Asthma and COPD Flashcards
What are the symptoms of chronic obstructive pulmonary disease (COPD)?
Cough, mucus hypersecretion, dyspnea (shortness of breath)
What causes COPD?
Air pollution, smoking and occupational exposures (firefighters, construction, asbestos)
What disorders does COPD include?
Chronic bronchitis (inflammation of the bronchi with mucus to plug airway and edema to narrow airway) and emphysema (destruction of alveolar structure causing airways to collapse during expiration and trap air) Irreversible
What is asthma characterized by?
Recurring episodes of hyper-responsiveness to stimuli that causes bronchoconstriction
Airway obstruction, air gets trapped in alveoli despite it not being damaged, inflammation, mucus secretion
Reversible
What are the symptoms of asthma?
Recurring episodes of cough, wheezing, tight chest and dyspnea (shortness of breath)
What are the two subtypes of asthma?
Extrinsic (allergenic) and intrinsic (non-allergenic)
What can happen if asthma is untreated?
Reversible asthma can lead to irreversible airway remodelling (increased muscle thickness, reducing size of airway) from the chronic inflammation
What causes airway remodelling?
Fibrosis (scar tissue), muscle hypertrophy (growth of cells)/hyperplacia (new cells), angiogenesis and mucus hypersecretion
What symptoms of asthma and COPD can be treated?
Excessive airway smooth muscle tone, inflammation, mucus plugging, pulmonary edema, cough?
What causes extrinsic (allergenic) asthma?
Environmental allergens (dust, mold, dander, food) trigger the plasma cells to produce antigen specific IgE antibodies IgE and/or antigens binding to mast cells result in degranulation and release of inflammatory mediators
What inflammatory mediators are released by mast cells?
Arachadonic Acid, Leukotrienes, Cytokines
What causes intrinsic (non-allergenic) asthma?
Triggered by anxiety, stress, cold air, dry air, exercise, viruses
May be caused by abnormalities in the autonomic regulation (Ach release) of airway function to increase responsiveness, innate immune system is involved.
What are the acute responses of asthma?
Bronchoconstriction (occurs in minutes) that is mediated by histamine, leukotrienes, prostaglandins directly from mast cell
What are the prolonged responses of asthma?
Vasodilation, mucus secretion, edema, bronchoconstriction (occurs in hours) from eosinophil and basophils
Lead to the hyperresponsiveness and airway remodelling
What does inflammation from inhaled irritants (smoke, air) cause?
Damages epithelial layer, causes them to shed, removing protective layer and allowing irritants to penetrate, exposure of sensory nerves which can activate and microvascular leaks and edema
Inflammation stimulates Ach release from cholinergic reflex, leading to inflammation
What are some examples of bronchodilators?
Beta2-adrenergic agonists, methylxanthines, anticholinergics, leukotriene modifiers
What neurotransmitters cause bronchodilation and bronchoconstriction?
Epinephrine on the beta-2 (SNS) causes bronchodilation
Acetylcholine on the M3 muscarinic (PNS) causes bronchoconstriction and increased secretion
What ion causes bronchoconstriction?
High intracellular Ca causes bronchoconstriction, low intracellular Ca causes bronchodilation
How does Ca cause bronchoconstriction?
Ach binding to M3 receptors activates PLC and Gq (DAG and IP3 hydrolysis) to increase cytoplasmic Ca
Ca-calmodulin activates myosin via MLCK which binds to actin which slides past and causes a contraction
Adenosine also activates PLC
How does Ca cause bronchodilation?
Activation of beta 2 activates Gs and adenylyl cyclase which converts ATP into cAMP and activates PKA which promotes Ca pumps to decrease cytoplasmic Ca and inhibits MLCK
What are some examples of beta-2 adrenergic agonists?
Albuterol, Salbutamol, Terbutaline (short acting), Salmeterol (long acting, 12 hours)
Come as inhalation and pill
How do beta 2 adrenergic agonists work?
Stimulate adenylyl cyclase which increases the formation of cAMP which acts to relax the airway smooth muscle (bronchodilation)
What is the drug of choice for acute asthma attacks?
Albuterol
What should be administered with beta 2 agonists?
Corticosteroids to improve the efficacy of the beta agonists and prevent the development of tolerance and desensitization by the beta 2 receptors
Which beta 2 agonists can be used in a severe asthma attack?
Subcutaneous injection of terbutaline or epinephrine (beta 1 and 2 agonist) along with corticosteroids
What are the adverse effects of beta 2 agonists?
Beta 1 receptors may get stimulated, causing tachycardia (increased dose)
Skeletal muscle tremor, tolerance
Insulin release
What are the drug interactions with beta 2 agonists?
Won’t be effective in patients taking propranolol (beta blocker)
What is an example of a methylxanthine?
Theophylline Administered aerosol (other routes can adversely affect the heart)
How does theophylline work?
High concentrations inhibit phosphodiesterase, thus increasing cAMP and relaxing the airway
Inhibits adenosine, which causes contraction
Stimulate contractility of diaphragm muscles to maintain structural frame of
What are the indications for theophylline?
2nd line treatment in acute asthma attacks but narrow therapeutic window
COPD
Preterm infants with apnea/bradycardia and breathing problems
What are the adverse effects of theophylline?
Headache, insomnia, tremors
Anaphylactic shock, nausea and vomiting, stimulates heart, fever and seizures
Interacts with CYP450
Found in chocolate, coffee, tea (don’t give to dogs)
What are some examples of anticholinergics?
Ipratropium (short acting), Tiotropium (long acting)
Aerosol
How do anticholinergics work?
Blocks muscarinic receptors, preventing bronchoconstriction and mucus secretion
Lowers vagal tone
No effect on inflammation
What is the indication for ipratropium?
Treatment of COPD and chronic bronchitis
Acute asthma attack in children, adults and those who are intolerant of beta agonists.
Can be effective treatment of severe asthma attacks in combination with beta agonists (enhances bronchodilation)
What are the adverse effects of ipratropium?
Generally well tolerated but excessive use can cause atropine like effects (dry mouth, dilated pupils, tachycardia)
What conditions should the use of ipratropium be used in?
Glaucoma (increased intraocular pressure) Prostatic hypertrophy (urinary retention)
What do leukotrienes do?
Activate PLC to increase Ca which cause bronchoconstriction, edema, vasodilation, chemotaxis of eosinophils and neutrophils, mucus secretion
How does zileuton work?
It is a leukotriene synthesis inhibitor that inhibits 5-lipoxygenase (enzyme that catalyzes formation of leukotrienes from arachidonic acid)
Give orally QID
What is the indication of zileuton?
Treatment of persistent asthma in adults and ASA-induced asthma. Intrinsic asthma
Prevention of exercise and antigen-induced bronchospasm
What should be checked periodically when on zileuton?
Liver enzyme levels due to possible hepatotoxicity
What are the drug interactions with zileuton?
Inhibits CYP450 which can interfere with the metabolism of theophylline, warfarin
How does aspirin induce asthma?
Inhibits COX-PGE synthesis from arachidonic acid metabolism, thus promoting leukotriene synthesis.
What are some examples of leukotriene receptor blockers?
Zafirlukast (oral, BID), Montelukast (oral, OD)
How do leukotriene receptor blockers work?
Selective reversible inhibitors of the cysteinyl leukotriene-1 (CysLT1) receptor, preventing leukotriene induced bronchoconstriction and edema. Prevents chemotaxis of neutrophils and eosinophils
What is zafirlukast indicated for?
The treatment of mild to moderate asthma.
Use in those >8 years.
Less effective than corticosteroids
What are some side effects of zafirlukast and monelukast?
Headache (zafir), GI disturbance (zafir), hepatotoxicity (check liver enzymes)
Interfere with warfarin, theophylline
What is montelukast indicated for?
Treatment of persistent asthma in adults and children.
Use in those >6 years.
Less effective than corticosteroids.
What are some examples of anti-inflammatory agents?
Corticosteroids, mast cell blockers, anti-IgE monoclonal antibody (omalizumab or xolair) and leukotriene modifiers
What are some examples of corticosteroids?
Beclometasone, flunisolide, fluticasone, budesonide, mometasone (inhaled), methylprednisolone (IV) and prednisone (oral)
How do corticosteroids work?
Blocks the release of arachidonic acid thus leukotriene production
Decrease numbers of inflammatory cells
Increase sensitivity of beta receptors and prevents their desensitization
Prevents long term changes in airways structure and function
What are corticosteroids indicated for?
Aerosol in most moderate cases of asthma and corticosteroids.
IV or oral may be required for severe exacerbations of asthma
First line anti-inflammatory therapy in all ages
What are the adverse effects of corticosteroids?
Aerosols may lead to thrush and hoarseness
Chronic use may suppress the adrenal glands, growth retardation in children, loss of glucose control in diabetics
May increase risk of osteoporosis, cataracts
1/4 patients have resistance to corticosteroids
What are some examples of mast cell blockers?
Cromolyn sodium (all ages), nedocromil (>12 years old) Aerosol (BID-QID)
How do mast cell blockers work?
Inhibits the release of mediators from mast cells (degranulation by blocking Cl/Ca channels) and neurotransmitter release from nerve endings
What are mast cell blockers indicated for?
Treatment of mild-moderate asthma, prevention of exercise-induced asthma, anti-inflammatory drug of choice for allergenic asthma in children
How will regular use of mast cell blockers help?
Does not reverse an ongoing bronchoconstriction but regular use will reduce bronchial hyperreactivity and inhibits phase 1 and phase 2 asthma attack
What is required to determine mast cell blocker efficacy?
Trial period of 4-6 weeks is required
What are the adverse effects of mast cell blockers?
Generally well tolerated, throat irritation, cough, dry mouth
Severe: Tight chest, wheezing, dermatitis, myositis, gastroenteritis
How does the anti-IgE monoclonal antibody work?
Prevents IgE binding to cells and reduced IgE levels. Both first and second (acute and prolonged) phase of bronchoconstriction is reduced
What is the anti-IgE monoclonal antibody indicated for?
For allergic asthma that is poorly controlled by corticosteroids
>12 years old
Subcutaneous injections
What are the adverse effects of anti-IgE monoclonal antibody?
May cause anaphylaxis in some patients
What are the goals of therapy in asthma and COPD?
Maintain normal activity levels, maintain near normal pulmonary function rates, prevent troublesome symptoms (cough, breathlessness), avoid medication adverse effects and drug interactions
How is very mild asthma treated?
Environmental control and education
Short acting beta-2 agonist on demand when symptoms become intermitted
How is mild asthma treated?
Environmental control and education
Short acting beta-2 agonist
Daily inhaled glucocorticoid (increase dose as severity gets worse)
How is moderately severe to severe asthma treated?
Environmental control and education
Short acting beta-2 agonist
Daily inhaled glucocorticoid
Additional therapy with long acting bronchodilators, anti-IgE antibodies
How is mild COPD treated?
Bronchodilators as needed
How is moderate COPD treated?
Bronchodilators and anti-inflammatory drugs
How is severe COPD treated?
Antibiotics, bronchodilators, anti-inflammatory drugs and oxygen therapy
