ASTHMA

Pharmacological Agents Used in Asthma Management

Agents acting on Beta Adrenergic Receptors albuterol ethylnorepinephrine (Ventolin,Prove isoetherine (Bronkosol) ntil) isoproterenol (Isuprel) bitolterol metaproterenol (Tomalate) (Alupent) ephedrine salmeterol (Serevent) epinephrine pirbuterol (Maxair) terbutaline (Brethine)

Anticholinergic Agent

Mast Cell Stabilizers

ipratropium bromide (Atrovent)

cromolyn sodium (Intal) nedocromil (Tilade)

Aerosol corticosteroids

Oral corticosteroids

beclomethasone (Banceril) dexamethasone (Decadron) flunisolide (AeroBid) fluticasone (Flovent) triamcinolone

methylprednisolone (Solu-Medrol) prednisone (Deltasone)

Methylxanthines

aminophylline oxtriphylline theophylline theo-dur slo-phyllin

Corticosteroids

Overview: Corticosteroids o Corticosteroid Effects: diminish bronchial reactivity increase airway diameter reduced frequency of asthma attacks Mechanisms of Action:corticosteroids o primary: inhibition of eosinophil-mediated airway mucosal inflammation pathway in asthmatic airways o Principal anti-inflammatory action: inhibition of cytokine productionthis or (probably central for inhaled antigen-initiation of inflammatory cascade o secondary: enhancement of beta-receptor agonist effects

Clinical Use: Corticosteroids in Asthma

Due to significant adverse effects associated with chronic corticosteroid administration, oral/parenteral corticosteroids are used: for management of acutely ill patients patients not adequately maintained with bronchodilators patients whose symptoms are worsening, despite reasonable maintenance treatment o Corticosteroids for urgent/emergent intervention: oral dose -- 30-60 mg prednisone per day or IV dose -- 1mg/kg methylprednisolone (Solu-Medrol) every six hours daily doses decrease gradually after improvement in airway obstruction systemic corticosteroid treatment: discontinued in 7-10 days (some patient's asthma may worsen at this point) o Adrenal Suppression by corticosteroids: Adrenal suppression: dose dependent diurinal variation of corticosteroid secretion administration of corticosteroids: early-morning (after endogenous ACTH secretion) nocturnal asthma: oral/inhaled corticosteroids -- late afternoon o Aerosol Treatment:
o

1. 2. 3.

Most appropriate way to decrease adverse systemic corticosteroid effects: Effective lipid-soluble corticosteroids -- administered by aerosol: beclomethasone (Banceril) triamcinolone (Aristocort) flunisolide (AeroBid) fluticasone (Flovent) budesonide (Rhinocort)

Toxicities/Cautions/Problems:

in switching from oral to inhaled treatment: taper oral therapy slowly to avoid causing adrenal-insufficiency chronic use of inhaled steroids (may cause adrenal suppression and high dosages); however, the risk is very small with normal doses compared to oral corticosteroid treatment. Inhaled topical corticosteroids: oropharyngeal candidiasis risk reduced by gargling with water and spitting after each inhalation Hoarseness: local effect -- vocal cords Possible concern: inhaled corticosteroids -- does-dependent linear growth slowing in some children/adolescence (perhaps will effect on final adult height); asthma: delays puberty Suppression of hypothalamic-pituitary-adrenal axis Decreased bone density Cataract formation Dysphoria High doses: dermal thinning glaucoma

Advantages of inhaled, chronic use of corticosteroids: Regular use: suppresses inflammation, decreases bronchial hyperresponsiveness, decrease asthma symptoms in patients with chronic disease Reduce symptoms; improve pulmonary function in mild asthma Reduces/eliminates need for oral corticosteroids in patients with severe asthma Bronchioles reactivity reduced: maximal reduction may be delayed (9-12 months) after treatment begins May be used as first-line treatment for mild asthma in combination with beta-agonist PRN (10-12 week treatment course; then re-evaluate); dosages may be with time decreased; some patients may be able to stop using the drug completely. Commonly prescribed (due to efficacy and safety) for patients who more than occasionally require beta-agonist inhalation