Lecture 22: Asthma

Question 1

Asthma

Answer 1

-episodic bronchospasm resulting from exaggerated bronchoconstrictor response to stimuli
-bronchial hyperreactivity from chronic bronchial inflammation

Question 2

Episodic bronchospasm causes

Answer 2

-dyspnea
-cough
-wheezing

Question 3

Types of asthma

Answer 3

-extrinsic
-intrinsic

Question 4

Extrinsic asthma

Answer 4

-hypersensitivity rxn induced by antigen exposure
-associated w allergy
-early onset in life
-inc IgE and eosinophil count
-driven by TH2 of CD4 T cells

Question 5

Intrinsic asthma

Answer 5

-nonimmune triggering mech (aspirin, infection, stress, exercise)
-no history of allergy
-IgE levels normal

Question 6

Phases of extrinsic asthma attacks

Answer 6

-acute bronchoconstriction (30-60 min)
-sustained bronchoconstriction (4-8 hours later)

Question 7

acute bronchoconstriction

Answer 7

-immediate asthmatic response (IAR)
-occurs after sensitization
-re-exposure to allergen triggers mast cell degranulation
-smooth muscle contraction
-vascular leakage

Question 8

mast cell degranulation

Answer 8

-release of mediators from mast cell
-histamine
-tryptase
-leukotrienes (LTC4 and LTD4)
-PGD2

Question 9

mast cell mediators cause

Answer 9

-smooth muscle contraction
-vascular leakage

Question 10

Direct stimulation of subepithelial vagal (PSNS) receptors provokes

Answer 10

-reflex bronchoconstriction

Question 11

sustained bronchoconstriction

Answer 11

-late asthmatic response
-3-6 hours late
-activation of TH2 cells
-cytokine production
-activation of eosinophils

Question 12

activation of TH2 cells

Answer 12

-attract and activate eosinophils
-stimulate mucus hypersecretion by bronchial epithelial cells
-stimulate IgE production by B lymphocytes

Question 13

activation of eosinophils

Answer 13

-release MBP, ECP, peroxidase which can cause tissue damage
-amplifies and sustains inflammation w/o additional exposure to antigen

Question 14

mediation of acute bronchoconstriction

Answer 14

-mediated by IgE produced in response to foreign proteins
-IgE binds FcER-1 on mast cells in airway mucosa

Question 15

Airway remodelling in asthma

Answer 15

-epithelium: HYPERplasia and HYPERsecretion
-thickening of basement membrane
-smooth muscle hypertrophy

Question 16

Pharmacologic treatment of asthma

Answer 16

-sympathomimetics
-inhaled corticosteroids
-leukotriene pathway inhibitors
-methylxanthine drugs
-antimuscarinic agents
-cromolyn and nedocromil
-monoclonal antibodies

Question 17

Most used drugs in asthma

Answer 17

-sympathomimetics
-inhaled corticosteroids

Question 18

Sympathomimetic drug mechanism

Answer 18

-binds B2 receptors in bronchial smooth muscle
-increase cAMP = relax cells

Question 19

Nonselective sympathomimetics

Answer 19

-epinephrine
-IV to relieve severe attack

Question 20

B selective sympathomimetics

Answer 20

-isoproterenol
-displaced by B2 selective drugs

Question 21

B2 selective drugs

Answer 21

-most used for treatment of asthma
-SABA and LABA

Question 22

B2 selective agonists SAR

Answer 22

-bulky N substitutions = B2 selectivity
-substitutions in phenyl ring = B2 selectivity and resistant to COMT
-only R-isomer is active

Question 23

B2 toxicities

Answer 23

-tachycardia, arrythmias (not as bad for B2)
-tremors
-induction of tachyphylaxis - reduction in bronchodilator response upon regular use