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 COPD, which are among the most common chronic diseases in the world. Both asthma and COPD are characterized by chronic inflammation of the airways, although there are marked differences in inflammatory mechanisms and response to therapy between these diseases (Barnes, 2008b; Postma and Rabe, 2015). 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 (Chapters 12 and 46).
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 (Chapter 31) or lung infections, including tuberculosis (Chapter 60), are covered elsewhere.
Abbreviations
AC: adenylyl cyclase
ACh: acetylcholine
ALT: alanine aminotransferase
BDP: beclomethasone dipropionate
cAMP: cyclic adenosine monophosphate
CCR3: C-C chemokine receptor type 3
COMT: catechol-O-methyl transferase
COPD: chronic obstructive pulmonary disease
CRTh2: chemokine receptor homologous molecule expressed on Th2 lymphocytes
CXCR2: C-X-C motif chemokine receptor 2
cys-LT: cysteinyl-leukotriene
DPI: dry powder inhaler
FDA: Food and Drug Administration
FEV1: forced expiratory volume in 1 second
FFA: free fatty acid
GABA: γ-aminobutyric acid
GR: glucocorticoid receptor
HDAC2: histone deacetylase 2
HFA: hydrofluoroalkane
ICS: inhaled corticosteroid
Ig: immunoglobulin
IL: interleukin
ILC2: innate type 2 lymphocyte
IM: intramuscular
IP3: inositol 1,4,5-trisphosphate
IV: intravenous
LABA: long-acting inhaled β2 agonist
LAMA: long-acting muscarinic antagonist
5-LO: 5′-lipoxygenase
LT: leukotriene
MAO: monoamine oxidase
MDI: metered-dose inhaler
MMAD: mass median aerodynamic diameter
MMP: matrix metalloproteinase
MOR: μ opioid receptor
NF-κB: nuclear factor kappa B
NMDA: N-methyl-D-aspartate
PAF: platelet-activating factor
PDE: phosphodiesterase
PG: prostaglandin
PKA: protein kinase A
PLC: phospholipase C
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
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 40–1) (Barnes, 2011b; Lambrecht and Hammad, 2015). Mast cell activation by allergens and physical stimuli releases ...