Treatment of Asthma Flashcards
- recurrent episodes of coughing, shortness of breath, chest tightness, and wheezing
- mild: occasional symptoms, on exposure to allergens or pollutants, after exercise or upper viral respiratory infection
- severe: frequent attacks of wheezing dyspnea especially at night –> limitation of activity
asthma
asthma:
- _______ of smooth muscle
- mucosal thickening from _______ and cellular infiltration
- airway lumen: thick, viscid mucus plug
contraction
edema
FEV1, FEV1/FVC, and peak expiratory flow rate may be _______ during an asthma attack
reduced
total lung capacity, functional residual capacity, and residual volume may be _______ as a consequence of airflow obstruction and incomplete emptying of lung units
increased
______ reaction of asthma: exposure to allergen - IgE - allergen reexposure - allergen antibody rxn - mast cell activation - mediator release - smooth muscle contraction - brochoconstriction - decreased FEV1
early reaction (within 2 hours)
______ reaction: cytokine and other factors, T cells, mast cells - eosinophils and neutrophils, proteases, PAF - increased edema and mucus hypersecretion - bronchoconstriction - increased bronchial reactivity - late fall in FEV1
late reaction (4-6 hours)
Beta-2 agonists _______ cAMP synthesis by adenylyl cyclase, PDE inhibitors _______ cAMP degradation
increase
slow
bronchoconstriction inhibited by muscarinic receptor __________, adenosine receptors ________
antagonists
albuterol, bitolterol, pirbuterol, metaproterenol, terbutaline, salmeterol, formoterol are what drug class?
beta2 agonists
salmeterol and formoterol?
long acting beta-2 agonists
epinephrine, ephedrine, isoprotereneol?
sympathomimetics
aminophylline, theophylline, dyphylline, pentoxifylline?
methylxanthines
ipatropium, tiotropium, atropine
muscarinic antagonists
- act by stimulating adenylyl cyclase to increase cAMP - smooth muscle relaxation and bronchodilation
- drug of choice for acute asthma attacks
- longer acting for prophylaxis
- max 30 min, lasts 3-4 hours
- skeletal muscle tremor, nervousness, weakness
beta-2 agonists
- tachycardia, arrythmia, worsening of angina due to stimulation of beta-1
- act rapidly in acute asthmatic attacks, inhaled or injected subQ
sympathomimetics (epi, ephedrine)
- used as oral sustained release or parenteral
- PDE inhibition, increase cAMP, cardiac stimulation, vascular smooth muscle relaxation
- reduced cytokine release
- adenosine antagonists
- bronchodilation, CNS stimulation
- positive inotropic and chronotropic effects may produce arrythmias and increase BP
- stimulate gastric acid, weak diuretics, improve diaphragmatic function
methylxanthines ( theophylline, aminophylline, theobromine)
- most effect methylxanthine bronchodilator
- relieve obstruction in acute attack, inexpensive, oral
- 12 hr, therapuetic and toxic levels related to plasma levels
- insomnia, anorexia, nausea, vomiting, headache
- metabolized by liver
theophylline
- block Ach binding at muscarinin receptors
- inhibit responses to vagal stimulation, relax bronchial smooth muscle, decreased mucus secretion
Muscarinic receptor antagonists ( ipratropium, tiotropium, atropine)
- given IV or inhalation, bronchodilation for 5 hours
- adverse: dry mouth, urinary retention, tachycardia, loss of accomodation, agitation
atropine
-aerosol or nasal spray, poorly absorbed and minimal CNS effects
ipratropium bromide
long duration of action, 24 hours, M antagonist
tiotropium
beclomethasone, budesonide, dexamethosone, flunisolide, fulticasone, mometasone
glucocorticoids
- don’t relax smooth muscle directly, inhibit the production of inflammatory cytokines
- reduce reactivity, reduce edema
- oral, injection, aerosol
glucocorticoids
- systemic delivery only in patients requiring emergency treatment
- inhaled: oral candidiasis, hoarseness
glucocorticoids
- LTD4 receptor antagonists
- given orally, in children unable to comply with inhalation therapy
montelukast, zafirlukast
inhibits binding of IgE to mast cells, lower plasma IgE, reduces bronchospastic antigen response, lessen corticosteroid requirement
omalizumab
- inhibits binding of IL-5 to mast cells
- reduces level of blood eosinophils
- in patients with worsening, severe asthma attacks
mepolizumab, reslizumab
- reduce mast cell degranulation
- effective prophylaxis
- protective before exercise or allergen exposure
- inhibit hyperreactivity in antigen/exercise induced asthma
- don’t affect bronchial smooth muscle or bronchospasm
- inhibit mast cell activation, reduce release of histamine
cromolyn sodium, nedocromil sodium
