Objectives
1. List the goals of chronic asthma management and respective efficacy monitoring
parameters.
2. For each class of medication utilized in the treatment of asthma, distinguish the:
1. place in therapy/indication
2. safety monitoring parameters/adverse drug reactions/BBW
3. drug interactions
4. route of administration
3. Given the patient case, evaluate patient-related and agent-related variables to construct a
treatment plant for asthma.
QUESTIONS
MEDICATION CLASSES
Goals of Chronic Asthma Management
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Achieve good control of symptoms
Maintain normal activity levels
Minimize the risk of asthma-related deaths, exacerbations, persistent airflow limitation,
and side-effects
Monitoring for Efficacy
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Decrease of symptoms
Decrease of short-acting B2 agonist
Decrease of avoidance of exacerbations
Increase or maintenance of activity level
Increase or maintenance of lung function
Increase patient satisfaction
MEDICATIONS
Short-Acting B2-Agonists (SABA)
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Role in Therapy
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Alternative reliever for breakthrough symptoms in chronic asthma
Reliever in acute asthma flares
Alternative therapy for exercise-induced bronchospasm (EIB)
Method of Action
o Increases cAMP production to relax bronchial smooth muscle, increases HR
Adverse Reactions
o Tachycardia
o Tremor
o Hypokalemia
Drug-Drug Interactions
o Non-selective beta blockers may blunt response to SABA or LABA
o Avoid if possible: Propanolol, Carvedilol, Labetalol, Timolol (oral and
ophthalmic)
Examples
o Albuterol (ProAir)
o ProAir HFA
o ProAir RespiClick
o Proventil HFA
o Ventolin HFA
o Xopenex HFA (Levobuterol)
Long-Acting B2-Agonists (LABA)
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Role in Therapy
o Part of preferred reliever combo for breakthrough symptoms in chronic asthma
o Part of ICS-based controller combo in chronic asthma
o Part of reliever in acute asthma flares (bud/formoterol only)
o Part of preferred therapy for EIB (bud/formoterol only)
o Should not be used as monotherapy
Method of Action
o Increases cAMP production to relax bronchial smooth muscle, increases HR
o More selective for B2 receptors (in the lungs)
Adverse Reactions
o Tachycardia
o Tremor
o Hypokalemia
Drug-Drug Interactions
o Non-selective beta blockers may blunt response to SABA or LABA
o Avoid if possible: Propanolol, Carvedilol, Labetalol, Timolol (oral and
ophthalmic)
Black Box Warning
o Increased risk of asthma-related death when given as a monotherapy
Examples
o Formoterol
o Oladaterol
o Salmerterol
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Vilanterol
Arformoterol
Inhaled Corticosteroids
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Role in Therapy
o Foundation of scheduled controller therapy in chronic asthma (with or without
LABA)
o May be used for as needed control whenever SABA is used for breakthrough
symptoms
o May be used for as needed control in combo with formoterol
Onset of Effect
o Days to weeks (1-2 weeks for max effect)
Method of Action
o Decrease inflammatory protein synthesis (Decreases eosinophils, mast cells,
macrophages)
o Decreases mucus secretion and cytokines mediators
Adverse Reactions
o Oral candidiasis (thrush) — Must wash mouth after use to prevent it
o Dysphonia
o Cough
Other pertinent information
o ICS use lows risk of death from asthma
o ICS use lowers risk of hospitalization from asthma
o How to Step Down ICS Therapy
▪ If on a high or medium dose ICS (or ICS/LABA): Decrease ICS by 2550%
▪ If on low dose ICS (or ICS/LABA): Either switch to once daily dosing or
switch to as-needed dosing
▪ Avoid discontinuation of LABA, if the patient is on LABA
Oral Corticosteroids
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Role in Therapy
o Foundation of scheduled controller therapy in chronic asthma (with or without
LABA)
o May be used for as needed control whenever SABA is used for breakthrough
symptoms
o May be used for as needed control in combo with formoterol
Onset of Effect
o Hours
Method of Action
o Decrease inflammatory protein synthesis (Decreases eosinophils, mast cells,
macrophages)
o Decreases mucus secretion and cytokines mediators
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Adverse Reactions
o Short term use (less than 2 weeks)
▪ Hyperglycemia, hypertension, fluid retention (edema), increased weight
gain and appetite, insomnia, mood changes, GI upset/PUD
▪ Usually given during breakfast (dosed in the morning) to avoid insomnia
and to avoid GI upset
o Long term use (more than 3 months)
▪ Adrenal suppression, Cushing's syndrome, decreased bone growth and
density, cataracts
Other pertinent information
o DOSING:
▪ Poorly controlled chronic asthma: Low dose prednisone <7.5 mg/day (or
equivalent)
▪ Acute exacerbation
▪ Adults & children older than 12 old: Prednisone 40-50 mg/day
qAM (or equivalent) for 5-7 days
▪ Children 6-11 years old: Prednisone 1-2 mg/kg/day qAM (or
equivalent) for 3-5 days
ICS/LABA Combinations
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ICS vs LABA Comparison
o When ICS is used alone
▪ Reduces inflammation (impacts the root of the problem)
▪ Takes 1-2 weeks to improve symptoms
▪ Reduces hospitalization & death from asthma
o When LABA is used alone
▪ Reduces bronchoconstriction (does not impact root of the problem)
▪ Reduces symptoms within minutes
▪ Increases risk of asthma-related death when used alone
Role in Therapy
o Preferred reliever for breakthrough symptoms in chronic asthma
(budesonide/formoterol only)
o Controller in chronic asthma (any ICS/LABA)
o Reliever in acute asthma (bud/formoterol only)
Short-Acting Muscarinic Antagonists (SAMA)
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Role in Therapy
o Only used in acute severe flare in ED and during hospitalization
Method of Action
o Blocks brochoconstrictor effect of ACh at M3 receptors on bronchial smooth
muscle
Adverse Reactions
o Cough
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Dry mouth
Urinary retention
Drug-Drug interactions
o Cumulative effect with other anticholinergics
▪ Atropine
▪ Scopolamine
Long-Acting Muscarinic Antagonists (LAMA)
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Role in Therapy
o Add-on therapy in patients uncontrolled on medium-to-high dose ICS/LABA
(Steps 4&5)
o Either add Spiriva (tiotropium) 1.25 mcg as a separate inhaler or switch to
Trelegy (fluticasone/umec/vilant) "triple therapy"
Method of Action
o Blocks brochoconstrictor effect of ACh at M3 receptors on bronchial smooth
muscle
Adverse Reactions
o Cough
o Dry mouth
o Urinary retention
Drug-Drug interactions
o Cumulative effect with other anticholinergics
▪ Atropine
▪ Scopolamine
Leukotriene Receptor Antagonists
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Role in Therapy
o Alternative controller in Step 2
o Non-preferred add-on to controller in Step3/4
Method of Action
o Prevents bronchoconstriction and mucosal edema by blocking leukotriene D4
Adverse Reactions/Black Box Warning
o Neuropsychiatric events
▪ Aggression, agitation, depression, sleep disturbances, suicidal ideation
o Monitor for behavioral changes
Azithromycin
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Role in Therapy
o Consider as add-on therapy in patients uncontrolled on high dose ICS/LABA in
specialist setting
Method of Action
o Immunomodulatory: Reduces pro-inflammatory cytokines
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Antimicrobial
Antiviral
Adverse Reactions
o QT Prolongation
o Diarrhea
o C Diff. infection
o Liver injury (hepatitis)
o Hearing loss (prolong use)
o Hypersensitivity
Drug-Drug Interactions
o Antipsychotics (IV haloperidol)
o Fluoroquinolones (Levofloxacin, Moxifloxacin)
o Antiemetics (IV Ondansetron)
Methylzanthines (Theophylline)
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Role in Therapy
o Limited use due to low efficacy and higher risk of side effects
o Previously used as alternative add-on therapy in Steps 2-4
Method of Action
o Inhibits phosphodiesterase which increases cAMP to cause bronchodilation and
gastric acid secretion
Adverse Reactions
o Insomnia
o N/V/GI upset
o Headache
o Tremor
o Arrhythmias
o Seizure
o Serum Concentration
▪ Therapeutic Drug Monitoring
▪ Required
▪ Target= 10-15 mcg/mL
▪ Toxicity common > 20 mcg/mL
▪ Measure in middle of dosing interval
▪ Wait 48 hours after any factor that may impact level
Drug-Drug Interactions
o Theophylline is a major substrate of CYP1A2
o Strong CYP1A2 inhibitors will increase theophylline concentrations by
decreasing theophylline clearance
▪ Cimetidine
▪ Ciprofloxacin
▪ Macrolides
▪ clindamycin; clarithromycin
▪ Propranolol
▪ Older age
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Strong CYP1A2 inducers will decrease theophylline concentrations by increasing
theophylline clearance
▪ Smoking
▪ Carbamazepine
▪ Phenobarbital
▪ Phenytoin
▪ Rifampin