Overview Therapeutic strategies for treating asthma include: decreasing inflammation increasing sympathetic tone There are 7 families of drugs that are commonly used: corticosteroids β-agonists muscarinic antagonists methylxanthines cromolyn antileukotrienes omalizumab Corticosteroids Inhaled corticosteroids are first line therapy for chronic asthma Examples mometasone fluticasone budesonide beclomethasone triamcinolone flunisolide Mechanism inhibiting the synthesis of virtually all cytokines upregulating expression of beta-adrenergic receptors inactivating NF-κB NF-κB is the transcription factor that induces the production of TNF-α and other inflammatory agents Toxicity oral candidiasis use spacers or post-inhalation mouth rinse to prevent β2-agonists Drugs short acting -- used for breakthrough symptoms and during acute exacerbation albuterol known internationally as salbutamol levalbuterol Others used much less commonly terbutaline metaproterenol (β2, minor β1) isoproterenol (nonselective) tachycardia may lead to cardiac death long acting -- used for maintenance in combination with inhaled corticosteroid (never without) salmeterol tremors, arrhythmia formoterol Mechanism β2 receptors are activated on bronchial smooth muscle to achieve bronchodilation stimulation of adenylate cyclase leading to closing of calcium channels and ultimately the relaxation of smooth muscles Methylxanthines Drugs theophylline (rarely used) Mechanism inhibition of phosphodiesterase leading to decreased cAMP hydrolysis causes bronchodilation metabolized by P-450 blocks actions of adenosine Toxicity seizures narrow therapeutic index nausea/vomiting arrhythmia Muscarinic antagonists Drugs ipratropium tiotropium Mechanism competitive inhibition of muscarinic receptors prevents bronchoconstriction Also used for COPD toxicity includes anticholinergic effects such as urinary retention Cromolyn Prophylaxis only! ineffective during an acute asthma attack Mechanism prevents release of mediators from mast cells Toxicity rare Antileukotrienes Drugs zileuton 5-lipoxygenase pathway inhibitor blocks conversion of arachidonic acid to leukotrienes zafirlukast, montelukast blocks leukotriene receptors particularly effective in aspirin-induced asthma Omalizumab Clinical use severe uncontrolled asthma with elevated IgE symptoms and activity refractory to standard therapies and oral glucocorticoids Mechanism anti-IgE antibody inhibits action of IgE with inflammatory cells asthma can be caused by uncontrollably high IgE response