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astma chronic
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Chronic Asthma
1
Goals of Therapy
• Reduce impairment
– prevent chronic, troublesome symptoms
– require infrequent use (≤ 2 days a week) of
inhaled SABA for quick relief of symptoms
– maintain (near-) normal pulmonary function
– maintain normal activity levels
– meet patients’ & families’ expectations of and
satisfaction with care
2
Goals of Therapy
• Reduce risk
– prevent recurrent exacerbations
– minimize need for visits/hospitalizations
– prevent loss of lung function
– prevent reduced lung growth in children
– minimal adverse effects of therapy
3
Nonpharmacologic Treatment
• Environmental control
• Manage comorbid conditions
• Self-management skills
– written action plans
– recognize early signs of deterioration
• Education
– asthma, role of medications, inhalation technique,
environmental control, how to use action plan
– reinforce every visit
4
Pharmacologic Treatment
• National Asthma Education Prevention
Program (NAEPP) recommendations
categorized by age
– 0 to 4 years
– 5 to 11 years
– ≥12 years
• Stepwise approach
– initial therapy based on asthma severity
– therapy adjusted based on asthma control
National Institutes of Health, National Heart, Lung, and Blood Institute. National Asthma Education and Prevention Program. Full Report of
the Expert Panel: Guidelines for the diagnosis and management of asthma (EPR-3) 2007. http://www.nhlbi.nih.gov/guidelines/asthma 5
Treatment
• Quick relief: SABA for all patients
• Long-term control
– preferred
• ICS for persistent asthma
• increased ICS dose or addition of long-acting β2-agonist
(LABA) for further control
– alternatives
• no to minimal difference in efficacy between alternatives
• cromolyn, nedocromil, leukotriene modifiers, theophylline
– omalizumab: severe uncontrolled asthma & atopy
6
Classifying Asthma Severity for Patients Not Currently Taking Long-Term
Control Medications (Children 0-4 and 5-11 years)
Persistent
Components Intermittent
Mild Moderate Severe
Symptoms ≤2 days/week >2 days/week but Daily Throughout the
not daily day
Nighttime awakenings None 1-2 times/month 2-3 times/month > Once a week
(0-4 yr)
≤twice/month
Impairment
Nighttime awakenings 3-4 times/month > Once per week Often 7
(5-11 yr) but not nightly times/week
SABA use for ≤2 days/week >2 days/week but Daily Several times per
symptom control not daily day
Interference with None Minor limitation Some limitation Extremely limited
normal activity
Lung function (5-11 yr) FEV1 >80% FEV1 >80% FEV1 60-80% FEV1 <60%
FEV1/FVC >85% FEV1/FVC >80% FEV1/FVC 75-80% FEV1/FVC <75%
Exacerbations Intermittent Persistent
Risk
(0-4 yr) 0-1/year ≥2 in 6 months or ≥4 wheezing episodes/1 yr lasting >1 day
(5-11 yr) 0-2/year >2 in 1 year
Recommended step for Step 1 Step 2 Step 3 and consider short course of
initiating treatment systemic oral corticosteroids
DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM: Pharmacotherapy: A Pathophysiologic Approach, 7th Edition: 7
http://www.accesspharmacy.com/
Classifying Asthma Severity for Patients Not Currently Taking Long-Term
Control Medications (≥12 years old)
Persistent
Components Intermittent
Mild Moderate Severe
Symptoms ≤2 days/week >2 days/week Daily Throughout the
but not daily day
Nighttime awakenings ≤twice/month 3-4 times/month > Once per week Often 7
but not nightly times/week
SABA use for symptom ≤2 days/week >2 days/week Daily Several times per
Impairment
control but not > once day
per day
Interference with normal None Minor limitation Some limitation Extremely limited
activity
Lung function (Normal FEV1 >80% FEV1 >80% FEV1 60-80% FEV1 <60%
FEV1/FVC: age 8-19 y FEV1/FVC FEV1/FVC FEV1/FVC reduced FEV1/FVC
85%; 20-39 y 80%; 40- normal normal 5% reduced > 5%
59 y 75%; 60-80 y 70%)
Intermittent Persistent
Risk
Exacerbations 0-2/year >2 in 1 year
Recommended step for Step 1 Step 2 Step 3 and Step 4 or 5
initiating treatment consider short
course of systemic
oral corticosteroids
DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM: Pharmacotherapy: A Pathophysiologic Approach, 7th Edition: 8
http://www.accesspharmacy.com/
Stepwise Approach for Asthma Management
9
Stepwise Approach for Asthma Management
10
Stepwise Approach for Asthma Management
11
Special Populations
• Young children, especially 0-4 years
– many recommendations based on extrapolated data
– studies of ICS show improvement
– combination therapy inadequately studied
• Elderly
– osteoporosis risk increased with high dose ICS
• Pregnancy
– budesonide preferred ICS
– albuterol preferred for quick relief
12
Inhaled Corticosteroids (ICS)
• Use: cornerstone of chronic asthma therapy
– improve lung function
– reduce severe exacerbations
– only therapy shown to reduce risk of asthma
death
• Low systemic activity
• Response delayed for several weeks
13
Inhaled Corticosteroids
• Products
– beclomethasone dipropionate
– budesonide
– flunisolide
– fluticasone propionate
– mometasone furoate
– triamcinolone acetonide
– ciclesonide
14
Inhaled Corticosteroids
• Adverse effects dose dependent
– systemic effects can occur at high doses
– oropharyngeal candidiasis
– dysphonia
• Growth retardation may occur
– dose-dependent
– transient
– susceptible populations
– studies suggest reaching predicted adult height not
affected
National Institutes of Health, National Heart, Lung, and Blood Institute. National Asthma Education and Prevention Program. Full Report of the Expert Panel:
Guidelines for the diagnosis and management of asthma (EPR-3) 2007 15
Kelly HW. Potential adverse effects of the inhaled corticosteroids. J Allergy Clin Immunol 2003;112:469–478.
LABAs
• Use: preferred adjunct/ICS combination
– adults & most children
– better control than increasing ICS dose alone
• Not for quick relief
• Provide long lasting bronchodilation (≥ 12
hours)
• Products
– formoterol
– salmeterol
16
LABAs
• Systemic side effects dose dependent
• Not to be used as monotherapy
– increased risk of severe, life threatening
exacerbation & asthma related death
– preliminary data suggest concomitant ICS may
prevent/decrease risk
Nelson HS, Weiss ST, Bleecker ER, Yancey SW, Dorinsky PM. The Salmeterol Multicenter Asthma Research Trial: A comparison of usual pharmacotherapy for
asthma or usual pharmacotherapy plus salmeterol. Chest 2006;129:15–26. 17
Kelly HW. Risk versus benefit considerations for the 2-agonists. Pharmacotherapy 2006;26:164S–174S.
Methylxanthines
• Mechanism: bronchodilation
– nonselective phosphodiesterase inhibitor
• isoenzyme III: airway smooth muscle
• isoenzyme IV: inflammatory cell regulation
– competitively inhibit adenosine
– stimulate catecholamine release
• Use declined due to risk for toxicity
– alternative/adjunct therapy
18
Theophylline
• Routine serum concentration monitoring
– significant bronchodilation by 5 mcg/mL
– most will not have toxic symptoms when <15
mcg/mL
• Much potential for interactions
– CYP-450 1A2, 3A3 metabolism
– age dependent clearance
19
Factors Affecting Theophylline Clearance
Decreased Clearance % Decrease Increased Clearance % Increase
Cimetidine -25 to -60 Rifampin +53
Macrolides -25 to -50 Carbamazepine +50
Allopurinol -20 Phenobarbital +34
Propranolol -30 Phenytoin +70
Quinolones -20 to -50 Charcoal-broiled meal +30
Interferon -50 High-protein diet +25
Thiabendazole -65 Smoking +40
Ticlopidine -25 Sulfinpyrazone +22
Zileuton -35 Moricizine +50
Systemic viral illness -10 to -50 Aminoglutethimide +50
Clinically significant interactions occur with ≥ 20% inhibition or ≥ 50% induction
DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM: Pharmacotherapy: A Pathophysiologic Approach, 7th Edition: 20
http://www.accesspharmacy.com/
Algorithm for Theophylline Titration
21
Theophylline
• Signs of toxicity
– nausea/vomiting
– tachycardia
– jitteriness
– difficulty sleeping
– tachyarrhythmias
– seizures
22
Mast Cell Stabilizer
• Mechanism
– no bronchodilatory effect
– inhibit neurally mediated bronchoconstriction
• Improvement in 1 to 2 weeks
• Alternative to initial ICS therapy but not as
effective
• Cromolyn
– MDI or nebulizer
23
Leukotriene Modifiers
Leukotriene receptor antagonists (LTRA)
zafirlukast
montelukast
5-lipoxygenase inhibitor
zileuton
Use: alternative/adjunct therapy
less effective than ICS
oral dosage form
Adverse effects
hepatic dysfunction
24
Anti-IgE: omalizumab
• Mechanism: recombinant anti-IgE antibody
– prevents binding of IgE to mast cells & basophils
• decreases release of mediators following allergen
exposure
• Use
– allergic asthma not well controlled by
corticosteroids
– ≥ 12 years old
– severe persistent asthma
25
Omalizumab
• Dosage/administration
– subcutaneous every 2 to 4 weeks
– dosage based on serum IgE level & weight
• Adverse effect
– anaphylaxis
• 70% occur within 2 hours
• may occur up to 24 hours after injection
26
Clinical Controversy
• Inhaled β2-agonists worsen asthma?
• SABAs
– regular administration did not worsen asthma
– patients with β-receptor genotyped as
homozygous Arg-16
• ~16% of population
• predisposed to worsening (lower PEFs)
• does not occur with as needed SABA use
27
Kelly HW. Risk versus benefit considerations for the β2-agonists. Pharmacotherapy 2006;26:164S–174S
Clinical Controversy
• Do LABAs produce the same effect?
– unknown
– retrospective data has not shown worsening or
whether concurrent ICS is protective
– patients do respond to acute use of β2-agonists
• Only use SABA as needed
28
Kelly HW. Risk versus benefit considerations for the β2-agonists. Pharmacotherapy 2006;26:164S–174S
Monitoring Therapy
• Regular follow up
– 1 to 6 month intervals depending on control
– 3 month interval if step down anticipated
• Evaluate asthma control
– symptoms
– lung function
– validated questionnaires
– medication adverse effects
– adherence, environmental control, comorbid
condition
29
Acknowledgements
Prepared By: Michelle Nguyen, Pharm.D.
Series Editor: April Casselman, Pharm.D.
Editor-in-Chief: Robert L. Talbert, Pharm.D., FCCP, BCPS, FAHA
Chapter Authors: H. William Kelly, Pharm.D.
Christine A. Sorkness, Pharm.D.
Section Editor: Robert L. Talbert, Pharm.D., FCCP, BCPS, FAHA
30
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