Treating Asthma Flashcards
Which disease is the leading cause of lost school days in children and work days among adults is what?
asthma
How do we differentiate mild from severe asthma?
- mild: occasional symptoms, usually upon some sort of exposure
- sever: frequent attacks, especially at hight, which limit activity
Describe airway changes in those suffering an asthma attack.
- bronchial and tracheal constriction
- mucosal thickening from edema and cellular infiltration
- the net result is narrow airways filled with thick mucous plugs
During an asthma attack, what measures of airflow are likely to be reduced?
all indices of expiratory flow:
- FEV1
- FVC
- FEV1/FVC
- peak expiratory flow rate
What is FEV1?
the volume of air expired in the first second of forced expiration
What is FVC?
the volume breathed out from a maximally forced expiratory effort
During an asthma attack, which measures of airflow are likely increased?
- total lung capacity
- functional residual capacity
- residual volume
- DLCO (diffusion capacity for CO)
What is the difference between functional residual capacity and residual volume?
- functional residual capacity is the residual volume left during normal breathing
- residual volume is the residual volume left after maximally forced expiratory effort
What role do bronchodilators and anti-inflammatory agents play in the treatment of asthma?
- bronchodilators are short-term relievers
- anti-inflammatory agents are long-term controllers
How does the airway of an asthmatic individual differ from that of a healthy individual?
the airway of an asthmatic is hyper-responsive to inflammatory mediators released in response to allergens, cold, exercise, etc.
Which inflammatory cells are involved in the early and late phase of an asthma attack?
- early: primarily mast cells
- late: T-cells, mast cells, eosinophils, and neutrophils
Why do severe asthmatics often experiences more symptoms at night?
because PNS tone is highest at night, which means that bronchoconstriction is more likely
How is bronchoconstriction mediated by the autonomic nervous system?
vagal efferents release acetylcholine onto muscarinic receptors on bronchial smooth muscle
Through what two mechanisms can inhaled irritants cause bronchoconstriction?
- they can induce release of chemical mediators from mast cells
- they can stimulate afferent vagal nerves to initiate reflex bronchoconstriction
What second messenger system regulates bronchial tone?
cAMP
Through what mechanism does the sympathetic nervous system act on bronchial smooth muscle?
- B2-adrenergic receptors are activated, activating AC
- cAMP levels rise and induce bronchodilation
Do high intracellular cAMP levels support bronchodilation or bronchoconstriction?
bronchodilation
What role does PDE play in regulating bronchial tone?
it degrades cAMP, promoting bronchoconstriction
How do phosphodiesterase inhibitors function in the treatment of asthma?
they inhibit the degradation of cAMP, promoting bronchodilation
How does theophylline function in the treatment of asthma?
it is an adenosine receptor antagonists that inhibits adenosine from inducing bronchoconstriction
Name two molecular signals that serve to initiate bronchoconstriction.
- acetylcholine
- adenosine
Bronchodilators fail to treat what aspect of asthma pathology?
mucous formation, edema, and cellular infiltration
Why are inhaled B2 agonists like albuterol relatively safe with few side effects?
- because inhalation, if done correctly, is essentially a topical administration without systemic effects of the drug
- that which is swallowed is either poorly absorbed or subject to a high first pass effect
What effect does albuterol have on potassium?
it increases insulin release and therefore induces a hypokalemia
What role do sympathomimetics play in the treatment of asthma?
- selective B2 agonists like albuterol are first line therapy
- however, less selective sympathomimetics like epinephrine and ephedrine have too many off target cardiovascular effects and are thus reserved for resolution of severe attacks
Drugs ending in the suffice “-phylline” are part of what class?
the methylxanthine bronchodilators
Why aren’t muscarinic antagonists a first line therapy for acute asthma given their bronchodilator effects?
because they have unpredictable efficacy due to varying involvement of parasympathetics in the bronchospasm of different people
What role do muscarinic antagonists play in the treatment of asthma?
- they relax bronchial smooth muscle and decrease mucus secretion
- however, they are only effective in those for whom parasympathetic involvement contributes significantly to their bronchospasms
- most useful for those with symptoms at night (symptoms often induced by increased PNS tone)
Through what mechanism of action do glucocorticoids function in the treatment of asthma?
- they inhibit the production of inflammatory cytokines
- they have no direct effect on bronchodilation
List three benefits of using glucocorticoids in those with asthma?
- reduce bronchial reactivity
- increase airway caliber by reducing edema
- reduce frequency of attacks
Many asthmatics require daily corticosteroids to prevent asthma attacks. How do we avoid the systemic symptoms of these treatments?
by prescribing inhaled corticosteroids
What are the side effects that accompany long-term inhaled corticosteroid use?
oropharyngeal candidiasis or hoarseness from vocal cord irritation
Drugs with the suffix “-lukast” act in what way?
they are leukotriene inhibitors used in the treatment of asthma
What role do leukotrienes play in asthma?
they especially help mediate the late phase of asthma
- LTB4 is a chemoattractant for eosinophils, monocytes, and neutrophils
- LTC4 and LTD4 are eosinophil chemoattractants, potent broncho-constrictors, and promoters of vascular permeability and mucous secretion
What is zileuton?
a 5-lipoxygenase inhibitor which impairs leukotriene synthesis and is used in the treatment of asthma
Leukotriene antagonists are most specific for which receptor?
the LTD4 receptor
What is omalizumab?
- an antibody against IgE, which inhibits binding of IgE to mast cells (doesn’t inactivate already bound IgE)
- lowers plasma IgE levels and reduces bronchospasms
- lessens asthma severity and reduces the need for corticosteroids
Which two monoclonal antibody drugs are useful in the treatment of asthma? What do they target?
- omalizumab: anti-IgE
- mepolizumab/reslizumab: anti-IL-5
What role do mepolizumab and reslizumab play in the treatment of asthma?
- inhibit binding of IL-5 to mast cells
- reduces severe asthma attacks by reducing number of eosinophils in the blood
- used for refractory asthma
What is the goal of asthma prophylaxis treatments?
reduce mast cell degranulation, thereby reducing the number of asthma attacks
What is cromolyn sodium?
a drug used to stabilize mast cells and prevent degranulation, thereby inhibiting asthma attacks
When are asthma prophylactic drugs used?
just before exercise or allergen exposure
For what kinds of asthma are prophylactic drugs like cromolyn sodium best?
allergen- and exercise-induced asthma
What is nedocromil sodium?
a mast cell stabilizer used as asthma prophylaxis
How do asthma prophylactics differ from daily anti-inflammatory drugs?
- prophylactics offer acute protection when an exposure is expected soon
- anti-inflammatory drugs are used daily to reduce the responsiveness of the airway and to prevent asthma attacks or limit their severity all the time
How do cromolyn sodium and nedocromil sodium stabilize mast cells?
- they alter delayed chloride channels in the cell membrane
- this inhibits mast cell activation and reduces release of histamine and other mediators
How is cromolyn sodium administered?
via inhalation since it experiences poor GI absorption
Describe the asthma treatment pyramid.
- offer a short-acting B2 agonist for symptom relief
- add a low dose ICS
- then add a long-acting B-agonist (oral formulation)
- then increase the dose of ICS
- finally, add an OCS if necessary
