Asthma Flashcards
SABA drugs
Albuterol and terbutaline
Inhaled corticosteroids drugs
Beclomethasone Budesonide Mometasone Fluticasone Ciclesonide
Leukotriene pathway inhibitor drugs
Zileuton
Zafirlukast
Montelukast
LABA drugs
Formoterol and salmeterol
Antimuscarinic drugs
Ipratropium and tiotropium
Methlxanthine drugs
Theophylline
Sympathomimetic agents MOA
- Primary mechanism: relax airway smooth muscle via b2-adrenergic activation; increase cAMP
- Inhibit the release of bronchoconstricting mediators from mast cells
- May inhibit microvascular leakage and increase mucociliary transport by increasing ciliary activity
Why do nebulizers require a higher dose versus an inhaler?
The particles are larger
Beta2-agonists adverse effects of inhaled
Tremulousness
Heart palpitations/arrhythmias
Cough/throat irritation
Contraindications: Cautiously use in patients with CV disease
Corticosteroids MOA
- Presumed to act by their broad anti-inflammatory actions
- Inhibits production of inflammatory cytokines
- Inhibits the infiltration of asthmatic airways by lymphocytes, eosinophils, and mast cells
Corticosteroids clinical use
- Aerosol controller therapy (minimal systemic absorption)
- Improves severity of symptoms, tests of airway caliber and bronchial reactivity, frequency of exacerbations, and quality of life
Corticosteroids adverse drug reactions
Oropharyngeal candidiasis, hoarseness, adults - possible risk of osteoporosis and cataracts
Children - slight delay in rate of growth
Leukotriene pathway inhibitors MOA
Block leukotriene D4 receptor (except zileuton)
LTC4 and LTD4 exert many effects in asthma, including…
Bronchoconstriction
Increased bronchial reactivity
Mucosal edema
Mucus hypersecretion
Leukotriene pathway inhibitors are less effective than inhaled corticosteroids for…
Airway caliber, bronchial reactivity, airway inflammation
Zileuton has been linked to…
Severe hepatotoxicity
Principal advantage for leukotriene pathway inhibitors
Oral formulations
Ingestion of aspirin causes…in some asthmatics
Profound bronchoconstriction and symptoms of systemic histamine release (flushing and abdominal cramping)
Leukotriene inhibitors ____ the response to aspirin challenge
Reduce
Cromolyn and nedocromil MOA
- Altering the function of delayed chloride channels in the cell membranes»_space;inhibiting cell activation
- Mast cells»_space; inhibition of degranulation
- Eosinophils»_space; inhibition of the inflammatory response to inhaled allergens
Cromolyn and nedocromil clinical use
- Non-seasonal asthma symptoms and reduced need for bronchodilators
- Allergic rhinoconjunctivitis
- Adverse drug reactions are minimal due to poor drug absorption
- Usage has diminished due to low-dose corticosteroid
LABA
- Potent selective agonists with a long duration of action (12+ hours; high lipid solubility)
- Can dissolve in the smooth muscle cell membrane in high concentrations
- Interact with inhaled corticosteroids to improve asthma control
- Have no anti-inflammatory actions of their own; not used as monotherapy
- Salmeterol (a partial agonist)
- Formoterol (a full agonist)
LABA adverse effects
Asthma-related death (black box) + SABA effects
Antimuscarinic agents clinical use
-Limited use (used for patients intolerant of beta-agonists)
Iprotropium
Aerosolized or nasal spray emergency addon
Poorly absorbed into circulation and the CNS (minimize systemic atropine-like effects)
Tiotropium
Long-acting antimuscarinic agent
Recently approved for the maintenance treatment of asthma in patients ≥6 years
Methylxanthines (theophylline) MOA
At high concentrations, inhibit phosphodiesterase (PDE) enzymes»_space; elevated levels of cAMP (or cGMP, tissue dependent)
Specifically PDE3 and PDE4 in the airway smooth muscle and on inflammatory cells
Inhibition of PDE3 relaxes airway smooth muscle
Inhibition of PDE4 in inflammatory cells reduces their release of cytokines and chemokines»_space; decreases immune cell migration and activation
Inhibition of cell surface receptors for adenosine»_space; adenosine can cause bronchoconstriction
Enhanced histone deacetylation (histone acetylation»_space; inflammatory gene transcription)
Theophylline pharmacodynamics
CNS (primarily caffeine but all have effects)
-Low doses: mild cortical arousal with increased alertness and deferred fatigue
-High doses: nervousness and tremor
-Very high doses: medullary stimulation and convulsions, maybe death
CV
(dose-dependent positive chronotropic and inotropic effects)
GI tract
(stimulates secretion of gastric acid and digestive enzymes)
Kidney (weak diuretics)
Smooth muscle (
bronchodilation)
Skeletal muscle
(strengthened contraction of isolated skeletal muscles in vitro; improve contractility and reverse fatigue of the diaphragm in patients with COPD)
Theophylline clinical uses
Most potent bronchodilator of the methylxanthines
- Relieves airflow obstruction in acute asthma
- Reserved for patients in whom symptoms remain poorly controlled despite the combination of regular treatment with an inhaled anti-inflammatory and as needed use of a b2-agonist
Theophylline cautions/adverse reactions
Narrow therapeutic window (blood levels monitored) Anorexia Vomiting Nausea Abdominal discomfort Headache and anxiety Insomnia Seizures Arrhythmias
Omalizumab
- Anti-immunoglobulin E (IgE) monoclonal antibody
- Binds free IgE»_space; at its constant region
- Prevents IgE from binding to the receptors on mast cells and other inflammatory cells
- Does NOT activate IgE already bound to these cells»_space; does not provoke mast cell degranulation
Omalizumab clinical use
Reduction in frequency and severity of asthma exacerbations (works best with more severe disease states)
Benralizumab
- IL-5 receptor alpha antibody
- Clinical: add-on maintenance treatment of severe asthma in adults and children >12 with an eosinophilic phenotype
- Adverse effects: antibody production, headache, pharyngitis
Mepolizumab and Reslizumab
Monoclonal antibodies against IL-5 (mep = subcutaneous; res = IV)
Clinical: eosinophilic severe asthma
Adverse effects: Mep - hypersnsitivity, headache, site reaction
Res - anaphylaxis (black box), oropharyngeal pain
