BRONCODILATORSDr. 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 agents4. Calcium channel blockers5. 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 Isoproterenolβ2- SELECTIVE DRUGS Albuterol Terbutaline Metaproterenol Pirbuterol Salmeterol long acting Formoterol

Toxicities of Sympathomimetic AgentsACUTE Cardiac arrhythmias HypoxemiaCHRONIC Tachyphylaxis Tolerance

METHYLXANTHINES Theophylline - Aminophylline Theobromine Caffeine

CHEMISTRY Methylated xanthine derivatives

Mechanism of ActionInhibit Phosphodiesterase Enzyme-PDE4 Higher concentrations of intracellular cyclic AMP Reduces release of cytokines and chemokines Resulting in decrease in immune cell migration &

activationInhibit cell-surface receptors for AdenosineEnhancement 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