Lecture 24: Drugs used in COPD Flashcards
Chronic Obstructive Pulmonary Disease (COPD)
-10% of adult population (mostly smokers)
-IRREVERSIBLE airflow obstruction
-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
-cigs is major cause
-asymptomatic until later stage of life
Pathophysiology of emphysema
-tissue damage by proteases
-oxidative injury by ROS
Mech of tissue damage by proteases in emphysema
-irritants in cig smoke cause inflammation in alveoli
-neutrophils and macrophages release proteases
=tissue damage
Mech of oxidative injury in emphysema
-ROS in cig smoke deplete antioxidants in lungs
-ROS inactivate a1-antitrypsin, which normally suppress protease activites
-activated neutrophils also release ROS
a1-antitrypsin
-protease inhibitor produced in liver
-inhibits neutrophil elastase
-limits lung tissue damage
a1-antitrypsin deficiency
-rare genetic disorder
-inc neutrophil migration
-inc lung damage via inflammation and protease
Chronic bronchitis
-chronic inflammation in bronchial tubes
-mucus hypersecretion
-fibrosis and narrowing of airways
-often coexists with emphysema
-smokers
Chronic bronchitis symptoms
-producing cough
-wheezing
-SOB
-chest pain
Pathophysiology of chronic bronchitis
-initiated by exposure ot irritants
-hypersecretion of bronchial mucous glands
-hypertrophy of mucus glands
-metaplastic formation of mucin-secreting goblet cells
-inflammation w infiltration of CD8 T cells, macrophages, neutrophils (no eisonophils)
-microbial infection might play a lil part 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 v COPD
-proximal
-childhood
-episodic
-mast, eosinophils, CD4
-IL-4, 5, 13
-less oxidative stress
COPD v asthma
-peripheral
-late adulthood
-progressive
-neutrophils, macrophages, CD8
-IL-8, TNFa
-oxidative stress
nonpharma Treatment of COPD
-smoking cessation
-exercise
-immunization
-long-term oxygen therapy
Pharma treatment of COPD
-bronchodilators (B2 agonist or M antagonist)
-methylxanthines
-corticosteroids for patients w exacerbations
-a1-antitrypsin therapy (rare)
B2 selective agonists
-SABA
-LABA
-Ultra-LABA
SABA (short acting selective B2 agonist)
-albuterol
-levalbuterol
-rapid onset
-better in asthma
LABA (long acting B2 selective agonists
-salmeterol
-formoterol
-q12h
-not for acute relief
Ultra-LABA
-indacaterol
-olodaterol
-vilanterol
-bambuterol
-qd
-monotherapy for COPD
-combo w Fluticasone/vilanterol for asthma
Antimuscarinic agents
-SAMA
-LAMA
SAMA (short acting antimuscarinic agents
-Ipratropium
-as effective for COPD as albuterol
LAMA (long acting antimuscarinic agents)
-tiotropium
-aclidnium
-umeclidinium
-qd
-approved for maintenance therapy of COPD
-quarternay amine salt
-combo as fluticasone furoate/umeclidinium bromide/vilanterol
Methylxanthines
-replaced as main therapy for COPD by LABA and antiMuscarinics
-theophylline
Theophylline
-methylxanthine
-used in patients who are intolerant to or cannot use inhaled bronchodilators
-bronchoDIALTION
-ANTI-inflammatory
-systemic admin might be beneficial on peripheral airways
Roflumilast
-PDE4 inhibitor
-inc cAMP as methylxanthines
-suppress release of cytokines and chemokines
-approved for COPD but not asthma
Corticosteroid use in COPD
-short-term systemic use for acute treatment
-inhalation for chronic COPD
Corticosteroid mech
-dec mucus release by reducing permeability
-suppress proteaase release from immune cells
-suppress prostaglandin production
a1-antitrypsin replacement therapy
-derived from donated blood
-prolastin, aralast, zemaira
-reduces lung tissue loss and destruction in patients w severe a1-antitrypsin deficiency
-v expensive
