Pulmonary pharmacology concerns understanding how drugs act on the lung and the pharmacological therapy of pulmonary diseases. Much of pulmonary pharmacology is concerned with the effects of drugs on the airways and the therapy of airway obstruction, particularly asthma and chronic obstructive pulmonary disease (COPD), which are among the most common diseases of the airways, although there are marked differences in inflammatory mechanisms and response to therapy between these diseases. This chapter discusses the pharmacotherapy of obstructive airways disease, particularly therapy with bronchodilators, which act mainly by reversing airway smooth muscle contraction, and anti-inflammatory drugs, which suppress the inflammatory response in the airways. This chapter focuses on the pulmonary pharmacology of β2 adrenergic agonists and corticosteroids; the basic pharmacology of these classes of agents is presented elsewhere (see Chapters 14 and 50).
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. Drugs used in the treatment of pulmonary hypertension (see Chapter 35) or lung infections, including tuberculosis (see Chapter 65), are covered elsewhere.
Abbreviations
ACh: acetylcholine
AUC: area under the curve
BDP: beclomethasone dipropionate
cAMP: 3′-5′ cyclic adenosine monophosphate, cyclic AMP
CCR: C-C chemokine receptor
COMT: catechol-O-methyl transferase
COPD: chronic obstructive pulmonary disease
CRTh2: chemokine receptor homologous molecule expressed on Th2 lymphocytes
cys-LT: cysteinyl-leukotriene
DPI: dry powder inhaler
FeNO: fractional exhaled nitric oxide
FEV1: forced expiratory volume in 1 sec
GI: gastrointestinal
GPCR: G protein-coupled receptor
GR: glucocorticoid receptor
HDAC: histone deacetylase
HFA: hydrofluoroalkane
HPA: hypothalamic-pituitary-adrenal
ICS: inhaled corticosteroid
Ig: immunoglobulin
IL: interleukin
ILC2: innate type 2 lymphocyte
IP3: inositol 1,4,5-trisphosphate
LABA: long-acting β2 agonist
LAMA: long-acting muscarinic antagonist
LTRA: leukotriene cys-LT1-receptor antagonist
5-LO: 5′-lipoxygenase
LT: leukotriene
MAO: monoamine oxidase
MAP: mitogen-activated protein
MDI: metered-dose inhaler
MMAD: mass median aerodynamic diameter
MMP: matrix metalloproteinase
NF-κB: nuclear factor kappa B
PDE: cyclic nucleotide phosphodiesterase
PG: prostaglandin
PKA: protein kinase A
pMDI: pressurized metered-dose inhaler
SABA: short-acting β2 agonists
SAMA: short-acting muscarinic antagonist
TAS2R: taste 2 receptor
Tc1 cell: cytotoxic T lymphocyte
TH17: T helper 17 cell
TH2: T helper 2 lymphocyte
TNF: tumor necrosis factor
TRP: transient receptor potential
TSLP: thymic stromal lymphopoietin
VIP: vasoactive intestinal polypeptide
Asthma is a chronic inflammatory disease of the airways that is characterized by activation of mast cells, infiltration of eosinophils, T helper 2 (TH2) lymphocytes, and innate type 2 lymphocytes (ILC2) (Figure 44–1) (Papi et al., 2018). Mast cell activation by allergens and physical stimuli releases bronchoconstrictor mediators, such as histamine, leukotriene (LT) D4, and prostaglandin (PG) D2, which cause airway smooth muscle contraction, vasodilation, microvascular leakage, and ...