Fant-Asthmic Parade Asthma Treatment

2.2 – “Fa “Fant nt nt--asthmic Parade Parade”: ”: Asthma treat treatment ment (β-2 selective agonists, leuk leukotriene otriene inhibitors, methy methylxanthines, lxanthines, cromo cromolyn, lyn, sulfate o omalizumab) malizumab) • Asthma involves two processes: o Widespread reversible narrowing of bronchial airways and increased responsiveness to inhaled allergens o Eosinophilic and lymphocytic inflammation of bronchial mucosa o Both bronchodilation therapy & anti-inflammatory therapy are important in asthma management. The level of control depends on the level of disease. • Classic allergic asthma is mediated by IgE produced in response to exposure to foreign antigens (dust, dander, pollen). IgE binds to high affinity mast cell receptors in airway mucosa, stimulating degranulation and release of histamine, tryptases, PGs, leukotrienes, all of which stimulate bronchoconstriction and vascular leakage (guy shooting mast cell beehive with IgE shaped gun) • Leukotrienes are involved in aspirin induced asthma. In 5-10% of patients with asthma, even small doses of aspirin or other NSAIDs can causes profound vasoconstriction and systemic inflammation. Thought to be d/t inhibition of COX pathway, shifting Arachidonic acid metabolism from prostaglandin synthesis toward leukotriene synthesis (ASA ump on balcony with Cox blocking activity) Manageme Management nt • Chronic or more severe is associated with more severe SSx (especially at night) with long-term constriction of airways → thickening of bronchial wall & remodeling, hyperplasia of secretory glands & goblet cells, SM, bronchial vasculature. Management is critical to prevent chronic irreversible loss of pulmonary function. Therapy is stepwise until appropriate management of symptoms is obtained. Dose or number of rx is increased as necessary until control is achieved. • Selective β2 agonists o albuterol, metaproterenol, pirbuterol o counter bronchoconstriction (dilated β2 bugles; -rol Roll Call sheet). o β2 selective are preferred d/t lack of CV activation. Terbutaline also (“Do not disturb” sign in window) o Available as metered dose inhalers – short acting β-agonists (SABAs). Rescue inhalers (tuba player with inhaler). o In mild asthma, symptoms only occur intermittently and may be managed with only SABAs. • low-dose inhaled corticosteroids o beclomethasone, budesonide, fluticasone o With persistent symptoms, may be used as daily maintenance therapy. o After immediate inflammation of asthma attack, there is a delayed response with influx of inflammatory cells into bronchial mucosa; cytokines produced by these infiltrating cells → mucus production & recruitment of further inflammatory cells. Corticosteroids block cytokine production (moon eclipsing inflammatory sun). o Daily maintenance inhalers (controllers). ↓bronchial hypersensitivity and ↓frequency of exacerbations. o Inhalation avoids systemic adverse effects of glucocorticoid use. o Adverse effects: Inhaled corticosteroids can result in oropharyngeal candidiasis (Canadian snow cone). Prevent by gargling water after each use. • Leukotriene inhibitors o LTA activity results from action of 5-lipoxygenase (LOX) on arachidonic acid (AA lacrosse league with coach LOX); synthesized by many airway inflammatory cells including mast cells, macrophages, eosinophils. ▪ Leukotrienes are important regulation of inflammation and include LT-B4, C4, D4, & E4 (lacrosse players in flaming jerseys) ▪ LTB4 is a chemoattractant for inflammatory cells including neutrophils (B4 fallen off truck and attracting neutrophil first responders) ▪ C4 & D4 are potent bronchoconstriction; increase vascular permeability, & mucus conduction (clamping down on airwayesque lacrosse sticks with lung-shaped nets) o Inhibitors can be used clinically in mild or moderate asthma, although less marked decrease in reactivity than corticosteroid. Two mechanisms: ▪ Include montelukast, zafirlukast (monte the broadcaster). ▪ Direct inhibition of binding of LTD4 (most potent LT) to CysLt1 receptor (lacrosse net being guarded) → dilate airways (bronchodilator scarf). ▪ Taken orally, so fewer issues with compliance than inhaled therapies (broadcaster popping pills). o Other approach to interrupting this pathway involves inhibition of lipoxygenase, preventing leukotriene synthesis. Include zileuton (Godzilla balloon falling on Coach Lox). ▪ Small risk of hepatotoxicity; monitor of LFTs (liver spot). Not recommended for routine use in asthma. • Long-acting β agonists (LABAs) (β bugle formation) o Salmeterol & formoterol (salute formation) o High lipid solubility → long duration of action (long tapering flag). Can last for 12+ hours. o Can be given as a daily control regimen. Always given in combination with inhaled corticosteroids. o This step-up therapy may involve increased dose of inhaled corticosteroids as well (elevated moon balloon in formation) • Methylxanthines (xanthine energy drink) o Theophylline (“you’ll be flying”) o Alternative therapy for mild to severe persistent asthma. Reduces severity of SSx in chronic asthma and can act acutely decrease airflow obstruction. Administered orally. o PDE inhibitors; increase intracellular cAMP → smooth muscle relaxation. Inhibit of cytokine release (“don’t phoster disinterest! Go Camping!” sign in background) o Adverse effects ▪ Not used as much anymore d/t safer, more effective treatment. ▪ Very narrow therapeutic index. Toxicity can be fatal & levels must be monitored ▪ CNS effects include nervousness & tremor (shaky kid) ▪ CV effects include tachycardia (heart watch) ▪ CYP450 metabolism (car with chrome bumper) • Omalizumab (limousine) o Adjunctive therapy for moderate or severe persistent asthma o Monoclonal activity directed against Fc potion of IgE, prevents mast cell sensitization (limo driver with IgG-shaped gun binding to Fc portion of IgE gun) o Limited to patients with evidence of allergic sensitization (e.g. demonstrated by skin test) • Cromolyn sodium (Lynn’s Bee Control chrome smoke dispenser) o Inhibits mast cell degranulation (preventing beehive degranulation) o Once widely used as a prophylactic, particularly in pediatric allergic asthma. Now, used much less widely d/t increased efficacy of the inhaled rx. Emergent tre treatment atment of acute aasthma sthma exacerbat exacerbation ion • Inhaled short acting β2 agonists (β2 tuba) • Systemic corticosteroids if no evidence of rapid improvement, or ASAP if patient has h/o severe asthma (ivy for IV) • Nebulized ipratropium bromide anticholinergic to treat acute severe exacerbation (caterpillar balloon) • Subcutaneous or intramuscular E can be used to treat severe exacerbation, especially with absence of rapid improvement (EPIC! Sign)