Chapter 36: Pulmonary Pharmacology

INTRODUCTION

This chapter discusses the pharmacotherapy of obstructive airways disease, particularly bronchodilators, which act mainly by reversing airway smooth muscle contraction, and anti-inflammatory drugs, which suppress the inflammatory response in the airways. The chapter focuses on the pulmonary pharmacology of β₂ agonists and corticosteroids; their basic pharmacology is presented elsewhere (see Chapters 12 and 42). This chapter also discusses other drugs used to treat obstructive airway diseases, such as mucolytics and respiratory stimulants, and covers the drug therapy of cough, the most common respiratory symptom, as well as drugs used to treat pulmonary hypertension. Drugs used in the treatment of lung infections, including tuberculosis (see Chapter 56), are covered elsewhere.

MECHANISMS OF ASTHMA

Asthma is a chronic inflammatory disease of the airways that is characterized by activation of mast cells (generally present in increased numbers), infiltration of eosinophils, and T helper 2 (T_H2) lymphocytes (Figure 36–1). Mast cell activation by allergens and physical stimuli releases bronchoconstrictor mediators, such as histamine, leukotriene D₄, and PGD₂, which cause bronchoconstriction, microvascular leakage, and plasma exudation (see Chapters 32 and 33). Many of the symptoms of asthma are due to airway smooth muscle contraction; thus, bronchodilators are important as symptom relievers. Whether airway smooth muscle is intrinsically abnormal in asthma is not clear, but increased contractility of airway smooth muscle may contribute to airway hyperresponsiveness, the physiological hallmark of asthma. The mechanism of chronic inflammation in asthma is still not well understood. It may initially be driven by allergen exposure, but it appears to become autonomous so that asthma is essentially incurable. The inflammation may be orchestrated by dendritic cells that regulate T_H2 cells that drive eosinophilic inflammation and IgE formation by B lymphocytes. Airway epithelium plays an important role through the release of myriad inflammatory mediators and through the release of growth factors in an attempt to repair the damage caused by inflammation.

Chronic inflammation may lead to structural changes in the airways, including an increase in the number and size of airway smooth muscle cells, blood vessels, and mucus-secreting cells. A characteristic histological feature of asthma is collagen deposition (fibrosis) below the basement membrane of the airway epithelium (see Figure 36–1).

MECHANISMS OF COPD

COPD involves inflammation of the respiratory tract with ...