Respiratory Pharmacology Flashcards
Asthma
A long-term respiratory condition in which the airway may unexpectedly and suddenly narrow, often in response to an allergen, cold air, exercise, or emotional stress
Asthma symptoms
Wheezing
Shortness of Breath
Chest tightness
Coughing
COPD
Chronic bronchitis an emphysema, a pair of two commonly co-existing diseases of the lungs in which the airways become narrowed
This leads to a limitation of the flow of air to and from the lungs causing shortness of breath
What is the cause of asthma (immunologically speaking)
An excessively active immune system
T effector cells
Critical mediators
Th cells
Determine the course of an inflammatory response
What cells are related to antibody-mediated immunity?
B cells
What cells are related to cell-mediated immunity?
Macrophages
What is the oversimplified view of the sequence of events leading to infiltration of eosinophils in the lung?
Allergen –> Mast cells –> Th2 –> Infiltration of Eosinophils
How do Th2 cells mediate inflammatory response in asthma leading to eosinophil infiltration of the lung?
By virtue of cytokines they produce
Th1 cells
Cell mediated immunity
Intracellular pathogens
Yeast, viruses, intracellular bacteria, cancer
Th2 cells
Humoral or antibody mediated immunity
Extracellular pathogen
Parasites, normal bacteria, toxins, allergens
What are the distinct asthma phenotypes?
Eosinophilic Asthma
Non-eosinophilic Asthma
What is the significance of having distinct asthma phenotypes?
They require distinct pharmacologic treatments
Eosinophilic Asthma
Eosinophils, basement membrane thickening Inhalational corticosteroids (ICS) are the first line of defense
Non-eosinophilic Asthma
No eosinophils, no basement membrane thickening
New treatment regimens needed
Refractory to treatment with ICS
What Th cells are related to asthma and other inflammatory disorders?
Th1
Th2
Th17
What disorders are Th1 cells related to?
Chronic inflammatory and autoimmune disorders
What disorders are Th2 cells related to?
Allergic (atopic) disorders
Eosinophilic asthma
What disorders are Th17 cells related to?
Chronic inflammatory and autoimmune disorders
Neutrophilic asthma
What can inflammation of the airway cause?
Bronchoconstriction
Mucus
Airway remodeling
What signaling molecules causes bronchoconstriciton?
Leukotrines (1000x more potent than histamine in the airway)
Cholinergic stimulation (COPD)
Histamine
What causes mucus buildup during inflammation?
Mediated by many proinflammatory compounds
How does airway remodeling occur?
Results from chronic inflammation
What are the three goals of asthma treatment?
1) Relieve or prevent bronchocontriciton
2) Inhibit airway inflammation (reduce mucus production)
3) Prevent airway remodeling
Theraputic goal: to manage the disease so that the patient is as symptom free as possible
What can be some cellular responses of COPD?
Fibrosis
Alveolar wall destruction
Mucus Hypersecretion
What cells are responsible for Fibrosis in COPD?
Fibroblasts
What cells are responsible for Alveolar wall destruction in COPD?
Tc1 cells and Proteases
What cells are responsible for Mucus hypersecretion in COPD?
Proteases
What are the goals of COPD treatment?
Relieve bronchoconstriction
Improve exercise tolerance (keep patient active)
Prevent and treat complications
Slow progress of the disease
What characteristics of Asthma make it different?
Onset is typically during childhood or adolescence
Bronchoconstriction part of allergic reaction
With treatment, near normal function and symptom-free life is possible
Late stage inflammation usually/sometimes involves eosinophil reqruitment
What causes mast cell degranulation in asthma?
Allergens
What does mast cell degranulation produce in asthma?
Release of Histamine, Cystidinyl leukotrines, Prostaglandins, and others
These agents lead to broncho-constriction
How do asthma drugs work?
Stymie the allergic response
Diminish the number of immune cells in the lung
Alter production of bronchoconstrictors
What types of drugs can be used to treat asthma?
B2 adrenergic receptor agonists Corticosteroids Leukotrine modifiers Anticholinergics Anti-IgE
What does smooth muscle contraction require?
Phosphorylaiton of the myosin light chain
What do B2 adrenergic receptor agonists produce?
Smooth muscle relaxation
PKA-mediated activation of K channels causes what?
Attenuation of myosin light chain kinase activity