Asthma Drugs Lecture PDF Flashcards
Asthma is a chronic ____ disorder, it is also completeely ____
Inflammatory, reversible
2 categories of quick relief medication used to treat asthma and how they work
- anticholinergics that inhibit muscarinic cholinergic receptors and reduce intrinsic vagal tone of the airway resulting in bronchodilation
- short acting bronchodilators to relax bronchial smooth muscle
Examples of quick relief anticholinergics used to treat asthma (2)
Ipratropium bromide, atrovent
Examples of SABAs used to treat asthma (3)
albuterol (proventil and ventolin), levalbuterol (xopenenx), and pirbuterol (maxair autohaler)
Long term control medications to treat asthma and how they work (5)
- Glucocorticoids with powerful anti-inflammatory action care for persistent asthma, exceptionally safe profile
- Immunomodulators that use anti-IgE monoclonal antibodies as adjunctive therapy for those with sensitivity to relevant allergens and persistent asthma
- Leukotriene receptor antagonists which block aspirin induced asthma and decrease symptoms assoc. with allergen exposure as an alternative but not preferred therapy
- LABAs inhaled bronchodilators with duration of at least 12 hours after single dose, not used as monotherapy but used alongside corticosteroids
- Theophylline used as alternative or adjunctive therapy for inhaled corticosteroids in patient with mild persistent asthma
Examples of gluocorticoids used to treat asthma (3)
Beclomethasone (QVAR), budesonide (pulmacort), prednisone
Examples of immunomodulators used to treat asthma (1)
-Anti IgE omalizumab (Xolair)
Leukotriene receptor antagonists and LABA’s are often used _____ with other long term treatment options
adjunctively
Examples of Leukotriene receptor antagonists to treat asthma (3)
-zarfirlukast, accolate and montelukast, singulair
Examples of long acting bronchodilating agents (LABA’s) used to treat asthma (2)
Salmeterol (Serevent) and formoterol (foradil)
Advantages of inhalation administration of antiasthmatic drugs (2)
- Therapeutic effects are enhanced by delivering drug to direct site of action minimizing systemic effects
- produces rapid relief of acute attacks
Inhaled corticosteroids have ______ side effects compared to oral corticosteroids
Many less
Metered dose inhalers (MDI)
Small hand held pressurized devices that deliver measured dose (typically 1 or 2 puffs) of drug with each activation requiring propellant HFA (hydrofluoralkane)
Problems with meter dose inhalers (2)
- Requires hand lung coordination
- only 10% of dose reaches lungs rest is swallowed even when used correctly
Spacer function and how does it impact drug delivery?
Attaches to a meter dose inhalers to increase delivery of drug to lungs from 10% to 21%
Nebulizer
Small machine that converts a drug to a mist alongside saline with droplets much finer than those from inhalers, occurs thru face mask or mouthpiece held between teeth and although portable, takes longer to deliver the same amount of drug than an MDI
Dry powder inhalers (DPI’s)
Deliver a drug to lungs in dry micronized powder that does not require propellant and is completely breath activated without hand lung coordination necessary (delivers more drugs to lungs, approx 20%)
B2 adrenergic agonist mech of action
Selectively activates b2 adrenergic receptors promoting bronchodilation reducing airway resistance in the same way as epi
Classification of B2 adrenergic agonists by their function (2)
- Short acting with effects beginning almost immediately and peaking 30-60 minutes and wearing off 3-5 hrs
- long acting (all PO agents and some inhaled agents) to use for long term prophylaxis but not abort ongoing attack
Usage of a SABA for symptomatic relief more than ____ suggests _____
2 days a week, need to increase dose or start an inhaled corticosteroids (long term control)
Inhaled SABA ADR (1)
- usually well tolerated
- minimal systemic effects
Inhaled LABA ADR (1)
-increase risk of severe asthma and asthma related death when used incorrectly
SMART Trial
Study that found that LABA should only be used in patients taking first line agent for long term control as supplementary and never used alone which can cause serious adverse effects
Oral LABA ADR’s (2)
- Cardiac B1 stimulation resulting in angina pectoris (rare, typically on excess dosage)
- tremor by stimulating B2 receptors on skeletal muscle
- These are reduced by lowering dosage and disappears with continued usage (tolerance)
2 oral agents used for long term control of asthma
-Albuterol or terbutaline
Methylxanthines function
CNS stimulants that cause bronchodilation, CNS excitation, and cardiac stimulation
Examples of methylxanthines (3)
- theophylline
- caffeine
- theobromine
Theophylline drug class, function, mech of action
- Methylxanthine
- a 2nd or 3rd choice antiasthmatic medication (no longer recommended for COPD) that produces bronchodilation by relaxing smooth muscle of bronchi
- unknown mechanism (theorized to inhibit phosphodiesterase increasing intracellular cAMP)
Theophylline is ____ than B2 agonists and glucocorticoids, but is ____
no more effective, more dangerous
Theophylline and plasma drug levels
Requires periodic assessment for safe and effective therapy, many patients respond to levels as low as 5 ug/mL and above 20ug/mL can cause serious ADR’s (N/V/D, dysrhythmia)
Theophylline drug interactions (2)
- Caffeine intensifies effects
- fluoquinolones increase levels
Aminophylline function
Theophylline salt that is considerably more soluble than theophylline used for IV administration slowly in emergent situations
Glucocorticoids mech of action
Reduce symptoms of asthma by suppressing inflammation, decrease airway mucus production and increase # of bronchial B2 receptors and their responsiveness to agonists
Glucocorticoids function in asthma
Used in prophylaxis of patients with chronic asthma administered on regular schedule and cannot abort ongoing attacks because actions develop slowly
PO vs Inhalation therapy of glucocorticoids
Systemic are reserved for severe asthma due to potential for ADRs while inhalation has low risk of serious side effects and should be used in conjunction with bronchodilators (B2 agonists to keep the dosage low
Oral corticosteroids ADR’s (4)
- osteoporosis
- hyperglycemia
- suppression of growth
- adrenal suppression
Inhaled corticosteroids ADR’s (2)
- Oropharyngeal candidiasis
- dysphonia
To prevent ADR’s of inhaled corticosteroids, these 2 things are recommended
- gargling after each administration
- usage of a spacer advice
Because short term therapy of high dose systemic steroids do not produce serious toxicities, asthma can be treated by….
….administering glucocorticoids for a short course and then maintainence of patient on inhaled corticosteroids after that.
Anticholinergics function in asthma/COPD
-Atropine derivatives approved for bronchospasm associated with emphysema and chornic bronchitis but useful in some patients with asthma used as alternative to SABA in patients who cannot tolerate them
Ipratropium (atrovent)/anticholinergics mech of action
Slower onset of action than SABA, considered a short acting antimuscarinic antagonist (SAMA) that blocks muscarinic receptors in bronchi resulting in bronchodilation making it effective against exercise or allergen induced asthma, has an additive effect with B2 agonists due to diff mech of actions
Tiotropium (spiriva) drug class and function
- Long acting antimsucarinic antagonist (LAMA)
- Anticholinergic with 24 hr duration of action previously approved for COPD now approved for asthma
Anticholinergic Inhalers and CV disease
-Studies are unsure but some evidence indicates that those with high risk for CV events can be put at increased risk in those that use anticholinergic inhalers
Zarfirlukast (accolate) drug class and mech of action
- 1st leukotriene receptor antagonist
- blocks leukotriene receptors attenuating pathogenic effects such as bronchoconstriction and inflammatory cell infiltration to treat chronic asthma in adults and children over 5
Zarfirlukast (accolate) ADR (2)
- Mild GI upset
- many drug and food interactions decreasing bioavailability
Montelukast (singulair) drug class, function, and ADR (1)
- Leukotriene receptor antagonist similar to accolate
- can be used to prevent exercise induced bronchospasm and relieve allergic rhinitis
- almost none, very few interactions
Cromolyn drug class and function
- Mast cell stabilizer preventing release of histamine
- Inhalational agent that suppresses bronchial inflammation for prophylaxis of mild to moderate asthma alternative to gluoccorticoids
Cromolyn therapeutic uses (3) and ADR (1)
- chronic asthma prophylaxis alternative to inhaled corticosteroids
- exercise induced bronchospasm 10-15 min before undergoing
- allergic rhinitis (intranasally)
-Safest of ALL antiasthma medications with no significant ADR’s
Omalizumab (xolair) drug class and function
- Monoclonal anti IgE antibody
- given subcutaneously that binds IgE reducing release of histamine
Omalizumab (xolair) ADR’s (2)
- anaphylactic rxn to drug
- increased incidence of malignant melanomas
Mepolizumab (Nucala) drug class and function
- Interleukin 5 antagonist monoclonal antibody
- Approved for maintenance treatment of severe asthma in patients >12 who have an eosinophilic phenotype
Eosiniophilic phenotype
A phenotype often seen in severe asthma patients (asthma that can only be controlled with high dose inhaled glucocorticoids and 2nd controller medication and/or systemic glucocorticoids or that remains uncontrolled) that have elevated blood and lung eosinophil levels.
Because IL-5 is a major cytokine responsible for eosinophil development, IL-5 antagonists prevent eosinophilic airway inflammation
Primatene mist function
OTC inhaled epinephrine approved by FDA (removed before because it contained ozone depleting CFC’s, now new formula has HFA propellants) that can bring immediate relief for asthma, but can also increase BP and HR, misuse can cause excessive inhalation or IV injection which may cause life threatening ADR’s, big concern about OTC usage*****
Drugs for asthma are administered with three objectives
1) relieve acute attacks
2) prophylaxis against future acute attacks
3) suppress chronic inflammation and reduction of bronchial hyperactivity
B2 stimulation 2 therapeutic uses
- Treatment of asthma (found in bronchial smooth muscle)
- delay of preterm labor (found in uterine smooth muscle tissue i think?)
LABA dosing schedule is…
…fixed, NOT PRN
Inhaled corticosteroids for asthma treatment should be administered alongside…
….B2 agonists
Examples of inhaled corticosteroid/LABA combinations (3)
- Budesonide/formoterol (symbicort)
- fluticasone furoate/vilanterol (breo ellipta)
- fluticasone proprionate/salmeterol - (advair diskus)
