Pharmacology
Summary
The synopsis of "Asthma Therapy" primarily focuses on understanding and managing the chronic condition of asthma. Effective treatment of asthma involves reversing two factors: the narrowing and increased bronchial responsiveness to inhaled stimuli and the inflammation of bronchial mucosa. For chronic management, consideration should be given to a dual approach involving bronchodilator therapy, such as inhaled beta agonists, and anti-inflammatory therapy, typically in the form of an inhaled steroid.
Allergic asthma is primarily mediated by IgE, which is produced due to exposure to foreign antigens. Dealing with the bronchoconstriction of asthma involves the use of sympathomimetic agents such as beta-2 selective agonists, prominently albuterol. These agents are also called short-acting beta-2 agonists, or SABAs, which work within 15 minutes and last for 3-4 hours, proving effective in acute asthma attacks. In conditions of persistent asthma, low dose inhaled corticosteroids are advised, which help to curb the chronic inflammation associated with asthma. Corticosteroids reduce the inflammation by inhibiting the production of inflammatory mediators.
Alternative agents can include leukotriene inhibitors, crucial in reducing bronchoconstriction and mucus secretion in the airways, and theophylline, which aids in bronchial smooth muscle relaxation and inhibiting cytokine release. Another essential agent is Omalizumab, a monoclonal antibody designed to prevent mast cell activity, which plays a critical role in the pathogenesis of asthma.
For severe asthma, long-acting Beta agonists, or LABAs, like salmeterol and formoterol, can be used, ideally in combination with a regimen of inhaled corticosteroids. Emergent treatment strategies for acute asthma exacerbation primarily consist of inhaled SABAs and systemic glucocorticoids, with the addition of nebulized ipratropium bromide and subcutaneous or intramuscular administration of epinephrine in severe cases.
Lesson Outline
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FAQs
Bronchodilators, specifically selective beta-2 agonists like albuterol, pirbuterol, and terbutaline, alleviate bronchoconstriction. Recognizable by their "-rol" suffix, these agents relax bronchial smooth muscles, enhancing airflow. They are often available as metered dose inhalers, offering immediate relief during acute episodes. For more persistent cases, long-acting beta-2 agonists such as salmeterol and formoterol, known for their extended duration of action, are utilized as daily controller inhalers.
Inhaled corticosteroids (ICS) like beclomethasone, budesonide, and fluticasone are foundational in chronic asthma management. Corticosteroids counter asthma by suppressing inflammation and cellular infiltration. For those with moderate to severe persistent asthma, an increased dose of ICS or the inclusion of agents like theophylline, a methylxanthine related to caffeine, may be necessary. Methylxanthines, which elevate cAMP by inhibiting phosphodiesterase, can be orally administered but come with side effects like nervousness, tremor, and tachycardia.
Leukotriene inhibitors, recognizable by their "-kast" suffix like montelukast and zafirlukast, block the receptor for LTD4, the most potent bronchoconstrictor. Originating from arachidonic acid (AA), leukotrienes play a role in inflammation. LTB4 attracts inflammatory cells like neutrophils, while LTC4, D4, and E4 increase airway vascular permeability, mucus production, and bronchoconstriction. Leukotriene inhibitors not only reduce symptoms but also facilitate bronchodilation. Zileuton, a direct lipoxygenase inhibitor, presents an alternative but carries hepatotoxicity risks.
Omalizumab, an anti-IgE monoclonal antibody, is tailored for moderate to severe persistent asthma. It targets the Fc portion of IgE, hindering mast cell sensitization, which otherwise leads to degranulation and the release of inflammatory mediators like histamine upon antigen binding. Cromolyn Sodium, on the other hand, preempts mast cell degranulation, preventing the release of histamine. Both agents provide more specific interventions in the asthma pathway.
During acute exacerbations, immediate relief is sought through inhaled short-acting beta-2 agonists, like albuterol. If required, systemic corticosteroids, either IV or orally administered, can be added. Other options include nebulized ipratropium bromide, an anticholinergic, or even subcutaneous or intramuscular epinephrine. Note that a risk oropharyngeal candidiasis arises when using inhaled corticosteroids.
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