It is a chronic inflammatory disorder of the airways characterized by reversible airflow obstruction and bronchospasm. Airways become narrow, the muscles around the airways tighten, and there is an increase in the production of sticky mucus It is also characterized by hyperresponsiveness of tracheo-bronchial smooth muscle to a variety of stimuli narrowing of air tubes (bronchoconstriction) increased secretion, mucosal edema, mucus plugging The inflammation makes the airways extremely sensitive to irritations and increases susceptibility to allergic reaction. The inflammatory process begins with binding of allergens molecules (eg, house dust mite) to antibody on mast cells. This causes mast cells to release an mediators like Histamine, LT, PG, Interleukins. Release of mediators stored in granules (immediate): histamine, protease enzymes, TNFα. Release of phospholipids from cell membrane followed by mediator synthesis (within minutes): PGs, LTs, PAF. Activation of genes followed by protein synthesis (over hours): Interleukins, TNFα. These mediators have two effects. cause bronchoconstriction activation of inflammatory cells ( Eosinophils, leukocytes, Macrophages) These inflammatory cells then release mediators of their own which cause bronchospasm, Prevention of AG:AB reaction: avoidance of antigen, hyposensitization - possible in extrinsic asthma and if antigen can be identified. Neutralization of IgE (reaginic antibody): Omalizumab. Suppression of inflammation and bronchial hyperreactivity: corticosteroids. Prevention of release of mediators: mast cell stabilizers. Antagonism of released mediators: leukotriene antagonists, antihistamines, PAF antagonists. Blockade of constrictor neurotransmitter: anticholinergics. Mimicking dilator neurotransmitter: sympathomimetics. Directly acting bronchodilators: methylxanthinesSide effects CNS: Nervousness, restlessness, dizziness, drowsiness, headache, insomnia Neuromuscular & skeletal: Trembling (Shaking), Muscle cramps, weakness CVS: Tachycardia, hypertension GI: Xerostomia (dry mouth due to reduced saliva flow), nausea, vomiting, bad taste in mouth Miscellaneous: Diaphoresis (excessive sweating), Chest pain, arrhythmias, hypersensitivity Provides mild-moderate bronchodilation by relaxing smooth muscle of the bronchi. Low dose has mild anti-inflammatory action. Given together with inhaled corticosteroid to treat moderate asthma that is difficult to control & must be taken daily. Dose Theophylline: 125mg 3-4 times PO daily after food. Aminophylline:100-300mg, 3-4times PO daily after meal. Side Effects Nausea & vomiting, diarrhea, stomachache, headache, rapid & irregular heartbeat, Muscle cramp, jittery (nervous feeling or hyperactivity). Works best when used along with inhaled short acting beta2 agonist (in severe asthma exacerbation). Competitive inhibitor of Ach at muscarinic receptor- blocks the contraction of airway smooth muscle & increase in secretion of mucus. Onset of action within 60 mins. Ip

1. Pharmacology I
Unit V
Drugs Acting on Respiratory System
Pabitra Subedi

2. How the lungs works??
1. Air comes into your body
2. Air fills your lung’s air sacs
3. Carbon dioxide moves from the blood into the air inside the
alveoli. At the same time, oxygen moves from the air into the
blood in the capillaries.
Bronchial tubes---- branch into thousands
of thinner tubes called bronchioles----
bronchioles end in clusters of tiny air sacs
called alveoli.
Alveoli has tiny blood vessels called
capillaries. The capillaries connect to a
network of arteries and veins that move
blood through your body.

4. Asthma
• It is a chronic inflammatory disorder of the airways characterized by reversible airflow
obstruction and bronchospasm.
• Airways become narrow, the muscles around the airways tighten, and there is an increase
in the production of sticky mucus
• It is also characterized by
hyperresponsiveness of tracheo-bronchial smooth muscle to a variety of stimuli
narrowing of air tubes (bronchoconstriction)
increased secretion,
mucosal edema,
mucus plugging
• The inflammation makes the airways extremely sensitive to irritations and increases
susceptibility to allergic reaction.

5. Causes
Airborne allergens such as pollen, dust mites, cockroaches, mold
Allergic reactions to certain food
Respiratory infections
Air pollutants and irritants
Certain medications (Aspirin)
Strong emotion and stress (changes in breathing patterns can
trigger an asthma attack)
Preservatives added to some foods
GERD (Gastroesophageal reflux disease) (Aspiration of acid particles in the trachea
can cause coughing, wheezing and pneumonia)
Extreme cold

8. Symptoms
Shortness of breath (SOB)
Chest tightness or pain
Trouble sleeping caused by shortness of breath
Coughing, which is worse at night or early in the morning.
Wheezing, the squeaky noise that occurs when you breathe.
Factors Determine to Get Asthma
A number of factors determine who would get asthma. Few of them are:
Genetics
Overweight
Smoking and passive smoking
Exposure to exhaust fumes or other pollution
Low birth weight

10. Pathophysiology
• The inflammatory process begins with binding of allergens molecules (eg, house dust
mite) to antibody on mast cells. This causes mast cells to release an mediators like
Histamine, LT, PG, Interleukins.
• Release of mediators stored in granules (immediate): histamine, protease
enzymes, TNFα.
• Release of phospholipids from cell membrane followed by mediator synthesis
(within minutes): PGs, LTs, PAF.
• Activation of genes followed by protein synthesis (over hours): Interleukins,
TNFα.
• These mediators have two effects.
cause bronchoconstriction
activation of inflammatory cells ( Eosinophils, leukocytes, Macrophages)
• These inflammatory cells then release mediators of their own which cause
bronchospasm,

11. Approaches To Treatment
1. Prevention of AG:AB reaction: avoidance of antigen, hyposensitization - possible in
extrinsic asthma and if antigen can be identified.
2. Neutralization of IgE (reaginic antibody): Omalizumab.
3. Suppression of inflammation and bronchial hyperreactivity: corticosteroids.
4. Prevention of release of mediators: mast cell stabilizers.
5. Antagonism of released mediators: leukotriene antagonists, antihistamines, PAF
antagonists.
6. Blockade of constrictor neurotransmitter: anticholinergics.
7. Mimicking dilator neurotransmitter: sympathomimetics.
8. Directly acting bronchodilators: methylxanthines.

12. Classification

13. Classification
1. Bronchodilators
a. β2 Sympathomimetics (β2 agonist)
• Inhaled (short acting): Salbutamol (Albuterol), Levalbuterol, Pirbuterol
• Inhaled (long acting): Formoterol, Salmeterol
• Oral: Bambuterol , Albuterol, Terbutaline, Ephedrine
b. Methylxanthines: Theophylline, Aminophylline, Doxophylline
c. Anticholinergics: Ipratropium bromide, Tiotropium bromide.

14. Classification
2. Anti Inflammatory
a. Corticosteroids
A. Oral: Hydrocortisone, Prednisolone and others glucocorticoids.
B. Inhalational: Beclomethasone dipropionate, Budesonide, Fluticasone
propionate, Flunisolide, Ciclesonide.
b. Mast cell stabilizers: Sodium cromoglycate, Ketotifen.
c. Leukotriene antagonists: Montelukast, Zafirlukast.

15. Beta2 Adrenergic Agonists
• These are sympathomimetic drugs that produce selective activation of beta2
adrenergic receptors.
Mechanism of Action
Activation of beta2 receptors directly relaxes the airway smooth muscle and
causes consequent bronchodilation.
Stimulation of beta2 adrenergic receptors also inhibits the function of
numerous inflammatory cells, including mast cells, basophils, eosinophils,
neutrophils, and lymphocytes.

16. Beta2 Adrenergic Agonists
Side effects
CNS: Nervousness, restlessness, dizziness, drowsiness, headache, insomnia
Neuromuscular & skeletal: Trembling (Shaking), Muscle cramps, weakness
CVS: Tachycardia, hypertension
GI: Xerostomia (dry mouth due to reduced saliva flow), nausea, vomiting, bad
taste in mouth
Miscellaneous: Diaphoresis (excessive sweating), Chest pain, arrhythmias,
hypersensitivity

17. Methylxanthines
• Provides mild-moderate bronchodilation by relaxing smooth muscle of the bronchi.
• Low dose has mild anti-inflammatory action.
• Given together with inhaled corticosteroid to treat moderate asthma that is difficult to
control & must be taken daily.
• Dose
Theophylline: 125mg 3-4 times PO daily after food.
Aminophylline:100-300mg, 3-4times PO daily after meal.
Side Effects
• Nausea & vomiting, diarrhea, stomachache, headache, rapid & irregular heartbeat,
Muscle cramp, jittery (nervous feeling or hyperactivity).

18. Anticholinergics (antimuscarinic)
• Works best when used along with inhaled short acting beta2 agonist (in severe asthma
exacerbation).
• Competitive inhibitor of Ach at muscarinic receptor- blocks the contraction of airway
smooth muscle & increase in secretion of mucus.
• Onset of action within 60 mins.
• Ipratropium bromide
Side Effects
• flushing of face, headache, blurred vision, constipation, dry mouth, decreased sweating,
allergic reaction- rashes, swelling, dizziness, difficult in breathing and itching.

19. Corticosteroids (Glucocorticoids)
• Most effective long-term-control therapy for persistent asthma.
• Administration: inhalation (effective, safe than oral), oral or IV
• Glucocorticoids are used for prophylaxis of chronic Asthma- beneficial effects develop slowly
• Risk of toxicity (increases with long term use)
Corticosteroids-MOA
Inhibit airway inflammation thereby reduce bronchial hyperactivity.
Decreased synthesis and release of inflammatory mediators (leucotrines, histamine,
prostaglandins)
Decreased infiltration and activity of inflammatory cells (eosinophils, leukocytes)
Decreased edema of the airway mucosa
Also decrease airway mucus production and increase the number of beta2 receptors and their
responsiveness to beta2 agonists.

20. Corticosteroids (Glucocorticoids)
Adverse Effects of Glucocorticoids
• Small risk for adverse events at recommended dosage.
• Inhaled: Adverse effects arise because of local deposition of inhaled glucocorticoids.
• Common adverse effects: oropharyngeal candidiasis and dysphonie (hoarseness, speaking
difficulty)
• Oral adverse effects: adrenal suppression, osteoporosis, hyperglycemia, peptic ulcer
disease, suppression of growth in children.
Reduce potential for adverse events by:
Using spacer and rinsing mouth
Using lowest dose possible
Using in combination with long-acting b2-agonists
Monitoring growth in children

21. Mast Cell Stabilizer (Cromolyn & Nedocromil)
• Used prophylactically (prior to exercise).
• Can be used in children.
Mechanism of action
Inhibit release of mediator from mast cell.
Inhibit eosinophilic mediate inflammatory response.
Inhibit leukocytes trafficking in asthmatic airways.
Side Effects
Throat irritation, mouth dryness, chest tightness, joint swelling, pain,
angioedema, headache, rashes, nausea & vomiting and bad taste.

22. Leukotriene antagonist
• Leukotrienes cause tightening of airway muscles and the production of excess mucus
and fluid.
• MOA--- Causes reduced diffusion/accumulation of inflammatory cells in tissue/cells,
blocks the inflammation, bronchoconstriction, airway edema and mucus secretion.
• Used in long term control therapy in mild persistent asthma to
 Improve lung function
 Prevent need of short-acting b2-agonists
 Prevent exacerbations
Side effects
• Systemic eosinophilia, vasculitis, headache, rhinitis, pharyngitis & stomach upset.

23. Prevent chronic and troublesome symptoms
 Maintain (near-) “normal” pulmonary function
 Prevent recurrent exacerbations
 Provide optimal pharmacotherapy with minimal or no adverse effects.
Management of Asthma
Initial Assessment and Diagnosis of Asthma
Methods for establishing diagnosis:
 Detailed medical history
 Physical exam
 Spirometry to demonstrate reversibility

24. Evaluation for asthma – spirometry
Forced Expiratory Volume(FEV): Instrument: Spirometer
The spirometer measures how much air was expelled.
The patient inhales completely and then exhales forcefully as possible into the spirometer.
Results are then compared to a predicted normal value for a healthy person of similar age, sex,
height and weight.
For a patient with asthma, the FEV might be 75% of the predicted value.
FEV1: Forced Expiratory Volume in 1 second.
Peak Expiratory Flow Rate (PEFR): Peak flowmeter
Defined as the maximum rate of airflow during expiration.
The patient exhales as forcefully as possible into a peak flowmeter
Patients should measure their peak flow every morning.
If the PEFR is less than 80% of their personal best, more frequent monitoring should be done.

25. Classification Based on Severity

26. Drugs For Cough
• Cough is a useful physiological protective mechanism that clears respiratory
passages of foreign material and excess secretions.
• Mechanism for clearing the tracheo-bronchial tress of secretions.
• Most of the time, coughing is beneficial
– Removes excessive secretions
– Removes potentially harmful foreign substances
– In some situations, coughing can be harmful, such as after hernia repair surgery
• Cough may be:
1. Useful (productive)
- Sputum is coughed up/drain the airway) and may be harmful if suppressed
2. Useless (nonproductive)
- Dry cough
Types of Cough

27. • Classified based on duration, characters, quality and timing
– Acute: Sudden onset/less than 3 weeks
– Sub-acute: 3-8 weeks
– Chronic: Longer than eight weeks
Classification of Cough

28. Mechanism of cough

29. Definition
• Antitussive: A drug which suppress coughing possibly by reducing activity of cough center
in the brain.
• Expectorant: A drug that enhances the secretion of sputum.
 Pharyngeal demulcents: Lozenges, linctuses containing syrup, Glycerine, Liquorice
 Expectorants:
1. Mucokinetics (Bronchial secretion enhancers): Sodium or potassium citrate, Potassium
iodide, Guaphenisin (Glyeryl guaiacolate), balsum of Tolu, Vasaka, Ammonium
chloride.
2. Mucolytics: Bromhexene, Ambroxol, Acetylcystein, Carbocystein
 Antitussives (Cough center supressants):
a) Opioids: Codein, Pholcodein
b) Non-opioids: Noscapine, Dextromethorphan, Chlophedianol c) Antihistaminics:
Chlorpheniramine, Diphenhydramine, Promethazine
 Adjuvant antitussives: Bronchodilators: Salbutamol, Terbutaline
Classification of Drugs

30. Classification of Drug
 Pharyngeal demulcents: Lozenges, cough drops, linctuses containing syrup,
Glycerine, Liquorice
 Expectorants:
1. Mucokinetics (Bronchial secretion enhancers): Sodium or potassium citrate,
Potassium iodide, Guaphenisin (Glyeryl guaiacolate), balsum of Tolu, Vasaka,
Ammonium chloride.
2. Mucolytics: Bromhexene, Ambroxol, Acetylcystein, Carbocystein
 Antitussives (Cough center supressants):
• a) Opioids: Codein, Pholcodein
• b) Non-opioids: Noscapine, Dextromethorphan, Chlophedianol c) Antihistaminics:
Chlorpheniramine, Diphenhydramine, Promethazine
 Adjuvant antitussives: Bronchodilators: Salbutamol, Terbutaline

31. Demulcents
• A substance that relieves irritation of the mucous membranes in the mouth by forming a
protective film.
• Pharyngeal demulcents
– sooth throat
– reduce afferent impulses from the inflamed/irritated mucosa symptomatic relief in dry
cough arising from throat
• Eg: Lozenges Cough drops Linctuses containing syrup Glycerine, Liquorice
• Glycerol may work as a demulcent in the pharynx by coating and lubricating the
pharyngeal surface. The moisturizing properties of glycerol may also help to soothe
inflamed mucosal surfaces in the pharynx.

32. Expectorant (Mucokinetics)
• Potassium iodide
– Secreted by bronchial glands
– Irritate airways mucosa
– Prolonged use---disturb thyroid function---iodism
– Not used now
• Guaiphenesin, Balsum of Tolu, Vasaka
– Plant products
– Enhance bronchial secretion
– Promotes Mucocilliary function secreted by tracheobronchial glands
• Ammonium chloride
– Ammonium salts
– Increase respiratory secretions

33. • Bromhexine (oral & injection)
– Derivative of vasicine obtained from Adhatoda vasica
– Potent mucolytic and mucokinetic
– Thinning & fragmentation of mucopolysaccaride fibers directly or by lysosomal
enzyme
– ↑ volume & ↓ viscosity of sputum
– Dose: adult 8mg TDS
– side effects: constipation, N/V, rhinorrhea
Expectorant (Mucolytics)

34. • Ambroxol (oral)
– A metabolite of bromohexine
– Dose: 15-30 mg TDS
– Mucolytic action, uses and side effects similar to bromhexine
• Acetylcysteine (oral & inhalation)
– Derivative of cysteine
– Opens disulfide bonds on mucoproteins present in sputum =↓ viscosity
– Also act as antioxidants
– reduce airway inflammation
– Uses:Cystic fibrosis, bronchitis, COPD
Expectorant (Mucolytics)

35. • Carbocysteine
– Liquefies viscid sputum
– Administered orally (250-750 mg TDS)
– May break gastric mucosal barrier--- contraindicated in peptic ulcer
– Side effects: GI disturbance, skin rashes
Expectorant (Mucolytics)

36. Antitussives
• Acts on CNS and raise threshold of cough center
• Act peripherally in respiratory tract
• Aimed to control the cough rather than eliminate
• Used only for dry, unproductive cough or if cough is unduly tiring, disturbs sleep /hazardous
Opioids: Codeine
– Opium alkaloid Less potent than morphine
– more selective for cough center
– standard antitussive: suppress cough for 6 hours
• Side effects: Abuse, Constipation is main drawback, At high dose, respiratory depression
and drowsiness
• Contraindications: Asthamatics, Patients with diminished respiratory reserve, Should be
avoided in children
• Dose: adult 10-30mg frequently used as syrup codeine phos. 4-8 ml

37. • Opioids: Ethylmorphine
– Closely related to codeine which is methylmorphine
– Has antitussive, respiratory depressant properties like codeine
– Believed to be less constipating
– Dose: 10-30 mg TDS
• Opioids: Pholcodeine
– Similar in efficacy as antitussive to codeine
– Long acting codeine (12h)
– Dose: 10-15 mg
Antitussives

38. Antitussives
Nonopioids: Noscapine
• Opium alkaloid of benzoisoquinoline
• Depresses cough but lacks narcotic, analgesic or dependence inducing properties
• Equipotent antitussive as codeine
• Useful in spasmodic cough
• Dose: 15-30 mg
• Side effect: headache and nausea, can produce bronchoconstriction by stimulating
histamine release

39. Nonopioids: Dextromethorphan
• A synthetic central NMDA (N-methyl D-aspartate) receptor antagonist
• d-isomer has antitussive action while L-isomer is analgesic.
• Effective as codeine
• Does not depress mucociliary function of the airway mucosa
• Dose: 10–20 mg
• Side effect: Dizziness, nausea, drowsiness
• At high doses hallucinations and ataxia may occur.
Antitussives

40. Antihistamines
• H1 blockers are added to antitussive/expectorants
• Antihistamines aren't technically considered cough medicines, but they may be useful if
an allergy is the cause as in hay fever or allergies with runny nose, sneezing and watery
eyes in addition to cough.
• Specially promoted for cough in respiratory allergic states
• Commonly used antihistanines:
– Chlorpheniramine (2-5mg)
– Diphenhydramine (15-25mg )
– Promethazine (15-25mg)
• Second generation antihistamines like Terfenadine, Loratadine are ineffective
Antitussives

41. Adjuvant Antitussives
Bronchodilators
• Bronchospasm can induce or aggravate cough
• Pulmonary receptor stimulation can induce both cough and bronchoconstriction in
individual with bronchial hyperreactivity
• Relieve cough and clear secretions by increasing surface velocity of airflow during
cough
• Not used routinely