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PCol I - Final Exam

Asthma drugs

early phase of asthma bronchospasm
late phase of asthma inflammation
B2 agonists (albuterol, salmeterol) MOA relaxation of bronchiole smooth muscle
mast calls & T-lymphocytes release which mediators histamine, tryptase, PGD2, LTC4, PAF, IL-4, IL-5, GM-CSF, TNF, TGF
eosinophils and neutrophils release which mediators ECP, MBP, Protease, PAF
corticosteriods (beclomethasone, budesonide) MOA broad anti-inflammatory actions
methylxanthines (theophylline) MOA relaxation of bronchiole smooth muscle, effects on T-cells & eosinophils, increased mucociliary clearance (all via increase in cAMP)
cromolyn, nedocromil MOA inhibit release of inflammatory mediators
leukotriene modifiers (zafirlukast, montelukast) MOA antagonize the actions of LTs in the airways
muscarinic antagonists (ipratropium) MOA muscarinic blockade in airways (blocks parasympathetic bronchoconstriction)
monoclonal antibodies (omalizumab) MOA block IgE binding to mast cells
non-selective beta-agonists (3) used for asthma epinephrine, ephedrine, isoproterenol
epinephrine - forms, onset & DA, adv rxns injectable, aerosolinhalation: onset in 15 minduration: 60-90 minadv rxn: tachycardia, arrythmias, MI, skeletal muscle tremor
ephedrine for asthma (compared to epi) oral adm; longer acting; more CNS effects; less potent
isoproterenol for asthma (compared to epi) more potent; short onset of 5 min; 60-90 min duration
B2-selectives - onset, peak and DA if inhaled onset at 1-5 min; peak at 30 min; lasts for 2-6 hrs
B2-selectives - oral DA ~ 4-8 hrs
B2-selective drugs albuterol (O/I), terbutaline (O/I), metaproterenol (O/I), bitolterol, pirbuterol, levalbuterol, salmeterol, formoterol
long-acting B2-selective drugs (12 hours or longer - useful for nocturnal symptoms) salmeterol, formoterol --> both are dry powder inhalers
% of dose from MDI that actually makes it into the lung 2 - 10% (90% deposited in the mouth)
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
drug interaction with selective B2 agonists interaction b/w non-selective beta-blockers and selective B2 agonist (counteract one aother)
Methylxanthine drugs (4) theophylline, aminophylline, enprofylline (3-propylxanthine), and Roflumilast (newest agent in clinical trials)
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)
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)
metabolism of methylxanthines (theophylline, aminophylline) CYP 450: 1A2 --> drug interactions
what's special about roflumilast newest methylxanthine in clinical trials - high specificity for PDE4 in the lungs, less AE
what's special about enprofylline potent bronchodilator that shows PDE4 inhibition, but no adenosine receptor antagonism
muscarinic antagonists for asthma (2) Ipratropium & Tiotropium: Ipratropium bromide (quaternary ammonium compound)Tiotropium (Spiriva) – new agent with 24-hr duration of action
muscarinic antagonists (Ipratropium & Tiotropium) - MOA blocking muscarinic receptors prevents parasympathetic bronchoconstriction - M3 receptor
which disease state should muscarinic antagonists be used carefully in glaucoma
muscarinic antagonists (Ipratropium & Tiotropium) - time to peak, DA Max effect in 30 min; duration of 3-5 hrs
Combivent (MDI) - 2 products albuterol (b2 selective agonist) + ipratropium (muscarinic antagonist)
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
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
Created by: Krafty