..

1. Dr. Fares Al Bahar

2. References
• Pharmacotherapy Dipiro: A Pathophysiologic
Approach, 10th ed (CH 33).
• Global Strategy for Asthma Management and
Prevention. Feb 2017. Global Initiative for
Asthma (GINA) http://www.ginasthma.org

3. Definition of asthma
Asthma is a heterogeneous disease, usually characterized by chronic
airway inflammation.
Asthma is a chronic inflammatory disorder of the airways in which
many cells and cellular elements play a role: in particular:
 mast cells
 Eosinophils
 T-lymphocytes
 Macrophages
 Neutrophils
 epithelial cells
It is defined by the history of respiratory symptoms such as wheeze,
shortness of breath (SOB), chest tightness and dry cough that vary
over time and in intensity, together with variable expiratory airflow
limitation.

5. • Asthma is a common and potentially serious chronic
disease that can be controlled but not cured.
• Asthma causes symptoms that vary over time in their
occurrence, frequency and intensity, such as:
– Wheezing
– shortness of breath (SOB)
– chest tightness
– Cough (dry).
• Symptoms are associated with variable expiratory
airflow, i.e. difficulty breathing air out of the lungs due
to:
– Broncho-constriction (airway narrowing)
– Airway wall thickening
– Increased mucus

7. Epidemiology
• Asthma is a problem worldwide, with an estimated 300
million affected individuals.
• It is estimated that asthma causes 346,000 deaths
worldwide every year.
• It is an under-diagnosed and under-treated condition.
• Asthma is the most common chronic disease of childhood.
• Children younger than 4 years of age have the highest rate
of emergency department visits (???) and hospitalizations.
– Can be life-threatening if not properly managed
• education is key to prevention of death from asthma
• by early adulthood, 30 to 70% will markedly improve or be
symptoms-free

8. Etiology
• Asthma is a partially heritable complex syndrome that results
from a complex interaction of genetic and environmental
factors.
– Genetic predisposition (predispose individuals to, or protect
them from, developing asthma)
• Atopy (genetically determined state of hypersensitivity
to environmental allergens)
– Environmental exposure (influence susceptibility to
development of asthma in predisposed individuals, precipitate
asthma exacerbations, and/or cause symptoms to persist)
• hygiene hypothesis

9. Factor Triggering Asthma:
The various triggers have relative degrees of importance from patient
to patient
viral
nasal polyps and sinusitis

10. Risk Factors for Asthma
• socioeconomic status
• tobacco smoke (Maternal smoking during
pregnancy or exposure to secondhand smoke
after birth increases the risk of childhood asthma)
• allergen exposure (tree and grass pollen, house
dust mites, household pets, molds)
• urbanization
• decreased exposure to common childhood
infectious agents (hygiene hypothesis)

11. Diagnosis of asthma
• The diagnosis of asthma should be based on:
– A history of characteristic symptom patterns vary over
time
– Evidence of variable airflow limitation, from
bronchodilator reversibility testing
• Document evidence for the diagnosis in the
patient’s notes, preferably before starting
controller treatment
– It is often more difficult to confirm the diagnosis after
treatment has been started.

12. Diagnosis of asthma – symptoms
• Increased probability that symptoms are due
to asthma if:
– More than one type of symptom (wheeze,
shortness of breath, dry cough (especially at
night), chest tightness)
– Symptoms often worse at night or in the early
morning
– Symptoms vary over time and in intensity

13. Spirometry
(measures the respiratory function test)

14. Abbreviations
• PFT: Pulmonary Function Test: measures lung function,
specifically the amount (volume (L)) and/or speed (air flow
(L/sec)) of air that can be inhaled and exhaled.
– FVC: Forced vital capacity: is the volume of air that can forcibly
be blown out (exhaled) after full inspiration, measured in
liters.
– FEV1: Volume that has been exhaled at the end of the first
second of forced expiration
– PEF: Peak expiratory flow: is the maximal flow (or speed)
achieved during the maximally forced expiration initiated at
full inspiration, measured in liters per second.

15. • KFT: kidney function test
• LFT: liver function test
• PFT: pulmonary function test
– Diagnosis
– Treatment follow up

16. • The single most useful test for ventilatory dysfunction is the FVC.
The FVC is measured by having the patient exhale into the
spirometer as forcefully and completely as possible after maximal
inspiration. The resulting volume curve is plotted against time so
that expiratory flow can be estimated.
• The FEV1 usually is expressed as a percentage of the total volume of
air exhaled and is reported as the FEV1 to FVC ratio.
• Healthy persons generally can exhale at least 75% to 80% of their
vital capacity in 1 second and almost all of it in 3 seconds. Thus, the
FEV1 normally is 80% of the FVC.
• The patient's breathing ability is compared against “predicted
normal” values for patients with similar physiologic characteristics,
because lung volumes depend on age, race, gender, height, and
weight. For example, an average-sized young adult male may have
an FVC of 4 to 5 L and a corresponding FEV1 of 3.2 to 4 L.

17. Speed or flow
PEF
4/5= x 100% = 80%

18. FVC
4
5
1.5
2.5
BD: Bronchodilator
volume

20. Exercise about PEF
• Asthmatic Male, 35 years, 170 cm…..what is
the PEF value for the healthy people in the
same patient condition PEF = 630 L/min
– Our patient PEF= 420 L/min (??) <<< 630
• healthy people in the same patient condition
Female 35 years, 170 cm ….. PEF = 450 L/min

21. Diagnosis of asthma – variable airflow limitation
• Confirm presence of airflow limitation
– Document that FEV1/FVC is reduced
– In healthy adults this should be approximately 70–
80%
• Confirm variation in lung function is greater than
in healthy individuals
– Excessive bronchodilator reversibility (increase in FEV1
>12%)
– Significant increase in FEV1 or PEF after 4 weeks of
controller treatment

22. Peak Expiratory Flow (PEF)
• Peak expiratory flow (PEF) measurements can be an important aid
in both diagnosis and monitoring and follow up of asthma.
• The PEF can be measured easily with various handheld peak flow
meters and commonly is used in emergency departments (EDs) and
clinics to quickly and objectively assess the effectiveness of
bronchodilators in the treatment of acute asthma attacks.
• Peak flow meters also can be used at home by patients with asthma
to assess chronic therapy.
• PEF measurements are ideally compared to the patient’s own
previous best measurements using his/her own peak flow meter.
• A healthy, average-sized young adult male typically has a PEF of 550
to 700 L/minute.

23. handheld peak flow meters

25. • Commercial peak flow meters come with a chart for
patients to determine their predicted normal PEFs
based on their gender, age, and height.
• Peak flow readings are often classified into 3 zones of
measurement according to the American Lung
Association; green, yellow, and red. Doctors and
health practitioners can develop an asthma
management plan based on the green-yellow-red
zones.

27. Zone Reading Description
Green
Zone
80 to 100
percent of the
usual or
normal peak
flow readings
are clear.
A peak flow reading in the
green zone indicates that
the asthma is under good
control.
Yellow
Zone
50 to 79
percent of the
usual or
normal peak
flow readings
Indicates caution. It may
mean respiratory airways
are narrowing and
additional medication may
be required.
Red
Zone
Less than 50
percent of the
usual or
normal peak
flow readings
Indicates a medical
emergency. Severe airway
narrowing may be
occurring and immediate
action needs to be taken.
This would usually involve
contacting a doctor or
hospital.
Partially controlled)

28. Diagnosis of asthma – physical examination
• Physical examination in people with asthma
– Often normal
– The most frequent finding is wheezing on auscultation,
especially on forced expiration
• Wheezing is also found in other conditions, for
example:
– Respiratory infections
– COPD
– Upper airway dysfunction
– Endobronchial obstruction
– Inhaled foreign body

29. The role of lung function in asthma
(FVC, FEV1, PEF)
• Follow up or Monitoring progress
– Measure lung function at diagnosis (baseline), 3-6
months after starting treatment (to identify
personal best), and then periodically
– Consider long-term PEF monitoring for patients
• Adjusting treatment?
– Utility of lung function for adjusting treatment is
limited by between-visit variability of FEV1 (15%
year-to-year)

30. GINA assessment of chronic Asthma
control
A. Symptom control
In the past 4 weeks, has the patient had:
Well-
controlled
Partly
controlled
Uncontrolled
• Daytime asthma symptoms more
than twice a week? Yes No
None of
these
1-2 of
these
3-4 of
these
• Any night waking due to asthma? Yes No
• Reliever needed for symptoms*
more than twice a week? Yes No
• Any activity limitation due to asthma? Yes No
‫جدا‬ ‫مهم‬
SABA

31. Assessment of risk factors for poor
asthma outcomes
Risk factors for exacerbations
include:
• Ever intubated for asthma
• Uncontrolled asthma symptoms
• Having ≥1 exacerbation in last 12 months
• Low FEV1 (measure lung function at start
of treatment, at 3-6 months to assess
personal best, and periodically thereafter)
• Incorrect inhaler technique and/or poor
adherence
• Smoking
• Obesity, pregnancy, blood eosinophilia

32. Chronic Asthma
• Asthma is classified as either:
• (a) intermittent asthma or
• (b) persistent (chronic) asthma that may be categorized
as mild, moderate, or severe.
– Initial assessment of severity is made at the time of
diagnosis, and initial therapy is based on this assessment.
– Assess asthma severity after patient has been on controller
treatment for several months
– Severity is not static – it may change over months or years,
or as different treatments become available

33. 3-6 days
7 days
‫حفظ‬
1
2
3
4
5
Daytime

34. Example
18 years old asthmatic male,
3 days / week every time the patient used the
reliever
Nighttime 3 /month
Symptoms lead to some limitation on his
normal activity
FEV1 65%
Stage?.....MODERATE

35. Patient case 1
A 20-year-old patient presents to the clinic for asthma
exacerbation. She states she has been using her
boyfriend albuterol inhaler on a regular basis for the
past 2 years. During the past month she has been using
the inhaler throughout the day on a daily basis and
sometimes at night. Which best classifies her asthma
severity?
A. Intermittent
B. Mild persistent
C. Moderate persistent
D. Severe persistent

36. Patient case 2
A 20-year-old woman presents to the clinic with an
asthma exacerbation. She states that she has been
using her boyfriend’s albuterol inhaler on a regular
basis for the past 2 years. During the past few
months, she has been using the inhaler on a daily
basis and sometimes at night. Which description
best classifies her asthma severity?
A. Mild intermittent.
B. Mild persistent.
C. Moderate persistent.
D. Severe persistent

37. Treating asthma to control
symptoms and minimize risk (of
exacerbation)

38. Goals of asthma management
• The short and long-term goals of asthma management
are
1. Symptom control: to achieve good control of symptoms and
maintain normal activity levels
2. Risk reduction: to minimize future risk of exacerbations,
fixed airflow limitation
• Achieving these goals requires a partnership between
patient and their families health care providers
– Ask the patient about their own goals regarding their asthma
– Good communication strategies are essential
– Consider the health care system, medication availability,
cultural and personal preferences.

39. • Desired Outcomes
• Maintaining long-term control using the least
amount of medications and minimizing adverse
effects.
• Treatment goals are to:
– prevent chronic and troublesome symptoms,
– maintain normal or near-normal pulmonary function,
– maintain normal activity levels,
– prevent morbidity and mortality : exacerbations of
asthma and the need for emergency department visits
or hospitalizations,
– prevent progressive loss of lung function,
– provide optimal pharmacotherapy with minimal or no
adverse effects.
– Improve QOL

40. Non-pharmacologic Therapy
• Nonpharmacologic therapy is incorporated into
each step of care, and patient education occurs
whenever health care professionals interact with
patients.
• Components of education involve asthma trigger
avoidance, proper administration of inhaled
medications
– Patients with aspirin-sensitive asthma acute asthma
may occur within minutes of receiving aspirin or
NSAIDs. These patients are advised against using
NSAIDs.

41. • The adult and child immunization schedule is
recommended for patients with asthma.
• A yearly influenza vaccine is recommended
for patients 6 months and older with asthma
to decrease the risk of complications from
influenza.
• The pneumococcal vaccine is recommended
as a one-time immunization before the age of
65 years and again after age 65.
Nonpharmacologic Therapy

42. • Nonselective β-blockers, such as carvedilol,
labetalol, nadolol, pindolol, propranolol, and
timolol (including ophthalmic preparations) may
worsen asthma control.
– These agents are avoided in patients with asthma
– For patients with asthma requiring β-blocker therapy,
a β1-selective agent such as metoprolol, bisoprolol or
atenolol is the best option.
– Because selectivity is dose related, the lowest
effective dose is used.
• In chronic asthma the patient can use selective
BB. But in asthma exacerbation the selective BB
should be avoided.

43. Non-pharmacologic Therapy
• Control of external triggers

44. Pharmacologic Therapy
• Treatment of chronic asthma involves the use of
long-term control and quick-relief medications.
• Long-term control medications (Controllers)
Scheduled include:
1) inhaled corticosteroids (ICS)
2) inhaled long acting β2-agonists (LABAs)
3) oral theophylline
4) oral leukotriene receptor antagonists (LTRAs),
5) Omalizumab (SC).
6) oral systemic corticosteroids (OCS) In patients with
severe asthma

45. Pharmacologic Therapy
• Quick-relief of symptoms medications
(reliever) PRN include:
– Inhaled short acting β2-agonists (SABAs)
– Inhaled short acting Anticholinergics or
antimascarinic (SAMAs)
• Note: Reliever = bronchodilator = SABA = PRN

46. Choosing between controller options –
individual patient decisions
Decisions for individual patients
Use shared decision-making with the patient/parent/carer to discuss the following:
1. Preferred treatment for symptom control and for risk reduction
2. Patient characteristics (phenotype)
• Does the patient have any known predictors of risk or response?
(e.g. smoker, history of exacerbations, blood eosinophilia)
3. Patient preference
• What are the patient’s goals and concerns for their asthma?
4. Practical issues
• Inhaler technique - can the patient use the device correctly after training?
• Adherence: how often is the patient likely to take the medication?
• Cost: can the patient afford the medication?

47. • Direct airway administration of asthma medications through inhalation is
the most efficient and safest route.
• Inhaled asthma medications are available in:
– metered-dose inhalers (MDIs)
– dry powder inhalers (DPIs)
– soft mist inhalers (SMIs)
– nebulized solutions.
– Spacer devices make inhalers easier to use and reduce systemic absorption
and side effects of inhaled glucocorticosteroids
• Selection of the appropriate inhalation device depends on patient
characteristics and medication availability.
• Poor inhaler technique results in:
– increased oropharyngeal deposition of the drug
– decreased efficacy
– increased adverse effects.
Drug Delivery Devices

48. dry powder inhalers
soft mist inhalers nebulized solutions
Spacer devices

52. 3-6 days
7 days
‫حفظ‬
1
2
3
4
5
Daytime

53. ‫جدا‬ ‫مهم‬
treatment

54. Reliever PRN in ALL steps
2-6 weeks
At least 3 months

55. Intermittent Asthma
Intermittent asthma includes:
• patients with exercise-induced bronchospasm
– Warming up prior to exercise and covering the mouth and nose
with a scarf or mask during cold weather may prevent exercise-
induced asthma.
– Pretreatment with an SABA 5 to 20 minutes prior to exercise is
the treatment of choice and will protect against bronchospasm
for 2 to 3 hours.
• seasonal asthma
• asthma symptoms associated with infrequent
trigger exposure.

56. Intermittent Asthma
Step 1:as-needed (PRN) reliever inhaler
– SABAs are highly effective for relief of asthma
symptoms.
– This option should be reserved for patients with
infrequent symptoms (less than twice a month) of
short duration, and with no risk factors for
exacerbations.
– Special case: Consider adding regular (scheduled)
low dose inhaled corticosteroid (ICS) for patients
at risk of exacerbations

57. Persistent Chronic Asthma
• Patients with persistent chronic asthma require:
– daily long-term control therapy.
• ICS are the long-term control medication of choice at all
levels of severity (mild, moderate, and severe) and in all age
groups.
– SABAs are prescribed for all patients with asthma for
use on an as-needed basis.
• After initiating therapy, patients are monitored
within 2 to 6 weeks to ensure that asthma
control has been achieved.
• Patients with controlled asthma are monitored at
1- to 6-month intervals to ensure that control is
maintained.

58. When to step up or down?
• 2-6 weeks : to step up
• At least 3 months (12 weeks): to step down

59. • A gradual step-down in long-term controller
therapy is attempted once control has been
maintained for at least 3 months (12 weeks).
– The ICS dose can be decreased before removing
the LABA, or the LABA can be discontinued while
maintaining the same ICS dose.
• Step-Up: after 2-6 weeks, Before increasing
therapy, the patient’s inhaler technique and
patient adherence to therapy are evaluated.

60. Asthma Medications

61. Patient case 3
A 20-year-old woman presents to the clinic with an
asthma exacerbation. She states that she has been
using her boyfriend’s albuterol inhaler on a regular
basis for the past 2 years. During the past few
months, she has been using the inhaler on a daily
basis and sometimes at night. Which is the best
asthma maintenance therapy for this patient?
A. Fluticasone low dose.
B. Montelukast.
C. Fluticasone low dose plus salmeterol.
D. Fluticasone high dose

62. Relievers
– Inhaled short acting β2-agonists (SABAs)
– Inhaled short acting Anticholinergics (SAMAs)

63. Controllers
• Long-term control medications (Controllers) include:
• inhaled corticosteroids (ICS)
• inhaled long acting β2-agonists (LABAs)
• oral theophylline
• oral leukotriene receptor antagonists (LTRAs),
• Theophylline and omalizumab.
• oral corticosteroids (OCS) In patients with severe asthma

64. β2-Adrenergic Agonists
(SABA and LABA)
• Inhaled β2-agonists are classified as either:
– short-acting (SABA)
– long-acting (LABA)
• Oral β2- agonists have increased adverse effects
and are not used for asthma treatment.
• The SABAs have significantly better
bronchodilating activity in acute asthma than
theophylline or anticholinergic agents.
– SABA>>>>SAMA

65. β2-Adrenergic Agonists
(SABA and LABA)
• Adverse effects of β2-agonists include:
– Tachycardia
– Skeletal muscles stimulation (tremor)
– hypokalemia.
• Adverse effects of β2-agonists at
– high doses of inhaled (SABA very frequent)
– oral

66. Short-Acting Inhaled β2-Agonists
(Albuterol, Levalbuterol)
• Onset of action: less than 5 minutes.
• Duration of action: 4 to 6 hours.
• Albuterol (ventolin®) (known as salbutamol
outside the United States), the most commonly
used inhaled SABA, is available as:
– an MDI
– solution for nebulization.
• Levalbuterol, the pure R-enantiomer of
albuterol, is available as an MDI and solution for
nebulization.

67. • During an asthma exacerbation, the usual
SABA doses are doubled and the regimen
changes from as-needed to scheduled use.
• /,/
• M.M.
• LMM..M
• N/;
Maintenance doses

68. • Four corticosteroids are currently marketed
for nebulization:
nebulized budesonide (BUD), beclomethason
e dipropionate (BDP), flunisolide (FLU),
and fluticasone propionate (FP).

69. Nebulization for asthma attacks
• Each Nebule (2.5 ml) contains 5 mg Albuterol

70. Long-Acting Inhaled β2-Agonists
(LABA)
• Indications:
– As add on therapy for patients not controlled on low to
medium doses of ICS.
– Adding LABA is as effective in improving symptoms and
decreasing asthma exacerbations as:
• doubling the dose of an ICS.
• Adding LABA to ICS therapy reduces the amount of ICS
necessary for asthma control (ADVANTAGE steroid sparing)
– Medium dose ICS = low dose ICS+ LABA
– LABAs should not be used as monotherapy for chronic
asthma. There may be an increased risk of severe
asthma exacerbations and asthma-related deaths when
LABAs are used alone ( black box warning)

71. Long-Acting Inhaled β2-Agonists
(LABA)
• Salmeterol and formoterol are LABAs that
provide up to 12 hours of bronchodilation after a
single dose.
– Because of the long duration of
bronchodilation, these agents are useful for
patients experiencing nocturnal symptoms.
• Salmeterol: partial agonist with an onset of
action of approximately 30 minutes.
• Formoterol: full agonist that has an onset of
action similar to that of albuterol (5 minutes)

72. • Salmeterol and formoterol are available as
single-ingredient products and as fixed-ratio
combination products containing an ICS:
– fluticasone propionate/salmeterol (Seretide).
– budesonide/formoterol (Symbicort).
– mometasone/formoterol.

73. • Combination products:
– increase adherence because of the need for fewer
inhalers and inhalations.
– offer less flexibility in dosage adjustment of
individual ingredients if that is necessary.

74. Corticosteroids
• Corticosteroids are the most potent anti-
inflammatory agents (as controller)
• Available for asthma treatment and are
available in:
– Inhaled (step 2 – 6)
– Systemic
• Oral (step 6)
• Injectable (step 6 or in exacerbation)

75. Corticosteroids
• ICSs are more effective than LTRA and theophylline in
improving lung function and preventing emergency
department visits and hospitalizations due to asthma
exacerbations.
• The primary advantage of using ICS compared with
systemic corticosteroids is the targeted drug delivery to
the lungs, which decreases the risk of systemic adverse
effects.
• Product selection is based on preference for dosage
form, delivery device, and cost. But not in efficacy

76. • All ICSs are equally effective if given in
equipotent doses.
• Cigarette smoking decreases the response to
ICS, so the patient has 2 choices:
• Smoking cessation (the preferred)
• Smokers require higher doses of ICS than nonsmokers.
• 2 weeks of therapy is necessary to see clinical
effects. Longer treatment may be necessary to
realize the full effects on airway inflammation.
So we need 2-6 weeks for step –up

77. Inhaled Corticosteroids
• ICSs are the preferred therapy for all forms of
persistent asthma in all age groups.
– beclometasone dipropionate
– budesonide
– Flunisolide (N/A in Jordan market)
– fluticasone propionate
– mometasone furoate
– triamcinolone acetonide
– ciclesonide (N/A in Jordan market)

78. – This is not a table of equivalence, but of estimated clinical comparability
– Most of the clinical benefit from ICS is seen at low doses
‫جدا‬ ‫مهم‬

79. Reliever PRN in ALL steps
2-6 weeks
At least 3 months
IgE

80. Patient case 4
An 8-year-old boy has been having daytime asthma
symptoms once or twice weekly and is awakened
twice weekly at night with coughing. In addition to
albuterol MDI 1 or 2 puffs every 4–6 hours as
needed, which is the best initial therapy for him?
A. Fluticasone MDI low dose 1 puff twice daily.
B. Fluticasone MDI medium dose puff 1 puff twice
daily.
C. C. Fluticasone/salmeterol ( medium dose ICS +
LABA) 1 puff twice daily.
D. Oral montelukast 10 mg/day.

81. • For most delivery devices, the majority of the drug is
deposited in the mouth and throat and swallowed.
– Local adverse effects of ICS include oral candidiasis
– Cough
– dysphonia (difficulty in speaking)
– hoarseness.
• The incidence of local adverse effects can be reduced by:
– Proper use of the inhaler
– using an MDI with a spacer (children, elder).
– having the patient rinse the mouth with water or normal saline
or mouth wash after using the ICS.
– Decreasing the dose reduces the incidence of hoarseness.
Side effects of ICSs

82. oral candidiaisis
• Prevention of oral candidiaisis:
– Proper use of the inhaler
– using an MDI with a spacer.
– having the patient rinse the mouth with water or
normal saline or mouth wash after using the ICS
• Treatment of oral candidiaisis:
– Antifungal (Nystatin)

83. Systemic Corticosteroids
(oral, IV, IM)
• Prednisone, prednisolone, and methylprednisolone are the
cornerstone of treatment for acute asthma not responding to
an SABA.
• The oral route is preferred in acute asthma; there is no
evidence that intravenous corticosteroid administration is
more effective. Both have same efficacy
• The duration of therapy usually ranges from 3 to 10 days.
– Therapy with systemic corticosteroids is continued until the PEF is
70% or more of the personal best measurement and asthma
symptoms are resolved.
– Cortisone dependent: should be kept systemic cortisone to be
controlled

84. Systemic Corticosteroids
• Because of serious potential adverse effects,
systemic corticosteroids are avoided as long-
term controller medication for asthma, if
possible.
– Systemic corticosteroids are only used in patients
who have failed other therapies including
immunomodulators.
– If systemic therapy is necessary, once-daily or every-
other-day therapy is used with repeated attempts to
decrease the dose or discontinue the drug.

85. Systemic Corticosteroids (oral or injectables) side effects
Failure to thrive
Increase BP

87. Anticholinergics (Antimuscarinics)
• Less effective bronchodilator than β2-agonists
– SAMA < SABA
– LAMA < LABA
• Ipratropium bromide (SAMA):
– Short acting
– onset of action is approximately 15 minutes
– duration of action is 4 to 8 hours.

88. Anticholinergics (Antimuscarinics)
An SABA (albuterol = salbutamol) combined with
ipratropium to increase bronchodilation is only
indicated in the emergency department setting (For
nebulization) during a moderate to severe asthma
exacerbation to improve pulmonary function and
decreases hospitalization rates in both adult and
pediatric patients.
• Inhaled ipratropium bromide produces a further
improvement in lung function of 10% to 15% over inhaled
β2-agonists alone
• SABA + SAMA > SABA alone > SAMA alone

89. • Tiotropium bromide (LAMA):
– long-acting inhaled anticholinergic.
– onset of action of 30 minutes.
– duration longer than 24 hours.
– Tiotropium decreases severe exacerbations,
improves lung function, and is steroid sparing.
– Because of its safety and efficacy profile,
tiotropium is the preferred anticholinergic agent
for chronic asthma treatment.
• Tiotropium could be used as alternative for step 5
therapy if the patient is < 18 years of age

90. LAMAs
• aclidinium (Genuair)
• glycopyrronium (Breezhaler)
• tiotropium (HandiHaler, Respimat, Spiriva)…
for Asthma
• umeclidinium (Ellipta)

91. • Anticholinergic drugs adverse effects (high
doses of inhaled):
– blurred vision, dry mouth, and urinary retention.
– Increased cardiovascular events have been
reported for ipratropium but not tiotropium.

92. Leukotriene Receptor Antagonists
(LTRAs)
• The LTRAs are anti-inflammatory medications
that either:
– inhibit 5-lipoxygenase (zileuton)
– antagonize the effects of leukotriene D4
(montelukast, zafirlukast).
• oral administration.
• significantly less effective than low ICS doses.
• Combining an LTRA with an ICS is not as effective
as an ICS plus an LABA
– ICS+LTRA <<<< ICS+LABA
– but is considered steroid sparing.

93. • Montelukast is generally well tolerated with minimal need for
monitoring and few drug interactions.
• Zileuton and zafirlukast are less commonly used because of
the risk of hepatotoxicity.
– Zileuton use requires liver function monitoring.
– Zafirlukast may increase prothrombin time in patients receiving
warfarin
• Zileuton and zafirlukast are metabolized through the CYP 2C9
hepatic pathway and have significant drug interactions.
• All three agents have reports of neuropsychiatric events, such
as:
– sleep disorders, aggressive behavior, and suicidal thoughts.
Leukotriene Receptor Antagonists
(LTRAs)

95. Methylxanthines (Theophylline)
• Old, sheap
• anti-inflammatory properties.
• Its use is limited because of:
– inferior efficacy as a long-term controller
medication compared with ICS.
– a narrow therapeutic index with potentially life-
threatening toxicity (need TDM).
• Target serum theophylline concentrations are 5 to 15
mg/L (if < 5 so ineffective, if > 15 toxic)
– multiple clinically important drug interactions.

96. • Side effects
• Headache, nausea, vomiting, and insomnia may
occur but are rare when the dose is started low
and increased slowly.
• More serious adverse effects (eg, cardiac
arrhythmias, seizures) can occur at high
concentrations.
• l;
• L;
• L;
• L’
• L’

97. Immunomodulators (Omalizumab)
• a recombinant anti-IgE antibody
• Use
– allergic asthma (high IgE level) ≥ 12 years old not
well controlled by corticosteroids
– severe persistent asthma (step 5 or 6)
– Omalizumab significantly:
– decreases ICS use
– reduces the number and length of exacerbations
– and increases asthma-related quality of life.
• However, its place in therapy is limited by its
high cost

98. • Adverse effect
– anaphylaxis
• 70% occur within 2 hours
• may occur up to 24 hours after injection
• Monitoring the patient for an anaphylactic reaction for
2 hours after medication administration is
recommended for the first 3 months
– increased risk of cardiovascular and
cerebrovascular events (eg, myocardial infarction,
transient ischemic attack (mild stroke), venous
thrombosis) and perhaps cancer, but the
magnitude of the increased risk is unclear.