BRONCODILATORS

Dr. Naila
Asthma is characterized
Clinically

Physiologically

Pathologically

Pathogenesis of Asthma
Exposure to allergen
Synthesis of IgE
Binding to mast cells in airway mucosa
On reexposure to allergen, antigen-antibody
interaction on mast cell surface
Release of mediators of anaphylaxis: histamine,
tryptase. PGD2, LTC4, PAF
Contraction of airway smooth muscle-early
asthmatic response

Pathogenesis of Asthma (contd.)
Cytokines
Interleukins
Eosinophils
Neutrophils
Late asthmatic response

REVERSAL OF ASTHMATIC
BRONCHOSPASM
1. Drugs reducing amount of IgE bound to mast cells
(Anti-IgE antibody)
2. Prevent mast cell degranulation (Cromolyn or
Nedocromil)
3. Sympathomimetic agents
4. Calcium channel blockers
5. Block the action of the products released
(Antihistamines & leukotriene-receptor antagonists)
6. Inhibit the release of acetylcholine released from vagal
motor nerves (muscarinic antagonists)
7. Directly relax airway smooth muscle (sympathomimetic
agents, theophylline)
REDUCING BRONCHIAL
RESPONSIVENESS
Corticosteroids- inhaled
Drug treatment of asthma
Relievers or Bronchodilators

Controllers or Anti-inflammatory agents
BRONCHODILATORS
Sympathomimetic Agents
Rapid acting
Short acting
Long acting
Methylxanthine Drugs
Theophylline
Theobromine
Caffeine
Antimuscarinic Agents
Ipratropium bromide
Tiotropium
SYMPATHOMIMETIC AGENTS
Adrenoceptors agonists have several
pharmacologic actions that are important in the
treatment of asthma
Relax airway smooth muscle
Inhibit release of bronchoconstricting mediators
from mast cells
Inhibit microvascular leakage
Increase mucociliary transport

Mechanism
Activate adenylyl cyclase via G-protein

Increase formation of intracellular cAMP
NON-SELECTIVE DRUGS
Epinephrine
Ephedrine
Isoproterenol
2- SELECTIVE DRUGS
Albuterol
Terbutaline
Metaproterenol
Pirbuterol
Salmeterol long acting
Formoterol

Toxicities of Sympathomimetic Agents
ACUTE
Cardiac arrhythmias
Hypoxemia
CHRONIC
Tachyphylaxis
Tolerance

METHYLXANTHINES
Theophylline - Aminophylline
Theobromine
Caffeine

CHEMISTRY
Methylated xanthine derivatives

Mechanism of Action
Inhibit Phosphodiesterase Enzyme-PDE4
Higher concentrations of intracellular cyclic AMP
Reduces release of cytokines and chemokines
Resulting in decrease in immune cell migration &
activation
Inhibit cell-surface receptors for Adenosine
Enhancement of Histone Deacetylation
Pharmacodynamics of Methylxanthines
CNS effects
CVS effects
GIT effects
Effect on the Kidneys
Effects on Smooth Muscle
Effects on Skeletal Muscle

Clinical Use of Methylxanthines
Theophylline most effective
Improves long term control of asthma
Sustained release preparations
Narrow therapeutic index
Plasma clearance varies widely
Inexpensive
3-4mg/kg every 6hrs

ANTIMUSCARINIC AGENTS
Atropine
Ipratropium bromide
Tiotropium

MECHANISM
Competitively inhibit the effect of
acetylcholine at muscarinic receptors
Clinical Use of Muscarinic Antagonists
Effective bronchodilation
Less effective than beta agonists
Ipratropium - selective quaternary
ammonium compound

Tiotropium - longer acting, selective
Inhalation
24 hour duration