Lecture 22: Asthma Flashcards
Asthma
-episodic bronchospasm resulting from exaggerated bronchoconstrictor response to stimuli
-bronchial hyperreactivity from chronic bronchial inflammation
Episodic bronchospasm causes
-dyspnea
-cough
-wheezing
Types of asthma
-extrinsic
-intrinsic
Extrinsic asthma
-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
Intrinsic asthma
-nonimmune triggering mech (aspirin, infection, stress, exercise)
-no history of allergy
-IgE levels normal
Phases of extrinsic asthma attacks
-acute bronchoconstriction (30-60 min)
-sustained bronchoconstriction (4-8 hours later)
acute bronchoconstriction
-immediate asthmatic response (IAR)
-occurs after sensitization
-re-exposure to allergen triggers mast cell degranulation
-smooth muscle contraction
-vascular leakage
mast cell degranulation
-release of mediators from mast cell
-histamine
-tryptase
-leukotrienes (LTC4 and LTD4)
-PGD2
mast cell mediators cause
-smooth muscle contraction
-vascular leakage
Direct stimulation of subepithelial vagal (PSNS) receptors provokes
-reflex bronchoconstriction
sustained bronchoconstriction
-late asthmatic response
-3-6 hours late
-activation of TH2 cells
-cytokine production
-activation of eosinophils
activation of TH2 cells
-attract and activate eosinophils
-stimulate mucus hypersecretion by bronchial epithelial cells
-stimulate IgE production by B lymphocytes
activation of eosinophils
-release MBP, ECP, peroxidase which can cause tissue damage
-amplifies and sustains inflammation w/o additional exposure to antigen
mediation of acute bronchoconstriction
-mediated by IgE produced in response to foreign proteins
-IgE binds FcER-1 on mast cells in airway mucosa
Airway remodelling in asthma
-epithelium: HYPERplasia and HYPERsecretion
-thickening of basement membrane
-smooth muscle hypertrophy
Pharmacologic treatment of asthma
-sympathomimetics
-inhaled corticosteroids
-leukotriene pathway inhibitors
-methylxanthine drugs
-antimuscarinic agents
-cromolyn and nedocromil
-monoclonal antibodies
Most used drugs in asthma
-sympathomimetics
-inhaled corticosteroids
Sympathomimetic drug mechanism
-binds B2 receptors in bronchial smooth muscle
-increase cAMP = relax cells
Nonselective sympathomimetics
-epinephrine
-IV to relieve severe attack
B selective sympathomimetics
-isoproterenol
-displaced by B2 selective drugs
B2 selective drugs
-most used for treatment of asthma
-SABA and LABA
B2 selective agonists SAR
-bulky N substitutions = B2 selectivity
-substitutions in phenyl ring = B2 selectivity and resistant to COMT
-only R-isomer is active
B2 toxicities
-tachycardia, arrythmias (not as bad for B2)
-tremors
-induction of tachyphylaxis - reduction in bronchodilator response upon regular use
