DRUGS USED IN THE TREATMENT OF BRONCHIAL ASTHMA AND COPD Characterized by hyper responsiveness of bronchial smooth muscle to a variety of stimuli” Resulting in: Narrowing of air ways Increased secretion Mucosal edema Mucus plugging

1. DRUGS USED IN THE TREATMENT OF
BRONCHIAL ASTHMA & COPD
RESPIRATORY SYSTEM - PHARMACOLOGY
PREPARED BY
GOWTHAMRAJ SAKTHIVEL M.Pharm.,
Department of Pharmacognosy.

2. TREATMENT OF BRONCHIAL ASTHMA
BRONCHIAL ASTHMA:
“Characterized by hyper responsiveness of bronchial smooth muscle to a variety of stimuli”
Resulting in:
 Narrowing of air ways
 Increased secretion
 Mucosal edema
 Mucus plugging

3. BRONCHIAL ASTHMA:
INFECTION, POLLUTION, EXERCISE, COLD AIR EXPOSURE
ANTIGEN: ANTIBODE REACTION (IgE antibody)
DEGRANULATION OF MAST CELL
RELEASE OF INFLAMMATORY MEDIATORS like HISTAMINE, LTs,
INFLAMMATION IN THE AIR WAYS
NARROWING OF AIRWAY
BREATHING DIFFICULTY, WHEEZING, COUGH (symptoms)
BRONCHIAL ASTHMA

4. I.BRANCHODILATORS:
β2 SYMPATHOMIMETICS
 SALBUTAMOL
 TERBUTALINE
 BAMBUTEROL
 SALMETEROL
 EPHEDRINE
METHYLXANTHINES
 THEOPHYLLINE
 AMINOPHYLLINE
 HYDROXY THEOPHYLLINE
ANTI CHOLONERGICS
 IPRATROPIUM BROMIDE
 TIOTROPIUM BROMIDE
II.LEUKOTRIENE ANTAGONISTS:
 MONTELUKAST,
 ZAFIRLUKAST.
III.MAST CELL STABILIZERS
 SODIUM CROMOGLYCATE,
 KETOTIFEN.
IV.CORTICOSTEROIDS
A. SYSTEMIC:
 HYDROCORTISONE,
 PREDNISOLONE
B. INHALATIONAL:
 BECLOMETHASONE
 DIPROPIONATE,
 BUDESONIDE,
 FLUTICASONE PROPIONATE,
 FLUNISOLIDE,
 CICLESONIDE.
V. ANTI-IGE ANTIBODY
 OMALIZUMAB
CLASSIFICATION OF DRUGS

5. BRANCHODILATORS:
β2 SYMPATHOMIMETICS
Fastest acting bronchodilator when inhaled
ADRENERGIC DRUG
ACTS ON β2 RECEPTOR
BRANCHODILATATION
Should be used cautiously in
HYPERTENSIVE PATIENTS, ISH DISEASE PATIENTS

6. SALBUTAMOL
 Highly selective β2 agonist
 Inhaled salbutamol produce branchodilatation with in 5 mins
 Duration of action 2-4 hrs
 Used to abort or to terminate asthmatic attack
 It cannot be used for prophylaxis
MECHANISM OF ACTION SALBUTAMOL
BINDS TO β2 RECEPTOR PRESENT IN THE BRONCHIAL SMOOTH MUSCLE
STIMULATION OF β2 RECEPTOR
INCREASE IN THE FORMATION OF CYCLIC AMP (CAMP)
RELAXATION OF SMOOTH MUSCLE
RELIEF FROM THE ASTHMATIC ATTACK

7. PHARMACOKINETICS:
 Administered by inhalation and injection
 Oral route is not preferred - Due to pre systemic metabolism in gut wall
 Oral bio availability is 50%
 Acts for 4 hours
 Oral route is used when the patients who cannot currently use in-halars
ADR:
 Muscle tremors
 Palpitation
 Restlessness
 Nervousness
 Throat irritation
USES:
 Used in terminating the attack of asthma

8. METHYXANTHINES
 Extensively used in asthma
 Cannot be used as first line drug
THEOPHYLLINE
 One of the naturally occuring methylated xanthine alkaloids
 Relatively weak bronchodilator
 Effective when adrenaline fails to relieve acute attack
MECHANISM OF ACTION:
ATP
ADENYLYL CYCLASE
CYCLIC AMP
THEPHYLLINE (blocks) PHOSPHODIESTERASE
5- AMP
 Increase in cyclic AMP level
 Vasodilatation
 Reduces the asthmatic attack

9. PHARMACOKINETICS:
 Well absorbed orally
 Distributed in all tissues
 Crosses the placenta and secreted in milk
 Metabolized in liver by demethylation & oxidation
 Excreted in urine
ADR:
 Gastric pain
 Head ache
 Tremors
 Vomiting
 Hypotension
 Convulsion
 Death
USES:
 Bronchial asthma & COPD

10. ANTI-CHOLINERGICS
IPRATROPIUM BROMIDE:
 Brancho dilatation by blocking the M3 receptor
 When it is combined with sympathomimetics produce most effective activity
MECHANISM OF ACTION:
IPRATROPIUM BROMIDE
BINDS & BLOCKS THE M3 RECEPTOR PRESENT IN THE LARGER AIRWAYS OF LUNGS
PREVENTS THE CONTRACTION OF LARGER AIRWAYS OF LUNGS
DILATATION
RELIEF FROM ASTHMATIC ATTACK
LEUKOTRIENE ANTAGONISTS
 cystenyl leukotrienes (LT-C4/D4) are important mediators of bronchial asthma,
 Two antagonist drugs were developed for the treatment of asthma
Eg: Montelukast and Zafirlukast

11. MONTELUKAST AND ZAFIRLUKAST
 Montelukast and zafirlukast are indicated for prophylactic therapy of mild-to-moderate asthma as
alternatives to inhaled glucocorticoids
 The efficacy is low
 They are very safe drugs
 In severe asthma, they have additive effect with inhaled steroids
 They are not to be used for terminating asthma episodes.
 LT1 antagonists are modestly effective in aspirin-induced asthma and exercise induced asthma, but
are of no value in COPD.
MECHANISM OF ACTION:
Montelukast and Zafirlukast
They competitively antagonize LT1 receptor
Decreases the LT1 receptor mediated bronchoconstriction, airway mucus secretion
Broncho dilatation, suppression of bronchial inflammation
Improvement from asthmatic attack

12. PHARMACOKINETICS:
 They are well absorbed orally,
 Highly plasma protein bound
 Metabolized by CYP2C9
 The plasma t½ of montelukast is 3–6 hours & zafirlukast is 8–12 hours.
ADR:
 Produce few side effects: headache and rashes.
 Eosinophilia and neuropathy are infrequent.
 Few cases: Churg-Strauss syndrome (vasculitis with eosinophilia).

13. MAST CELL STABILIZERS
Eg:Sodium cromoglycate (Cromolyn sod)
 It is a synthetic chromone derivative
 It is not a bronchodilator and does not antagonize constrictor action of histamine, ACh, LTs
 It is ineffective if given during an asthmatic attack.
 Bronchospasm induced by allergens, irritants, cold air and exercise may be attenuated.
MECHANISM OF ACTION:
Mast cells are cells found in connective tissues including the airways
Mast cells release histamine and other inflammatory substances in response to allergens
The process of releasing inflammatory mediators by mast cells is referred to as "degranulation."
[ Sodium cromoglycate ]
Inhibits mast cell degranulation
Blocking the release of inflammatory mediators (histamine, LTs, PAF, interleukins, etc)
Decreases the cellular inflammatory response; bronchial hyperactivity
Anti asthmatic activity

14. PHARMACOKINETICS:
 It 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.
 Only a small fraction of the inhaled drug is absorbed systemically
 Rapidly excreted unchanged in urine and bile.
ADVERSE EFFECTS:
 Bronchospasm,
 Throat irritation
 Cough Uses
 Bronchial asthma
 Allergic rhinitis
 Allergic conjunctivitis

15. CORTICOSTEROIDS
 Glucocorticoids are not bronchodilators.
 They reduces bronchial hyperreactivity, mucosal edema
 Corticosteroids afford more complete and sustained symptomatic relief than bronchodilators or
cromoglycate;
 Improve airflow; reduce asthma, retarding disease progression.
 Also increase airway smooth muscle responsiveness to β 2 agonists
 Inhaled corticosteroids have thus markedly changed the outlook on asthma therapy.
 Long-term systemic steroid therapy may be worse than asthma itself
SYSTEMIC STEROID THERAPY
Systemic steroid therapy can be used in the following situations
(i) Severe chronic asthma:
 It is not controlled by bronchodilators and inhaled steroids, or when there are frequent recurrences of
increasing severity
 Shall be treated with prednisolone 20–60 mg daily Dose reduction after 1–2 weeks of good control
 Then the patient can be shifted to inhaled steroid.
(ii) Status asthmaticus/acute asthma exacerbation:
 When asthma attack not responding to intensive bronchodilator therapy:
 Treatment shall be start with high dose of a rapidly acting i.v. glucocorticoid which generally acts in 6–
24 hours,
 Patients to be shifted to oral therapy for 5–7 days and then discontinue abruptly or taper rapidly.

16. (iii) COPD
 A short course (1–3 week) of oral glucocorticoid
 May benefit some patients of COPD during an exacerbation.
INHALED STEROIDS:
 These are glucocorticoids with high topical and low systemic activity (due to poor absorption and/or
marked first pass metabolism).
 Beclomethasone dipropionate,
 Budesonide
 Fluticasone
 Ciclesonide is a later addition.
 Inhaled steroids suppress bronchial inflammation, increase peak expiratory flow rate, reduce need for
rescue β2-agonist inhalations and prevent episodes of acute asthma.
 They have no role during an acute attack or in status asthmaticus.
 Peak effect is seen after 4–7 days of instituting inhaled steroids and benefit persists for a few weeks
after discontinuation.

17. ANTI-IgE ANTIBODY
OMALIZUMAB
 It is a humanized monoclonal antibody against IgE.
 Administered s.c.
 It neutralizes free IgE in circulation without activating mast cells and other inflammatory cells.
 It is very expensive
 Use is reserved for resistant asthma patients with positive
 Skin tests or raised IgE levels who require frequent hospitalization.

18. COPD
Chronic Obstructive Pulmonary Disease (COPD)
 It is a chronic disease of the lungs that damages both the airways and the lung tissue, making it difficult to
breathe.
 A person with COPD may have obstructive bronchiolitis, emphysema, or a combination of both conditions.
 People with COPD often use several kinds of medicines to help control symptoms.
 There is no cure; medicines can help improve your quality of life
 The goals of effective COPD management are to:
 Prevent disease progression
 Relieve symptoms
 Improve exercise tolerance
 Improve health status
 Prevent and treat complications
 Prevent and treat exacerbations
 Reduce mortality
 The most common medications for treating chronic obstructive pulmonary disease (COPD) are

19. BRONCHODILATORS AND STEROIDS
 Both make breathing easier, but do this in different
ways.
I.BRONCHODILATORS
 β2 SYMPATHOMIMETICS
 SALBUTAMOL
 TERBUTALINE
 BAMBUTEROL
 SALMETEROL
 EPHEDRINE
 METHYLXANTHINES
 THEOPHYLLINE
 AMINOPHYLLINE
 HYDROXY THEOPHYLLINE
 ANTI CHOLONERGICS
 IPRATROPIUM BROMIDE
 TIOTROPIUM BROMIDE
II.CORTICOSTEROIDS
 SYSTEMIC:
 HYDROCORTISONE,
 PREDNISOLONE
 INHALATIONAL:
 BECLOMETHASONE
 DIPROPIONATE,
 BUDESONIDE,
 FLUTICASONE
 PROPIONATE,
 FLUNISOLIDE,
III.ROFLUMILAST
 It have not been mentioned have not as yet been
proven to be effective in the treatment of COPD.
 It is a new medication that may decrease the
number of exacerbations
IV. AZITHROMYCIN
 Long-term use may decrease the number of
exacerbations
V.OTHER MEDICATIONS
 Antibiotics for bacterial infection,
 Mucolytics to thin mucus (phlegm or sputum),
 Oxygen to treat low oxygen levels
CLASSIFICATION OF DRUGS