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INTRODUCTION

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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).

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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.

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ABBREVIATIONS

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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

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MECHANISMS OF ASTHMA

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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 bronchoconstrictor mediators, ...

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