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Asthma 1
Asthma
 Definition
o Obstructive disease of the airways that is caused by hyperreactivity of airway
smooth muscle, increased mucus secretion, or inflammation, and is
completely reversible either spontaneously or with treatment.
 Epidemiology
o Asthma affects ~ 14-15 million Americans (roughly 5% of the population)
o Most common pulmonary disease
o Children > adults, boys > girls
o African Americans have 19% higher incidence than whites and are twice as
likely to be hospitalized 
 Morbidity / Mortality
o >5000 deaths occur yearly in the U.S. due to asthma
o Estimated that 80-90% of the deaths could have been prevented
o Mortality increasing (may be due to pollutants, non-compliance with
medications, or inadequate access to health care) 
 Risk factors for early recurrent wheezing
o Low Birth Weight
o Male Gender
Etiology
Atopy
o Parental Smoking
Genetic Predisposition
Genetically determined state of
hypersensitivity to environmental
Occupational 
 Major risk factors for asthma
allergens (production of IGE in response
Atopy
o Parental History
to normal household allergens or things
found in the environment)
 Minor risk factors for asthma
Presence can indicate a poor prognosis
o Eosinophilia
o Wheezing without colds
o Allergic rhinitis 
 Indicator of poor prognosis: _Atopy_(can cause asthma, allergic rhinitis, eczema)
 Asthma triggers
If have acid in
stomach, lay down at
night, aspirate that
and cause damage to
lungs and trigger
asthma exacerbations
Respiratory
Infections
Other diseases
Allergens
Environment
Emotions
Exercise
Drugs/preservatives
Occupational Stimuli
RSV, rhinovirus, flu, parainfluenza, Mycoplasma pneumonia
Sinusitis/rhinitis, premenstrual/pregnancy, nocturnal asthma,
GERD, smoking
Airborne pollen, house-dust mites, animal danders,
cockroaches, fungal spores, foods
Cold air, fog, ozone, sulfur dioxide, nitrogen dioxide, tobacco
smoke, wood smoke
Anxiety, stress, laughter
Cold, dry climate
ASA, NSAIDS, sulfites, benzalkonium chloride, beta blockers,
iodinated radiocontrast media, ACEI
Bakers, farmers, chemical workers, plastics, rubber, wood
workers
Bronchial Constriction, SOB
Asthma 2
Mucus in airways,
inflammatory cascade
is kicking in
 Pathophysiology
o Early asthmatic reaction
o Late asthmatic reaction
o BHR – bronchial hyperresponsiveness 
Clinical Relevance of Phases:
 Not all pts will develop LAR or BHR, however seen in
most patients with moderate & severe persistent asthma
 Identifies ways to interfere with disease process
 Determines how meds are used
 Significance of repeated trigger exposure
 End result (late asthmatic response/BHR)
 Increases lung vascular permeability
 Leads to edema
Prolong exposure
 Increased mucus production/secretion
to triggers
 Eosinophils/inflammatory mediators continue to flood to the lung tissue
 Inflammatory cascade potentiated

 Clinical Presentation
o Symptoms caused by 
 Inflammation, Mucus plug, Bronchoconstriction
 Signs/Symptoms of Asthma
 Cough
 Wheeze
 Dyspnea and chest tightness
 Tachypnea and tachycardia
 Hypoxemia
 Hypercapnia and respiratory acidosis
 Pulsus paradoxus
 Diagnosis
 Spirometry
-FEV1 – volume of air exhaled in 1st sec
 < 80 abnormal
-FEV1/FVC – flow in 1st sec over total volume of air expired
 < 80% = obstruction to airflow in the airways
 Peak flow rates
 Predicted vs. personal best
 Predicted values
-Based on ht, wt, sex
-Reported as % predicted
-Normal > 80%
 Peak expiratory flow rate (PEFR)
-Air exhaled in 1st 10 msec
-Personal best is preferred
-Green zone: > 80% “go”
-Yellow zone: 50-80% “caution”
-Red zone: <50% “stop”
Asthma Histopathy
 Edema
 Mast cell activation
 Infiltration of inflammatory cells:
 Neutrophils
 Eosinophils
 Lymphocytes
To diagnose asthma,
abnormal PFTs should
improve 15% or more,
following bronchodilator
administration
Want people to use their peak
flow meter in the morning
when they get up and in the
afternoon (when get home
from school), # should be
close to each other
Staging Asthma
•Severe Persistent
•Allergic asthma
•Moderate Persistent
•Exercise-induced asthma
•Mild Persistent
•Nocturnal asthma
•Mild Intermittent
Asthma 3
 Staging asthma
SYMPTOMS
STEP 4
SEVERE
PERSISTENT
STEP 3
MODERATE
PERSISTANT







STEP 2
MILD
PERSISTENT


STEP 1 
MILD
INTERMITTENT
Continual symptoms
Limited physical activity
Frequent exacerbations
Daily symptoms 
Daily use of inhaled short
acting beta 2 agoninsts
Exacerbations affect activity
Exacerbations > 2 times a
week; may last days
Symptoms > 2 times a
week but < once a day
Exacerbations may affect
activity
 Symptoms < 2 times a week
 Asymptomatic and normal
PEF between exacerbations
 Exacerbations brief (from a
few hours to a few days);
intensity may vary
 MANAGING ASTHMA 
NON PHARMACOLOGIC THERAPY
o
o
o
o
Dysphonia:
problems with
vocal cords
Immunotherapy
Flu shot yearly
Avoid triggers
Environmental control
NIGHTTIME
SYMPTOMS
LUNG FUNCTION
Frequent
 FEV1 or PEF < 60% predicted
 PEFR variability > 30%
> 1 time a week
 FEV1 OR PEFR > 60% < 80% predicted 
 PEFR variability > 30% 
> 2 times a month
 FEV1 OR PEFR >80% predicted
 PEFR variability 20-30%
< 2 times a month
 FEV1 or PEF > 80% predicted
 PEFR variability < 20%
Environmental Control:
–Vacuuming carpets
–Air conditioning
–Dehumidifier
–No smoking
–Avoid exercise during pollution
–Avoid fumes
 LONG TERM CONTROLLERS VS. QUICK ACTING AGENTS
INHALED CORTICOSTEROIDS (ICS)  BEST DRUG FOR CONTROLLING ASTHMA
Indication
o Long term prevention of symptoms
o Suppression, control, and reversal of inflammation
o Reduces need for oral corticosteroids
MOA: blocks late reactions to allergen and reduces airway hyperresponsiveness
o Inhibits cytokine production, adhesion protein activation, and inflammatory cell
migration and activation
o Reverses beta 2 receptor down regulation
Potential Adverse effects
Rinse mouth with water after use, use spacer to minimize
o Cough, dysphonia, oral thrush
o In high doses – systemic effects may occur (although studies are not
conclusive – clin sig has not been established)
 Adrenal suppression, osteoporosis, skin thinning, easy bruising
Place in therapy
o Preferred long term controller
if have asthma that you don’t treat long
o Most evidence to support reducing airway remodeling
term, the chronic inflammation of the
lung can lead to COPD
# of different products
o Differ with regard to potency
Asthma 4
o No one is “better than another,” just more potent
Clinical pearls of ICS
o High dose monotherapy not preferred; marginal benefit with increasing dose from
medium range
o Spacer / holding chamber decreases local side effects and systemic absorption
o Risks of uncontrolled asthma usually outweigh the risks of ICS
o Most effective long term controller – decreases airway remodeling
o Growth controversy
-Long term data say that inhaled steroids may delay growth but it doesn’t stunt growth
o Titrate to minimum dose required
o Education points: rinse mouth with water, impt of compliance, time to onset,
proper technique
Estimated Comparative Daily Dosages for Inhaled Corticosteroids
Adults
Drug
Beclomethasone dipropionate
42mcg/puff
84mcg/puff
Beclomethasone HFA
(40 or 80 mcg/puff)
Low Dose
168-504 mcg
4-12 puffs
2-6 puffs
80-240 mcg
Medium Dose
504-840 mcg
12-20 puffs
6-10 puffs
240-480 puffs
High Dose
>840 mcg
>20 puffs
>10 puffs
>480 mcg
Budesonide Turbuhaler
200mcg/dose
Flunisolide
250mcg/puff
Fluticasone propionate
MDI:44, 110, 220 mcg/puff
600-1200 mcg
3-6 inhalations
1000-2000 mcg
4-8 puffs
264-660mcg
2-6 puffs – 110 mcg
DPI: 50, 100, 250mcg/dose
200-600 mcg
1-3 inhalations
500-1000mcg
2-4 puffs
88-264 mcg
2-6 puffs – 44 mcg
2 puffs – 110 mcg
2-6 inhalations – 50 mcg
Triamcinolone acetonide
100mcg/puff
400-1000mcg
4-10 puffs
1000-2000 mcg
10-20 puffs
>1200 mcg
>6 inhalations
>2000mcg
>8 puffs
>660 mcg
>6 puffs – 110 mcg
>3 puffs – 220 mcg
>6 inhalations – 100 mcg
>2 inhalations – 250 mcg
>2000 mcg
>20 puffs
Beclomethasone dipropionate
42mcg/puff
84mcg/puff
84-336 mcg
2-8 puffs
1-4 puffs
336-672 mcg
8-16 puffs
4-8 puffs
>672 mcg
>16 puffs
>8 puffs
Beclomethasone HFA
(40 or 80mcg / puff)
Budesonide Turbuhaler (DPI)
200mcg/dose
Flunisolide
250mcg/puff
Fluticasone propionate
MDI:44, 110, 220 mcg/puff
80-160mcg
160-320mcg.
>320mcg
200-400 mcg
DPI: 50, 100, 250mcg/dose
2-4 inhalations – 50mcg
400-800 mcg
2 –4 inhalations
1000-1250 mcg
4-5 puffs
176-440 mcg
4-10 puffs – 44mcg
2-4 puffs – 110mcg
2-4 inhalations – 100mcg
Triamcinolone acetonide
100mcg/puff
400-800mcg
4-8 puffs
800-1200mcg
8-12 puffs
>800 mcg
>4 inhalations
>1250 mcg
>5 puffs
>440 mcg
>4 puffs – 110mcg
>2 puffs – 220mcg
>4 inhalations – 100mcg
>2 inhalations – 250mcg
>1200mcg
>12 puffs
3-6 inhalations – 100 mcg
Children
500-750 mcg
2-3 puffs
88-176 mcg
2-4 puffs – 44mcg
Product
Budesonide (Pulmicort Respules)
0.25,0.5/2ml inhalation solution

Dosage
Low dose: 0.5 mg
Medium: 1 mg
High: 2.0 mg
Comments
Don’t mix with other neb solns
Rinse mouth after use
Asthma 5
 LONG ACTING BETA AGONISTS 
Indications
o Long term prevention of symptoms (especially nocturnal)
o Added to anti-inflammatory therapy
NEVER MONOTHERAPY
o Prevention of exercise induced bronchospasm
MOA: bronchodilation
Potential adverse effects
o Tachycardia
o Skeletal muscle tremor
o Hypokalemia
o Prolongation of QTC interval in overdose
o Diminished bronchoprotective effect?
Place in therapy: moderate and severe persistant asthma
Clinical pearls
o Not to be used to treat acute symptoms or exacerbations
Should NEVER take
o Tolerance?  down regulation of B2 receptors from chronic use
more than one puff of
o NOT MONOTHERAPY  SMART study (salmeterol vs. inhaled steroid,
Servent or Advair at
one time. Don’t
monotherapy showed an increase risk of mortality)
dispense script:
o
May
provide
more
effective
symptom
control when added to standard doses of
Advair 2 puffs bid
TOO MUCH!
ICS, compared to increasing the ICS dose
o Still need short acting beta agonist (like Albuterol)
Medication
Takes
30 min
to work
Works
within 5
minutes
Dosage Form
Adult Form
Child Dose
Salmeterol Diskus
DPI: 50mcg/blister
1 blister q12h
1 blister q12h
Albuterol SR
4mg tablet
4mg q12h
Formoterol
Actuator
12mcg/blister
12 mcg cap (puff) q12h
0.3-0.6mg/kg/day,
not to exceed
8mg/day.
>5y.o. 12 mcg puff
q12h
Comments
May use one dose nightly for
symptoms
Not to be used to treat acute
symptoms or exacerbations.
Can use for exercise induced
asthma
Onset of action within 5
minutes – can be used for
exercise induced asthma –
must use 15 minutes before
challenge
MAST CELL STABILIZERS  Long term controller
MOA: anti-inflammatory. Block early and late reactions to allergens. Stablizes mast
cells to inhibit activation and release of mediators from eosinophils and epithelial
cells
o Inhibits acute response to exercise, cold, dry air, and sulfur dioxide
Place in therapy
o Alternative to ICS for mild-persistent asthma Biggest use, Pt that always have problem around
spring (ragweed season) can give mast cell
o Exercise induced AND Seasonal asthma
stabilizer but give 1 month before!
ADR’s
o Unpleasant taste
Time to onset: 4-6 weeks to see full effect
Education points
o Importance of compliance
o Spacer may decrease bad taste
Asthma 6
Regimen: cumbersome (4x a day with unpleasant taste)
Clinical pearls
o Safety is primary advantage to these agents
o Little data of additive efficacy in combo with ICS
Medication
Cromolyn
Dosage Form
MDI 1mg/puff
Nebulizer solution
20mg/amp
Adult Form
2-4 puffs TID – QID 1
amp TID – QID
Child Dose >2y.o.
1-2 puffs TID – QID
1 amp TID – QID
Nedocromil
MDI: 1.75mg/puff
2-4 puffs BID-QID
1-2 puffs BID-QID
>6y.o.
Comments
One dose prior to exercise
(10-60minutes before) or
allergen exposure providers
effective prophylaxis for 12
hours
METHYLXANTHINES (theophylline)
Never for
preferred
therapy
MOA
o Not fully understood. Bronchodilator?: smooth muscle relaxation by inhibiting
phosphodiesterase (↑ cAMP)
More important in
o Thought to increase diaphragm contractility and mucociliary clearance  COPD patients
Place in therapy
o Alternative to low dose ICS for mild persistent (as monotherapy)
o Alternative (in combo with ICS) for moderate persistent
Clinical kinetics
o Therapeutic range
 Traditional 10-20mcg/ml
 Contemporary 8-12mcg/ml
• Still derive benefit, but decreases risk of ADRs
Potential ADR
Caffeine is a methylxanthine
o Dose related acute toxicities
o ADR at usual doses (hint: transient caffeine like effects)
 Insomnia, gastric upset, aggravation of GERD, can worsen
Drinking caffeine will
make ADRs worse
hyperreactivity in kids, H/A, nervousness, irritability
o >20mcg/ml: N/V/D, H/A, irritability, insomnia
o >40mcg/ml: cardiac symptoms
o >50mcg/ml: severe CNS manifestations such as seizures may occur
 seizures have been reported at levels as low as 25mcg/ml
 Not well controlled with antiepileptics
BASIC pharmacokinetics review
Terminology
o S – salt form
o F – bioavailability factor
 Usually 1 (especially if drug given IV)
o Bioavailability of drug = (S) X (F) X total dose
Absorption
o Non-sustained-release tablet and liquid F=100%
 Absorption is rapid and complete
 Peaks in 1-2 hours
o Sustained-release products: most are completely absorbed, but the duration
of absorption varies
Example: If pt. is
on
luoroquinolone
o treat COPD
exacerbation and
hey are on
heophylline
chronically, cut
Asthma 7
 As duration increases, dosing interval may be decreased Variability among
products, especially those dosed once daily Peak levels usually obtained 4 hours after
dose
Hospitals use
o Rectal; complete, but erratic absorption
aminophylline for
IV form
o IV: aminopylline is used parenterally
o SALTS
Form
Theophylline
Aminophylline
Oxtriphylline
S (fraction of labeled dose that is theophylline)
1.0
0.8
0.65
o Distribution
o Protein binding ~40%
o Vd
 0.5L/kg in adults and children (range of 0.4 to 0.7L/kg)
 0.7L/kg in neonates (up to one year of age)
o Dosing weight in obese subjects controversial – use IBW if ABW >30% IBW for
calculations
If have pt. with asthma who is pregnant and on
o Crosses placenta and enters breast milk
theophylline, consider d/c theophylline and increasing
inhaled therapy. (B/c most inhaled therapies are topical,
o Pregnancy category C
not systemically sbsorbed.)
Clearance
o Primarily (>90%) cleared by liver, metabolized by cytochrome P450 (specifically CYP
1A2)
o Premature neonates excrete 50% dose unchanged in urine
o Non linear pharmacokinetics
 Renal impairment – no effect on clearance; no dosage adjustments needed
o Factors causing increased clearance
 Smoking
 Cystic fibrosis
 Drugs
 High protein, low carb diets (ATKINS diet)
o Factors causing decreased clearance (  level of theophylline)
 CHF
 Severe COPD
 Liver disease
 Age: neonates and elderly
 Drugs
o When several factors are present; its hard to predict drug levels
DRUG Interactions
Asthma 8
Take famotidine,
zantac, or
anitidine instead
of cimetidine.
No DI with these.
Drugs that INHIBIT metabolism of
theophylline
SIGNIFICANT (>30% inhibition)
Drugs that INDUCE metabolism of
theophylline ( level of theophylline)
Phenytoin
Fluoroquinolones (enoxacin, cipro, norflox)
Rifampin
Cimetidine( doses >1000mg/d)
Fluvoxamine (SSRI mainly for OCD)
Oral contraceptives
Disulfram
Propafenone
Ticlopidine
Zileuton
MODERATE inhibitory interations
(10-30%)
Erythromycin, clarithromycin
Isoniazid
Allopurinol at large doses (> 300mg BID)
Carbamazepine
Phenobarbital
Ritonavir (for HIV)
Moricizine
Cigarette smoking
St. John’s Wort
COPD pts taking
theophylline and
still smoking,
once get them to
stop smoking,
watch
theophylline
levels
Pro
duct
sele
ctio
n
o S
ustained release products preferred (Immediate release theophylline not used a lot)
o Release characteristics of some products may be affected by food
o SR products NOT interchangeable
o Avoid other oral salt forms
Characteristics of selected slow-release formulations
FORMULATION
Capsule
• Slo-bid Gyrocap
• Theo-24
Time to peak serum
concentration
Comments
• 3-7 hours after morning dose
when given q 12 h
• can be opened and sprinkled on a spoonful of soft food for kids
who can’t swallow the capsule; contents must be swallowed
without chewing; complete absorption occurs with or without
food
• incomplete absorption occurs when taken after an overnight
fast; pH-dependent dissolution causes much more rapid and
complete absorption when taken after food or in the evening
• scored tablets can be split without affecting absoroption
characteristics; complete absorption occurs in the presence or
absence of food
• Variable depending on whether
taken in the am after an overnight
fast, after breakfast, or in the pm
Tablet
• Theo-Dur
• 3 to 7 hours after am dose when
given every 12 hours
• Uni-Dur
• 8 to 12 hours after once daily
evening dose
• Uniphyl
• 8 to 12 hours after once-daily
evening dose
• formulation similar to TheoDur tablets but more slowly
absorbed; near complete absorption occurs in the presence or
absence of food
• incomplete absorption occurs when taken after overnight fast;
more complete absorption occurs when taken after food or in the
evening
Weinberger M and Hendeles L. Theophylline in Asthma. NEJM 1996; 1380 - 1388


For general initiation, start at lower doses and titrate up over 9 days to avoid transient side
effects
Dosing strategy for those WITHOUT risk factors for impaired theo clearance
Asthma 9
o Initial dose
 For infants 6 weeks – 1 year, initial daily dose is calculated using:
• 0.2 (age in weeks) + 5 = initial dose in mg/kg/day
When to measure level when titrating?
-NO SOONER THAN Q 3 DAYS
• divide q 6 hours if > 6 months and q 8 hours if < 8 months

For children > 1 year and adults begin with 10mg/kg/day with MAX dose of
300mg
o First incremental increase (o.k. to do if no side effects seen)
 13mg/kg/day; max 400-450mg/day
o Second increment
 16mg/kg/day; max 600mg/day
o Measure serum concentration after 3 days at highest tolerated dose
o Dose increases should be made no sooner than q3 days and if the dose is
well tolerated

For patients with risk factors that may decrease theophylline clearance, use
pharmacokinetic equation
Not used in practice very much
o D = (Css x Cl x τ)/F x S
(D=dose, Css = concentration at steady state (average), τ=dosing interval)
o Initial dose should not exceed 400mg/day (16mg/kg/day) without checking a serum
level

ORAL dose adjustments of theo; dose increases should be limited to ~25% of total daily
dose
Rule of thumb
Theophylline maintenance dose adjustments
Measured serum conc
(mcg/ml)
5-7.5
Dose adjustment
Increase dose 25%; recheck serum conc in 3 days
Increase dose 25% only if patient is symptomatic; recheck serum
conc in 3 days and q 6-12 months
7.5-10
10-20
20-25
25-30
No change; consider decreasing dose if > 15mcg/ml
Decrease dose by 10-25%; recheck in 3 days and q 6-12 months
Hold one dose; decrease maintenance dose by 25%; recheck in 3
days and q 6-12 months
Hold two doses; decrease maintenance dose by 50%; recheck to
guide dosage adjustment; consider activated charcoal for toxicity
> 30
Monitoring
 IV; estimated when steady state will occur and obtain level
 ORAL
o Obtain level at steady state (4-5 half lives)
o In most cases, concs should not be obtained until a patient has received a given
dosage for 3 days
o Trough levels more reliable, peaks estimated via kinetics
o Peaks may be associated with toxicity
o
o
For SR oral products, can check level mid-interval
Once pt stable, check level annually
 Level warranted if s/sx of tox are present
Theophylline (getting levels)
Any other time a level is warranted?
-Annually
-Symptoms of toxicity present
-Pediatrics
Leukotriene
eceptor
antagonists
Asthma 10
o
Children may require more freq monitoring


LEUKOTRIENE MODIFIERS  usually for kids that have a problem w/ inhaled drugs, good compliance
MOA: selective competitive inhibitor of LTD4 and LTE4 receptors
(zileuton – 5lipoxygenase inhibitor)
Place in therapy
o Can be used as monotherapy for mild persistent asthma (alternative to ICS)
 CAMP study: LT modifiers inferior as monotherapy to ICS
o Prefer oral medication
Not a preferred agent.
Adverse effects
o Usually well tolerated
o Might have to monitor LFT (Zileuton)
Education points
o Doesn’t work for everyone
o Singulair - FDA indication for allergic rhinitis
Clinical Pearls
-Singular
 Other FDA indications
 Approved for peds 12 months and up
Medication
Montelukast
Dosage Form
10 mg tablet 5 mg
chewable tablet 4mg
chewable tablet
Adult Form
10 mg PM for pts >14yrs
Child Dose
4mg PM for children
2-5y.o. 5 mg PM for
children 6-14 yrs
Comments
Well tolerated with no signifcant
DI PEDIATRIC INDICATION
(> 12 mo) (>2 yrs if using for
alleric rhinitis) Administer
without regard to meals
Zafirlukast
20mg tablet
40mg daily (20mg BID)
N/A
Administer at least 1 hour before
or 2 hours after meals.
Competitive inhibitor of Cyp
2C9
Zileuton
300mg tablet 600mg
tablet
2400 mg daily (600mg
QID)
N/A
Monitor ALT Not used much 2/2
liver monitoring and DI
Cyp 3A4 inhibitor
5-lipoxygena
e inhibitor
Hard for kids to be compliant with this
must take on empty stomach
XOLAIR (olimizumab)
o Will learn during in-service
MOA: Anti IgE (Binds to IgE)
 Prevents IgE from binding to high affinity IgE receptors on mast cells and
basophils
 Mediators released are reduced (histamine)
Place in therapy:
Monitoring:
Education points: Usually requires health insurance prior auth 2/2 cost
Usual dose:
Asthma 11
Everyone with
asthma should
have access to a
short acting
agent!
Not going to
work as well
when actually
need it if it
has been
overused
No one with
asthma
should be
getting
Combivent
(ipratropium
& albuterol)!
Quick acting agents
SHORT ACTING BETA AGONISTS
Albuterol, Albuterol HFA, pirbuterol, levalbuterol
MOA: BRONCHODILATION. Smooth muscle relaxation following adenylate cyclase activation
Use 10-15 min
before exercise
and increase in cyclic AMP production
o functional antagonism of bronchoconstriction
Place in therapy: DOC for acute bronchospasm (DOC for quick relief, exercise induced)
ADRs: tachycardia, skeletal muscle tremor, H/A
(poor perceiver: perceive their breathing is
Education points: carry with you at all times, over-reliance  worse than it really is)
o >1 canister per month (not controlled)
o >2 canisters / month (RED FLAG, increase risk of death from asthma, call physician!)
Clinical pearls
o tolerance  (down regulation of B2 receptor) tolerance can develop, especially when pt. is
using it more than they probably need to
 Loss of bronchoprotective effect after routine use
Xopenex (Levalbuterol)
o R enantiomer of racemic albuterol
o Beta 2 receptor agonist
o Only available via nebulizer solution
o Decreased incidence of cardiovascular adverse effects v. Albuterol (claim to fame)
 Less tachycardia, less anxious
Very expensive.
o Duration of action: may last up to 8 hours
Should try albuterol first.
Lasts a lot longer than albuterol.
o Usual dose: 0.63mg via neb q 6-8 hours
Don’t know role in acute SOB episodes.
o Clinical pearls
Albuterol has studies. Albuterol lasts 4-6 hours.
 Must not mix with other neb solutions
Medication
Albuterol
Dosage Form
90 mcg/puff, 200
puffs *DPI 200
mcg/capsule
**Nebulizer 5
mg/ml (0.5%)
Adult Dose
2 puffs Q 5 min prior to
exercise *1-2 caps Q
4-6hrs PRN & prior to
exercise **1.25-5 mg in
2-3 ml of saline Q 4-8 hrs
Child Dose
1-2 puffs 5 min prior to
exercise *1 capsule Q
4-6 hrs PRN & prior to
exercise **0.05 mg/kg
(min 1.25 mg, max 2.5
mg) in 2-3 ml of saline
Q 4-6 hrs
2 puffs tid-qid prn *Not
established
Bitolterol
370 mcNebg/puff,
300 puffs
*Nebulizer 2 mg/ml
(0.2%)
2 puffs tid-qid prn
*0.5-3.5 mg in 2-3 ml of
saline Q 4-8 hrs
Pirbuterol
200 mcg/puff, 400
puffs
2 puffs tid-qid prn
2 puffs tid-qid prn
Levalbuterol
0.63 mg/3ml, 1.25
mg/3ml sol
0.63 – 1.25 mg nebulized
TID
< 12 yrs N/A
Comments
***May mix with cromolyn
or ipratropium neb solutions.
May double dose for mild
exacerbations.
May not mix with other
nebulizer solutions
Not currently in MDI


IPRATROPIUM 
MOA: ANTICHOLINERGIC (NOT for routine management! Only for acute exacerbation of asthma)
Place in therapy: acute exacerbations in combo with SABA. Usually only given in ER.
o Evidence has shown if given in ER, can help decrease hospitalizations
Asthma 12
NOTES: Inappropriate to use at home!
Medication
Anticholingeric
Ipratropium
Can use chronic
po steroids for
pt. who has
constant daily
symptoms,
constantly have
RED-YELLO
W peak flow,
never get back
to normal
Dosage Form
18 mcg/puff, 200 puffs
*Nebulizer 0.25 mg/ml
(0.025%)
Adult Dose
2-3 puffs Q 6 hrs
*0.25-0.5 mg Q 6 hrs
Child Dose
1-2 puffs Q 6 hrs
0.25 mg Q 6 hrs
PO STEROIDS
MOA: quick acting generalized anti inflammatory
Place in therapy: adjunct to inhaled therapy for acute exacerbations
o “burst” 3-10days to gain prompt control of inadequately controlled persistent asthma
(prevents inflammation from getting worse)
o severe persistent asthma (constant symptoms): long term prevention of symptoms
o suppression, control, and reversal of inflammation
Goal if use po
steroids is get them
Adverse effects
off as soon as
o Short term: hyperglycemia, increased appetite, fluid retention,
possible b/c of
horrible side effects
weight gain, mood alteration, hypertension, GERD
of chronic steroids
o Long term: adrenal axis suppression, skin thinning, HTN, DM, Cushing’s syndrome,
cataracts, muscle weakness, and rarely – impaired immune function
Education points: use as directed Educate patients that it is not an anabolic steroid, it is a glucocorticoid
Clinical pearls
o Use at lowest effective dose (qod if needed)
o Long term use: alternate day AM dosing produces least toxicity
NOTES: Take steroid in the morning!
Medication
Methylprednisolone
Dosage Form
2,4,8,16,24,32
mg tablets
Prednisolone
5mg tabs,
5mg/5ml,
15mg/5ml
Adult Form
2-60mg daily in a
single dose or qod
as needed for
control
Short-course
“burst”: 4060mg per
day as single or 2
divided doses for
310 days
Child Dose
0.25-2mg/kg
daily in single
dose or qod as
needed for control
Short course
“burst”:
1-2mg/kg/day,
maximum
60mg/day for
3-10 days
Comments
Short courses or “bursts”
are effective for
establishing control when
initiating therapy or during
a period of gradual
deterioration. The burst
should be continued until
patient achieves 80% PEF
personal best or symptoms
resolve. This usually
requires 3-10 days but may
require longer. There is no
evidence that tapering the
dose following
improvement prevents
relapse.
Prednisone
_1,2.5,5,10,20,25,50
mg tabs; 5mg/ml _

If patient has history of severe exacerbations, can give prescription for steroid (prednisone) that
they can keep at home. Give specific instructions(action plan) of when to use it to prevent going
to hospital or ER.
Asthma 13


Can assess a pt.
into a category
based on what
drug they are on.
PUTTING IT ALL TOGETHER - STEP WISE APPROACH TO TREATMENT
Medications required to maintain long term control
Step 4
Severe Persistent
Step 3
Moderate Persistent
Step 2
Mild Persistent
Need SABA. If
use albuterol
>1-2x/week
consider
tepping up to
next level or
reating with
anti-inflammat
ory
Step 1
Mild intermittent
(Not a lot of symptoms, not on daily meds,
generally in green zone)


Preferred treatment: 
High dose ICS 
AND 
 Long acting beta agonist 
AND if needed 
 Corticosteroid tablets or syrup long term (2mg/kg/day,
generally do not exceed 60mg/day) (make repeat attempts to
reduce systemic corticosteroids and maintain control with high
dose ICS)
Preferred treatment: (Advair)
 Low to medium dose ICS AND long acting beta agonist
Alternative treatment 
 Increase ICS within medium dose range 
OR 
 Low to medium dose ICS and EITHER leukotriene modifier
or theophylline
Preferred treatment:
 Low dose ICS 
Alternative therapy (Any long term controller) 
 Cromolyn, leukotriene modifier, nedocromil, OR sustained
release theophylline to serum conc (5-15mcg/ml)


No daily medication needed 
Severe exacerbations may occur, separated by long periods
of normal lung function and no symptoms. A course of
corticosteroids is recommended
QUICK RELIEF 
 ALL PATIENTS 
 Short acting bronchodilator: 2-4 puffs SABA prn symptoms 
 Intensity of treatment will depend on severity of exacrbation 
 Use of SABA >2 x / week in intermittent asthma may indicate the need to initiate long term
control therapy

Two Options for Chronic Add-On:
Step up vs. step down therapy
Last drug added
 Step down: review treatment every 1-6 months; a gradual stepwise reduction in treatment
is first drug to d/c
Step down is used
when stepping
more often
may be possible
down
 Step up: if control is not maintained, consider step up. First, review patient medication
technique, adherence, and environmental control

Special considerations
o Exercise induced bronchospasm

Pre-treatment (30 min before exercise, use 1-2 puffs short acting inhaler)
Example: Pt. has mild intermittent
asthma.
Step Up: Start on therapy for mild
intermittent
Step Down: Start therapy for
moderate persistent and then step
them down when controlled.
Asthma 14
Very safe
o
Pregnancy may
make asthma
better, worse, or
no change.
o
o
o
 Beta Agonists
Short acting agents will
help 2-3 hrs.
 Cromolyn/nedocromil
Long acting agents will
 Lengthy warm-up period
help 10-12 hrs.
Seasonal asthma
30-45 min
-Anti-inflammatory
 Prior to onset of symptoms
-Mast cell stabilizers (Cromolyn, Nedocromil)
-ICS
 Long term anti-inflammatory initiated prior to anticipated onset of
symptoms: start therapy a month before anticipated onset of symptoms
Pregnancy
(Educate pt. to continue med therapy. Get pt. off po meds + on
Stress
inhaled meds b/c local effect, not systemic)
Pediatrics
-Close to adult algorithm
-Differ with regard to delivery devices
 Masks
 Nebulizers
 Spacers
-Leukotriene Modifiers
 By mouth
 Powder
Stepwise Approach for Managing Infants and Young children (5 years of age and younger)
with acute or chronic asthma symptoms
Long-term Control
Preferred treatment:
Step 4
 High-dose inhaled corticosteroid with spacer
Severe Persistent
holding chamber and face mask AND
 Long acting inhaled beta 2 agonist
AND IF needed,
 Add systemic corticosteroids tablets or syrup
2mg/kg/day (generally, do not exceed 60mg/day)
Make repeat attempts to reduce systemic
corticosteroids and maintain control with high
dose inhaled corticosteroids
Quick Relief
Bronchodilator as needed for symptoms
(see step 1) up to 3 times a day
Asthma 15
Step 3
Moderate
Persistent
Step 2
Mild Persistent
Step 1
Mild
Intermittent
Preferred Treatment:
Bronchodilator as needed for symptoms
 Low dose inhaled CS with spacer/holding
(see step 1) up to 3 times a day
chamber and face mask
AND
 Long acting beta 2 agonist
OR
 Medium-dose inhaled CS
Alternative treatment:
 Low dose inhaled CS and either leukotriene
receptor antagonist OR theophylline IF NEEDED
(particulary in patients with recurring severe
exacerbations)
Preferred treatment
 Medium dose ICS AND long acting beta agonist
Alternative therapy
 Medium dose inhaled CS and either leukotriene
receptor antagonist or theophylline
Preferred treatment:
Bronchodilator as needed for symptoms
 Low-dose inhaled CS (nebulizer or MDI with
(see step 1)
spacer/holding chamber with or without face
mask or DPI)
Alternative therapy
 Cromolyn (neb is preferred) or MDI with
holding chamber OR leukotriene receptor
antagonist
No daily
Bronchodilator as needed for symptoms <2 times a week. Intensity of
medication needed treatment will depend upon severity of exacerbation. Either:
Inhaled short-acting beta 2 agonist by nebulizer or face mask and
spacer/holding chamber
OR
Oral beta 2 agonist for symptoms
With viral respiratory infection:
Bronchodilator q 4-6h up to 24 hours (longer with physician consults) but, in
general,
repeat no more than once every six weeks
Consider systemic corticosteroid if : severe exac, or hx of previous severe
exacerb’s
ASTHMA EXACERBATIONS


Classify severity based on s/s and objective information
Categorize generally into mild, moderate, or severe
-NOT exact
-Majority of symptoms fall into one category; go with that
Defining exacerbations
If pt. is acutely feeling worse, it is an
 Time FRAME
exacerbation. If pt. is always in the
 Symptoms
yellow zone, don’t feel good
chronically, it is just bad control
 Peak flow rates
Classifying Severity of Asthma Exacerbations
MILD
MODERATE
SEVERE
Respiratory Arrest
Imminent
Asthma 16
Symptoms
While talking
(infant – softer,
shorter cry;
difficulty feeding)
Prefers sitting
While at rest
(infant – stops
feeding) Sits
upright
Sentences
Phrases
Words
Alertness
May be agitated
Usually agitated
Signs
Usually agitated
Respiratory rate
Increased
Increased
Often >30/min
Use of accessory
muscles:
suprasternal
retractions
Wheeze
Usually not
Commonly
Usually
Moderate, often
only end
expiratory
Loud; throughout
exhalation
Breathlessness
While walking Can
lie die
Talks in
Drowsy or confused
Paradoxical
throacoabdominal
movement
Usually loud;
Absence of wheeze
throughout
inhalation and
exhalation
Pulse/minute
<100
100-120
>120
Bradycardia
Pulsus paradoxus
Absent <10mm Hg May be present
Often present >25 Absence suggests
10-25mm Hg
mm Hg (adult) 20- respiratory muscle
40 mm Hg (child)
fatigue
Functional Assessment
PEF
>80%
Approx 50-80% or
<50% predicted or
response lasts <2
personal best
hrs
PaO2 (on air)
Normal (test not
>60mm Hg (test
<60 mm Hg;
usually necessary) not usually
possible cyanosis
necessary)
PCO2
<42mm Hg (test
<42mm Hg (test
≥42 mm Hg;
not usually
not usually
possible
necessary)
necessary)
respiratory failure
SaO2% (on air) At
>95% (test not
91-95%
<91%
sea level
usually necessary)
•The presence of several parameters, but not necessarily all, indicates the general classification of the
exacerbation
•Many of these parameters have not been systematically studied, so they serve only as general guides
Guide to rates of breathing in awake children:
Age
Normal rate
<2 months
<60/minute
2-12 months
<50/minute
1-5 years
<40/minute
6-8 years
<30/minute
Guide to normal pulse rates in children
Age
Normal rate
2-12 months
<160/minute
1-2 years
<120/minute
2-8 years
>110/minute
Dosages of Drugs for Asthma exacerbations in emergency medical care or hospital
Medications
Albuterol Nebulizer
Solution (5mg/ml)
Adult Dose
Child Dose
Inhaled Short-Acting Beta2-Agonists
2.5-5mg q 20 minutes
0.15mg/kg (minimum
for 3 doses, then
dose 2.5mg) q 20
2.5-10mg q
minutes for 3 doses,
1-4h as needed, or
then 0.15-0.3mg/kg up
10-15mg/hr continuously to 10mg q 1-4 h as
needed, or 0.5mg/kg/hr
by continuous nebulizer
Comments
Only selective beta2-agonists
are recommended. For optimal
delivery, dilute aerosols to
minimum of 4ml at gas flow of
6-8 L/min
Asthma 17
Albuterol MDI
(90mcg/puff)
4-8 puffs q20 minutes up
to 4 hours, then q1-4 hrs
as needed
4-8 puffs q 20 minutes
for 3 doses, then q 1-4
hrs inhalation maneuver.
Use spacer/holding
chamber
As effective as nebulized therapy
if pt is able to coordinate
Bitolterol Nebulizer
solution (2mg/ml)
See albuterol dose
See albuterol dose;
thought to be half as
potent as albuterol on a
mg basis
Has not been studied in severe
asthma exacerbations. Do not
mix with other drugs
Bitolterol MDI
(370mcg/puff)
Pirbuterol MDI
(200mcg/puff)
See albuterol dose
See albuterol dose
See albuterol dose
See albuterol dose;
thought to be half as
potent as albuterol on a
mg basis
Has not been studied in severe
asthma exacerbations
Has not been studied in severe
asthma exacerbations
Epinephrine 1:1000
(1mg/ml)
0.3-0.5mg q 20 minutes
for 3 doses SQ
Terbutaline (1mg/ml)
0.25mg q 20 minutes for
3 doses SQ
Systemic (injected beta2-agonists)
0.01mg/kg up to 0.30.5mg q 20 minutes for
3 doses SQ
0.01mg/kg a 20 minutes
for 3 doses then q 2-6
hrs as needed SQ
No proven advantage of
systemic therapy over aerosol
No proven advantage of
systemic therapy over aerosol
Anticholinergics
Ipratropium bromide neb
solution (0.25mg/ml)
0.5mg q 30 minutes for
3 doses then q2-4h as
needed
0.25mg q20 minutes for
3 doses, then q 2-4
hours
MDI (18mcg/puff)
4-8 puffs as needed
4-8 puffs as needed
Prednisone
Methylprednisolone
Prednisolone
Corticosteroids
120-180mg/day in 3 or 4 1mg/kg q6 h for 48 hours
divided doses for 48
then 1-2mg/kg/day
hours, then 60(maximum
80mg/day until PEF
= 60mg/day) in 2 divided
reaches 70% of
doses until PEF
predicted or personal
70% of predicted or
best
personal best
May mix in same neb with
albuterol. Should not be used
as first-line therapy; should be
added to beta2-agonist therapy
Dose delivered from MDI is low
and has not been studied in
asthma exacerbations
For outpatient “burst” use 4060mg in single or 2 divided doses
for adults (children: 12mg/kg/day, maximum
60mg/day) for 3-10 days
Management of exacerbations include
 inhaled B2 agonist to provide prompt relief of airflow obstruction
Do things like dose
 systemic corticosteroids, for moderate to severe exacerbations
+ efficiency of B2
agonist:
 systemic corticosteroids, for patients who rail to respond promptly and completely
-double dose of
to an inhaled BA
inhaled steroid for
couple days
 oxygen, to relieve hypoxemia for moderate to severe exacerbations
-adding po steroid
 monitoring response to therapy with serial measurements of lung function
-putting pt. on
oxygen if in
hospital to manage
exacerbation
Management of asthma exacerbations at home:
Asthma 18
Appendix III. Managing exacerbations – ER / hospital
Treating Exacerbations in the ER
 Oxygen
 Combinations
-Albuterol
-Ipratropium
 IV vs. PO steroids
 Admit?
In general, people who present
to ER/hospital can assume that
they have moderate-severe
exacerbation
Goals of therapy (see appendix II) 






Maintain normal activity levels (exercise/activity)
Maintain (near)“normal” pulmonary function
Prevent chronic and troublesome symptoms (coughing or breathlessness at HS, early AM,
or after exertion)
Prevent recurrent exacerbations of asthma and minimize need for ER visits /
hospitalizations
Provide optimal pharmacotherapy with minimal or no ADRs
Meet patients’ and families’ expectations of satisfaction with asthma care
MONITORING

Subjective
o Symptoms
 Frequency of symptoms
 Signs/symptoms of dz (goals of therapy) & drug therapy
 Compliance
Asthma 19

 Refill history
 Albuterol or quick relief use
o Efficacy of medications
 Adverse effects experienced (e.g. thrush, sore throat)
Objective
o Pulmonary function
 Peak flow rates at home
 Recommended for all patients with moderate – severe persistent
asthma
 PFT
 Diagnosis
 Have “personal best” established
o Technique
 Peak flow
 Devises
 Action plan (usually filled out by physician)
o Compliance assessment
 Refill history
o Missed work / school days
o Impact on ADL / QOL
o Psychosocial effects

Environmental control
o In compliant patients with good technique that are still not controlled, an
environmental control plan may need to be instituted.
 An on-site inspection of the patients home / workplace / school
should take place
 Cockroaches, carpets, pets, dander, dust, mold / mildew, etc.

ASTHMA ACTION PLAN
o
o
o
o
o
COPY (see appendix I)
Can serve as physician’s order for school nurses
All patients with moderate to severe persistent
Symptom based
Peak flow based
Maintaining Control of Asthma
 Once control is achieved and sustained for several weeks or months, a reduction
in p’col therapy – STEP DOWN – is appropriate and helpful to ID the minimum
therapy for maintaining control
 This process SHOULD BE GRADUAL!
-Last med added, should be the first subtracted
 If optimal control of asthma is NOT achieved and sustained at any step of care,
several actions may be considered
-Pt adherence and technique should be assessed
-Temporary increase in anti-inflammatory therapy may be indicated to
reestablish control
-Other factors that diminish control may be ID and addressed
Asthma 20
-Step up to next step of care may be necessary
-Consultation with an asthma specialist
Factors that can lead to poor control
Indoor pets
Moist damp rooms
Cockroaches
Mold
Smoking
Second hand smoke
Unvented stoves
Wood burning stoves
Unvented heaters
Allergic Rhinitis
Foods
Meds (Beta blockers, ASA/NSAIDs)
PATIENT EDUCATION
 Quick relief medicine versus long term controller medicines
o Rationale (for “relief” vs “long-term controller”)
o Importance of compliance
 Devise technique
o Amount of drug delivered
o content
 explain importance, describe rationale, demonstrate, patient demonstrates
to you, give written instructions
o Follow up periodically
 no substitute for observing technique
o Storage, replacement, cleaning
 Spacer / holding chamber technique
 Peak flow meter – use, interpret, & adjusting
 Environmental control and asthma action plan
 OTC medications for asthma
o Types
 Inhalers – short acting beta agonists (Primatene Mist, Bronkaid Mist,
AsthmaHaler Mist)
 Less specific for lungs, so more adverse effects
 Shorter duration – lasts < 1 hour
 Oral – bronchodialtors and/or theophylline
o Toxicities
 Dose related toxicities
 Increased toxicities if use with similar rx item (theophylline)
o Perceptions/ misconceptions
o Bottom line: rx Items MORE EFFECTIVE AND LESS TOXIC
Follow-up
 Regular follow-up visits are essential
 Clinicians can assess if control is maintained and step down is appropriate
 Follow-up at 1 to 6 month intervals