L24 drugs used in COPD Flashcards
COPD
chronic obstructive pulmonary disease
COPD affects more than ____ of the US adult population
10%
COPD is the _____ leading cause of death in US in 2018
4th
_____- of COPD pateints are smokers
85%
COPD irreversible airflow obstruction due to
emphysema
chronic bronchitis
COPD symptoms
-chronic cough
-sputum
-dyspnea
-barrel chest
emphysema
-permanent enlargement of bronchioles and alveoli due to destruction of their walls
-dyspnea due to insufficient gas exchange
-cigarette smoking is the major cause
-frequently asymptomatic until the later stage of life
patholphysiology of emphysema
tissue damage by proteases
oxidative injury by reactive oxygen species (ROS)
tissue damage by proteases
-irritants in cigarette smoke cause inflammation in alveoli.
-Neutrophils and macrophages accumulate.
-Activated neutrophils and macrophages release proteases (ex. neutrophil
elastase), resulting tissue damage.
oxidative injury by reactive oxygen species (ROS)
-ROS in cigarette smoke deplete antioxidants in the lungs (ex. superoxide
dismutase, glutathione).
-ROS inactivate ⍺1-antitrypsin, which normally suppresses the protease activities.
-Activated neutrophils also release ROS
alpha 1-antitrypsin
-Protease inhibitor produced in the liver (53 kDa)
-Inhibits neutrophil elastase.
-Limits lung tissue damage
alpha 1-antitrypsin deficiency
-Rare genetic disorder leading to insufficient ⍺1-Antitrypsin activity
-increased neutrophil migration
-Increased lung damage via inflammation and protease activity
chronic bronchitis
-chronic inflammation in bronchial tubes
(mucus hypersecretion and fibrosis and narrowing of airways)
-frequently coexists with emphysema
-cigarette smoking is the major cause
symptoms of chronic bronchitits
-producing cough
-wheezing
-shortness of breathe/ chest pain
pathophysiology of chronic bronchitis
-Initiated by the exposure to irritants (cigarette smoke or other air pollutants)
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)
-Microbial infection may paly a secondary role in maintaining inflammation and
exacerbating symptoms.
tissue remodeling in COPD
-Fibrosis of small airways
-Hyperinflation of lungs:
Alveolar enlargement
Alveolar wall destruction
-Mucus hypersecretion
asthma vs COPD in site
asthma; proximal airways
COPD; peripheral airways
asthma vs COPD in onset
asthma; childhood
COPD; late adulthood
asthma vs COPD in symptoms
asthma; episodic attack
COPD; progressive deterioration of pulmonary function
cells affects in asthma vs COPD
asthma: mast cells, eosinophils, CD4+ T cells
COPD; neutrophils, macrophages, CD8+ T cells
key mediators in asthma vs COPD
asthma: IL-4, IL-5, IL-13
COPD; IL-8, TNF-alpha, IL-1b, IL-6
nonpharmacological therapy treatment of COPD
-Smoking cessation
-Exercise
-Immunization
-Long-term oxygen therapy
pharmacological therapy in treatment of COPD
-Bronchodilators
β2 selective agonists (short-acting, long-acting, and ultra-long-acting)
-Antimuscarinic agents (short-acting and long-acting)
-Methylxanthines
-Corticosteroids for patients with exacerbations
-alpha 1-antitrypsin replacement therapy (rare)
beta 2 selective agonist: short-acting (SABA)
-Albuterol, levalbuterol
-Repid onset, but the response is less than seen in asthma.
beta 2 selective agonist long acting (LABA)
-Salmetrol, formoterol
-Every 12 hours
-Not for acute relief of symptoms
beta 2 selective agonist: ultra long acting (Ultra LABA)
-Indacaterol, olodaterol, vilanterol, bambuterol
-Once a day
-Can be used as monotherapy for COPD (not for asthma).
-Combination
Fluticasone furoate/vilanterol
antimuscarinic agents: short acting (SAMA)
-ipratropium
-As effective as albuterol in patients with COPD
antimuscarinic agents: long acting (LAMA)
-Tiotropium, aclidinium, umeclidinium
-Once a day
-Approved for maintenance therapy of COPD.
-Quaternary amine salt like ipratropium
-Combination
Fluticasone furoate/umeclidinium
bromide/vilanterol
mathylxantines
-Once considered first-line therapy for COPD.
-Mostly replaced by LABA and antimuscarinics.
-Theophylline
methylxantines: theoohylline
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
roflumilast
Phosphodiesterase-4 (PDE4) inhibitor
Increases the intracellular cAMP concentration as methylxanthines.
Suppresses the release of cytokines and chemokines
Approved for COPD, but not for asthma
corticosteroids uses in COPD
-Short-term systemic use for acute exacerbations
-inhalation therapy for chronic stable COPD
mechanisms of cortiosteroids
Decrease mucus release by reducing capillary permeability
Suppress protease release from immune cells
Suppress prostaglandin production
alpha 1-antitrypsin replacement therapy: products
-Derived from donated blood
-Prolastin® , Aralast®, Zemaira®
alpha 1- antitrypsin replacement therapy
-Reduces lung tissue loss and destruction in patients with severe ⍺1-Antitrypsin deficiency.
-Expensive (>$50k a year)
short acting beta 2 selective agonist (SABA)
-Albuterol
-Levalbuterol (Xopenex®)
long acting beta 2 selective agonist (LABA)
-Salmetrol (Serevent ®)
-Formoterol
ultra long acting beta 2 selective agonists
-Indacaterol (Arcapta® )
-Olodaterol (Strieverdi®)
-Vilanterol (
-Bambuterol (Bambec ®, Oxeol ®)
methylxanthine
theophylline
antimuscarinic
-Ipratropium (Atrovent ®)
-Tiotropium (Spiriva ®)
-Aclidinium (Tudorza ®, Pressair®)
-Umeclidinium (Incruse Ellipta ®)
PDE4 inhibitor
Roflumilast (Daliresp ®)
combinations
-Fluticasone furoate/vilanterol (Breo
Ellipta ®)
-Fluticasone furoate/umeclidinium
bromide/vilanterol (Trelegy Ellipta ®)
