Pathogenesis of asthma involves activation of ______, ________ production & release, and ________ of bronchial mucosa.
eosinophils, IgE, remodeling
Remodeling involves what?
thickening of lamina reticularis, hyperlasia of smooth muscle cells and goblet cells
Drug treatment options for asthma
bronchodilators and anti-inflammatory agents
What is the most common bronchodilator class?
The beta2 agonists consist of what drugs?
Albuterol, terbutaline, formoterol, metaproterenol, salmeterol
What is the route of administration that is preferred?
What are the non-selective beta2 agaonists?
Epinephrine and Isoproterenol
What is the problem with non-selective beta2 agonists?
they have bad CV side effects so they are rarely used
What are some of the effects beta2 agonists have on the airways?
relax airway smooth muscle
inhibit release of leukotrienes and histamine
Increase ciliary activity
Aerosol deposition depends on what 3 things?
pattern of breathing
geometry of airways
_____% of total dose is deposited in the mouth and pharnyx
What is the duration of most inhaled beta2 agonists?
Which two beta2 agonists have a duration >12 hours?
salmeterol and formoterol
What drug is currently in development with a duration of >24 hours?
SQ injections of _______ are available for emergency situations.
ADEs of beta2 agonists
tachycardia, palpitations, tremors, HYPOkalemia, possible tolerance, increased insulin, lactate, glucose, pyruvate, and free fatty acids
What are the 3 methylxanthines?
What are the general MOAs of methylxanthines?
Inhibit PDE enzymes, inhibit adenosine receptors, promote apoptosis of eosinophils and neutrophils, regulate inflammatory gene transcription
Which of the methylxanthines have toxicity issues?
Why do blood levels of Theophylline need to be monitored?
narrow therapeutic window, plasma clearance varies widely
ADEs of Theophylline
anorexia, nausea, vomitting, HA, Gi upset, anxiety, seizures
Clinical usage of Theophylline
severe asthma and COPD
Is Theophylline used alone or in combo?
alone or in combo with corticosteroids
What are the anti-muscarinic agents?
ipratropium bromide, tiotropium bromide, prototype atropin
What is the bronchodilator of choice for COPD?
Whats the problem with prototype atropin?
lots of side effects
Is Tiotropium bromide short or long acting?
What receptors does Tiotropium bromide bind?
M1, M2, and M3 receptors
Which receptor does Tiotropium bromide dissociate away from rapidly?
ADE of inhaled Ipratropium bromide
AE of nebulized ipratropium bromide
Prednisone, Triamcinolone, Ciclesonide
Which corticosteroid is taken orally?
Which corticosteroid is an aerosol preparation?
Triamcinolone and Ciclesonide
What is Ciclesonide activated by?
anti-inflammatory: inhibit PLA2
DO NOT act as direct bronchodilator, but potentiate beta agonist effects
Regular corticosteroid therapy is maintained with which dosage form?
Oral and parenteral corticosteroids are used for emergency in which patients?
when bronchodilator shows little improvement or worsening symptoms despite therapy
Two common ADEs of corticosteroids
hoarsness and oropharyngeal candidiasis
What can be done to help with the ADE of oral candidiasis?
gargle water after inhaled treatment
ADE of corticosteroid in kids
ADE of corticosteroids in adults
increased risk of osteoporosis and cataracts
2 aerosols that are insoluble salts that are only used for PROPHYLAXIS
Cromolyn and Nedocromil
MOA of Cromolyn and Nedocromil
Alters function of delayed chlorine channels so inhibits cell activation
Which one inhibits cough?
Special population for cromolyn and nedocromil
Cromolyn and nedocromil also reduce symptoms of what?
two words that describe the ADEs of cromolyn and nedocromil
Mild and Rare
LTB4 is a what?
potent neutrophil chemoattractant
LTC4 and LTD4 contribute to asthma how?
bronchoconstriction, increased bronchial reactivity, mucosal edema, and mucus hypersecretion
two classes of leukotriene pathway inhibitors
5'-lipoxygenase enzyme inhibitors
LTD4 receptor antagonists
What is the one 5' lipoxygenase enzyme inhibitor?
What are the LTD4 receptor antagonists?
montelukast, zafirlukast, pranlukast
Which of the LTD4 receptro antagonists is not available in the US?
Leukotriene pathway inhibitors are _______ effective than corticosteroids in asthma symptoms.
Route of administration of leukotriene pathway inhibitors
Montelukast is approved for as young as what age?
6 years old
Leukotriene pathway inhibitors play an important role in what type of asthma?
occasional liver toxicity
Which leukotriene pathway inhibitor is most commonly prescribed?
Montelukast and zafirlukast have _______ toxicity.
Omalizumab is a ________.
Anti-IgE Monoclonal antibody
What is the benefit of Omalizumab?
reduces exacerbations requiring hospitalization by 88%, enables a reduction in corticosteroid treatment