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Transcript
Medications for the Acute
Management of Asthma
A. Shaun Rowe, Pharm.D., BCPS
Risk Factors for Death
• Social History
– Low socioeconomic status or inner-city residence
– Illicit drug use
– Major psychosocial problems
• Co-morbidities
– Cardiovascular disease
– Other chronic lung disease
– Psychiatric disease
Physical Exam
• Shortness of breath
• Accessory muscle
use
• Wheezing
• Tachypnea
• Cough
• Tachycardia
• Anxiety
• Hypoxia
Functional Assessment
• FEV1 or PEF
– Severity of airflow obstruction
– Patient’s response to treatment
• Oxygen Saturation
– Pulse oximetry
– SpO2 > 90%
Goals of Treatment
• Correction of significant hypoxemia
• Rapid reversal of airflow obstruction
• Reduction of the likelihood of recurrence
Treatment
• Beta2 agonists
• Anticholinergics
• Systemic corticosteroids
• Adjunct therapies
Therapies Not Recommended
• Antibiotics
• Aggressive hydration
• Chest physical therapy
• Mucolytics
• Sedation
Short-Acting Beta2-Agonists
• Albuterol (Proventil HFA®)
– Nebulizer solution & MDI
• Levalbuterol (Xopenex HFA®)
– Nebulizer solution & MDI
• Pirbuterol (Maxair®)
– MDI
MOA & Indication
• Stimulates beta adrenergic receptors causing
bronchial smooth muscle dilation
• Most potent and rapidly acting
bronchodilators for relief of acute asthma
symptoms
• Adequacy of response related to contribution
of bronchospasm in producing airway
obstruction
Albuterol (Proventil®)
> 6 years old
Albuterol
2.5-5mg q 20 min x
nebulizer soln 3 doses, then 2.5(0.63mg/3ml, 10mg q 1-4 h prn
1.25mg/3ml,
2.5mg/3ml,
5mg/ml)
10-15mg/h
continuously
Albuterol MDI 4-8 puffs q 20 min
(90mcg/puff) up to 4 h, then q
1-4 h prn
< 6 years old
0.15mg/kg (min dose
2.5mg) q 20 min x 3
doses, then 0.150.3mg/kg up to 10mg q
1-4 h prn
0.5mg/kg/h
continuously
4-8 puffs q 20 min x 3
doses, then q 1-4 h
prn; use VHC; add
mask in < 4 yo
Levalbuterol (Xopenex®)
Levalbuterol
nebulizer soln
(0.63mg/3ml,
1.25mg/0.5ml,
1.25mg/3ml)
> 6 years old
< 6 years old
1.25-2.5mg q 20
min x 3 doses, then
1.25-5mg q 1-4 h
prn
0.075mg/kg (min
dose 1.25mg) q 20
min x 3 doses, then
0.075-0.15mg/kg up
to 5mg q 1-4 h prn
5-7.5 mg/h
continuously
0.25 mg/kg/h
continuously
Levalbuterol MDI 4-8 puffs q 20 min
(45 mcg/puff)
up to 4 h, then q
1-4 h prn
4-8 puffs q 20 min x 3
doses, then q 1-4 h
prn; use VHC; add
mask in < 4 yo
Albuterol Kinetics
• Onset: 5 – 15 minutes
• Peak effect: 30 – 60 minutes
• Duration: 3 – 6 hours
Albuterol Adverse Effects
• Common
• Less common
– Tremor
– Hypokalemia
– Nervousness
– Tachycardia
– Palpitations
– Dizziness
– Insomnia
– Headache
– HTN
– EKG changes
Levalbuterol vs Albuterol
• Levalbuterol is R-isomer of albuterol
• Administered in one-half the mg dose of
albuterol
• Provides comparable efficacy and safety
• Significant cost difference
Anticholinergics
• Ipratropium (Atrovent®)
– Nebulizer solution & MDI
• Ipratropium with albuterol (Combivent®
Respimat®, DuoNeb®)
– Nebulizer solution & MDI
MOA & Indication
• Relaxes smooth muscles of bronchi and
bronchioles through competitive inhibition of
cholinergic receptors
• Does not inhibit release of anti-inflammatory
mediators
• Used with albuterol for relief of acute asthma
symptoms
Ipratropium (Atrovent®)
> 6 years old
< 6 years old
Ipratropium
0.5mg q 20 min x
nebulizer soln 3 doses, then prn
(0.25mg/ml)
0.25mg q 20 min x 3
doses, then prn
Ipratropium
8 puffs q 20 min
prn up to 3 hours
MDI
(18mcg/puff)
4-8 puffs q 20 min prn
up to 3 hours
Ipratropium with Albuterol
®
®
(Duoneb , Combivent )
> 6 years old
< 6 years old
Ipratropium with albuterol
nebulizer soln
(3ml vial; 0.5mg
ipratropium & 2.5mg
albuterol)
3ml q 20 min x
3 doses, then
prn
1.5ml q 20 min
x 3 doses, then
prn
Ipratropium with albuterol
MDI
(18mcg ipratropium;
90mcg albuterol/puff)
8 puffs q 20 min 4-8 puffs q 20
prn up to 3
min prn up to 3
hours
hours
Ipratropium Kinetics
• Onset: 5 – 30 minutes
• Peak effect: 1 – 2 hours
• Duration: 4 – 5 hours
Ipratropium Adverse Effects
• Limited adverse effects due to limited
systemic absorption
• Most common
– Blurred vision
– Tachycardia
– Headache
– Dry mouth
Inhaled Ipratropium
• Not recommended for monotherapy due to
more gradual bronchodilation
• Addition of ipratropium to a selective SABA
produces additional bronchodilation
• Results in fewer hospital admissions,
particularly in patients with severe airflow
obstruction
• May be used up to 3 hours in initial
management of severe exacerbations
Systemic Corticosteroids
• Prednisone (Deltasone®)
– Oral tablets
• Methylprednisolone (Solu-Medrol®, Medrol®)
– Injection
– Oral tablets
• Prednisolone (Prelone®)
– Oral solution
MOA & Indication
• Decreases inflammation and reduces
inflammatory response to cytokines released
during inflammation
• Component of treatment for acute asthma
exacerbation
• Also used for prevention of acute asthma
exacerbation
Systemic Corticosteroids
> 6 years old
Prednisone
40-80 mg/day in 1
or 2 divided doses
until PEF reaches
Methylprednisolone
70% predicted
< 6 years old
1 mg/kg in 2
divided doses
(max 60mg/d)
until PEF 70%
predicted
Prednisolone
“Burst”: 40-60 mg
in single or 2
divided doses
x 5-10 days
“Burst”: 1-2
mg/kg/d
(max 60 mg/d)
x 3-10 days
Corticosteroid Kinetics
• Onset: ~ 3 hours for oral prednisone & 1 hour
for intravenous methylprednisolone
• Peak effect: 12 hours for oral & 5 hours for
intravenous
Corticosteroid Adverse Effects
• Acute
– Hypertension
– Fluid retention
– Hyperglycemia
• Chronic
– Cushing’s syndrome
– Osteoporosis
– Leukocytosis
– Peptic ulcer disease
– Depression
– Adrenal suppression
– Euphoria
– Impaired wound
healing
– Stunted growth
Role of Systemic Corticosteroids in ED
• Moderate or severe exacerbations or
incomplete response to initial SABA
• Oral equivalent to IV
• 5 – 10 day course following d/c from ED
• IM depot injections for nonadherence
• Supplemental doses to pts who take
corticosteroids regularly, even in mild
exacerbations
Pediatric Status Asthmaticus
• Beta-adrenergic agonists
– Albuterol
– Bind to beta2-adrenergic
receptors in the airway
smooth muscle to produce
bronchodilation
– Start with intermittent
nebulizations and switch to
continuous if inadequate
response
– May need 20 – 30 mg/hr
– Tachycardia and
hypertension
• Corticosteroids
– Systemic not inhaled in this
case
– Give oral if they can
tolerate but IV if not
– High dose Beta agonists
can impair gut absorption
– Early administration
improves outcomes
– 2mg/kg/day of prednisone
or methylprednisolone
– No evidence that higher
doses are better
Carroll CL, Sala KA. Pediatric Status Asthmaticus. Critical Care Clinics. 2013:153-66.
Pediatric Status Asthmaticus
• Second line treatments
– Magnesium
• Causes bronchodialation through calcium inhibition in the smooth
muscle
• Weakness, respiratory depression, and cardiac arrhythmias
– Anticholinergics
• Ipratropium
• Works well as an adjunct when added to albuterol
– Terbutaline
• IV beta-agonist
• Good for those that can’t inhale enough albuterol to be effective
• cardiotoxicity