Respiratory Pharmacology and Anti-asthmatic drugs.Asthma ◦ Chronic obstructive pulmonary disease (COPD) ◦ Allergic rhinitis Associated with persisting cough Precautions, Asthma: Goals of Therapy, Inflammation in asthma, Broncial Asthma Etiology, Pathology, Histopathology, Patho-physiloogy, Bronchial Asthma.

1. Respiratory Pharmacology and
Anti-asthmatic drugs
Presented By
Arasana Dhariwal
M.Pharm. Pharmacology Ist Sem
Department of Pharmaceutical sciences
Bhimtal

2. Common respiratory
diseases
◦ Asthma
◦ Chronic obstructive pulmonary disease
(COPD)
◦ Allergic rhinitis
 Associated with persisting cough

3. Cont..
 Asthma is a chronic disease
characterized by hyperresponsive
airways
 COPD, includes emphysema and
chronic bronchitis
 Allergic rhinitis is characterized by itchy,
watery eyes, runny nose, and a
nonproductive cough

4. Cont..
 Coughing is an important defensive
respiratory response to irritants and has
been cited as the number-one reason why
patients seek medical care
 A troublesome cough may represent
several etiologies such as:
◦ The common cold
◦ Sinusitis
◦ An underlying chronic respiratory disease

5. Precautions
 Respiratory conditions can be controlled through
a appropriate lifestyle changes and medications
 Drugs can be delivered topically to the nasal
mucosa, inhaled into the lungs, or given orally or
parenterally for systemic absorption
 Local delivery methods, such as nasal sprays or
inhalers, are preferred to target affected tissues
while minimizing systemic side effects
 Clinically useful drugs mitigate the specific
pathology, such as by relaxing bronchial smooth
muscle or modulating the inflammatory response

6. Asthma
 Inflammatory disease of the airways
characterized by episodes of acute
bronchoconstriction causing shortness
of breath, cough, chest tightness,
wheezing, and rapid respiration
 Symptoms may resolve spontaneously,
with nonpharmacologic relaxation
exercises, or with use of “quick-relief”
medications, such as a short- acting β2-
adrenergic agonist

7. Asthma
Asthma is a chronic disease with an underlying
inflammatory pathophysiology
If untreated, may cause airway remodeling,
resulting in increased severity and incidence
of exacerbations and/ or death .
Deaths due to asthma are relatively infrequent
Significant morbidity results in high costs,
numerous hospitalizations, and decreased
quality of life

8. Asthma: Goals of Therapy
 1. Reducing impairment: by decreasing the
intensity and frequency of asthma symptoms
 Prevent chronic and troublesome symptoms
 Require infrequent use (≤2 days a week) of
inhaled short-acting β2 agonist for quick
relief of symptoms
 Maintain (near) “normal” pulmonary function
 Maintain normal activity levels
 Meet expectations of the patient and family

9. Goals of therapy cont…
 2. Reducing risk: decreasing the adverse
outcomes associated with asthma and its
treatment
 Prevent recurrent exacerbations of asthma, and
minimize the need for emergency department
visits or hospitalizations
 Prevent progressive loss of lung function and,
for children, prevent reduced lung growth
 Provide optimal pharmacotherapy with minimal
or no adverse effects.

10. Inflammation in asthma
Airflow obstruction in asthma is due to broncho-
constriction that results from
◦ Contraction of bronchial smooth muscle
◦ Inflammation of the bronchial wall
◦ Increased secretion of mucus
Asthmatic attacks may be related to recent
exposure to allergens or inhaled irritants leading
to bronchial hyperactivity and inflammation of the
airway mucosa
The symptoms of asthma may be effectively
treated by several drugs, but no agent provides a
cure

16. Bronchial asthma
 Types of asthma based on etiology:
• Extrinsic asthma: – Allergy-induced –
Commonly suffer from other atopic diseases,
– Mostly episodic, Less prone to status
asthmaticus
• Intrinsic asthma: – No immunological basis for
their condition – Negative skin test to
common inhalant allergens – Normal serum
concentrations of IgE, – Perennial, – More
prone to status asthmaticus

17. Cont..
 Types of Asthma based on clinical condition:
• Mild episodic asthma:
• Seasonal asthma:
• Mild chronic asthma:
• Moderate asthma with frequent exacerbations:
• Severe asthma:
• Status asthmaticus/Refractory asthma

19. Classification of drugs for
asthma
BRONCHODILATORS:
1. β-Sympathomimetics: Salbutamol, Terbutaline,
Bambuterol, Salmeterol, Formoterol, Ephedrine
2. Methyl Xanthines: Theophylline, Aminophylline,
Choline theophyllinate, Hydroxyethyl theophylline,
Doxophylline.
3. Anticholinergics: Ipratropium bromide, Tiotropium
bromide
LEUKOTRIENE ANTAGONISTS: Montelukast,
Zafirlukast
MAST CELL STABILIZERS: Sodium chromoglycate,
Ketotifen
CORTICOSTEROIDS 1. Systemic: Hydrocortisone,
Prednisolone 2. Inhalational: Beclomethasone,
Budesonide, Fluticasone, Flunisolide
ANTI Ig-E ANTIBODY: Omalizumab

20. Sympathomimetics
• Mechanism of action: – β2 stimulation
increased cAMP formation in bronchial
muscle cell relaxation – Also decreases
mediator release • E.g. Salbutamol,
Terbutaline, Bambuterol, Salmeterol,
Formoterol, Ephedrine

21. Sympathomimetics
Salbutamol – Highly selective β2 agonist – Inhaled
Salbutamol produces bronchodilatation in 5 min
and action lasts for 2-4 hrs – Side effects:
Palpitations, restlessness, nervousness, throat
irritation, ankle edema – Uses: Reserved for
patients who cannot correctly use inhalers, Used
as an adjuvant in severe asthma – Not suitable
for round the clock prophylaxis
Terbutaline: – Similar to Salbutamol

22. Cont..
 Salmeterol:
• It is the first long acting selective β2 agonist
(LABA) with slow onset of action
• Used by inhalation on a twice daily schedule
• Used for maintenance therapy and nocturnal
asthma
Formeterol:
• Another LABA • Acts for 12 hrs • Compared to
Salmeterol it has faster onset of action

23. Methyl Xanthine
Naturally occuring Methyl Xanthine alkaloids are
Caffein, Theophylline and Theobromine
• Mechanism of action:
– Inhibition of phosphodiesterase (PDE)
increased cAMP Bronchodilatation, cardiac
stimulation, vasodilation
– Blockade of adenosine receptors relaxes
smooth muscles – Release of Ca2+ from
sarcoplasmic reticulum, especially in skeletal and
cardiac muscle (only at higher concentrations)
• E.g: Theophylline, Aminophylline, Choline
theophyllinate, Hydroxyethyl theophylline,
Doxophylline

24. Methyl Xanthine
Theophylline: – Well absorbed orally
– T1/2 is 7-12 hrs
– Side effects: gastric pain (with oral), rectal
inflammation (with rectal suppositories), pain at
site of injection (i.m), Rapid IV can cause
precordial pain, syncope and sudden death.
Interactions: – metabolism is induced by
smoking, phenytoin, rifampicin, phenobarbitone
– Metabolism is inhibited by erythromycin,
ciprofloxacin, cimetedine, OCPs, allopurinol
– Uses: Bronchial asthma and COPD, Apnoea in
premature infant,

25. Anticholinergics
Atropinic drugs cause bronchodilatation by
blocking cholinergic constrictor tone
• Act primarily in larger airways
• Produce slower response than inhaled
sympathomimetics
• Better suited for regular prophylactic use
• Combination of inhaled Ipratropium with β2
agonists produce more marked and longer
lasting bronchodilatation.
• E.g: Ipratropium bromide, Tiotropium
bromide

26. Leukotriene antagonists
• Competitively antagonize cysLT1 receptor
mediated bronchoconstriction, increased
vasodilatation and recruitment of eisonophils
• Indicated for prophylactic therapy of mild to
moderate asthma as alternative to inhaled
glucocorticoids
• May obviate need for inhaled glucocorticoids
• Safe drugs
• Side effetcs: headache, rashes • E.g:
Montelukast, Zafirlukast

27. Mast cell stabilizers
Inhibits degranulation of mast cells
• Release of mediators like Histamine, LTs, PAF,
ILs, etc is restricted
• Not absorbed orally, administered as an aerosol
through metered dose inhaler (MDI)
• Uses: Long term prophylaxis in mild to moderate
Bronchial asthma, Allergic rhinitis, Allergic
conjunctivitis
• Side effetcs: Bronchospasm, throat irritation,
cough • E.g: Sodium chromoglycate, Ketotifen

28. Corticosteroids
These do not cause bronchodilatation,
• Reduce bronchial hyper-reactivity, mucosal
edema, by supressing inflammatory response to
AG:AB reaction
• Two forms are used Systemic and Inhalational
1. Systemic/Oral Cortico Steroid (OCS) – Used in
severe chronic asthma and Status asthmaticus –
E.g: Hydrocortisone, Prednisolone
2. Inhalational Cortico Steroid (ICS) – Step one for
all asthma patients – Safe during regnancy –
Side effetcs: mood changes, osteoporosis,
bruising, petechiae, hyperglycemia
E.g: Beclomethasone, Budesonide, Fluticasone,
Flunisolide

32. Thank You