08- Treatment of Asthma Flashcards
asthma
recurrent episodic bouts of coughing and difficult breathing resulting from airway inflammation
-associated with genetic linkage and environmental factor related to immunological challenge
airway hyperresponsiveness
a characteristic feature of asthma and consists of an increased sensitivity of the airways to an inhaled constrictor agonist (environmental irritant)
- asthmatic episodes can be triggered in absence of the aggravating allergen
- goal of long-term therapy is to reduce airway hyper-responsiveness
allergen
a substance that causes an exaggerated immune response to something that is normally harmless to the body
bronchodilation
an increase in the diameter of the bronchioles thus decreasing the resistance to passage of air through the bronchioles
-asthma causes bronchoconstriction
cAMP
an intracellular second messenger that is stimulated by Beta-2 agonist increase in adenyl cyclase, like Albuterol, and induces relaxation of bronchial smooth muscle for short term relief during acute asthma attacks
-broken down by phosphodiesterase which is prevented by Theophylline thus inc. cAMP levels and leading to bronchodilation
chemotactic factors
chemokines and lipid mediators that attract macrophages and other cells to the site of inflammation (thus releasing mediators of an inflammatory response)
early reaction
initial asthmatic reaction that can be controlled by prophylactic corticosteroids and cromolyn
-once inhibited, symptoms may be palliated with B2-adrenergic receptor agonists
eosinophils
cells that degranulate and release inflammatory mediators when activated (involved in allergic and asthmatic reactions)
histamine
inflammatory mediator that causes vasodilation and increased capillary permeability
-can cause itchyness, rash, and pain hypersensitivity
inflammatory mediators
anything that mediates the inflammatory response
-e.g.- histamine, cytokines, leukotrienes, etc.
late reaction
can be reduced or prevented by inhaled corticosteroids at or before initiation of the early reaction
leukocyte
cell that circulates in the blood and body fluids and is involved in counteracting foreign substances and disease; a white (blood) cell
-several types, including lymphocytes, granulocytes, monocytes, and macrophages
leukotriene
produced from lipoxygenase and mediate airway inflammation seen in asthma
e. g.- bronchial constriction, neutrophil and eosinophil chemotaxis and degranulation
- blocked by corticosteroids through blocking PLA2 and Zileuton through blocking lipoxygenase
mast cells
a cell filled with basophil granules, found in numbers in connective tissue and releasing histamine and other substances during inflammatory and allergic reactions
-degranulation inhibited by Cromolyn
phosphodiesterase
any enzyme that breaks a phosphodiester bond
-clinically we give phosphodiesterase inhibitor to prevent degradation of cAMP thereby increasing cAMP levels which increases the relaxation of bronchial smooth muscles
PLA2
expression results in increased inflammatory mediator production (prostanoids and leukotrienes) and release by eosinophils and mast cells (leukotrienes)
-corticosteroids act to inhibit PLA2 expression and activity (due to annexin [lipocortin] expression) which results in reduced mediator release by mast cells and eosinophils
albuterol
-fast acting Beta-2 agonist. Stimulates adenyl cyclase to produce cAMP which induces relaxation of bronchial smooth muscle
salmeterol
- Long acting beta-2 agonist (12hrs or more). Stimulates adenyl cyclase to produce cAMP which induces bronchial smooth muscle relaxation.
- Often combined with corticosteroids, such as Fluticasone, when used as part of maintenance therapy
- not effective in an emergency
beclomethasone
- inhaled corticosteroid, low bioavailability outside of airway.
- Inhibition of PLA2, reduced synthesis of chemotactic factors, reduces recruitment and proliferation of leukocytes, reduces localized TH2 immune response.
- Mechanisms dependent on altered protein expression, NOT a rapid process
budesonide
- inhaled corticosteroid, low bioavailability outside of airway.
- Inhibition of PLA2, reduced synthesis of chemotactic factors, reduces recruitment and proliferation of leukocytes, reduces localized TH2 immune response.
- Mechanisms dependent on altered protein expression, NOT a rapid process
fluticasone
- inhaled corticosteroid, low bioavailability outside of airway.
- Inhibition of PLA2, reduced synthesis of chemotactic factors, reduces recruitment and proliferation of leukocytes, reduces localized TH2 immune response.
- Mechanisms dependent on altered protein expression, NOT a rapid process
triamcinolone
- inhaled corticosteroid, low bioavailability outside of airway.
- Inhibition of PLA2, reduced synthesis of chemotactic factors, reduces recruitment and proliferation of leukocytes, reduces localized TH2 immune response.
- Mechanisms dependent on altered protein expression, NOT a rapid process
prednisone
- Oral or intravenous used when not adequately controlled by maintenance therapy
- systemic administration can lead to abnormal glucose metabolism, diabetes, hypertension, Cushing’s Syndrome, and increased susceptibility to infection
zileuton
- 5-lipoxygenase inhibitor inhibits synthesis of LTB4 and LTD4
- effectiveness varies greatly among individuals
- Liver toxicity due to inhibition of cytochrome P450, decreases metabolism of other drugs
montelukast
- LTD4 receptor antagonist reduces bronchoconstriction and edema associated with inflammatory process
- oral administration
zafirlukast
- LTD4 receptor antagonist reduces bronchoconstriction and edema associated with inflammatory process
- oral administration
cromolyn
- inhibits granulation of mast cells and possibly Ca channels
- inhibition of Cl channels may contributed to reduced nerve activity and cough inhibition
- poorly soluble, inhaled powder aerosol
nedocromil
- inhibits granulation of mast cells and possibly Ca channels
- inhibition of Cl channels may contributed to reduced nerve activity and cough inhibition
- poorly soluble, inhaled powder aerosol
ipratropium
- quaternary ammonium derivative of atropine.
- inhaltion, slower/less effective as compared to Beta-2 agonists
- only inhibits parasympathetic responses, which varies
- useful in patients intolerant of Beta-2 agonists
theophylline
- inhibits phosphodiesterase degradation of cAMP, may also block adenosine receptors
- oral administration which significant variability in metabolic clearance. Serum levels must be monitored, therapeutic plasma level 10-20 mcg/mL
