ST.

JOHN INSTITUTE OF PHARMACY

AND RESEARCH PALGHAR.

PHARMACOLOGY OF ASTHMA AND

COPD.
Presented by-Kendhale Raghunath J.
Roll No. 10
 Content
• Introduction of asthma.
• Pathophysiology of asthma.
• Introduction of COPD.
• Classification of drug.
• Inhalational devices.
• Steps involved in asthma.
 Asthma
• Asthma is a chronic, obstructive & reversible
lung disease in which there is inflammation &
narrowing of bronchial lumen.
• It is a hyperactive response to certain stimuli
characterized by wheezing, dysperia, coughing
& chest tightness.
 Three step problem
i. Airways inflammation.
ii. Airways hyper response to stimuli.
iii. Stimuli within airways contract
(bronchospasm).
Different types of airways in asthma
Types of Asthma
 Causes of asthma

▪ Infection
▪ Stress
▪ Exercise (cold air)
▪ Pets
▪ Seasonal changes
▪ Emotional conditions
▪ Some drugs as aspirin, β-bockers
Different symptoms
Pathophysiology of asthma
 COPD
CHRONIC

OBSTRUCTIVE
PULMONARY

DISEASE
 COPD:
• Chronic obstruction of the flow of air
through the airways & out of the
lungs.
• which is progressive & irreversible
COPD includes emphysema,
chronic bronchitis, bronchiectasis
& irreversible asthma.
• Chronic bronchitis: cough
associated with inflammation of the
bronchioles.
• Emphysema: permanent destruction
and enlargement of the airspaces
distal to the bronchioles
Causes and Symptoms of COPD
Pathophysiology of COPD
I Bronchodilators B. Methylxanthines
A.β2 Sympathomimetics: Theophylline (anhydrous),
Salbutamol, Aminophylline,
Terbutaline, Choline theophyllinate,
Bambuterol, Hydroxyethyl theophylline,
Salmeterol, Theophylline ethanolate-
Formoterol, of piperazine,
Ephedrine. Doxophylline.

C. Anticholinergics: II. Leukotriene antagonists

Ipratropium bromide, Montelukast,
Tiotropium bromide Zafirlukast.
III. Mast cell stabilizers
Sodium cromoglycate,
Ketotifen.
IV. Corticosteroids
A. Systemic:
Hydrocortisone,
Prednisolone and others.
B. Inhalational:
Beclomethasone dipropionate,
Budesonide,
Fluticasone propionate,
Flunisolide, V. Anti-IgE antibody-
Omalizumab
Ciclesonide.
Mechanism of Bronchodilation…
 Classification of  agonists

➢ Non selective  agonists:

epinephrine - isoprenaline
➢ Selective 2 – agonists (Preferable).
Salbutamol (albuterol)
Terbutaline
Salmeterol
Formeterol
 Short acting ß2 agonists drug,
Salbutamol:

MOA:

Salbutamol
Activation of Increased Reduced Smooth
binds and
adenylyl cyclic AMP intracellular muscle
activates Beta
cyclase levels calcium relaxation
2 receptors
 Short acting ß2 agonists drug,
Salbutamol:
Pharmacokinetics:
By inhalation for asthma. Short-acting (3–5h); can
be given i.v. in acute severe asthma.
Mainly excreted
unchanged.
 Short acting ß2 agonists drug,
Salbutamol:
Uses:
The acute asthmatic attack – used ‘as needed’. To
prevent exercise-induced asthma.
For chronic obstructive airways disease.
Side Effects:
Tremors, tachycardia, sometimes dysrhythmias,
nervousness, some peripheral dilatation.
Long acting selective ß2 agonists drug,
Salmeterol :

• Salmeterol are given by inhalation

• are not used to relieve acute episodes of asthma
• used for nocturnal asthma.
• combined with inhaled corticosteroids to control
asthma (decreases the number and severity of
asthma attacks).
Long acting selective ß2 agonists drug,
Salmeterol :

MOA:
Long acting selective ß2 agonists drug,
Salmeterol :
• Pharmacokinetics: By inhalation for asthma.
Long-acting (8–12h); Mostly metabolized by
P450 with significant amount lost in faeces.
Long acting selective ß2 agonists drug,
Salmeterol :
Advantages of selective ß2 agonists
• Minimal CVS side effects
• suitable for asthmatic patients
• CV disorders as hypertension or heart failure.

Disadvantages of selective ß2 agonists

• Skeletal muscle tremors.
• Nervousness, Tolerance.
• Overdose may produce tachycardia due to
β1stimulation.
Methylxanthine Bronchodilators…
• Methylxanthine are third or fourth line drugs in the
treatment of asthma.
• Methylxanthines are well absorbed after oral and
parenteral administration.
• Caffeine, theophylline and theobromine are naturally
occurring xanthine alkaloids which have qualitatively similar
actions.
• Theophylline and its derivatives are most commonly used
for the treatment of COPD and asthma.
Methylxanthine Bronchodilators drug,
Theophylline :

Mechanism of action :
Inhibit the
Theophylline phosphodiesterase

Changes the conc. the conc. Of

Of Ca2+ ion intracellular cAMP

Bronchodilation
Pharmacological action
Methylxanthine Bronchodilators drug,
Theophylline :
• Pharmacokinetics:

• Absorption: Absorbed orally; rectal absorption form

suppositories is erratic.
• Distribution: All tissues; cross BBM; crosses placenta
and is secreted in milk; 50% plasma protein bound
• Metabolism: Metabolized in liver (CYPP1A2) by
demethylation and oxidation.
• Excretion: Excreted in urine; 10 % of total
administration excreted unchanged form. Elimination
rate various considerably with age (age dependent
excretion).
Methylxanthine Bronchodilators drug,
Theophylline :

• Adult t1/2 is around 7-12 h. Children elimination is

much faster (t1/2 3-5 h); In premature infants has
prolonged t1/2 (24-36 h).

• In higher dose pharmacokinetics changes form first

order to zero order.
Methylxanthine Bronchodilators drug,
Theophylline :
Adverse effects of Theophylline :

Theophylline
Methylxanthine Bronchodilators drug,
Theophylline :

Bronchodilatation

Relationship between efficacy and toxicity of

Theophylline with its plasma concentration.
The depicted concentration ranges are approximate
Methylxanthine Bronchodilators drug,
Theophylline :
Drug interactions with Theophylline :
• Cimetidine/ciprofloxacin/erythromycin x
theophylline increases the action aminophylline.

Uses of Theophylline :
• Bronchial asthma and COPD
• Premature apnoea in infants.
 Anticholinergics or Muscarinic
Antagonists Bronchodilators…
• Ipratropium bromide and Tiotropium bromide are
atropine substitutes.
• Selectively blocks the effects of Ach in bronchial
smooth muscle and cause bronchodilation.
• Slow onset of action and are less effective.
• These drugs are preferred in COPD.
• Administered by inhalation route.
• Combination with B2- adrenergic
agonist have better effects.
 Anticholinergics drug,
Ipratropium Bromide
MOA: Ipratropium Block M3
Inhibit the
conversion of
Bromide receptors
PIP2 to IP2

Bronchodilator Decreases the

action Ca2+ion
 Anticholinergics drug,
Ipratropium Bromide
Pharmacokinetics :
• Ipratropium bromide is a short acting (duration
4–6 hours) inhaled anticholinergic
bronchodilator, while tiotropium bromide is long
acting (duration 24 hours).
• Both are less efficacious than inhaled β2
sympathomimetics in bronchial asthma.
• However, patients of asthmatic bronchitis, COPD
and psychogenic asthma respond better to
anticholinergics.
 Anticholinergics drug,
Ipratropium Bromide
Uses
• Main choice in chronic obstructive pulmonary diseases
(COPD).
• In acute severe asthma combined with β2 agonists &
corticosteroids.
 Leukotriene Antagonists…
• These drugs competitively blocks the effects of
cysteinyl leukotrienes (LTC4, LTD4, LTE4) on
bronchial smooth muscle.
• Produce bronchodilation.
• Suppress bronchial inflammation
• Decrease hyper-reactivity
• Well absorbed after oral administration.
• Highly bound to plasma protein.
• Effective in prophylactic treatment of mild
asthma.
• Well tolerated and has less side effects.
Leukotriene Antagonists drug,
Montelukast
 Leukotriene Antagonists drug,
Montelukast
Pharmacokinetics
• They are well absorbed orally.
• These are highly plasma protein bound and
metabolized by CYP2C9.
• The plasma t½ of montelukast is 3–6 hours.
 Leukotriene Antagonists drug,
Montelukast
Uses
• Not effective in acute attack of asthma.
• Prophylaxis of mild to moderate asthma.
• Aspirin-induced asthma
• Antigen and exercise-induced asthma
• Can be combined with glucocorticoids
(additive effects, low dose of
glucocorticoids can be used).
 Leukotriene Antagonists drug,
Montelukast
Side effects:
• Montelukast is very safe drugs; produce few side
effects like headache and rashes.
• Eosinophilia and neuropathy are infrequent
changes.
 Mast cell stabilizers…

• Sodium cromoglycate, Nedocromil sodium,

Ketotifen. (SoNe Ka mahal)
• They are not bronchodilators.
• Inhibits release of various mediators-histamine,
LTs, PGs PAF etc.
• Stabilizes the mast cell membrane.
 Mast cell stabilizers drug ,
Sodium cromoglycate

• Influx Ca+2.
• Prevent the bronchospasm in certain condition ( cold air
& allergen).
• Not antagonist bronchoconstriction- acute asthma &
status asthma.
 Mast cell stabilizers drug ,
Sodium cromoglycate
Pharmacokinetics
• Sod. cromoglycate is not
absorbed orally.
• It is administered as an
aerosol through metered
dose inhaler delivering 1
mg per dose: 2 puffs 4 times
a day.
 Mast cell stabilizers drug ,
Sodium cromoglycate
Uses :
• Prophylactic therapy in asthma especially in
children.
• Allergic rhinitis, Conjunctivitis.
Side effects :
• Bitter taste
• minor upper respiratory tract irritation (burning
sensation, nasal congestion)
 CORTICOSTEROIDS…
• They are controller or preventors of asthma.
• Systemic route & inhalational route.
• They are not bronchodilator but they have strong anti-
inflammatory action.
• Indicated in all cases of chronic or persistent asthma.
• Not useful in acute attack of asthma but they can
reduce exacerbation.
• Suppress the bronchial hyperreactivity &
inflammatory response to Ag : Ab reaction.
• useful as prophylactic in seasonal & exercise induced
asthma.
• Reduces airways remodeling and there retards disease
progression. Improves airways.
 CORTICOSTEROIDS…

MOA-
• Inhibition of phospholipase A2 decreased
production of PGs & LTs.
• Inhibition of genes regulating cytokines &
chemokines inhibition of chemotaxis &
activation of Th2 lymphocytes.
• Enhance histone deacetylation decreases NF-KB
& AP1.
• Upregulation of Beta 2 receptors prevention of
tolerance to SABA & LABA.
 Systemic corticosteroids

1. Severe chronic asthma:

• Not controlled bronchodilators & ICS.
• Oral - prednisone, prednisolone & methylprednisolone.
• Less HPAaxis suppression.

2. Status asthmatics
• IV hydrocortisone is drug of choice.
• IV methylprednisolone.
 Systemic corticosteroids
3.Acute asthma exacerbation:
After SABA, oral prednisolone may be given for 7-10 days

4.COPD: A short course (1–3 week) of oral

glucocorticoid may benefit some patients of COPD
during an exacerbation
 Systemic corticosteroids
Hydrocortisone
MOA -
GCs interact with intracellular receptors that
control transcription of specific genes.
Hydrocortisone
 Systemic corticosteroids
Hydrocortisone
Pharmacokinetics
Short-acting. Given orally, by injection, topically.
The main effect occur only after 2–8 h because
protein synthesis of mediators and enzymes is
required.
 Systemic corticosteroids
Hydrocortisone
Uses-
Inflammatory, hypersensitivity and
autoimmune diseases (rheumatoid arthritis,
asthma, anaphylactic shock etc.); to prevent
graft rejection; in some cancers.
Replacement therapy in adrenal failure
Adverse effects of the corticosteroids
Hydrocortisone
 INHALED STEROIDS…

• These are Glucocorticoids & which have high

topical and low systemic activity.
• ICS given in all cases chronic persistent asthma.
• Not useful in mild and episodic asthma.
• They supresses the BI, increases peak expiratory
flow rate (PEFR) & decreases the need for Beta-
2 agonist inhalation.
• No role in status asthmaticus.
• They can use in COPD in high dose only.
 INHALED STEROID DRUG,
Beclomethasone dipropionate
MOA: Reduces the activation of inflammatory
cells and the release of mediators especially
cytokines.
 INHALED STEROID DRUG,
Beclomethasone dipropionate
Pharmacokinetics -
Given by inhalation
with metered-dose
inhaler; the full action
takes weeks to occur.
 Beclomethasone dipropionate

Uses
• Added to bronchodilator therapy if this is
inadequate.
• An i.v. glucocorticoid (e.g. hydrocortisone)
is life-saving in acute severe asthma (status
asthmaticus).
 ANTI-IgE ANTIBODY DRUG,
Omalizumab
• It prevents binding of IgE to mast cell, thus
prevent mast cell de-granulation.
• It has no effects on IgE already bound to mast
cells.
• Administered parenterally.
• Used in moderate to severe asthma and allergic
disorders such as nasal allergy, food allergy, etc.
approved for use in patient above 12 years of
age.
Omalizumab :
 Omalizumab

Pharmacokinetics:
Given by subcutaneously route at 2–4 week
intervals.
 Omalizumab

Uses:
For persistent allergic asthma not completely
controlled with inhaled corticosteroid plus
long-acting β2-agonist.
Adverse effect:
Hypersensitivity reactions.
Inhalational devices
Spacers devices / Holding chamber
Dry powder inhalers
Nebulizers
Summary
 Videos about asthma
Bronchial Asthma
https://www.youtube.com/watch?v=S04dci7NTPk
https://www.youtube.com/watch?v=4aK76DoxKGk

COPD
https://www.youtube.com/watch?v=NICVVDHQB
gs
https://www.youtube.com/watch?v=T1G9Rl65M-Q
 Reference
• K.D Tripathi Essentials of Medical Pharmacology 8th
Edition.
• RANG & DALE’S Pharmacology Flash card 7th Edition.
Thank You