Asthma Pharmacology Flashcards
What are the causes of airway narrowing in acute ashtma?
Constriction of smooth muscle
inspissation of viscid mucous plugs
Thickening of bronchiole mucosa due to edema, infiltration, and hyperplasia
What cause is most easily reversed?
Smooth muscle constriciton (by B-androceptor stimulants)
How is long term control of asthma most readily acheived
Inhaled corticosteroid
Less effectively with LT pathway antagonist or mast cell stabilizer
What is the pathogenesis of Asthma?
Allergens provoke IgE production, IgE binds to mast cells on re-exposure crosslinks are formed causing mast cell degranulation releasing histamine, tryptase, LTC4, LTD4 and PGD2
Characterize the asthmatic response
Early asthmatic response is acute bronchoconstriction, often it is followed in 3-6 hours by the late asthmatic response which is the result of the influx of inflammatory cells that may hypersensitize the airway.
Mediators of the late response are thought to be controlled by TH2 mediated cytokines.
How is broncial reactivity assessed?
Measuring drop in FEV1 after administration of serially strong doses of methacholine.
What are the “relievers” of asthma?
Adrenoceptor agonists and sympathomimetic agents
What are the controllers of asthma?
Inhaled corticosteroids and anti-inflammatory agents
What are the general actions of adrenoceptor agonists?
Relax airway smooth muscle
Prevent mediator release
Increase heart rate
Causes skeletal muscle tremors
Why are isoproterenol and epinephrine reserved for special situations?
Because they increase the heart rate through stimulation of B1
What is the best method of delivery for B-agonists?
Inhalation
Most direct action, least systemic toxicity
80-90% still lost to mouth and pharynx
Slow inhalation and breath holding for five seconds maxiize dose response
What B agonists are rarely used for asthma?
Epinephrine, ephedrine, and isoproterenol
What is the mechanism of antimuscarinic agents?
Inhibit acetylcholine
What is the mechanism of theophylline?
Inhibits PDE, keeping cAMP active leading to continuous bronchodilation.
Most commonly affects PDE4 whose inhibitions causes decreases release of cytokines
What is the mechanism of B-agonists?
Stimulate cAMP through B2 receptors
What are the primary B2 selective agonists?
Albuterol, terbutaline, metaproterenol, pirbuterol
All have large substitutions near the amino and hydroxyl group
What are salemeterol and formoterol?
Long acting B2 selective agonists, salmeterol is a partial B agonist
Both have a high lipid solubility which permits them to dissolve in smooth muscle in high concentrations
They interact with inhaled corticosteroids to improve asthma control.
o antiinflammatory action so they are not recommended for monotherapy
What are the important methylxanthines?
Theophylline, theobromine, and caffeine
Aminophylline is the theophylline prep commons used for therapeutic purposes
What is the function of antimuscarinic agents in acute bronchospasm?
They are less effective than B-agonists but can add to bronchodilation when co-administered
What is the mechanism of corticosteroids?
Broad anti-inflammatory activity
No direct relaxation of smooth muscle but reduce bronchial reactivity
Potentiate B agonist activity
How are corticosteroids administered?
Usually by inhalation (fluticasone 4x daily)
Oral and parental are usually reserved for severe situations in order to avoid systemic effects.
What is ciclesonide?
Oral corticosteroid given as a prodrug that is activated in the bronchial epithelial cells
When in the serum it is tightly bound to proteins so it does not have access to other receptors
What is the effect of leukotriene inhibitors?
They inhibit the lipoxygenase pathway or block the LTB4 receptor which leads to a decrease in the production of inflammatory cytokines and chemokines.
Have suffix Kast
Taken orally
What is the mechanism of aspirin-induced asthma?
Cox inhibitors shunt the metabolism of arachadonic acid toward Lipoxygenase pathway which increases Leukotrienes and causes inflammatory exacerbation.
Blocked by inhibitors of Lox
