08- Treatment of Asthma

Question 1

asthma

Answer 1

recurrent episodic bouts of coughing and difficult breathing resulting from airway inflammation
-associated with genetic linkage and environmental factor related to immunological challenge

Question 2

airway hyperresponsiveness

Answer 2

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

Question 3

allergen

Answer 3

a substance that causes an exaggerated immune response to something that is normally harmless to the body

Question 4

bronchodilation

Answer 4

an increase in the diameter of the bronchioles thus decreasing the resistance to passage of air through the bronchioles
-asthma causes bronchoconstriction

Question 5

cAMP

Answer 5

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

Question 6

chemotactic factors

Answer 6

chemokines and lipid mediators that attract macrophages and other cells to the site of inflammation (thus releasing mediators of an inflammatory response)

Question 7

early reaction

Answer 7

initial asthmatic reaction that can be controlled by prophylactic corticosteroids and cromolyn
-once inhibited, symptoms may be palliated with B2-adrenergic receptor agonists

Question 8

eosinophils

Answer 8

cells that degranulate and release inflammatory mediators when activated (involved in allergic and asthmatic reactions)

Question 9

histamine

Answer 9

inflammatory mediator that causes vasodilation and increased capillary permeability
-can cause itchyness, rash, and pain hypersensitivity

Question 10

inflammatory mediators

Answer 10

anything that mediates the inflammatory response

-e.g.- histamine, cytokines, leukotrienes, etc.

Question 11

late reaction

Answer 11

can be reduced or prevented by inhaled corticosteroids at or before initiation of the early reaction

Question 12

leukocyte

Answer 12

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

Question 13

leukotriene

Answer 13

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

Question 14

mast cells

Answer 14

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

Question 15

phosphodiesterase

Answer 15

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

Question 16

PLA2

Answer 16

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

Question 17

albuterol

Answer 17

-fast acting Beta-2 agonist. Stimulates adenyl cyclase to produce cAMP which induces relaxation of bronchial smooth muscle

Question 18

salmeterol

Answer 18

• 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

Question 19

beclomethasone

Answer 19

• 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

Question 20

budesonide

Answer 20

• 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

Question 21

fluticasone

Answer 21

• 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

Question 22

triamcinolone

Answer 22

• 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

Question 23

prednisone

Answer 23

• 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

Question 24

zileuton

Answer 24

• 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

Question 25

montelukast

Answer 25

• LTD4 receptor antagonist reduces bronchoconstriction and edema associated with inflammatory process
• oral administration

Question 26

zafirlukast

Answer 26

• LTD4 receptor antagonist reduces bronchoconstriction and edema associated with inflammatory process
• oral administration

Question 27

cromolyn

Answer 27

• 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

Question 28

nedocromil

Answer 28

• 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

Question 29

ipratropium

Answer 29

• 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

Question 30

theophylline

Answer 30

• 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