3. • Chronic inflammatory airway disease associated with
increased airway responsiveness and reversible airway
obstruction.
• It can present at any age; majority of cases
diagnosed in childhood
• Most of them become asymptomatic by adolescence
• Disease severity rarely progresses; patients with
severe asthma have it at the onset.
Pharmacotherapy of
bronchial asthma
What is bronchial asthma?
4. Asthma is one of the most common disease
encountered in clinical practice
300 million people suffer from asthma worldwide
out of which 30 million asthmatics are in India
According to WHO, India has the largest number of
asthma deaths in the world, contributing to 22.3% of
all global asthma deaths
Pharmacotherapy of
bronchial asthma
Burden of disease
5. Recurrent episodes characterized by:
• Breathlessness
• Wheezing
• Coughing- especially at night or early morning
• Tightness in the chest
• Hyperinflation
• Increased mucus production
Pharmacotherapy of
bronchial asthma
Clinical features
13. Mechanism:cause bronchial smooth muscle
relaxation by decreasing calcium, opening potassium
channels, inhibiting myosin light chain kinase (MLCK)
and stimulating myosin light chain
phosphorylase(MLCP)
Short acting drugs :Onset of action is 5
minutes,duration of action (4-6 hrs) & hence are drug
of choice for acute attack
Long acting drugs:Duration of action (12 hrs)&
hence at BD doses used for prophylaxis
Pharmacotherapy of
bronchial asthma
Beta-2 Agonists
14. Ultra long acting drugs : duration of action is
24 hrs & hence used at OD doses for
prophylaxis of asthma
Side effects :Tremors are most common due
to β2 receptor stimulation in skeletal muscles
Other-palpitations, QT prolongation
Pharmacotherapy of
bronchial asthma
Beta-2 Agonists Contd…
17. • Trials comparing salmeterol with placebo found increased
mortality and exacerbations in salmeterol group
• Discontiuation of ICS after LABA results in increased markers
of inflammation
• Black box warning issued by FDA on all LABA
• Postulated mechanisms are:
A direct deleterious effect on bronchial smooth muscle
Maintenance of lung function despite worsening inflammation; so
that patients tend to delay seeking treatment for an
exacerbation
Pharmacotherapy of
bronchial asthma
Safety issues of LABA
18. • These drugs mainly cause dilation of large airways
• Less effective than beta-2 agonists as they inhibit
only the cholinergic reflex component of
bronchoconstriction
• These drugs are not approved by FDA but used off
label in patients not responding to or intolerant to β2
agonists
• Combined with β2-agonists in treating acute severe
asthma
Pharmacotherapy of
bronchial asthma
Anticholinergics
20. • Ipratropium : short acting (6 hrs) & hence can
be used for an acute attack of bronchial
asthma
• Oxitropium: Intermediate acting & can be
used in nocturnal asthma
• Tiotropium : longest acting(24 hrs) & used in
long term prophylaxis in combination with
corticosteroids
Pharmacotherapy of
bronchial asthma
Anticholinergics Contd…
21. Drugs include :
Theophylline, Aminophylline, Theobromine
Mechanism :
Act by inhibiting Phosphodiesterase which is involved
in breakdown of cAMP & by blockade of adenosine
receptors
Inhibition of phosphodiesterase in lymphocytes gives
additional anti-inflammatory effect
Pharmacotherapy of
bronchial asthma
Methylxanthines
22. Theophylline can be used by oral route at a dose of 8
mg/kg BD for persistent asthma along with inhalational
corticosteroids
Aminophylline can be used by I.V route with a loading
dose of 6mg/kg followed by 0.5 mg/kg/hr for
treatment of Acute attack of asthma
Pharmacotherapy of
bronchial asthma
Methylxanthines Contd…
Theophylline has a low therapeutic index and hence
therapeutic monitoring is done to maintain plasma
concentration within range i.e 5-15 mg/L
23. These are potent anti-inflammatory drugs & also
decrease bronchial hyperactivity & mucosal edema.
Mechanism: Arachidonic acid (AA) is released
from the membrane phospholipids with the help of
enzyme phospholipase A2 that is
inhibited by corticosteroids. AA is converted to PG
and TX by cyclooxygenase and to LT
with the help of enzyme 5-lipooxygenase (5 LOX).
Thus, these mediators are not generated
when corticosteroid therapy is initiated
Pharmacotherapy of
bronchial asthma
Corticosteroids
24. • Steroids are used if patient has to use SABA more
than 2 times a week for symptomatic relief
• Systemic steroids have a lot of adverse effects,
therefore are reserved for resistant severe chronic
asthma and in status asthmaticus
• Hydrocortisone( 100 mg bolus) is I.V. Steroid of
choice as it is fastest acting systemic steroid
• Oral prednisolone can be used for persistent asthma
Pharmacotherapy of
bronchial asthma
Corticosteroids
25. • Inhalational corticosteroids are drug of choice for
persistent asthma
Pharmacotherapy of
bronchial asthma
Corticosteroids Contd..
Beclomethasone dipropionate 200-400 g BD
Flunisolide 25 g BD
Budesonide 200-400 g BD
Fluticasone propionate 100-250 g BD
Ciclosenide 40 – 160 g OD
26. Synergism between steroids and β2 agonists
• They interact with each other to potentiate their
actions
• Steroids:
a) Increase transcription of β2 receptor gene in airway
mucosa
b) Prevent downregulation of β2 receptors
• β2 agonists:
a) Enhance binding of Glucocorticoid Receptors to
DNA
b) Increase in translocation of Glucorticoid Receptors
to the nucleus
27. • Lipooxygenase inhibitors:
Zileuton inhibits synthesis of LTB4 (chemotactic) ,
LTC4 and LTD4 (bronchoconstrictor).
Limitions- short duration of action and hepatotoxicity.
• Leukotrine receptor antagonists:
Montelukast and zafirlukast inhibit the
bronchoconstrictor action of Leukotrines
Prophylactic agents for bronchial asthma, few cases of
Churg Strauss syndrome (vasculitis with eosinophilia)
have been associated with their use.
Pharmacotherapy of
bronchial asthma
28. • Sodium cromoglycate and nedocromil prevent the
degranulation of mast cells by trigger
stimuli indicated only for prophylaxis of bronchial
asthma given by inhalational route.
• Ketotifen has antihistaminic action apart from mast
cell stabilizing property and is specially indicated for
patients with multiple disorders (atopic dermatitis,
perennial rhinitis, conjunctivitis etc.).
Pharmacotherapy of
bronchial asthma
Mast cell stabilizers
29. Omalizumab is a monoclonal antibody against
IgE and is indicated to prevent the attack of
bronchial asthma in patients not responding to
combination of long acting β2 agonist and a
high dose of inhalational steroid. It is
administered by Subcutaneous route
Pharmacotherapy of
bronchial asthma
Drug inhibiting IgE Action
30. Allergic asthma :
Most easily recognized asthma phenotype
Often commences in childhood
Associated with a past and/or family history of
allergic disease such as eczema, allergic rhinitis, or
food or drug allergy.
Examination of sputum reveals eosinophilic airway
inflammation
Respond well to inhaled corticosteroid (ICS)
treatment.
Pharmacotherapy of
bronchial asthma
Phenotypes
31. Non-allergic asthma :
The sputum of these patients may be neutrophilic,
eosinophilic or contain only a few inflammatory cells
(paucigranulocytic).
Patients with non-allergic asthma often respond less
well to Inhaled corticosteroids
Pharmacotherapy of
bronchial asthma
32. Late-onset asthma :
Women, present with asthma for the first time in
adult life, non-allergic and often require higher doses
of ICS or are relatively refractory to corticosteroid
Asthma with obesity :
Some obese patients with asthma have prominent
respiratory symptoms and little eosinophilic airway
inflammation
Pharmacotherapy of
bronchial asthma
33. Acute severe asthma :
Uncontrolled asthma progress to an acute state in
which inflammation, airway edema, mucus
accumulation and severe bronchospasm - profound
airway narrowing, poorly responsive to bronchodilator
therapy.
Chronic Asthma :
Asthma can vary from chronic daily symptoms to only
intermittent symptoms.
Intervals between symptoms may be days, weeks,
months or years.
Pharmacotherapy of
bronchial asthma
35. The long-term goals of asthma management are:
• To achieve good control of symptoms and maintain
normal activity levels
• To minimize future risk of exacerbations, fixed
airflow limitation and side-effects.
It is also important to elicit the patient’s own goals
regarding their asthma, as these may differ from
conventional medical goals.
Pharmacotherapy of
bronchial asthma
Goals of manangement
36. Identify and reduce exposure to risk factors
• Clinician should evaluate potential role of allergens,
particularly indoor inhalant allergens
• Reduce, if possible, exposure to allergens to which
the patient is sensitized
• Avoid exposure to environmental tobacco smoke and
other respiratory irritants
• Avoid exertion outdoors when levels of air pollution
are high
37. Pharmacotherapy of bronchial
asthma
Pharmacological and non-pharmacological treatment
is adjusted in a continuous cycle that involves
assessment, treatment and review
Asthma outcomes have been shown to improve after
the introduction of control-based guidelines
CONTROL-BASED ASTHMA MANAGEMENT
38. Pharmacotherapy of bronchial
asthma
Medication is adjusted up or down in a Stepwise
approach to achieve good symptom control and minimize
future risk of exacerbations, fixed airflow limitation
and medication side-effects. Once good asthma control
has been maintained for 2–3 months, treatment may be
stepped down in order to find the patient’s minimum
effective treatment
.
STEPWISE approach for asthma Rx
41. For Step 4 treatment, add-on tiotropium is now
extended to patients aged ≥12 years with a history of
exacerbations
For Step 5 treatment, add-on treatment options for
patients with severe asthma uncontrolled on Step 4
which includes mepolizumab (anti-IL5) for patients
aged ≥12 years with severe eosinophilic asthma
Pharmacotherapy of
bronchial asthma
What’s new in GINA 2016 guidelines
42. Pharmacotherapy of bronchial
asthma
If a patient has persisting symptoms and/or
exacerbations despite 2–3 months of controller
treatment, assess and correct the following common
problems before considering any step up in
treatment:
• Incorrect inhaler technique
• Poor adherence
• Persistent exposure to agents such as allergens,
tobacco smoke, indoor or outdoor air pollution, or to
medications such as beta-blockers or NSAIDs
• Comorbidities that may contribute to respiratory
symptoms and poor quality of life
• Incorrect diagnosis
43. Pharmacotherapy of bronchial
asthma
o For adults and adolescents, the preferred step-up
treatment is combination ICS/long-acting beta2-agonist
(LABA).
o For children 6–11 years, increasing the ICS dose is
preferred over combination ICS/LABA.
• Consider step down once good asthma control has
been achieved and maintained for about 3 months, to
find the patient’s lowest treatment that controls both
symptoms and exacerbations
44. Status Asthmaticus
• Acute asthmatic attack not responding to
routine treatment & β2 agonist, life
threatening condition
• Precipitated by:
– Acute respiratory infection
– Abrupt cessation of steroid therapy
– Pharmacological stimuli/allergens
– Acute emotional stress
45. Status Asthmaticus (Cont’d
• Hydrocortisone Hemisuccinate 100mg iv stat 4-8
hourly infusion (take 6 hours to act)
• Nebulized salbutamol (2.5-5mg) + Ipratropium
Bromide (0.5mg)
• High flow humidified O2
• Salbutamol/Terbutaline 0.4mg S.C/I.M
• Intubation and mechanical ventilation
• Antibiotics
• Saline + Sod. Bicarbonate
47. Exercise-induced bronchospasm
• Pretreatment before exercise-
Inhaled beta2-agonists- prevent EIB in more than
80 percent
SABA use may be helpful for 2–3 hours
LABAs can be protective up to 12 hours
Leukotrine receptor antagonist can attenuate EIB in
up to 50 percent of patients
Cromolyn or nedocromil taken shortly before
exercise is an alternative
48. Surgery and Asthma
• Attempts made to improve lung function
preoperatively
• Short course of oral systemic corticosteroids may
be required
• For patients who have received oral systemic
corticosteroids during the past 6 months and for pts
on a long-term high dose of ICS
• 100 mg hydrocortisone every 8 hours i.v during the
surgical period & reduce dose rapidly within 24 hours
after surgery
49. Pregnancy and Asthma
• Asthma increases risk of preterm birth, IUGR and
perinatal mortality.
• NEVER WITHHOLD TREATMENT
• Monitoring of asthma status during prenatal visits
• Albuterol is the preferred SABA because it has an
excellent safety profile
• ICS are the preferred treatment for long-term
control medication
• Budesonide is the preferred ICS because more data
are available
52. METERED DOSE INHALER
1. Take off the
cap. Shake the
inhaler well.
2. Breathe out
though your
mouth.
3. Place the inhaler
between your lips. As
you start to breathe
in, press the top end
of the inhaler and
keep breathing in
steadily and deeply.
4. Remove the inhaler
from your mouth. Hold
your breath for 10
seconds or as long as
you find comfortable.
Breathe out.
53. The Spacer is a holding chamber which can be
attached to the Metered Dose Inhaler.
1. Assemble the
Spacer by
pushing the
notch of one half
into the slot of
the other half.
2. After shaking
the inhaler well,
fit it into the
Spacer.
3. Breathe out
through your
mouth. Then close
your lips around
the Spacer.
4. Press the top
end of the
inhaler. Then,
breathe in
deeply though
your mouth.
SPACER
54. Dry Powder Inhalers
1. Insert the
transparent end of
the Rotacap into
the raised square
hole of the
rotahaler.
2. Hold the top of
the Rotahaler firmly
with one hand.
Rotate the base until
the capsule breaks.
3. Breathe out
through your mouth.
Then, placing the
Rotahaler between
your lips (as shown),
breathe in though
your mouth as deeply
as possible.
4. Remove the Rotahaler
from your from your
mouth. Hold your
breathe for 10 seconds
or as long as you find
comfortable. Breathe
out.
55. Attach the hose and mouthpiece to the
medicine cup
Place the mouthpiece in your mouth.
Breathe through your mouth until all the
medicine is used, about 10-15 minutes.
Wash the medicine cup and mouthpiece
with water, and air-dry until your next
treatment
NEBULISERS
2 types: Jet nebulisers
Ultrasonic nebulisers
57. INDICATEROL:
Inhaled once-daily β2 agonist
Onset of action faster than salmeterol
Duration of action ~ 24 hrs
Has been approved only for COPD
Clinical trials in asthma underway to test safety and
efficacy of once-daily combination of indacaterol
with mometasone
Pharmacotherapy of
bronchial asthma
61. Mapracorat: Selective glucocorticoid receptor
agonist that targets receptors for inflammation only
& is devoid of systemic side effects
Abediterol: Ultra LABA under trial for bronchial
asthma prophylaxis
Recently MgSo4 by I.V. and inhalational route has
been tried for acute severe asthma.
Recent advances Contd…
62. Pharmacotherapy of bronchial
asthma
Allergen-specific immunotherapy may be an option if allergy
plays a prominent role, e.g. asthma with allergic
rhinoconjunctivitis.
There are currently two approaches:
Subcutaneous immunotherapy (SCIT) and
Sublingual immunotherapy (SLIT).
Allergen Immunotherapy
63. Bronchial Thermoplasty
• Catheter introduced through a
bronchoscope
• It delivers thermal energy to the
airway wall to reduce excess
smooth muscle
• Increases symptom-free days,
improves PEFR and reduces the
use of reliever medicines.
• FDA approval obtained in 2010
for treatment of severe asthma.
Cho JY. Recent Advances in Mechanisms and Treatments of Airway Remodeling in Asthma: A Message from
the Bench Side to the Clinic. Korean J Intern Med 2011; 26:367-383
64. Influenza causes significant morbidity and mortality
in the general population, and the risk can be reduced
by annual vaccination. Influenza contributes to some
acute asthma exacerbations, and patients with
moderate-severe asthma are advised to receive an
influenza vaccination every year
Pharmacotherapy of
bronchial asthma
Vaccination
65. Asthma is a serious global health problem affecting
all age groups
Despite of better understanding of
Pathophysiology
Presence of reliable diagnostic tools,availability of a
wide range of effective & affordable drugs
Simplified national and international asthma
management guidelines
Asthma remains poorly managed across the globe
Pharmacotherapy of
bronchial asthma
SUMMARY
66. Global Initiative for Asthma. Global Strategy for Asthma
Management and
Prevention, 2016. Available from: www.ginasthma.org
Asthma insights & management in India; JAPI
(SEP. 2015 vol.63)
Medicine Update 2016:volume 2 (Gurpreet
S Wander,kk Pareek)
Crofton & dougla’s respiratory diseases:5th edition
Goodman and Gilman's -12th The Pharmacological basis of
therapeutics
Pharmacotherapy of
bronchial asthma
REFERENCES
67. Principles of pharmacology-HL Sharma & kk sharma
Harrison’s principles of internal medicine:19th edition
Tiotropium respimat:a review of its use in asthma poorly
controlled with ICS & LABA { DRUGS vol.75}
Pharmacotherapy of
bronchial asthma