Asthma drugs
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| early phase of asthma | bronchospasm
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| late phase of asthma | inflammation
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| B2 agonists (albuterol, salmeterol) MOA | relaxation of bronchiole smooth muscle
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| mast calls & T-lymphocytes release which mediators | histamine, tryptase, PGD2, LTC4, PAF, IL-4, IL-5, GM-CSF, TNF, TGF
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| eosinophils and neutrophils release which mediators | ECP, MBP, Protease, PAF
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| corticosteriods (beclomethasone, budesonide) MOA | broad anti-inflammatory actions
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| methylxanthines (theophylline) MOA | relaxation of bronchiole smooth muscle, effects on T-cells & eosinophils, increased mucociliary clearance (all via increase in cAMP)
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| cromolyn, nedocromil MOA | inhibit release of inflammatory mediators
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| leukotriene modifiers (zafirlukast, montelukast) MOA | antagonize the actions of LTs in the airways
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| muscarinic antagonists (ipratropium) MOA | muscarinic blockade in airways (blocks parasympathetic bronchoconstriction)
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| monoclonal antibodies (omalizumab) MOA | block IgE binding to mast cells
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| non-selective beta-agonists (3) used for asthma | epinephrine, ephedrine, isoproterenol
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| epinephrine - forms, onset & DA, adv rxns | injectable, aerosolinhalation: onset in 15 minduration: 60-90 minadv rxn: tachycardia, arrythmias, MI, skeletal muscle tremor
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| ephedrine for asthma (compared to epi) | oral adm; longer acting; more CNS effects; less potent
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| isoproterenol for asthma (compared to epi) | more potent; short onset of 5 min; 60-90 min duration
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| B2-selectives - onset, peak and DA if inhaled | onset at 1-5 min; peak at 30 min; lasts for 2-6 hrs
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| B2-selectives - oral DA | ~ 4-8 hrs
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| B2-selective drugs | albuterol (O/I), terbutaline (O/I), metaproterenol (O/I), bitolterol, pirbuterol, levalbuterol, salmeterol, formoterol
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| long-acting B2-selective drugs (12 hours or longer - useful for nocturnal symptoms) | salmeterol, formoterol --> both are dry powder inhalers
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| % of dose from MDI that actually makes it into the lung | 2 - 10% (90% deposited in the mouth)
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| tolerance to B2-selective agents tends to develop in response to which effect | tolerance to anti-inflammatory effects (mast cells and lymphocyets) more than tolerance to brochodilation
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| drug interaction with selective B2 agonists | interaction b/w non-selective beta-blockers and selective B2 agonist (counteract one aother)
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| Methylxanthine drugs (4) | theophylline, aminophylline, enprofylline (3-propylxanthine), and Roflumilast (newest agent in clinical trials)
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| two proposed methylxanthine MOA's (theophylline, aminophylline) | Increased cAMP results in:1) inhibtion of PDE4 (requires high conc.), 2) blockade of adenosine receptors, A1 in bronchiole sm (seen at therapeutic concentrations)
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| therapeutic index/range for methylxanthine drugs (theophylline, aminophylline) | 10-20 micrograms/ml (SEs appear around 20-25 micrograms/ml; higher than 40 can lead to seizures or arrhythmias)
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| metabolism of methylxanthines (theophylline, aminophylline) | CYP 450: 1A2 --> drug interactions
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| what's special about roflumilast | newest methylxanthine in clinical trials - high specificity for PDE4 in the lungs, less AE
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| what's special about enprofylline | potent bronchodilator that shows PDE4 inhibition, but no adenosine receptor antagonism
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| muscarinic antagonists for asthma (2) | Ipratropium & Tiotropium: Ipratropium bromide (quaternary ammonium compound)Tiotropium (Spiriva) – new agent with 24-hr duration of action
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| muscarinic antagonists (Ipratropium & Tiotropium) - MOA | blocking muscarinic receptors prevents parasympathetic bronchoconstriction - M3 receptor
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| which disease state should muscarinic antagonists be used carefully in | glaucoma
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| muscarinic antagonists (Ipratropium & Tiotropium) - time to peak, DA | Max effect in 30 min; duration of 3-5 hrs
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| Combivent (MDI) - 2 products | albuterol (b2 selective agonist) + ipratropium (muscarinic antagonist)
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| MOA for Cromolyn (Intal) & Nedocromil (Tilade) | inhibition of mast cell degranulation; inhibit mediator release from bronchial mast cells inhibition of parasympathetic & cough reflexes; not bronchodilators; no direct effects on smooth muscle
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| uses for for Cromolyn (Intal) & Nedocromil (Tilade) (mast cell degranulation inhibitors) | only prophylactic use – decrease immediate & late-phase asthmatic response to antigen-, exercise-, and irritant-induced asthma; effective when given before exercise or exposure to irritants
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