Drugs used in Asthma Flashcards
What is extrsinic asthma?
- allergic or classical asthma
- onset is early in life
- elevated serum IgE levels and eosinophil count
- driven by Th2 subset and CD4+ T cells
what is intrinsic asthma?
- nonimmune triggering mechanism
- no personal or family history of allergy
- serum IgE levels are normal
what are the main events for acute bronchoconstriction?
- IAR (30-60min)
- after sensitization
- mast cell degranulation from re-exposure to allergen
- smooth muscle contraction
what are the main events for sustained bronchoconstriction?
- LAR (4-8 hrs)
- caused by activation of TH2 cells and cytokine production
- attract/ activate eosinophils
- stimulate mucus hyper-secretion
what is the role of IgE in the pathology of extrinsic asthma?
- elevated IgE serum levels and eosinophil count
- acute bronchoconstriction mediated by IgE
- IgE production stimulated in sustained BC
what is the role of mast cells in the pathology of extrinsic asthma?
- in acute they are degranulated and produced LLTC/LTD, PGD2, H, tryptase
- after sensitization IgE binds to FceR-l on mast cells
what immune cells are responsible in asthma?
mast cells, eosinophils, Th2, B cells,NKT cells
what is the role of vagal (PSNS) receptors in bronchoconstriction?
direct stimulation provoke reflex bronchoconstriction
what drugs are SABAs?
- metaproterenol
- terbutaline
- albuterol
- pirbuterol
What drugs are LABAs?
- salmeterol
- formoterol
What drugs are ICS?
- triamcinolone acetonide
- beclomethasone dipropionate
- flunisolide
- budesonide
- mometasone furoate
- ciclesonide
- fluticasone propionate
what drugs are leukotriene pathway inhibitors?
- zileuton
- montelukast
- zafirlukast
what drugs are methylxanthine?
- theophylline
- theobromine
- caffeine
what drugs are antimuscarinic agents?
ipratropium
what drugs are mast cell stabilizers?
- cromolyn
- nedocromil
what drugs are MABs?
- omalizumab
- mepolizumab
- reslizumab
- benralizumab
what meds are mostly used in asthma?
sympathomimetics and ICSs
what is metaproterenol?
- resorcinol analogue of isoproterenol
- somewhat selective for B2 receptor
- least potent B2 agonist
- 5 min onset and 4 hr duration
- good bioavailability
what is terbutaline?
- greater B2 selectivity
- good bioavailability
- 3-fold greater potency than metaproterenol at B2 receptors
- N-t-butyl analogue of metaproterenol
what is albuterol?
- most widely used
- 5 min onset and 4-8 hr duration
- R isomer to levoalbuterol
– more potent and expensive - salicyl alcohol in the phenyl ring -> resistant to COMT
what is pirbuterol?
- analogous to albuterol except pyridine ring
- comparable duration of action as albuterol
- less potent
what is salmeterol?
- available as powder
- greater lipid solubility; dissolve in cellular membranes
- 20 min onset and 12 hr duration
what is formoterol?
- available as powder
- resistant to COMT and MAO
- more rapid onset with comparable duration of action
what is ciclesonide?
21 ester prodrug associated with less candidiasis
1. ICS
what is zileuton?
- 5-lipoxygenase inhibitor
- racemic
- N-hydroxy essential for activity
- good bioavailability
- alternative to LABA in addition to ICS
- not for acute asthma attacks
- requires periodic monitoring of liver function
what is montelukast?
- blocks binding of LTC4, LTD4, and LTE4 to receptor
- QD dosing
- good bioavailability
- little toxicity
- reduce frequency of asthma exacerbations
what is theophylline, theobromine, caffeine?
- theophylline (most effective and specific for smooth muscle)
- used to be treatment for asthma but replaced by LABAs
- low cost and still used in some countries
what is ipratropium?
- bronchodilator
- quaternary amine of atropine
- poorly absorbed after inhaled
- minimal bioavailability
- relatively free of systemic atropine-like effects
what are cromolyn and nedocromil?
- inhibit mast cell degranulation
- once widely used especially in children
- current indication is allergic conjuntivitis in eye grops
what is omalizumab?
- inhibit IgE binding to mast cells
- severe asthma/ allergic sensitization
- anti- IgE
– recognize portion of IgE that binds on immune cells (FcER-l and 2)
what is mepolizumab and reslizumab?
- anti-IL-5 MAB
- maintenance therapy for severe asthma in pts with eosinophilic phenotype
what is benralizumab?
- anti-IL-5 receptor MAB
- maintenance therapy for severe asthma in pts with eosinophilic phenotype