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ASTHMA
PATHOPHYSIOLOGY
 Asthma is associated with a specific chronic inflammation of the mucosa of
the lower airways
 One of the main aims of treatment is to reduce this inflammation
 The chronic inflammatory response has several effects on the target cells of
the airways, resulting in the characteristic pathophysiologic and remodeling
changes associated with asthma
 The characteristic structural changes are increased airway smooth muscle,
fibrosis, angiogenesis, and mucus hyperplasia
 Airway Hyperresponsiveness is the characteristic physiologic abnormality of
asthma and describes the excessive bronchoconstrictor response to multiple
inhaled triggers that would have no effect on normal airways
CLINICAL SIGNS
TREATMENT:
The main drugs for asthma can be divided into:
 Symptomatic drugs:
1. Short- acting Beta2-Agonists-they are used only to control the symptoms of asthma,
and to prevent the seizure of bronchoconstriction induced by exercise
2. Short-acting Anticholinergics-Ipratropium Bromide is considered an alternative (but
weaker) bronchodilator drug for patients who experience side effects of β2-agonists
3. Oral glucocorticosteroids used for a short time in order to control exacerbations of
asthma
 Drugs to control the disease (taken regularly)
1. Inhaled glucocorticosteroids-preferred because they are the most effective
(significantly better pulmonary function, reduce the symptoms of the disease,
bronchial hyperreactivity and the frequency and severity of exacerbations, improve
quality of life
2. LABA (Salmeterol ,Formoterol , Vilanterol)- should always be used in conjunction with
ICS
3. Long-acting Anticholinergics ( Tiotropium)
4. Antileukotriene drugs (Montelukast, Zafirlukast)
5. Methylxanthine (Theophylline in a sustained release form)
6. Cromones (Cromoglycate and Nedocromil sodium)
BETA-2-ADRENERGIC AGONISTS:
 Activate β2-adrenergic receptors, which are widely expressed in the airways
 Relax airway smooth-muscle cells of all airways, where they act as functional
antagonists, reversing and preventing contraction of airway smooth-muscle
cells

Inhibition of mast cell mediator release, reduction in plasma exudation, and
inhibition of sensory nerve activation
Short-acting Beta2-Agonists ( SABA)
 Use only to control the symptoms of asthma or to prevent
bronchoconstriction induced by exercise
 SABAs should be used only on an as -needed basis at the lowest dose and
frequency required. Increased use, especially daily use, is a warning of
deterioration of asthma control and indicates the need to reassess treatment
 They bring fast relief of breathlessness: onset of action after a few minutes, a
peak at ~ 15 min, the effect lasts for 4-6 h
Long-acting Beta2-Agonists (LABA)
 Formoterol, a LABA, is approved for symptom relief because of its rapid onset
of action, but it should only be used for this purpose in patients on regular
controller therapy with ICS
INHALED CORTICOSTEROIDS:
 are the most effective controllers and the most effective anti-inflammatory
agents in asthma
 reduce inflammatory cell numbers and their activation in the airways
 reduce eosinophils in the airways and sputum and the numbers of activated T
lymphocytes and surface mast cells in the airway mucosa (these effects may
account for the reduction in airway hyperresponsiveness)
 Glucocorticosteroids can be administered via nebulizers, ‘spacer’ devices,
metered-dose inhalers or as dry powders
 ICSs are usually given twice daily, but some may be effective once daily in
mildly symptomatic patients
 They are effective in preventing asthma symptoms, such as exercise-induced
asthma and nocturnal exacerbations, but also prevent severe exacerbations
 Early treatment prevent irreversible changes in airway function that occur
with chronic asthma
INHALED CORTICOSTEROIDS, SIDE EFFECTS:
 A hoarse voice may develop due to a laryngeal myopathy at high doses (this is
reversible and its occurrence is minimized by the use of a ‘spacer’)
 Candidiasis of the pharynx or larynx occurs in 10–15% of patients (using the
minimum effective dose, or a ‘spacer device’, or gargling after dosing,
minimizes this problem
 There has been concern about systemic side effects from lung absorption, but
many studies have demonstrated that ICS have minimal systemic effects
 Effective control of asthma with ICS reduces the number of courses of OCS
that are needed and, thus, reduces systemic exposure to ICS
COMBINATION THERAPY: LABA+ Inhaled Corticosteroids
 Combinations therapy can be used both:
 as a regular treatment ( control treatment)
 as an emergency treatment (max. dose of Formoterol is 72 ug per day)
 The addition of LABA to ICS improves clinical asthma outcomes and reduces
the number of exacerbations, does not increase the risk of asthma- related
hospitalizations, and achieves clinical control of asthma in more patients, more
rapidly, and at a lower dose of ICS than with ICS given alone
 LABAs including Formoterol and Salmeterol, are indicated in asthma only when
given in addition to ICS
ANTICHOLINERGICS :
 Short-acting Anticholinergic-use in patients who cannot tolerate β2-agonists,
and in the exacerbation of asthma as a secondary drug
 Long-acting Anticholinergic- inhaler type soft mist (SMI) 5 ug twice daily- as an
additional drug in patients, who suffer from exacerbations of asthma (despite
treatment step 4 or 5)
ANTILEUKOTRIENES:
 Antileukotrienes such as Montelukast and Zafirlukast block the actions of
Cysteinyl-Leukotrienes at the CysLT1 receptor
 Cysteinyl-Leukotrienes are potent bronchoconstrictors, cause microvascular
leakage, and increase eosinophilic inflammation through the activation of cysLT1-receptors
 Leukotriene receptor antagonists are given orally, usually in the evening
MONTELUKAST :
 It reduced the requirement for glucocorticosteroid and improved symptoms
in chronic asthma. It is also useful in the prophylaxis of exercise- or antigeninduced asthma. It is effective in aspirinsensitive asthma
MONTELUKAST, ADVERSE EFFECTS:
 Montelukast is generally well tolerated, but side effects include:
 gastro-intestinal upsets, asthenia and drowsiness, rash, fever,
elevation of serum transaminases
 Dosage: 10 mg 1 × daily . p.o
CROMONES
Cromolyn sodium and Nedocromil sodium are:
 Asthma controller drugs that appear to inhibit mast cell and sensory
nerveactivation
 Effective in blocking trigger-induced asthma such as EIA and allergen

Have relatively little benefit in the long-term control of asthma due to their
short duration of action
 Rarely used in adults because of weak anti-inflammatory action
 Side-effects are minimal (headache, cough) . Nedocromil has a bitter taste
 The powder can (very rarely) produce bronchospasm or hoarseness
THEOPHYLLINE:
 It is less effective than inhaled medications and often causes significant side
effects
 Long-term therapy: Theophylline is a relatively weak bronchodilator and
when given in a low dose, has modest anti-inflammatory properties
 It is available in a sustained-release formulations that are suitable for once-or
twice -daily administration
 Theophylline is an add-on option for adult patients whose asthma is not well
controlled with ICS or ICS/LABA
 Dosage: 50-350 mg twice daily
SYSTEMIC CORTICOSTEROIDS
 They are often required in exacerbation of asthma and in the most severe
cases of uncontrolled asthma
 Prednisone, prednisolone and methylprednisolone is recommended
 If patients require maintenance treatment with OCS, it is important to
monitor bone density
 Oral Corticosteroids should be taken once a day in the morning, continuing
the use of ICS
 If OCS are to be administered on a long-term basis, attention must be paid to
measures that minimize the systemic side effects
Systemic Corticosteroids-adverse effects:
 The systemic side effects of long-term oral or parenteral corticosteroid
treatment include osteoporosis, arterial hypertension, diabetes,
hypothalamic-pituitary-adrenal axis suppression, obesity, cataracts,
glaucoma, skin thinning leading to cutaneous striae and easy bruising, and
muscle weakness
 Caution and close medical supervision are recommended when considering
the use of systemic corticosteroids
 Adverse effects of short-term high dose systemic therapy (corticosteroid
‘bursts’) are uncommon but include reversible abnormalities in glucose
metabolism, increased appetite, fluid retention, weight gain, rounding of the
face (‘moon facies’) , mood alteration, insomnia, hypertension, peptic ulcer,
and aseptic necrosis of the femoral head
ANTI-IGE MONOCLONAL AB:
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Omalizumab is a blocking antibody that neutralizes circulating IgE without
binding to cell-bound IgE and, thus, inhibits IgE-mediated reactions
This treatment has been shown to reduce the number of exacerbations in
patients with severe asthma and may improve asthma control
Indicated in uncontrolled allergic asthma, reduce the dose of Corticosteroids,
improves asthma control and reduces exacerbations
Omalizumab - dosage: 75-600 mg s.c - depending on baseline IgE levels and
the body weight, 1-4 injections every 2-4 weeks
Side effects include rashes, urticaria, pruritus, sinusitis, gastro-intestinal
upsets, injection site reactions
The choice of drug depends on the current level of control of asthma and treatment
history. There are 5 levels of treatment:
STEP 1 (Reliever therapy: As -needed SABA )
 Other options: regular low dose ICS for patients with exacerbation risks
STEP 2 (Preferred controller choice: low dose ICS. Reliever therapy: as-needed SABA)
 Other controller options:
1. LTRA ( Leukotriene receptor antagonists)
2. Low dose of Theophylline
STEP 3 (Preferred controller choice : Low dose ICS/LABA. Reliever therapy: as-needed
SABA, or low dose ICS/formoterol )
 Other controller options: Medium/high dose ICS; Low dose ICS+LTRA ( or +
Theophylline)
STEP 4 (Preferred controller choice: medium/high ICS/LABA . Reliever therapy: as-needed
SABA or low dose ICS/formoterol )
 Other controller options:
1. Add Tiotropium
2. High dose ICS + LTRA ( or + Theophylline)
STEP 5 (Preferred controller choice : Refer for an add-on treatment e.g anti-IgE. Reliever
therapy: as-needed SABA or low dose ICS/formoterol )
 Other controller options:
1. Add Tiotropium
2. Add low dose OCS
TREATMENT OF ACUTE EXACERBATIONS
Short-acting Beta2-Agonists are the drugs of first choice for relief of bronchospasm
during acute exacerbations of asthma and for the pretreatment of exercise-induced
bronchoconstriction . Repeated inhalation are best to endure airflow obstruction
 Dosage of Salbutamol in acute exacerbation
Oxygen
Systemic Corticosteroids should be used in all asthma exacerbations (except the
lightest) because they mitigate the course and prevent their progression and early
relapse
 A typical short-term treatment with systemic Corticosteroids in exacerbation
of asthma lasts 5-7 days
 Dosage of Glucocorticosteroids
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If there is no improvement, after administration of β2-agonist in a patient
with moderate or severe exacerbation, consider adding Ipratropium Bromide
Dosage of Ipratropium Bromide
Magnesium sulfate - consider in a serious exacerbation, when other drugs are not
effective enough
Methylxanthines i.v - exceptionally, only when previous treatment is ineffective
Antibiotics should only be used in case of bacterial respiratory tract infections
 After the exacerbation of asthma, the dose of drug control should be
increased by 2-4 weeks
 A patient who has not previously been treated regularly should start using ICS