Asthma Flashcards
A respiratory disease characterized by recurrent reversible obstruction to airflow in the bronchiolar airways
asthma
Symptoms such as chest tightness, wheeze and cough, together with bronchial hyperresponsiveness
Asthma
Most common chronic disease in children, prevalence of 83 cases/1000 and affecting 6 million children
ashma
5 things with the pathophys of asthma
Airflow obstruction Bronchospasm, edema Bronchial hyperresponsiveness (BHR) Airways inflammation Chronic inflammation may lead to airway remodeling
what 4 things do inflammation cause in asthma
Inflammation causes recurrent episodes of wheezing, breathlessness, chest tightness and coughing
2 phases of asthma attacks
Immediate and late phase
what occurs Occurs on exposure to eliciting stimulus
Consists mainly of bronchospasm.
Bronchodilators are effective in this early phase
Immediate-phase response
what occurs Several hours later
Consists of bronchospasm, vasodilatation, edema and mucous secretion
Caused by inflammatory mediators and neuropeptides released from axon reflexes
Anti-inflammatory drug action needed for prevention and treatment.
late-phase response
what are allergen environmental triggers of asthma?
dust mites, pet dander, cockroaches, pollens, molds, viral URIs
what are non-allergen environmental triggers of asthma
smoke, acid reflux, weather changes (cold air), exercise, occurs at night, occupational irritants/chemical irritants, drugs
what are Co-morbid conditions with asthma
allergic rhinitis, sinusitis, GERD, depression
what drugs may trigger asthma
Cardioselective and non-selective Beta Blockers, Calcium antagonists, Dipyridamole, NSAID’s
what symp of acute and subacute asthma exacerbation?
Shortness of breath, cough, wheezing, and chest tightness
Can be combination of symptoms
Decreases in expiratory airflow
what kind of WBCs are found in the airways of asthmatics with a little less sudden onset - hours to days
Eosinophils
what kind of WBCs are found in the airways of asthmatics with a sudden onset less than 6 hours
neurtophils
what are PE findings that may indicate asthma?
Hyperexpansion of the thorax
Sounds of wheezing
Increased nasal secretion, mucosal swelling and nasal polyps
Atopic dermatits/eczema
what is FVC?
Forced vital capacity (FVC)
Total amount of air that can be exhaled
what is FEV1?
Forced expiratory volume in 1 second (FEV1)
Volume of air exhaled during the first second
what are the goals of tx in asthma?
To achieve and maintain clinical control
Minimal or no chronic symptoms day or night
Minimal or no exacerbations
No limitations on activities; no school missed
Maintain (near) normal pulmonary function
Minimal use of short-acting inhaled beta-2 agonist (< 2 days/week)
Minimal or no adverse effects from medications
what 6 classes of drugs are for use in LTC of asthma
Corticosteroids: inhaled (ICS) and systemic Long-acting beta2-agonists (LABA) Leukotriene modifiers Methylxanthines Cromolyn Anti IgE
what 3 classes of drugs are used in quick relief of asthma?
Short-acting beta2-agonists (SABA)
Anticholinergics
Systemic corticosteroids
what are the 3 Major advantages of inhaled therapy
deliver drugs directly to the airways
deliver higher drug concentrations locally
minimize systemic side effects
what are nebulizers for? 4
Convert a solution of drug into aerosol for inhalation
Used to deliver higher doses of drug to the lungs
Are more efficient than inhalers
Used in hospitals for status asthmaticus and treatment of severe asthma
what is the MOA of ICS?
depress the inflammatory response and edema in the respiratory tract and diminish bronchial hyper-responsiveness.
- Reduced mucous production
- Decreased local generation of prostaglandins and leukotrienes, with less inflammatory cell activation
- Adrenoceptor up-regulation
- Long-term reduced eosinophil and mast-cell infiltration of bronchial mucosa.
what are the 3 ROA of CS?
metered dose inhaler
oral
what are the indications for ICS? most what in asthma? Reduces what? what is it used in combo with?
Most effective long-term control therapy for persistent asthma
Only therapy shown to reduce the risk of death from asthma even in low doses
Often used in combination with β2 agonist or other asthma agents.
when should symptoms improve with ICS?
1-2 weeks; max in 4-8 weeks
FEV1 and peak expiratory flow require _____ for max improvement
3-6 wks
what is true about use with ICS?
Note- inhaled corticosteroids must be used regularly to be effective.
what are contraind for ICS?
Caution in growing children
what are local adrs for ICS?
Oropharyngeal candidiasis (Thrush)
Dysphonia
Reflex cough and bronchospasm
what are systemic adrs for ICS?
Hypothalamic-pituitary-adrenal suppression
Impaired growth in children
Dermal thinning-Dose Dependant
in adults what may be effects of ICS? is this true for kids as well?
Bone mineral density
Data suggest cumulative dose relationship
If risk for osteoporosis consider bone-protecting therapy
Ocular effects
High cumulative lifetime exposure may increase prevalence of cataracts
Increase risk of glaucoma if family history
Not for kids
how do you reduce ADRs of ICS? 4
Using a holding chamber Rinse mouth (rinse and spit) Using lowest dose possible Using in combination with long-acting beta2-agonists (LABA)
what are examples of ICS? 7
Fluticasone budesonide beclomethasone flunisolide triamcinolone mometasone Ciclesonide
what are some ICS and LABA combos? 2
-Fluticasone/salmeterol
Advair
-Budesonide/formoterol
Symbicort
what are some LABAs?
- Salmeterol
- Formoterol
- Arformoterol tartrate = Brovana
- Formoterol fumarate = Perforomist
what is not appropriate as monotherapy?
LABAs
LABAs are not a sub for …
anti-inflammatory
what is LABA beneficial for?
add to inhaled steroids
what is onset of LABA?
20 min
what is true about LABA and tolerance? and what does it lose protective effect against? what is decreased and what is not decreased?
Tolerance with chronic administration Partial loss of protective effect against Methacholine Histamine Exercise Bronchodilator response not decreased Responsiveness to SABA slightly decreased Increase dose of SABA by 1 puff
what is the BB warning on LABAs
Long acting Beta 2 agonists have a black box warning “may increase the chance of severe asthma episodes, and death when those episodes occur”
what are the drug int of LABA? what does it cause?
Concomitant use of CYP3A4 inhibitors increase salmeterol plasma levels
Avoid: Ketoconazole, ritonavir, atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, saquinavir, telithromycin
Prolonged QTc intervals
Palpitations
Tachycardia
what are 3 leukotriene antagonists?
Montelukast (Singulair)
Zafirlukast (Accolate)
Zileuton (Zyflo)
what is the MOA of Leukotriene Receptor Antagonists
Competitively antagonize leukotriene receptors D4 and E4 in the bronchiolar muscle, antagonizing endogenous leukotrienes causing bronchodilation.
what does Zileuton inhibit?
Zileuton inhibits 5-lipoxygenase—an enzyme necessary for leukotriene synthesis.
___ ____ are thought to cause airway narrowing which is sometimes seen with the use of NSAIDs.
endogenous leukotriens
how does NSAIDs promote airway narrowing
NSAIDS inhibit cycloxygenase and divert arachidonic acid breakdown via the lipoxygenase pathway, liberating leukotrienes.
what are indications for Leukotriene Receptor Antagonists
Alternative treatment of mild persistent asthma
what are contraind for Leukotriene Receptor Antagonists? what about zileuton specifically?
Pregnancy
Caution in elderly
z - in patients with active liver disease
wjat are the ADRs of Leukotriene Receptor Antagonists? Ziland Zarf specifically? Zaf and mont specifically?
GI disturbances (stomach pain, heartburn)
HA
Zileuton and Zafirlukast liver toxicity
Zafirlukast and montelukast can increases respiratory infections in elderly patients
what are the interactions with zafirlukast? drug and food?
Interaction with Warfarin – increase in prothrombin time (~35%)
Food can reduce bioavailability
Take 1 hour before or 2 hours after meals
What are the drug int of zileuton?
Theophylline – doubles theophylline concentration
Warfarin – increase prothrombin time
Propranolol- doubles propranolol AUC
what is FDA investigating now with montelukast?
behavior/mood changes, suicidality and suicide
what are theophylline and aminophylline?
Methylxanthines
what is the moa of Methylxanthines
Appear to increase cAMP levels in the bronchial smooth muscle cells by inhibiting phosphodiesterase, an enzyme which catalyses the hydrolysis of cAMP to AMP. Increased cAMP relaxes smooth muscle, causing bronchodilation.
what is Methylxanthines used for?
mono and adj tx with ICS
what are contraind of Methylxanthines
Not recommended in children < 4 years
Cardiac disease
HTN
Hepatic impairment
why is Methylxanthines infreq used?
due to narrow therapeutic window, drug-drug interactions and safer alternatives
what is Significant drug/disease interactions in Methylxanthines
Viral illness, CHF, cirrhosis, cigarette smoking,etc
what is Significant drug/drug interactions with Methylxanthines
Cimetidine, macrolides, quinolones, etc
CYP1A2 and 3A4 substrate
what can be present in up to 50% of patients with serum concentrations of 10-20 mcg/mL; Common with concentration >20 mcg/mL of Methylxanthines
Nausea, irritability, insomnia, headache, vomiting
what can Methylxanthines do to the heart?
Tachyarrhythmias
>20-30 mcg/mL
Ventricular arrhythmias, seizures
>40 mcg/mL
what do not always occur before severe, life-threatening effects in Methylxanthines
minor SE
what are Cromolyn sodium (Intal); Nedocromil (Tilade)
Mast cell stabilizers
what is the MOA of Mast cell stabilizers
stabilize mast cells preventing the release of inflammatory mediators
what are indications for Mast cell stabilizers
Patients < 20 y/o with severe allergic disease and moderate asthma; pregnancy
what are ADRs of mast cells stabilizers
Cough
Transient bronchospasm
Throat irritation
Neocromil has a bitter taste
what Must be utilized regularly for several weeks before effects are noted. Not indicated for acute asthma
mast cell stabilizers
what is Omalizumab
Immunomodulator
what is the MOA of Omalizumab
Recombinant monoclonal antibody that binds IgE on mast cells and basophils limits release of mediators of allergic response
what is the indication for omalizumab?
Reserved for moderate-to-severe persistent asthma in patients 12 years of age or older who are not controlled on other therapies (not first line therapy)
when is omlizumab admin?
Administered once every 2-4 weeks; SubQ
what is BB warning of omalizumab?
anaphylaxis
can anaphyl be delayed in omalizumab?
May be delayed up to 24 hours
what is MOA of systemic corticosteroids?
Decrease inflammation by suppression of migration of leukocytes and reversal of increased capillary permeability.
what is ind for Systemic Corticosteroids
Control chronic symptoms in people with severe asthma
what are o Albuterol o Pirbuterol o Metaproterenol o levalbuterol
SABAs
Stimulation of β2-adrenoceptors leads to
a rise in intracellular cAMP levels and subsequent smooth muscle relaxation and bronchodilation.
β2-adrenoceptor agonist may also prevent
activation of mast cells as a minor effect
β2-adrenoceptor agonist are potent
bronchodilators with little if any β1 stimulating properties.
what are indications for Beta2-adrenoceptor Agonist (5) 1 big
-Relieve bronchospasm during acute exacerbations
-Pretreatment for exercise induced bronchoconstriction
-Treat the symptoms of asthma but not the underlying disease.
Does not improve control of symptoms
-Alone in mild asthma
-Adjunct to corticosteroids
-rescue
what are the ADRs of Beta2-adrenoceptor Agonist
Fine tremor
Tachycardia
Hypokalemia w/ high doses
Some patients have increased risk of exacerbations, some have decreased lung function - Does not appear to occur with prn use
what are ipratropium,and tiotropium
Anticholinergics (Antimuscarinics)
what are indications of Anticholinergics (Antimuscarinics) in asthma? and what is it not ind for?
Relief of acute bronchospasm
Not indicated for chronic therapy
ipratropium may provide additive effects when added to something in acute setting
Ipratropium may provide additive effects to B2-agonists, in acute setting
Anticholinergics (Antimuscarinics) are alternative for pts with____ intolerance
with B2-agonist intolerance
when is Anticholinergics (Antimuscarinics) TOC?
Treatment of choice for bronchospasm due to B-blockers
what is the MOA for Anticholinergics (Antimuscarinics)
Parasympathetic vagal fibers provide a bronchoconstrictor tone to the smooth muscle of the airways. Activated by reflex with stimulation of sensory receptors in the airway walls.
Muscarinic antagonists act by blocking muscarinic receptors, especially M3 subtype, which responds to this parasympathetic brochoconstrictor tone.
what are contraind for Anticholinergics (Antimuscarinics)
Glaucoma
Pregnancy
what it imp use of systemic corticosteroids
Important in the treatment of severe acute exacerbations
what do systemic corticosteroids prevent? Reduce? 2 ea?
Prevent progression of asthma exacerbation
Reduce need for referral to ER and hospitalization
Prevent early relapse after emergency treatment
Reduce morbidity of the illness
More than ____courses of therapy with systemic corticosteroids → re-evaluate asthma management plan
3 courses/yr
Long-term Control Medication Depends on
age and severity
Quick-relief medication for EVERY patient?
SABA as needed for symptoms.
Increasing use of SABA or use >2 times a week for symptom control (not prevention of EIB) indicates inadequate control and the need to step up treatment
Step 1 (Mild Intermittent) symptoms and meds…
Symptoms < 2 nights/month; Brief exacerbations
No daily medication needed; quick relief only
Step 2 (Mild Persistent) symptoms and meds..
Symptoms > once/wk but < 1/day; >2 nights/month, Exacerbations may affect activity and sleep
Preferred Tx = low-dose inhaled steroids (ICS), prn rapid acting beta-2 agonist
Alternative Tx = cromolyn or nedocromil, leukotriene modifier, or theophylline
Step 3 (Moderate Persistent) meds and symptoms
Symptoms daily; > 1 night/wk, Exacerbations may affect activity and sleep, Requires daily use of inhaled short acting beta-2 agonist
Preferred Tx = low dose ICS and long-acting inhaled beta-2 agonist, prn rapid acting beta-2 agonist
Alternative Tx = med or high dose ICS or low dose ICS+ leukotriene modifier or theophylline
Step 4 (Severe Persistent) meds and symptoms
Continuous symptoms, limitation of physical activity
Preferred Tx: Medium or high dose ICS and long-acting inhaled beta-2 agonist or if needed oral glucocorticosteroid
what are symptoms of acute asthma exacerbation?
Anxious
Dyspnea, SOB
Chest tightness / burning
whats found on PE for acute asthma exacerbation?
Vital signs: tachycardia, tachypnea
Wheezing
If severe obstruction may not hear any wheezing
Dry hacking cough
Pale/cyanotic skin
Supraclavicular and intercostal retractions
what are found lab wise for acute asthma exacerbation?
Signs of hypoxemia
Decreased oxygen saturation of blood hemoglobin (_ SaO2)
Decreased partial pressure of blood oxygen (_ PO2)
Mixed respiratory and metabolic acidosis if severe exacerbation
Lung function tests
Decreased PEF or FEV1
who gets COPD?
Mainly in long-standing smokers, or occupation-related long-term exposure to substances such as coal dust, asbestos, etc.
what 2 diseases are COPD associated with?
w/bronchitis and emphysema
do ppl with COPD get relief from bronchodilators and anti-inflammatory agents
some..Less marked than asthmatics
No proven benefits upon life-expectancy
Long-term oxygen therapy also utilized
describe the pathophys of COPD
Inflammation in the peripheral airways and lung parenchyma.
At the site of lung destruction, macrophages activated by cigarette smoke and other irritants release neutrophil chemotactic factors. Activated macrophages and neutrophils release proteases that break down connective tissue in the lung parenchyma leading to emphysema and mucus production. Cytotoxic T cells contribute to destruction of alveolar walls through release of porphyrins and TNF-α.
what is chronic bronchitis?
Associated with chronic or recurrent excess mucous secretion into the bronchial tree
Cough that occurs on most days during a period of at least 3 months of the year for at least 2 consecutive years.
what is emphysema?
Abnormal, permanent enlargement of the airspaces distal to the terminal bronchioles
Accompanied by destruction of their walls, without obvious fibrosis
Oxygen
Administered to any patient in respiratory distress except COPD patients who retain _____. Caution should be used in these patients not to administer ____to depress their respiratory drive.
CO2
Too much O2
what is the DOC in COPD
Anticholinergic agents and B2 agonists
what is the combo used in copd?
Combo of albuterol and ipratroprium (Combivent) provides greater bronchodilation than either drug alone
what does antichol and b2 agonist do for COPD?
Increase airflow, alleviate symptoms, decrease exacerbation of disease
when are ICS used in COPD
Inhaled steroids restricted to patients with moderate to severe reduction in airflow in which optimal bronchodilator therapy has failed
what do you add to tx to avoid raising dose in COPD?
LABA
what are used to reduce hospitalizations and and to provide better resolution of symptoms in acute exacerbation in COPD?
Antibiotics.
