Asthma Flashcards
asthma definition
- chronic inflammatory disorder (excess mucus)
- bronchoconstriciton
- release of inflammatory mediators
inflammatory mediators in asthma
mast cells
basophils
eosinophils
t cells
asthma triggers
allergens cold air exercise pollutants drugs (aspirin) viral infections
2 phases of asthma
early phase: acute bronchoconstriction
late phase: influx of inflammatory cells and second wave mediator release
asthma therapy options
- patient education
- BSM: bronchodilators
- inflammation: slow/reverse progression
- specific mediators
COPD definition
progressive
mostly irreversible airflow obstruction
strongly associated with smokin
Clinical features of COPD
- dyspnea on exertion
- sputum production
- chronic cough
- includes chronic bronchitis and emphysema
Targets of COPD drug therapy
- pulmonary infections: vaccine
- hypoxemia: O2
- BSM: bronchodilators
- inflammation
bronchodilators
target airway constriction
anti-inflammatory agents for airway diseases
inflammation as underlying cause
inhibitors of mediator release and action in airway disease
specific mediators contribute to both acute and chronic disease
Localized admin of inhalation
convenient
faster onset
reduce systemic side effects
___um is optimal for deposition on small airway surface
1-5um
larger particles are deposited where and smaller particles deposited where?
large: oral cavity
small: exhaled
Why is patient education crucial for inhaled drugs?
efficacy is compromised if patients fail to admin correctly
Delivery devices of inhaled drugs
MDI
DPI (dry powder inhalers)
nebulizers
MDI
- drug suspended in compressed gas propellant
- actuation and inhalation must be coordinated
- difficult to use correctly
roughly ____% of MDI dose reaches lungs
10%
HFC or CFC MDI used today?
HFC
DPI
- dry micronized powder
- proper use: forceful deep inhalation
Who is DPI not ideal for?
children
elderly
Nebulizers
- less portable/convenient
- air bubbled through drug solution
- easiest for children, elderly, ill
Swallowed inhaled drugs go where?
liver: inactivated
GI: bloodstream –> systemic effect + inactive
What drugs are good for inhalation?
bad orally
most widely used bronchodilators
B2 agonist
B2 agonist MOA
- Increase cAMP
- relax smooth muscle
- regulation of K channels
t/f B2 agonist is replacement therapy for asthma
False!
NOT!
effective target
nonselective B agonist
epinephrine
Short acting B2 agonist
albuterol
long acting B2 agonist
salmeterol
formoterol
albuterol use
- actue bronchoconstriction
- exercise induced
- as needed
- short action (not for maintenance)
another name for albuterol
albutamol
albuterol PK
- inhalation
- 1-5 min onset
- 2-6 hr duration
- racemic
albuterol adverse effects
- tachycardia
- muscle tremor
- some CNS stimulation
Overuse of albuterol
- associated with increased mortality
- receptor desensitization
- worsening of disease
- treat symptom, not pathology
Long acting B2 agonists PK
high B2 selectivity long DOA (due to lipophilic nature)
Salmeterol long DOA
lipophilic tail binds to specific exosite on B2 receptor
Formoterol long DOA
no specific anchor
Salmeterol structure
Catecholamine like activation moiety
ancho/tail moiety
IS salmeterol or formoterol have faster onset for asthma?
formoterol
T/F salmeterol can be used for acute bronchoconstriction
false!
use albuterol if on salmeterol or formoterol
salmeterol use
long term asthma
COPD
overnight suppression of nocturnal asthma
T/F formoterol must not be used for treating acute bronchoconstriction
true
formoterol use
long term asthma
prevention of exercise induced bronchospasm
COPD
Salmeterol/formoterol side effects
- typical B2 agonist
- for asthma, always together with inhaled anti-inflammatory steroid
BBW salmeterol/formoterol
asthma related death
T/F LABA are safe used alone in COPD
true
LABA alone for asthma
increases mortality
LABA used only in combo with what?
anti-inflammatory steroids for asthma
Oral albuterol considerations
- less effective
- more systemic side effects
- slower onset
- longer DOA
oral albuterol uses
children
patients whose cough worsened by inhaled aerosols
first line therapy for asthma
glucocorticoids
used alone or combo with bronchodilators
- Prednisone
ICS drugs
fluticasone
budesonide
ICS MOA
- do not relax airway smooth muscle
- bind glucocorticoid receptors
- alter transcription of diverse genes
- suppressive effects on inflammatory cells
- equal effectiveness and differing potencies
ICS and bronchoconstriction
indirectly reduce
ICS uses
mild to moderate persistent asthma
prophylaxis
ICS have altered the outlook for asthmatics
- control symptoms
- improve lung function
- reduce irreversible airway changes
- improve QOL
- dosage/use may be lowered
- decrease SABA use
T/F fluticasone and budesonide are short acting
false
long acting
ICS have high affinities for what receptor?
GC
ICS adverse effects
- minimal at typical doses
- increase with dose
- hoarseness, pharyngeal candidiasis
- GC side effects
- steroid resistant asthma
ICS and LABA uses
- often combined because different targets
- convenient for long term control
LABA not for asthma mono therapy
ISC alone use
asthma
LABA + ICS
asthma
LABA alone use
COPD
Prednisone use (airway)
severe chronic asthma
parenterally for acute attacks
Side effects of prednisone (airway)
- all GC effects greater with systemic
- less selective for GC
- increased BP, glucose intolerance, glaucoma, imunnosuppresion
- taper off
Methylxanthines
theophylline
theophylline MOA
relatively weak bronchodilators
- think phosphodiesterase inhibition
- alters cellular Ca regulation
- long term effects on histone deacetylases
theophylline use
- add on in acute asthma
- adjunct in long term preventative therapy
- decrease symptoms in persistent and nocturnal asthma
Theophylline admin
- orally, multiple times per day
- short DOA
- not for inhalation
theophylline inhibits
PDE
theophylline adverse effects
- narrow therapeutic index
- large variability in metabolism
- increase metabolism in infants and smokers
- drug interactions
high doses of theophylline
- nausea
- nervousness
- anxiety
- HA
- insomnia
- abnormal heart rhythm
toxic levels of theophylline
- severe cardiac arrhythmias
- seizures
