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Transcript
UNIVERSITY OF PRINCE EDWARD
N232 INTRODUCTORY PHARMACOLOGY
ASTHMA
Asthma is a common, chronic disorder that occurs in children and adults. Characteristic signs
and symptoms are a sense of breathlessness and tightness in the chest, wheezing, dyspnea, and
cough. The underlying cause is immune-mediated airway inflammation. This chapter discusses
basic considerations in asthma, anti-inflammatory drugs, bronchodilators, glucocorticoid/longacting beta2 agonist (LABA) combinations and the management of chronic asthma.
Words/Concepts to Know:
asthma
dry-powder inhalers (DPIs)
exercise-induced bronchospasm (EIB)
forced expiratory volume in 1 second (FEV1)
forced vital capacity (FVC)
leukotriene modifiers
mast cell stabilizers
metered-dose inhaler (MDI)
methylxanthines
peak expiratory flow (PEF)
Learning Objectives:
After reading and studying this chapter, the student should be able to do the following:
A. State a reasonably accurate definition of asthma that includes an understanding of the
roles and involvement of airway smooth muscle hyperresponsiveness and inflammation
in the disease. Describe the typical signs and symptoms that would lead to the diagnosis
of a respiratory disorder as asthma.
B. State the criteria used to classify severity of asthma based on impairment and risk.
C. Summarize the mechanisms of action, roles, and limitations of the following drugs in the
therapy of asthma:
1.
2.
3.
4.
5.
6.
7.
Beta-adrenergic agonists
Glucocorticoids
Methylxanthines
Mast cell stabilizers
Leukotriene modifiers
Anticholinergic drugs
Glucocorticoid/LABA combinations
D. Describe the two basic goals in the treatment of chronic asthma.
E. Compile a list of drugs or drug groups that are relatively or absolutely contraindicated for
patients with asthma, and state their main problems.
F. Discuss some nondrug interventions that might be used to decrease the frequency and
severity of asthma attacks.
KEY POINTS:
Asthma is a chronic inflammatory disease characterized by inflammation of the airways,
bronchial hyperreactivity, and bronchospasm. Allergy is often the underlying cause.
Asthma is treated with anti-inflammatory drugs and bronchodilators.
KEY POINTS:

Most drugs for asthma are administered by inhalation, a route that increases therapeutic
effects (by delivering drugs directly to their site of action), reduces systemic effects (by
minimizing drug levels in blood), and facilitates rapid relief of acute attacks.

Three devices are used for inhalation: MDIs, DPIs, and nebulizers. Patients will need
instruction on their use.
KEY POINTS:

Beta2 agonists promote bronchodilation by activating beta2 receptors in bronchial smooth
muscle.

Inhaled short-acting inhaled beta2 agonists (SABAs) are the most effective drugs for
relieving acute bronchospasm and preventing exercise-induced bronchospasm.

Three inhaled beta2 agonists—arformoterol, formoterol, and salmeterol—have a long
duration of action, and hence are indicated for long-term control.

Inhaled SABAs rarely cause systemic side effects.

Excessive dosing with oral beta2 agonists can cause tachycardia and angina by activating
beta1 receptors on the heart. (Selectivity is lost at high doses.)

Inhaled LABAs can increase the risk of asthma-related death, but only when used
incorrectly. Accordingly, LABAs should be used only by patients taking an inhaled
glucocorticoid for long-term control, and only if the glucocorticoid has been inadequate
by itself.
KEY POINTS:

Glucocorticoids are the most effective antiasthma drugs available.

Glucocorticoids reduce symptoms of asthma by suppressing inflammation. As an added
bonus, glucocorticoids promote synthesis of bronchial beta2 receptors, and increase their
responsiveness to beta2 agonists.

Inhaled and systemic glucocorticoids are used for long-term prophylaxis of asthma—not
for aborting an ongoing attack. Accordingly, they are administered on a fixed schedule—
not PRN.

Unless asthma is severe, glucocorticoids should be administered by inhalation.

Inhaled glucocorticoids are generally very safe. Their principal side effects are
oropharyngeal candidiasis and dysphonia, which can be minimized by employing a
spacer device during administration and by gargling after.

Inhaled glucocorticoids can promote bone loss. To minimize loss, dosage should be as
low as possible, and patients should perform regular weight-bearing exercise and should
ensure adequate intake of calcium and vitamin D.

Inhaled glucocorticoids can slow the growth rate of children, but they do not reduce adult
height.

Prolonged therapy with oral glucocorticoids can cause serious adverse effects, including
adrenal suppression, osteoporosis, hyperglycemia, peptic ulcer disease, and growth
suppression.

Because of adrenal suppression, patients taking oral glucocorticoids (and patients who
have switched from oral glucocorticoids to inhaled glucocorticoids) must be given
supplemental doses of oral or IV glucocorticoids at times of stress.
KEY POINTS:




Cromolyn is an inhaled anti-inflammatory drug used for prophylaxis of asthma.
Cromolyn reduces inflammation primarily by preventing release of mediators from mast
cells.
For long-term prophylaxis, cromolyn is taken daily on a fixed schedule. For prophylaxis
of exercise-induced bronchospasm, cromolyn is taken 15 minutes before anticipated
exertion.
Cromolyn is the safest drug for asthma. Serious adverse effects are extremely rare.
KEY POINTS:










There are four classes of chronic asthma: intermittent, mild persistent, moderate
persistent, and severe persistent. Diagnosis is based on current impairment and future
risk.
For therapeutic purposes, asthma drugs can be classified as long-term control medications
(eg, inhaled glucocorticoids) and quick-relief medications (eg, inhaled SABAs).
In the stepwise approach to asthma therapy, treatment becomes more aggressive as
impairment and/or risk becomes more severe.
The goals of stepwise therapy are to prevent symptoms, maintain near-normal pulmonary
function, maintain normal activity, prevent recurrent exacerbations, minimize the need
for SABAs, minimize drug side effects, minimize emergency department visits, prevent
progressive loss of lung function, and meet patient and family expectations about
treatment.
The step chosen for initial therapy is based on the pretreatment classification of asthma
severity, whereas moving up or down a step is based on ongoing assessment of asthma
control.
Intermittent asthma is treated PRN, using an inhaled SABA to abort the few acute
episodes that occur.
For persistent asthma (mild, moderate, or severe), the foundation of therapy is daily
inhalation of a glucocorticoid. An inhaled LABA is added to the regimen when asthma is
more severe. A short-acting beta2 agonist is inhaled PRN to suppress breakthrough
attacks.
For acute severe exacerbations of asthma, patients should receive oxygen to reduce
hypoxemia, a systemic glucocorticoid (to reduce airway inflammation), and a nebulized
SABA plus nebulized ipratropium (to relieve airflow obstruction)
To prevent exercise-induced bronchospasm, patients can inhale a SABA just prior to
strenuous activity.
Patients should avoid allergens that can cause airway inflammation and triggers that can
provoke exacerbations. Important sources of allergens are the house dust mite, warmblooded pets, cockroaches, and molds. Important triggers are tobacco smoke, wood
smoke, and household sprays.
Asthma Severity
Intermittent
Mild
Persistent
Moderate
Persistent
Severe
Persistent
Symptoms
2 or less days per
week
More than 2
days per week
Daily
Throughout
the day
Nighttime
Awakenings
2 X's per month or
less
3-4 X's per
month
More than once
per week but
not nightly
Nightly
Rescue Inhaler
Use
2 or less days per
week
More than 2
days per week,
but not daily
Daily
Several times
per day
Interference
With Normal
Activity
None
Minor limitation
Some limitation
Extremely
limited
Lung Function
FEV1 >80%
predicted and
normal between
exacerbations
FEV1 >80%
predicted
FEV1 60-80%
predicted
FEV1 less
than 60%
predicted