Final Exam Flashcards
Major pathophysiological characteristics of asthma
airway narrowing & inflammation mostly in medium-sized bronchi
airway hyperresponsiveness
Th2 cell response
Th2 high inflammation asthma
early onset allergic asthma, adult-onset eosinophilic nonallergic asthma, & exercised-induced
respond well to inhaled corticosteroids (ICS), monoclonal antibodies to IgE, and Th2-targeted therapeutics
adult-onset eosinophilic nonallergic asthma
chronic sinusitis, nasal polyps, exacerbated by aspirin
high eosinophils in sputum & blood
tx= ICD & IL-5 monoclonal antibodies
nonallergic, Th2 low asthma
severe adult onset
high neutrophils in sputum
triggered by= URI, pollution, smoke. Obesity worsens
*Poor response to ICS
preferred method of measuring expiratory flow to dx asthma > 5 y/o
spirometry (* may be normal if asx)
peak expiratory flow can be used if needed
3 things to measure asthma control
freq/severity of sx
use of SABA
impact on life (restricting activity? impacting sleep?)
non-pharm interventions for asthma sx control
no smoking
physical activity; warm up & take SABA 5-20 min before
occupational exposure
stop NSAIDs if worsen sx
beta blocker to cardioselective
allergens
weight loss, avoid sulfites (beer, wine, shrimp, dried fruit)
vaccinations (flu, covid)
emotions
weather
outdoor pollen/allergens ***all patients w/ asthma tested for allergens
long term/maintenance med classes for asthma
inhaled corticosteroids (ICS)
inhaled long-acting beta agonists (LABA)
oral leukotriene receptor antagonists (LTRA)
inhaled long acting muscarinic antagonists (LAMA)
biologic agents
quick relief meds for asthma
short acting beta agonist (SABA)
ICS-formoterol (steroid + LABA)
short acting muscarinic antagonist (SAMA)
short bursts of systemic corticosteroids
theophylline’s place in asthma/COPD therapy & why fallen out of favor?
higher risk of SE and not recommended; weak efficacy.
nausea and other gastrointestinal disturbances, cardiac arrhythmias, and CNS excitation, leading to a narrow therapeutic window.
who qualifies for ICS tx in asthma
all people w/ persistent asthma at least 2 days each month
ICS dosing considerations
flat dose-response curve
smoking decreases response
2 weeks of therapy needed to see significant clinical effects
ICS adverse effects & interactions
oral candidiasis
cough
dysphonia
pneumonia in high dose
long term- decreased BMD, adrenal suppression
genetic variant causes wide range of response to ICS
interaction= cushings & adrenal insufficiency when potent inhibitors of CYP3A4 (ritonavir, itraconazole, ketoconazole) with high dose ICS so avoid
last line for asthma tx
systemic corticosteroids when all other add on tx options have been expended
assess barriers to asthma control before adding
when are LABAs (long acting inhaled beta 2 agonists) used for asthma & ex
acts as bronchodilator
add-on maintenance not controlled on ICS alone
as effective as doubling ICS dose or adding LTRA
**black box= NEVER used alone w/o ICS bc risk exacerbations/death
ex- salmeterol, formoterol, vilanterol
LAMAs (long acting muscarinic antagonists)
mech. of action, indication, SE, ex (w/ onset/duration)
mechanism of action: inhibit acetylcholine effect on muscarinic receptors in airways and protect against cholinergic mediated bronchoconstriction
indication: uncontrolled asthma, already taking ICS or ICS & LABA
SE=(think anticholinergic) urinary retention, dry mouth, HA, URI
ex: tiotropium bromide; onset 30 min x24 hr; umeclidinium
LTRA (leukotriene receptor antagonists)
mech. of action, indication, SE & interactions
mech. of action= anti-inflammatory that either inhibit 5-lipoxygenase or antagonize leukotriene D4 effects. Oral med so convenient but significantly less effective than ICS
indication= steroid sparing; *beneficial for asthma + allergic rhinitis, aspirin sensitivity, exercise-induced bronchospasm
SE = **black box warning serious mental health SE for montelukast; neuropysch SE (sleep disorder, aggression, suicide)
hepatotoxicity (zileuton & zafirlukast)
CYP 2C9 metabolism= drug interactions
biologic agents for asthma indication & action
poor sx control despite all recommendations
target Th2 inflammation to reduce steroid use, fewer exacerbations, improved lung function
anti-IgE monoclonal antibody for asthma
action, indication, SE, ex
omalizumab
action= inhibits binding of IgE to receptors on mast cells & basophils that decreases inflammation & allergic response
indication= mod-severe asthma, not controlled on ICS, positive skin test or reactivity to aeroallergens & high IgE
SE= injection site reaction, anaphylaxis rare but possible so *monitor x2 hours x3 months then reduce to 30 min. *rx epinephrine
IL-5 & IL-5R antagonist monoclonal antibody
indication, action, SE, ex
indication= severe exacerbations, high eosinophils
action= prevention of eosinophils
ex= mepolizumab, reslizumab, benralizumab
SE= nasopharyngitis, HA, hypersensitivity, worse asthma, URI. Long term effects unknown
IL-4 receptor alpha antagonist monoclonal antibody
indication, action, SE, ex
dupilumab
high IgE and eosinophil count
inhibit IL-4 and IL-13 signaling in Th2 inflammation
SE= injection site pain, transient blood eosinophilia
macrolides & asthma
indication, action, ex
azithromycin 500mg 3x/week decreases asthma sx
uncontrolled medium-high dose ICS/LABA
benefits from anti-inflammatory NOT antimicrobial properties
tx x6 months
SABAs for asthma
indication, action, use, SE, ex
action= reverse acute airway obstruction d/t bronchoconstriction & block early-phase response to antigen in asthma exacerbation. Increase mucociliary clearance and stabilize mast cell membranes. PRN only, not scheduled
onset < 5 min, lasts 4-6 hours
indication= asthma exacerbation; use with ICS
use= 4-10 puffs Q20 min up to 1 hour in severe acute exacerbation. Shouldn’t have repeated use over 1-2 days
SE= use without ICS increases risk of death, reduced lung function, urgent healthcare!
tachycardia, tremor, hypokalemia
ICS (budesonide)-formoterol
low dose ICS-formoterol as maintenance and reliever therapy (MART) is recommended for all adolescents and adults (80/4.5 mcg); maxium dose of formoterol 72 mcg