (bronchi and blood vessels) and inhibit the release of slow-reacting substance of anaphylaxis (SRSA) and histamine. They are no longer first-choice drugs due to a narrow margin of safety and dose-related adverse effects ranging up to seizures and death; importantly, substances in cigarettes stimulate the liver metabolism of xanthines, requiring careful dose adjustment if a patient alters smoking habits. Sympathomimetics (e.g., albuterol, epinephrine) mimic the sympathetic nervous system by stimulating beta2-receptors in the bronchi, increasing the rate and depth of respiration. Epinephrine is the preferred agent for acute bronchospasm, but long-acting beta-agonists (LABAs) like salmeterol carry a black box warning regarding increased risk of asthma-related deaths unless combined with an inhaled corticosteroid. Anticholinergics (e.g., ipratropium, tiotropium) relax bronchial smooth muscle by blocking acetylcholine's action at vagal-mediated receptor sites, offering an alternative for patients unable to tolerate sympathomimetics. The second main treatment group involves drugs addressing inflammation. Inhaled steroids (e.g., budesonide, fluticasone) decrease the inflammatory response, improving airflow, but they are maintenance drugs that require 2 to 3 weeks to reach effective levels and are not suitable for acute attacks. Leukotriene receptor antagonists (e.g., montelukast, zafirlukast) competitively block or antagonize receptors for the production of leukotrienes D4 and E4, thereby blocking the edema, bronchoconstriction, and inflammation seen in asthma, and must also not be used for acute relief. For premature infants experiencing Respiratory Distress Syndrome (RDS) due to insufficient surfactant, Lung Surfactants (e.g., beractant) are instilled directly into the trachea to reduce surface tension and allow alveolar expansion. Additional therapies include alpha1-protease inhibitors for hereditary emphysema and, for idiopathic pulmonary fibrosis (IPF), newer drugs like nintedanib and pirfenidone. Across the lifespan, children often benefit from leukotriene receptor antagonists for long-term prophylaxis, while older adults require careful monitoring due to increased susceptibility to adverse effects like confusion and cardiovascular issues.