Exam 3 - Asthma and COPD Flashcards
What are the symptoms and factors causing airway obstruction in asthma?
- Symptoms – Wheezing, breathlessness, chest tightness, coughing, night time dyspnea, airway inflammation leading to obstruction
- Factors – Widespread narrowing of airways is due to contraction of airway smooth muscle from airway inflammation, mucosal thickening (edema, cellular infiltration), and mucous plugs. Can be caused by genetics or hypersensitivity reactions.
What are the symptoms and factors causing airway obstruction in croup (acute layngotracheobronchitis)?
- Symptoms – Seal like barking cough
- Factors – Common ages 6 months – 5 years, Caused by viral RSV (rhinorrhea, sore throat, fever)
What are the symptoms and factors causing airway obstruction in COPD?
Chronic bronchitis and Emphysema combined
Bronchitis:
* Symptoms – Hypersecretion of mucous with chronic productive cough
* Factors - Inspired irritants increase mucus production by increasing the size and number of mucous glands.
Emphysema:
* Symptoms - Dyspnea and wheezing
* Factors - Abnormal permanent enlargement of the gas exchange airways accompanied by destruction of alveolar walls; results in loss of elastic recoil.
Describe airway function tests?
-
FEV1 – Bronchial hyperreactivity testing.
-Positive if significant fall in forced expiratory volume in 1 second provoked by inhaling increasing concentrations of histamine or methacholine - PEF – Peak expiratory flow. Maximum flow of forced expiration.
Describe the dendritic cells role in the immune response to an allergen?
- Dendritic cell is found on airway mucosa and binds to the allergen
- When bound to the allergen it, it breaks it down and presents the antigen peptide on its surface via a MHCII receptor becoming an antigen presenting cell
- The cell migrates to the closest lymphnode and presents to a T-cell.
Describe the T cells role in the immune response to an allergen?
What drug works here to decrease allergic response?
- Releases IL-4 and activates the antibody producing B cells
- Dupixent is a MAB that prevents IL-4 from binding to B cell
Describe the B cells role in the immune response to an allergen?
B cells produce antibodies to the antigen and then become plasma cells (antibody producing factories) and B memory cells
Describe the plasma cells role in the immune response to an allergen?
Plasma cells produce IgE antibodies to the specific antigen that will bind to and sensitize mast cells and basophils.
Describe the mast cells role in the immune response to an allergen?
Mast cells are in the connective tissues of the airway and GI tract. They will become sensitized to the antibody and express them on the cell wall.
When the antigen is encountered again, they will degranulate causing release of histamine and leukotrines.
Describe the neutrophils and eosinophils role in the immune response to an allergen?
Cause release of proteases that break down cell wall proteins leading to swelling and airway edema.
What are the mediators released in early stage of asthma? What are their effects?
- Histamine – induces smooth muscle contraction and bronchospasms, increases mucosal edema and secretions. (Antihistamines are more beneficial for allergy treatment than asthma treatment.)
- Prostaglandins – Potent bronchoconstrictor that is proinflammatory; also works via GPCR. It also enhances the effects of histamine.
- Leukotrienes - released in the early stage, but are slow acting and do not have their affect until the late stage
What are the mediators released in late stage of asthma? What are their effects?
- Leukotryines – Slow reacting substance, produced by the lung during inflammation during the early phase. Works via GPCR to cause bronchospasms, mucous secretion, microvascular permeability, and airway edema.
- Cytokines – proinflammatory chemical released from T lymphocytes that activate eosinophils and neutrophils.
- Proteases – Released by neutrophils/eosinophils and they break down proteins that hold cells together and can infiltrate into the smooth muscles can cause contraction. This causes “leaky” vessels leading to swelling and airway edema.
List the primary pathways of arachidonic acid and their main products?
What are the sympathetic and prasympathetic effects of airway diameter?
- Parasympathetic- Normal resting tone is maintained by vagal stimulation and muscarinic receptors. Activation causes bronchoconstriction. During an asthma attack, sympathetic stimulation can temporarily open airways, but will be followed by a strong parasympathetic mediated bronchoconstriction.
- Sympathetic – B2 adrenergic receptors cause bronchodilation when activated. Catecholamines cause a greater effect than direct innervation.
What are alpha adrenergic receptors role in airway diameter?
Alpha adrenergic receptors are found in the major resistance airways (large bronchi) and cause bronchoconstriction when activated, alpha blockers are not helpful in asthma because bronchoconstriction happens mainly in bronchioles.
What are the major classes of drugs used in the treatment of COPD and asthma?
Green is short acting and blue is long acting
Describe the MOA of beta agonists used in COPD and asthma?
What are some of these drugs?
B2 selective agonists cause relaxation of airway smooth muscle by increasing activity of adenylyl cyclase which incresaes cAMP leading to bronchodilation.
Beta 2 selective: SABA - Albuterol, terbutaline. LABA - salmoterol, formoterol.
Non-selective beta: Epinephrine, isoproterenol (can cause tachycardias and arrythmias, increases mortality)
Describe the MOA of methylxanthines used in COPD and asthma?
What are some of these drugs?
Proposed to inhibit PDE, preventing the breakdown of cAMP and increasing bronchodilation. Causes urination by inhibiting adenosine receptors.
Theophylline, theobromine, caffeine - found in tea, very narrow therapeutic index
Caffeine and theobromine
Describe the MOA of antimuscarinics used in COPD and asthma?
What are some of these drugs?
Causes bronchodilation by acetylcholine inhibition.
Atropine - very low dose
Ipratropium bromide (Atrovent) - more selective than atropine, can be comined with B2 agonists for synergistic effect.
Titotropium - primarily used in COPD, lasts the longest ~24 hours
Describe the MOA of steroids used in COPD and asthma?
What are some of these drugs? Side effects?
- Inhibits the immune response by blocking or increasing transcription/translation of different factors.
- Produces anti-inflammatory effect by inhibiting cytokines, lymphocytic, and eosinophilic airway mucosal inflammation.
Side effects: increase osteoporosis, slow growth rate, supress immune response, oropharyngeal candidasis.
Fluticasone
Describe the MOA of MAB used in COPD and asthma?
What are some of these drugs?
Blocks binding of IgE to mast cells (Xolair)
Block IL-4 and activation of B cells (Dupixent)
What are the treatment considerations for mild, moderate, and severe asthma?
Mild: B2 receptor agonists prn
Moderate: add anti-inflammatory like inhaled corticosteriod and/or oral leukotriene receptor antagonist
Severe: Add oral corticosteroids, consider anti-IgE antibody
Differentiate the drug treatmens for asthma and COPD?
Describe the pathogenisis of asthma?
Can be intrinsic or extrinsic
Intrinsic - caused by genetics, many involved in inflammation
Atopic (extrinsic) - induced by type 1 hypersensitivity reactions - see pathway
