Clinical Pharmacy

ASTHMA
Lecture # 1
By
Ms. Fakhsheena Anjum
 Learning objectives
At the end, the students will be able to:
• Know etiology of the disease
• Learn about pathophysiology of the
disease
• Distinguish the clinical features of the
disease
• Know about the diagnosis of the disease
 Introduction
• Attacks of breathlessness, wheezing and
chest tightness, usually reversible
spontaneously or on treatment,
characterized by wide variations in intra
pulmonary airways resistance over short
periods of time
• Attacks associated with airways
inflammation and increased bronchial
hyperactivity to a variety of stimuli
 Contd…
• Extrinsic or episodic asthma
• Intrinsic or cryptogenic asthma
• Indicators of poorer prognosis are
1. Severe or early onset
2. Persistent attacks
3. An atopic patient
4. Family history of atopy
5. Female sex
 Etiology
• Specific abnormality is hypersensitivity of
lungs in patients with chronic bronchitis
and allergic rhinitis (to a lesser extent)
• Most common trigger factor is allergen in
feces of house dust mite
• Causes precipitating asthma can be
environmental, medical or occupational
Asthma
 Pathophysiology
• Underlying problem is intense airway
inflammation causing bronchial hyper
reactivity
• Inflammation present in asymptomatic
patients
• Following viral respiratory tract infection,
airways of non asthmatics more sensitive
than usual for up to 6 weeks
 Contd..
• Asthmatics up to 100 times more sensitive
than normal subjects
• Precise cause of this hyper reactivity
unknown
• Most significant factor is inflammation
• In acute attack, epithelium is damaged
 Contd..
• Variety of inflammatory mediators are
released causing bronchiolar smooth
muscle contraction, marked edema of
bronchial mucosa, epithelial shedding and
receptor exposure
• Goblet cell hyperplasia causes
hypersecretion of mucus which may plug
smallest airways
 Contd..
• Broncho-constriction may also be
mediated by cholinergic action via vagus
nerve
• About 80% asthmatics suffer nocturnal
attacks (morning dipping), during which
peak flow may fall by as much as 50%
• Tendency to nocturnal attacks
exacerbated by allergen exposure;
principal factor is physiological changes
 Contd..
• Fish oil diet may be beneficial by
promoting formation of 5 series
leukotrienes from arachidonic acid
• Exercise induced asthma in younger
people
• Occupational asthma causes about 5-10%
of cases in age 20-44 years
 Clinical features
• Classic symptoms are attacks of
breathlessness, wheezing and cough
which start within 15 minutes
• Depending on attack’s severity, peak flow
may fall to 25-75% of those recorded
between attacks and usually recover over
a period of 60-90 minutes without
treatment, but more promptly on use of a
bronchodialtor (in 20% patients)
 Contd..
• About 50% of asthmatics experience
delayed attacks and 30% suffer both
immediate and delayed attacks
• Dyspnoea in asthmatics
• In a severe attack, there will be
hyperventilation and hyperinflation
 Contd..
• Peak flow may fall below 100L/ml and
heart rate may exceed 120/ minute with
palpable pulsus paradoxus and peripheral
cyanosis
• Many patients experience a variety of non
respiratory symptoms before attack
 Diagnosis
• Based on history, examination and
investigation
• Patients with episodic asthma may appear
completely normal between attacks unless
they have chronic symptoms or
provocation testing is used
 Thanks
Any questions??
• Reference

• Pathophysiology and therapeutics for

Pharmacists, 2nd ed. By: Russell J Greene,
Norman D Harris.
• Pages 235-261
Clinical Pharmacy
ASTHMA
Lecture # 2
By
Ms. Fakhsheena Anjum
 Learning objectives
At the end, the students will be able to:
Investigations
Diagnostic problems
General management measures
general aspects of pharmacotherapy
Investigations for acute attacks
• Forced expiratory ratio < 0.65
(Fe1V1/FVC)
• FeV1/FVC = 80% (normal)
• FeV1/FVC = 50% (moderate disease)
• FeV1/FVC =30% (severe disease)
• PEF reduced to 80% of predicted normal
value or less
 Contd..
• Flow volume loop show air trapping with
increased TLC and RV
• Blood gases
• WBC
• Reversibility with inhaled B agonist
Investigations for severe attacks
• Retention of carbondioxide may be
indicated; central cyanosis is a serious
sign
• Pulsus paradoxus may be present in
severe attack
• A difference in pulse pressure between
inspiration and expiration greater than 5-
10 mmHg is abnormal; may be difference
of 20-40 mm Hg between weak and strong
beats
 Other investigations
• IgE blood levels raised and determined by
RAST procedure
• Prick testing with allergens to ascertain
etiology
• Bronchial challenge
• Exercise stress testing
 Diagnostic problems
• Cough
• Diagnosis in very young children
• Delayed attacks
• Recurrent chest colds or wheezy
bronchitis in children
• Persistent air flow obstruction in older
patients
 Contd..
• Paroxysmal nocturnal dyspnoea (PND)
• Cor pulmonale
• Recurrent respiratory tract infections
• Persistent large airways obstruction
 Management
Aims are
• To control symptoms, minimize anxiety
and permit as normal a life is possible
• To educate the patient about disease and
its treatment
• To identify triggers, thus minimizing
morbidity and preventing mortality
General management measures
• Environmental control
• Reduce stress
• Control infections promptly
• Physiotherapy
• Patient counseling
 General aspects of
pharmacotherapy
• Drug treatment often thought of in terms of
either prophylaxis or relief of symptoms
• Both approaches can be used
concurrently and combination therapy is
normal
 General strategy
1. Inflammation and bronchial hyper reactivity:
Reduce (a) eosinophil recruitment and
activation, (b) lymphocyte activity, (c) toxicity
to epithelial cells and (d) mast cells etc.
degranulation.
• Corticosteroids like beclometasone,
budesonide and prednisolone are used (a-c)
and Inhibitors of mediator release like sodium
cromoglicate, selective B2 agonist and
theophylline can be used (d)
 Contd..
2. Bronchoconstriction: for Bronchodialtion, (a)
increase sympathmimetic activity, (b) block
parasympathetic activity, (c) increase cAMP
levels in bronchiolar muscle cells
 Contd..
Selective B2 agonists like salbutamol,
terbutaline, fenoterol, etc used. Besides,
long acting bambuterol, salmeterol and
eformoterol used for (a)
Antimuscarinics like ipratropium used for
(b), phosphodiesterase inhiitors like
aminophylline, theophylline and sodium
cromoglicate used for (c)
 Contd..
• Stepwise addition of medication used after
diagnosis
• If attacks are frequent, or moderate to
severe, prefer to gain control of symptoms
promptly with greater initial intervention
and to ‘step down’ treatment once this has
been achieved
 Contd..
• All changes of treatment should be
validated monitoring carefully PEF and
medicine usage
• Sedatives must never be used as may
further depress an already compromised
respiratory function
 Treatment in an acute attack
• Occasional attacks be treated with an
inhaled selective B2 agonist
bronchodilator
• If a consistent trigger can be identified,
prior use of a short acting bronchodilator
inhaler or regular use of corticosteroid
inhaler is used
 Contd..
• For more frequent or severe episodes,
routine prophylactic treatment with B2
bronchodilator plus inhaled regular
corticosteroids esp. in adults be done
• In children >4 years, a cromone be used
as regular prophylactic esp. sodium
cromoglicate for exercise induced asthma
 Contd..
• For children <4 years, ipratropium bromide
is useful
• Nedocromil sodium more appropriate for
adults
• May take 3-4 weeks to establish level of
response to prophylactic inhalation
therapy, so persistence is required
 Contd..

• Patients aged > 50 years should receive

antimuscarinic agent ipratropium bromide
• High dose inhaled corticosteroids are for
those who do not respond adequately to
normal doses
 Contd..
• Alternatively, an inhaled long acting B
agonist, e.g. formoterol or salmeterol may
be added to a low dose corticosteroid.
Sodium cromoglicate may also be helpful
• Oral slow release methylxanthines like
theophylline may be introduced too
• They should be tried first when oral
steroids are contemplated
 Contd..

• However, sever acute exacerbations may

require short course of an oral steroid
• For morning dipping, inhaled long acting
B2 agonist is used
• Bambuterol may also be useful
 Thanks
Any questions??
• Reference

• Pathophysiology and therapeutics for

Pharmacists, 2nd ed. By: Russell J Greene,
Norman D Harris.
• Pages 235-261
Clinical Pharmacy
ASTHMA
Lecture # 3
By
Ms. Fakhsheena Anjum
 Learning objectives
At the end, the students will be able to:
1. Know about chronic adult asthma and its
treatment
2. Know about childhood asthma and its
necessary treatment
3. Know about immunotherapy of asthma
 Chronic adult asthma
• Management is same as that for acute
attack, but the basis being a high dose
inhaled corticosteroid with a short acting
B2 agonist reliever fro breakthrough
attacks
• Long acting B2 agonists and a
methylxanthine may be added later
 Contd..
• If necessary, a further bronchodilator may
be added, including an inhaled
antimuscarinic or an oral modified release
long acting B2 agonist
• High dose inhaled steroids are always
needed but many patients will need oral
prednisolone in addition
 Contd..
• Even with oral steroid medication, high
dose inhaled corticosteroids should always
be continued to minimize oral dose
required.
• In exceptional circumstances, cytotoxic
drugs have been used to spare oral
corticosteroid dose
• Morning dipping is best managed with bed
time dose of a long acting inhaled B2
agonist
 Acute and severe life threatening
asthma
• These attacks are not relieved by patient’s
normal medication and is sometimes
called status asthmatics
• Most such attacks do not develop very
acutely but preceded by warning signs
which are indications for aggressive
therapy to abort them
 Contd..
• The signs are:
1. Decreasing exercise tolerance
2. Increasing respiration rate, dyspnoea
and sleep disturbance
3. Increasing diurnal variation in PEF
4. Medication becoming less effective, with
increased bronchodilator usage
 Contd..
• Acute severe asthma is characterized by:
1. Pulse ≥ 110 beats/min in adults or ≥
120/min in children under 5 years
2. Respiration rate ≥ 25 breaths/min at rest
in adults, ≥ 40/min in children under 5
years
3. In young children, use of accessory
muscles of respiration
 Contd..
4. Inability to speak in complete sentences
or in young children, inability to talk or feed
5. Decreasing PEF, which may drop below
100 L/min or 34-50% of patient’s predicted
or best value in adults, and ≤ 50% in
children who can give reliable readings
6. Diurnal variation in PEF > 25%
 Contd..
• In an acute life threatening attack there may
also be:
1. A silent chest or a feeble respiratory effort
2. Bradycardia
3. Exhaustion
4. Confusion or coma in adults, agitation or
reduced consciousness in young children, who
may not appear to be distressed
 Contd..
5. Cyanosis in adults
6. Peak flow ≤ 33% of patient’s predicted or
best value
7. If blood gases are measured, PaCO2 ≥ 6
kPa i.e. acidosis (pH < 7.35); and severe
hypoxia, PaO2 < 8 kPa
 Contd..
• Sometimes severity of symptoms may be
masked by over enthusiastic use of B2
agonists, esp. with a nebulizer
• A severe attack is impending and treat
aggressively at first signs to gain control
and prevent deterioration as its more
difficult to treat severe symptoms once
established
 Contd..
• Even large doses of B2 agonist
bronchodilators and corticosteroids are
safe in short term
• Patients are often unresponsive to
bronchodilators in severe attacks, so it
may be dangerous to persist with because
they may aggravate hypoxia
 Contd..
• If patient is unresponsive to a nebulized
or parenteral B2 agonist, it may be better
to use iv aminophylline, having different
mode of action
• Patients at most risk are aged between 12
and 25 years of age, who are immigrants,
migrant workers and holidaymakers
 Contd..
• Patients may also include those who:
1. Were in hospital for asthma in the
previous year
2. Have a history of severe attacks
3. Use regular or occasional oral or
nebulized corticosteroids
4. Initiated an emergency call
 contd..
• In addition, these patients may have:
1. Progressive symptoms or signs
2. Exposure to seasonal or occupational
allergens
3. Psychological problems
 Contd..
• General management strategy is empirical
and needs to be considered in in the light
of patient’s current therapy
• A nebulized B2 adrenergic bronchodilator
and oral corticosteroids can be given with
slow iv bolus of aminophylline
 Contd..
• If patient is already taking oral
theophylline, iv dose should be halved and
patient observed for cardiac arrhythmias
• Lack of satisfactory response then
indicates need for an iv steroid and
oxygen as required and patient being
admitted to hospital
• Emergency self admission schemes may
be life saving
 Contd..
• Following admission, PEF, blood gases
and serum electrolytes are monitored.
• There may be risk of severe hypokalemia
• Self management plans should be
educated to patients regarding dose of
inhaled corticosteroid or antibiotics
 Contd..
• A few patients are brittle asthmatics and
suffer severe attacks with very few or none
warning signs
• Peak flow charts of these patients show a
chaotic pattern
• They need reserve oral corticosteroid
supply and nebulizer for immediate
intensive treatment; must also obtain
expert assistance
 Childhood asthma
• A range of specially designed spacers and
face masks for use with MDIs is available
for young children
• For older children, breath actuated MDIs
or dry powder inhalers are preferred
• Nebulized drugs or oral medication may
be used at any age, esp. in infants and
during severe attacks
 Contd..
• However, route of administration has to be
tailored according to children
• Regular monitoring is important
• Management is similar to that in adults
• However, adrenergic bronchodilators are
ineffective in young children as only a
small dose reaches the lungs; nebulized
ipratropium bromide or oral
methylxanthines can give better results
 Contd..
• Methylxanthines be used carefully as
theophylline use has been associated with
behavioral and learning difficulties
• For first line prophylaxis, sodium
cromoglicate or low dose corticosteroids
are recommended and sodium
cromoglicate or long acting B2 agonist for
exercise induced bronchoconstriction
 Contd..
• Higher dose of inhaled corticosteroids are
can be administered via spacer device if
required
• Use of oral corticosteroids be avoided as
they retard growth, even if given in
alternate day dose and nebulized
budenoside can be helpful
• Growth retardation can also be a
consequence of severe asthma
 Immunotherapy:hyposensitization
• Desensitize patient to allergens
• Episodic asthma associated with high
levels of IgE, so prevent its production and
resultant hypersensitivity reaction, if
possible
• Atopic patients can be sensitized to other
allergens as well later
• The term immunotherapy includes
blocking of release or actions of
inflammatory agents
 Thanks
Any questions??
• Reference

• Pathophysiology and therapeutics for

Pharmacists, 2nd ed. By: Russell J Greene,
Norman D Harris.
• Pages 235-261