lecture 24 (COPD) Flashcards
exam 3
characteristics of COPD
irreversible airflow obstruction due to:
- emphysema
- chronic bronchitis
symptoms:
- chronic cough
- sputum
- dyspnea
- barrel chest
characteristics of emphysema
characteristics:
- permanent enlargement of bronchioles and alveoli due to wall destruction
- dyspnea due to insufficient gas exchange
- cigarette smoking is the major cause
- frequently asymptomatic until the later stage of life
pathophysiology of emphysema
tissue damage by proteases:
- irritants in cigarette smoke cause inflammation in alveoli
- neutrophils and macrophages accumulate
- activated neutrophils and macrophages release proteases, resulting in tissue damage
oxidative injury by ROS:
- ROS in cigarette smoke deplete antioxidants in the lungs
- ROS inactivates ⍺1-antitrypsin, which normally suppresses the protease activities
- activated neutrophils also release ROS
characteristics of chronic bronchitis
chronic inflammation in bronchial tubes:
- mucus hypersecretion
- fibrosis and narrowing of airways
symptoms:
- productive cough
- wheezing
- SOB/chest pain
frequently coexists with emphysema
cigarette smoking is the major cause, other causes include pollutants, respiratory infections, and genetics
pathophysiology of chronic bronchitis
initiated by exposure to irritants:
- hypersecretion of the bronchial mucous glands
- hypertrophy of mucous glands
- metaplastic formation of mucin-secreting goblet cells
- inflammation with infiltration of CD8+ T cells, macrophages, and neutrophils (no involvement of eosinophils)
frequent viral and bacterial infections may play a role in maintaining inflammation and exacerbating symptoms
key mediators and immune cells involved in COPD
IL-8
TNF-⍺
IL-1b
IL-6
neutrophils
macrophages
CD8+ T cells (TH1)
nonpharmacological therapy
smoking cessation
vaccinations (influenza, pneumococcal, and Tdap)
exercise
long-term oxygen therapy
SABA
albuterol and levalbuterol
rapid onset, but the response is less than in asthma
LABA
salmeterol and formoterol
every 12 hours
not for acute relief of symptoms
ultra-LAMA
indacerol (arcapta), olodaterol (strieverdi), vilanterol (ellipta), and bambuterol (bambec, oxeol)
once a day
high affinity for receptor, COMT/MAO resistant, high lipophilicity
combination product: fluticasone furoate/vilanterol (brea ellipta)
SAMA
ipratropium (atrovent)
as effective as albuterol in patients with COPD
acute symptom relief in exacerbations
combined with albuterol in rescue inhaler
LAMA
tiotropium (spiriva), aclidinium (tudorza, pressair), and umeclidinium (incruse ellipta)
once a day
approved for maintenance therapy of COPD
quaternary amine salt like ipratropium
combo products:
fluticasone furoate/umeclidinium, bromide/vilanterol (trelegy ellipta)
methylxanthines
once considered first line therapy in COPD
- might be used in resource-limited settings where inhalers are not available
replaced mainly by LABAs and antimuscarinics
theophylline or aminophylline (prodrug)
- used in patients who are intolerant to or cannot use inhaled bronchodilators
- bronchodilation and anti-inflammatory action
- systemic administration may be beneficial on peripheral airways (aminophylline)
- theophylline is oral, maintenance adjunct therapy, risks- NTI, arrhythmias
- aminophylline is IV, used in acute exacerbations, risks- seizures, cardiac toxicity
PDE4 inhibitor
roflumilast (daliresp)
increases the intracellular cAMP concentration similar to methylxanthines
suppresses the release of cytokines and chemokines to reduce airway inflammation
approved for COPD but not asthma
NOT for acute exacerbations/quick ROS
often used in combination with bronchodilators and/or ICS
corticosteroids
uses in COPD:
- short-term systemic use for acute exacerbations
- inhalation therapy for chronic stable COPD
- NOT used as a monotherapy
mechanism:
- decrease mucus release by reducing capillary permeability
- suppress protease release from immune cells
- suppress prostaglandin production
key differences in pharmacological treatments of asthma and COPD
SABAs/LABAs can be used as monotherapy for COPD
SABAs have higher response in asthma
corticosteroids NOT used as a monotherapy in COPD
⍺1-antitrypsin deficiency and COPD
⍺1-antitrypsin is a protease inhibitor produced in the liver
- inhibits neutrophil elastase
- limits lung tissue damage
deficiency (genetic mutation <1%) leads to:
- increased neutrophil migration
- increased lung damage via inflammation and protease activity
replacement therapy:
- reduced lung tissue loss and desctruction in patients with severe deficiency
- derived from donated human plasma, given IV once a week
- prolastin, aralast, zemaira
- contraindications: known IgA deficiency with antibodies against IgA (risk of anaphylaxis)
