Lecture 23: Asthma Drugs Flashcards
Short-acting B2 agonist (SABA) use
-PRN for acute attacks
SABA drugs
-albuterol
-terbutaline
-metaproterenol
-pirbuterol
Long acting B2 agonists (LABA) uses
-additional therapy in pts using inhaled glucocotricoids
-daily use
-not for acute attacks
LABA black box warning
-not an anti-inflammatory
-should NOT be used as monotherapy for asthma
LABA drugs
-salmeterol
-formoterol
-commonly available with cortiosteroids
Metaproterenol
-SABA
-4 hour
-analog of isoproterenol
-least potent B2 agonist
-good oral availability
Terbutaline
-SABA
-N-t-butyl analog of metaproterenol
-greater B2 selectivity
-3x more potent than metaproterenol
-good oral availability
Albuterol
-SABA
-most used
-4-8hour
-salicyl alcohol in phenyl = COMT resistant
Levalbuterol
-R-isomer or albuterol
-greater potency
-more expensive
Pirbuterol
-SABA
-analogous to albuterol except the pyridine ring
-similar duration but less potent than albuterol
Salmeterol
-LABA
-available as powder
-greater lipid solubility;dissolve in cell membranes
-12 hour
Formoterol
-LABA
-available as powder
-more rapid onset but similar duration to salmeterol
-resistant to COMT and MAO
Inhaled Corticosteroids (ICSs)
-maintenance therapy for persistant asthma
-not curative (effective only when taken)
-systemic/oral admin for severe cases only
-most effective way to minimize systemic effects
Inhaled corticosteroids (ICSs) drugs
-triamcinolone acetonide
-beclomethasone dipropionate
-budesonide
-flunisolide
-mometasone furoate
-fluticasone propionate
-ciclesonide
ICS adverse effects
-candidiasis
-hoarseness (effect on vocal cords)
-long-term inc risk of osteoporosis and cataracts
-1 cm reduction of growth of children in the first year
Candidiasis treatment
-clotrimazole
-reduced by gargling water after each use
-ciclesonide (21-ester prodrug) associated w less effects
Leukotrienes
-produced from arachidonic acid by 5-lipoxygenase
-involved in inflammatory diseases and anaphylaxis
LTB4
-potent neutrophil chemoattractant
-leukotriene
LTC 4 and LTD4
-bronchoconstriction
-inc bronchial reactivity
-mucosal edema
-mucus hypersecretion
Leukotriene pathway inhibitors
-improve asthma control
-reduce freq of exacerbations
-not as effective as ICSs
-effective orally
-reduce response to aspirin in aspirin-induced asthma
Types of leukotriene pathway inhibitors
-5-lipoxygenase inhibitor
-cysLTI receptor ANTagonists
5-lipoxygenase drug
zileuton
cysLTI ANTagonist drugs
-Zafirlukast
-Montelukast
Zileuton
-5-lipoxygenase inhibitor
-good oral availability
-alternative to LABA in addition to ICSs
-NOT for acute attack
-requires periodic monitoring of liver function
Montelukast
-blocks binding of LTC, LTD, LTE4 to receptor
-once daily
-good oral bioavailability
-reduces frequency of asthma exacerbations
-little toxicity
Methylxanthine drugs
-theophylline
-theobromine
-caffeine
-replaced by B2 agonists but used in some countries bc it cheap
Methylxanthine SAR
-6-ring next to 5 ring
Methylxanthine drug mechanism
-inhibit phosphodiesterase
-inc cAMP
-bronchodilation
-suppress histamine release
-block adenosine action (constriction and H release)
-histone deacetylation (suppresses inflammatory genes)
Methylxanthine toxicity
-nausea
-vomiting
-tremulousness
-arrhythmias
-narrow therapuetic index
Antimuscarinic agents
-anticholinergics
-for pts intolerant of B agonists
Antimuscarinic mechanism
-inhibit acetylcholine at muscarinic receptors
-doesn’t allow bronchoconstriction and mucus secretion
Antimuscarinic drug
Ipratropium
Ipratropium
-bronchodilator
-4’ amine derivative of atropine
-poorly absorbed into circulation after inhaled
-minimal oral bioavailability
-relatively free of systemic atropine-like effects
Mast cell stabilizers
-inhibit mast cell degranulation
-no direct action, use daily
-poorly absorbed
-little toxicity
-not a potent or effective as glucocorticoids
-currently used for allergic rhinoconjuctivitis eye drops
Mast cell stabilizer drugs
-Cromolyn
-Nedocromil
Omalizumab
-inhibits IgE binding to mast cells
-reserved for patients w severe asthma and allergic sensitization
IL-5
-attracts and activates eosinophils
Anti-IL-5 mABs
-mepolizumab
-Reslizumab
Anti-IL-5 receptos mABs
-Benralizumab
Anti IL-5 therapy
-used as maintenance therapy of severe asthma in pats w eosinophillic phenotype
