Asthma and COPD Flashcards
b2 agonist
Albuterol, Salmeterol
Leukotriene antagonist
Montelukast
Muscarinic antagonist
Ipratropium (nonselective), Tiotropium (M1, M3 but not M2 inhibitor) – quaternary amine derivatives of atropine
Inhaled corticosteroid
Fluticasone
Monoclonal Anti-IgE antibody
Omalizumab
Increased Raw – Obstructive Lung Disease
Decreased airflow (decreased FEV1) Airflow is limited during expiration (E)
decreased L-CW compliance – Restrictive Lung Disease
Parenchyma fibrosis
Decreased forced vital capacity (decreased FVC)
Asthma
spasmodic contraction of smooth muscle in the bronchi; airflow obstruction (bronchospasm), bronchial hyperresponsiveness, and an underlying inflammation
Chronic obstructive pulmonary disease
Bronchitis - inflammation of the bronchi and bronchioles
Emphysema – alveolar destruction
Combination!;
Progressive decrease in lung function (clinically relevant in aged population)
↓ FEV1
Limited reversibility
FACTORS THAT DETERMINE AIRWAY RESISTANCE
Structure of the airways
Airway smooth muscle contraction
Lumen obstruction (mucus)
Elasticity of lung parenchyma
“Hallmark” of asthma
reversibility with bronchodilator
Positive correlation of asthma symptoms with
Total IgE levels
asthma involves
INFLAMMATION, REMODELING, and NERVE HYPER-REFLEXIVITY
what leads to decreased airflow in COPD?
↓ aveoli structure: ↓ elastic recoil: ↓ structural support: bronchiole collapse: ↑ Resistance: ↓ Airflow
asthma cell infiltration
Eosinophils, Mast Cells, Basophils
COPD cell infiltration
Neutrophils, Macrophages
b-adrenoceptor agonists
Actively cause bronchodilation
leukotriene and muscarinic antagonists
Inhibit specific inflammatory mediators
corticosteroids
Reduce inflammation
anti-IgE antibodies
Prevent inflammation – for asthma only
b Adrenoceptor agonists MOA
Activation of β2 adrenoceptors on bronchial smooth muscle – ↑ cAMP ->relaxation -> bronchodilation
Facilitates sequestration of Ca2+
Inactivates MLCK
Inactivates MLC20
b Adrenoceptor agonists Therapeutic Uses
Short-acting (e.g. albuterol)
Rescue for asthma and COPD
Long-acting (LABA) (e.g. Salmeterol)
Control for asthma and COPD
Leukotriene Antagonist MOA
CysLT1 antagonist
Prevents Cys-LT-induced bronchospasm, ↓ immune cell infiltration, no ↓ AHR, very mild reversal of remodeling
Leukotriene Antagonist Therapeutic Uses
Control for asthma
Muscarinic Antagonists MOA
Blocks acetylcholine-induced activation of muscarinic receptors on:
Airway smooth muscle (M3) –↓ bronchospasm
Epithelial mucosal glands (M3) –↓ mucus secretion
Muscarinic Antagonists Therapeutic Uses
Rescue for asthma
Control for COPD
ACh activates neuronal M2 receptor
as negative feedback control of ACh release
Inhaled Corticosteroids MOA
Anti-inflammatory, ↓ infiltration of eosinophils/basophils/mast cells, minor ↓ AHR, mild reversal of remodeling
↓ pro-inflammatory protein production (e.g. IL-4 and IL-5)
↑ anti-inflammatory protein production
MODULATION OF PROTEIN EXPRESSION IS SLOW-ONSET (>12 hours)
Inhaled Corticosteroids therapeutic use
Control for asthma (inhalation, nasal)
Control for COPD – limited relief
Corticosteroid: Mechanism of Action – COPD
Corticosteroids have little effect on neutrophilia
Corticosteroids have no effect on MORTALITY
Anti-IgE Antibodies MOA
Binds to free IgE (Fc region), promotes destruction
↓ IgE from binding to FCeR1 and FCeR2
↓ expression of FCeR1 on mast cells/basophils
↓ allergen-induced IgE crosslinking on mast cells/basophils
Prevents allergen-induced bronchospasm, ↓ immune cell infiltration, ↓ exacerbations, no ↓ AHR, effect on remodeling is unclear.
Anti-IgE Antibodies Therapeutic Uses
Control for severe, steroid-resistant asthma
Anti-IgE Antibodies Rate of onset
Circulating IgE destroyed in hours/days
Takes more than a week for mast cell-attached IgE to reduce
