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ASTHMA

Definition
Asthma is a chronic inflammatory
disorder in which the airways
constrict occasionally, become
inflamed and lined with excess
mucus usually in response to one or
more triggers.

Etiology
Allergens:( e.g. pollen, house dust mites)
Occupational exposures: (e.g. chemical
irritants )
Viral irritants: (e.g. common cold viruses)
Exercise
Emotions: (e.g. anxiety, hard laughter or
crying)
Environmental exposures: (e.g. weather
changes, strong odors, fumes)
Drugs: (e.g. NSAIDs esp. aspirin and other )

Pathophysiology
Airway obstruction: a result of
bronchoconstriction,airway wall edema,mucus
plug formation.
Airway inflammation: contributes to airway hyper
responsiveness, airway obstruction,respiratory
symptoms and disease chronicity.
Inflammatory cells: (e. g. mast cells, eosinophils)
secrete mediators and influence the airways
directly or via neural mechanisms.
Hyper responsiveness: this an exaggerated
response to certain stimuli.

Classification
Mild intermittent: symptoms less or equal to 2x
a week
Mild persistent: symptoms > 2x a week but not
every day.
Moderate persistent: daily symptoms with daily
use of inhaled short acting beta agonist.Attacks
affect daily activity.
Severe persistent: continual symptoms: limited
physical activity, frequent exacerbations.
Chronic persistent asthma: manifests as regular
coughing, wheezing and breathlessness
Acute severe asthma: potentially life
threatening.

Signs and symptoms


Acute exacerbations may have a sudden or gradual
onset.Symptoms are often nocturnal or occur in the
early morning hours or may be exercise induced:
Shortness of breath (dyspnea)
Wheezing
Chest tightness
Cough
Tachypnea & tachycardia

Complications of asthma
Pneumothorax: accumulation of air in
the pleural space , during an acute
asthma attack.
Atelectasis: or collapsed lung, inhibits
gas exchange during expiration and
may occur as a result of airway
obstruction.
Impaired/reduced physical activity
Deformities i.e. barrel chest,decreased
diaphragmatic excursion.
`

Treatment objectives

The treatment goals include:


- Prevent chronic and troublesome symptoms
- Maintain (near to) normal pulmonary function
- Maintain normal activity levels (including
exercise & other physical activity)

Prevent recurrent exacerbations of asthma &


reduce the need for emergency department
visits and hospitalizations.

Pharmacological treatment

Selective beta2 agonists


Glucocorticoids
Xanthines
Mast cell stabilizers
Leukotriene receptor antagonists
Anticholinergics
Other systemic drugs

1. Selective beta2 agonists


Short-acting eg salbutamol, fenoterol,
hexoprenaline and terbutaline.
Long acting for long-term, regular
treatment of asthma and other
conditions eg salmeterol, formoterol.

1. Salbutamol
MOA: stimulate 2 causing
bronchodilation and improved
mucociliary clearance.
Pharmacokinetics: metabolized in the GI
wall and liver; excreted in the urine.
Has quick onset on action but effects are
short-lived.
bronchodilation occurs in 5-15 minutes if
IV or within 30minutes after oral dosing.

Salbutamol contd
Contraindications:
use with caution in cardiac conditions.
may delay labor if given near term.
Drug interactions:
Corticosteroids: risks of hypokalemia,hyperglycemia
and pulmonary edema are increased.
Adverse effects:
Fine tremors, nervousness, headache, cardiac
stimulation with tachycardia and palpitations.
Forms
Available in oral, aerosol and injectable forms

2. Glucocorticoid
Classification
Short-acting e.g. hydrocortisone (8-12hrs).
Intermediate acting e.g. prednisone (8-36hrs).
Long-acting e.g. Dexamethasone (36-54hrs).
Mode of Action: suppress the inflammation by:
1.reducing production of inflammatory mediators
2. Decreasing mucus production

Glucocorticoids (contd)
Pharmacokinetics: metabolized in the liver;
excreted in the urine, highly protein bound
Interactions: Concurrent use of Cyt.P450
inducers(e.g. rifampicin) enhances steroid
metabolism and may reduce efficacy.
Forms: Oral, inhaled & injectables
Examples:
Inhaled: beclomethasone, budenosine
Oral: fluticasone, prednisone,
dexamethasone

Precautions
Systemic corticoids should be carefully monitored in
patients with diabetes, hypertension, CHF, peptic ulcer
disease, immunosuppression, osteoporosis, chronic
infection etc.
Patients who receive moderate to high doses of inhaled
steroids via metered dose hailers should be provided
with spacers and counseled on how to use them.
Patients on inhaled corticosteroids should be advised to
gargle, rinse their mouth and throat and expectorate
after each administration. These interventions reduce
oropharyngeal deposition, local adverse reactions like
dry mouth, hoarseness and fungal infection of the
mouth and throat and also reduce GI absorption.

Withdrawal of steroids
Prolonged therapy may result in suppression
of steroid genesis & in the event of abrupt
withdrawal, endogenous levels may be
insufficient to meet bodily demands, hence
tapering or gradual withdrawal of the drug is
recommended.
If complete withdrawal is not possible, the
lowest dose that can control the disease
should be used.

3.Xanthines
Examples
Theophylline
Aminophylline a combination of
theophylline with ethylenediamine which
dissociates in the stomach to be
absorbed as theophylline.
Ethylenediamine is added to confer
greater solubility in water.

Theophylline
MOA:
Cause bronchodilation, reduced mucus
secretion, enhanced mucociliary transport,
improved diaphram contractility and antiinflammatory activity.
Pharmacokinetics
Has a very narrow therapeutic index. Therapeutic
drug monitoring is done to achieve & maintain
therapeutic non-toxic levels.
An overdose may cause seizures or potentially fatal
arrhythmias.
NB: Half life is prolonged in premature infants and the
elderly.

Theophylline contd
Contraindications
Theophylline is contraindicated ischemic heart
disease, peptic ulcer disease and uncontrolled
seizures.

Drug interactions
Cimetidine, erythromycin- hepatic
biotransformation, therefore plasma theophylline
levels.
Smoking, hepatic enzyme inducers, alcohol,
barbiturates- hepatic metabolism hence
efficacy.
Adverse effects
GI effects: nausea, anorexia, diarrhea.
Mental: Insomnia, dizziness, seizures

4. Mast cell stabilizers .eg. sodium cromoglycate.


MOA:
Antiinflammatory - stabilize mast cells and inhibit
mast cell degranulation.
Use in Prophylaxis
Prevents asthma induced by exercise, cold air,
sulfur dioxide.
It is not effective during an asthma exacerbation
Side Effects
Bronchospasm, wheezing, coughing, nasal
congestion and irritation or dryness of the throat.

5. Leukotriene receptor antagonists


(e.g. Montelukast and Zafirlukast)
Have both bronchodilator and antiinflammatory activity by blocking the effects of
Leukotrienes in airways.
They have additive effects to inhaled
corticosteroids.
Are effective orally and response is within
24hours.

Montelukast
Pharmacokinetics: Oral bioavailability is 60-70%.
Duration of action is up to24hrs. Extensively metabolized
in liver, excreted via bile.
C/I: Caution in severe hepatic impairment.
Pregnancy & lactation: avoid.
Paeds: avoid in children under 6 years of age.
S/Es: Abdominal pain, dyspepsia, diarrhea, dizziness,
headache, fever, rash, nasal congestion, cough.
Hypersensitivity reactions: anaphylaxis, angiedema,
pruritus, urticaria.
Adult dose: oral, 10mg daily at bedtime.
Pediatric dose: Oral, 6-14 years, 5mg daily at bedtime.

Zafirlukast
Precautions, adverse effects & C/Is-same as for
Montelukast.
Drug interactions:
Warfarin -enhanced anticoagulant effects
Erythromycin&terfenadine - levels of zafirlukast
Theophylline - levels of zafirlukast
Dosing:
Adult dose: oral, 20mg twice daily, at least 1
hour before or 2 hours after meals.
Pediatric dose: Safety and efficacy not
established in children under 12 years.

6. Anticholinergics eg Ipratropium bromide:


MOA: Bronchodilation -block muscarinic
receptors
Pharmacokinetics: slow onset starting after 30
minutes & lasts 4 hrs.
C/I- Caution in prostatic hypertrophy or narrow
angle glaucoma.
Pregnancy: use if very necessary. Lactation- safe.
S/Es: Dry mouth, bitter taste, urinary retention,
constipation.

Other systemic drugs eg Ketotifen


Has antihistaminic effects and a stabilizing effect on
mast cells. May be a useful adjunct to bronchodilator
therapy in highly allergic children < 3 years who have
atopic eczema or hay fever in addition to asthma.
Adult dose: Oral, initially 0.5mg in the evening,
gradually to 1mg twice daily ( max 2mg twice daily).
Slow release: 2mg at night swallowed whole.
Pediatric dose: 14 kg, 0.3mg b.d daily, 14-25kg,
0.5mg b.d daily. Above 25kg, 1mg b.d daily. Slow
release, over 25kg, as for adults.

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