Pharmacotherapy of Asthma

1. Pharmacotherapeutics of
Asthma
By:
Dr. Sarita Sharma
Associate Professor
Pharmacology
MMCP, MMDU

2. INTRODUCTION
ASTHMA :
The term Asthma is Derived from the Greek word meaning to stay
Awake in order to Breathe or Difficulty in Breathing.
Defination:
Asthma is a chronic inflammatory disease in which the patients
suffers with Reversible episodes of Airways, obstruction Inflammation
can lead to irreversible Airways obstruction.
It is characterised by hyperresponsiveness of tracheobronchial
smooth muscle to a variety of stimuli, resulting in narrowing of air
tubes.

4. Bronchoconstriction:
The airways of asthma patients are "hypersensitive" to
certain triggers, also known as stimuli . It is usually classified
as type I hypersensitivity. In response to exposure to these
triggers, the bronchi .
Bronchial inflammation:
The "hygiene hypothesis" postulates that an imbalance in the
regulation of these TH cell types in early life leads to a long-
term domination of the cells involved in allergic responses
over those involved in fighting infection.

5. Adrenoceptor mediated bronchospasm
2 Types: alpha & beta
Direct
Indirect
Airway Injury & Inflammation
Injury
Mediators
Immune dysregulation

7. Types of asthma:
Mild persistent: Possible chronic cough production.
Moderate persistent: Shortness of Breath on
excretion possible chronic cough production.
Severe persistent: Shortness of Breathe, Reduced
excise tolerance.

8. Respiratory infection : Respiratory syncytial virus (RSV), rhinovirus, influenza,
parainfluenza, Mycoplasma Pneumonia
Allergen: Airborne pollens (grass, trees, weeds), house-dust mites, animal
danders, cockroaches, fungal spores
Environment: Cold air, fog, ozone, sulfur dioxide, nitrogen dioxide, tobacco
smoke, wood smoke
Emotions: Anxiety, stress, laughter
Exercise: Particularly in cold, dry climate
Drugs/preservatives: Aspirin, nonsteroidal antiinflammatory drugs
(cyclooxygenase inhibitors), sulfites, benzalkonium chloride, nonselective β-
blockers
Occupational stimuli: Bakers (flour dust); farmers (hay mold); spice and enzyme
workers; printers (arabic gum); chemical workers (azo dyes, anthraquinone,
ethylenediamine, toluene diisocyanates, polyvinyl chloride); plastics, rubber, and
wood workers (formaldehyde, western cedar, dimethylethanolamine, anhydrides)

9. Coughing. Coughing from asthma often is worse at night or
early in the morning, making it hard to sleep.
Wheezing. Wheezing is a whistling or sound that occurs
when you breathe.
Chest tightness, pain or pressure
Shortness of breath.

10. Issues
 -receptor mediated
bronchoconstriction
 Complex
inflammatory/allergic
response
Goals
 Acute (quick) relief
Healing/reverse of
inflammatory/allergic
response
Requires a comprehensive approach from multiple directions

11. I. Bronchodilators
 β2 Sympathomimetics: Salbutamol, Terbutaline, Ephedrine.
 Methylxanthines: Theophylline , Aminophylline
 Anticholinergics: Ipratropium bromide
II. Leukotriene antagonists: Montelukast, Zafirlukast.
III. Mast cell stabilizers: Sodium cromoglycate, Ketotifen.
IV. Corticosteroids
A. Systemic: Hydrocortisone, Prednisolone
B. B. Inhalational: Beclomethasone dipropionate, Fluticasone propionate
V. Anti-IgE antibody: Omalizumab

12. Salbutamol: Also known as Albutrol.
M.O.A.:
-They act by directly stimulating the β2 adrenergic
receptor present in the smooth muscle OR bind with
respiratory tract
smooth muscle.
-They increase the conversion of cAMP from ATP
catalysed by adenelyl cyclase – leads to
bronchodilation effect/ muscle relaxation

13. inhibition of inflammatory mediator release
inhibition of smooth muscle proliferation
stimulation of mucociliary transport
cytoprotection of respiratory mucosa
attenuation of neutrophil activation

14. . Respiratory tract:
-β2 adrenoceptor present in the smooth muscles of bronchus
-stimulation of β2 receotors cause bronchodilation
2.Eye:
-stimulation of β2 adrenoceptor will induce the production of aqueous
humour
3. GIT:
-β2 adrenoceptor present in the GIT smooth muscle
-stimulation of β2 adrenoceptor will cause relaxation of smooth muscle of
GIT which is leading to constipation.

15. 4. Genito-urinary system:
-β2 adrenoceptor present in the genito-urinary tract
-β2 effect will cause relaxation in pregnant uterus (contraction in non
pregnant)
-Urinary bladder-relaxation of detrussor muscle leading to micturation
5. CNS:
-does not produce any marked CNS effect because of the poor penetration
in brain
-other minor effects: restlessness, tremor, apprehension
6. CVS:
-Less cardiac effect due to its selective β2 stimulation

16. -Asthma
-COPD
-Cystic fibrosis ( salbutamol + ipratropium bromide or acetyl cysteine)
-Congenital myasthenic syndrome
-Tocolytic hyperkalemia
-Spinal muscle atropy: under trial
-To reduce uterine contraction in pre mature labor
Dose
Oral- 2 to 4 mg x TDS or QID for adult
Parenteral: 0.25 to 0.5 mg i.m or s.c
Inhalation: 100 to 200 μg

17. 1.CNS:
-anxiety, tremor, headache, nervousness, restlessness, palpitation
2.GIT:
-dry mouth, constipation
3. Allergic reaction:
-urtricaria, angioedema, hypotension, paradoxial bronchospasm
4. High dose:
-Hypokalemia, Renal failure
5. Others:
-Tachycardia, Arrythmia, Flushing, Myocardial ischaemia (rare)

18. -Chronic diabetic
-Renal disease
-Crohn’s disease
Precaution:
-Used in patient with caution suffering from CVS disease because they
can still stimulate ( though minimally) β1 of heart.

19. Theophylline: have been extensively used in asthma, but are not
considered first line drugs any more. They are used more often in COPD.
-Theophylline is methyl xanthine derivative
-Alkaloid obtained from Thea sinensis ( Tea )
Mechanism of action:
- (a) They inhibit the phosphodiesterase enzymes i.e. responsible for the
degradation of cAMP.
- Thus due to the inhibition of phosphodiesterase enzyme, the intra cellular
conc of cAMP is increased thus reduced the bronchial tone producing
bronchodilator.
(b) Blockade of adenosine receptors: inhibition of such receptor,
bronchoconstriction is prevented.

20. 1) On bronchial smooth muscles
- Theophylline causes direct relaxation of bronchial smooth
muscles.
- It also inhibit the release of inflammatory mediators from
mast cells in bronchi.
2) On CNS
-They are CNS stimulant and causes euphoria, enhance motor
activity, performance enhancement.
-Also stimulates vasomotor and respiratory centre in medulla.
-In higher dose, they cause nervousness, insomnia, tremors,
convulsion, delirium, restlessness, excitement.
-Vomiting at high dose is due to gastric irritration and CTZ
stimulation.

21. 3) Diuretic effect (kidney)
-They have mild diuretic effect due to decrease tubular
reabsorption of sodium ion and water.
4) On mast cells and inflammatory cells
-They decrease release of histamine from mast cells and
activated inflammatory cells
-This may contribute its therapeutic effect in bronchial asthma.
5) On skeletal muscle
-They cause contraction of skeletal muscle.
- this contraction is useful in patient with COPD as it decreases
diaphragmatic fatigue and reduce dyspnoea.

22. 6) On CVS
a) Heart
- Methyl xanthine directly stimulate the heart and produce positive
inotropic effect( increase force of myocardial contraction), tachycardia,
increase cardiac output, arrhythmia( in high dose)
b) Blood vessels
- Produce vasodilation.
c) Blood pressure
- Vasomotor centre and direct cardiac stimulation can produce increased
BP.
- Vagal stimulation and direct vasodilation can produce decreased BP

23. 1) Absorption : well absorbed from GIT
2) Distribution: all parts of body and cross placenta
3) Metabolism : in liver
4) Excretion : excreted unchanged in urine
5) Half life : children ( 3-5 hrs) ; adults (7-12 hrs)
USES
-Asthma
-COPD
-Anti inflammatory effect
-Treatment of recurrent apnea in premature infants
DOSE: Poorly water soluble, cannot be injected. 100–300 mg TDS (15
mg/kg/day)

24. -They have narrow therapeutic index so TDM is required.
-Its toxicity can be treated with beta blockers.
-Gastric irritation, nausea, vomiting, headache, dizzyness,
increased heart rate, diarrhoea, arrhythmia, CNS excitement,
insomnia, seizures, irritability.
Contraindications: Peptic ulcer, heart disease
Precautions
-rapid IV administration of theophylline( in therapeutic doses)
may cause cardiac arrhythmia so it should be administered
slowly to avoid toxic effect.

25. -Rifampicin, phenytoin, phenobarbitone increase the metabolism
of theophylline( i.e. decreased plasma level of theophylline).
-Ciprofloxacin, cimetidine, allopurinol, erythromycin decrease
the metabolism of theophylline( i.e. increase the plasma level of
theophylline).
-Theophylline enhance the efficacy of hypoglycemic, oral
anticoagulant and diuretic.

26. -Ipratropium bromide:It is the semi synthetic derivative of
atropine.
-It is a anticholinergic drugs.
MOA
- They bind with muscarinic recceptors on bronchial smooth
muscles and competitively inhibit the bronchoconstrictive
action of acetylcholine released from parasympathetic
nerves.
- Thus they cause relaxation of bronchial smooth muscle.
less efficacious than sympathomimetics
Combination of inhaled ipratropium with β2 agonist produces more
marked and longer lasting bronchodilatation.

27. 1) Absorption- poorly or not absorbed from GIT on oral administration.
- Given by aerosol inhalation or nebulized form.
2) Metabolism: in liver
3) Excretion: - Urine
4) Half life : - 2 hrs
Dose: Salbutamol + Ipratropium
DUOLIN INHALER: 100 μg + 20 μg per metered dose
Uses
-COPD ( inhalation)
-Combine with salbutamol( in asthma)
-0.03% (Rhinorrhoea)

28. Dry mouth, sedation, skin flushing, headache, urinary retention, tachycardia,
acute angle closure glaucoma, nausea, palpitation, bad taste.
Contraindication
-Hypersensitivity to it.
-Glaucoma
-Urinary retention
-Obstruction in GIT
Drug interaction
- Theophylline + ipratropium bromide+ beta adrenergic agonist can increase
the dilating efffect on bronchi.

29. Montelukast & zafirlukast: Both have similar
actions and clinical utility
MOA: They competitively antagonize cysLT1 receptor
mediated bronchoconstriction, increased vascular permeability
and recruitment of eosinophils.
Both are indicated for prophylactic therapy of mild-to-
moderate asthma as alternatives to inhaled glucocorticoids.

30. safe drugs; few side effects like headache and rashes.
Eosinophilia and neuropathy are infrequent.
Pharmacokinetics:
They are well absorbed orally,
highly plasma protein bound and metabolized by CYP2C9
The plasma t½ of montelukast is 3–6 hours, while that of
zafirlukast is 8–12 hours.
Dose: Montelukast: 10 mg OD; children 2–5 yr mg OD, 6–14 yr 5
mg OD;
Zafirlukast: 20 mg BD; children 5–11 yr 10 mg BD;

31. It is a synthetic chromone derivative.
MOA:
inhibits degranulation of mast cells (as well as other
inflammatory cells) by trigger stimuli.
Release of mediators of asthma like histamine, LTs, PAF,
interleukins, etc. is restricted. The basis of this effect is not well
understood.
Pharmacokinetics:
Not absorbed orally. It is administered as an aerosol through
metered dose inhaler delivering 1 mg per dose: 2 puffs 4 times a
day.
rapidly excreted unchanged in urine and bile.

32. 1.Bronchial asthma:
2. Allergic rhinitis
3. Allergic conjunctivitis
Dose: Inhaler: 1 mg metered dose aerosol; 2 puffs 4 times daily.
Adverse effects:
 Bronchospasm,
throat irritation
cough
Rarely nasal congestion headache, dizziness, rashes.

33. They are not bronchodilators. They benefit by reducing
bronchial hyperreactivity, mucosal edema and by suppressing
inflammatory response to AG:AB reaction or other trigger
stimuli.
These drugs are given in conbination of other anti asthmatic
drugs.
They can be given by inhalation & systemic route.

34. Omalizumab:
 It is a humanized monoclonal antibody against IgE.
Administered i.v. or s.c., it neutralizes free IgE in circulation
without activating mast cells and other inflammatory cells.
On antigen challenge, little IgE is available bound to the mast
cell surface receptors (FcεR1) to trigger mediator release and
cause bronchoconstriction.

35. oMedications come in several forms
oTwo major categories of medications are:
Long-term control
Quick relief
1)Long term control:
Taken daily over a long period of time
Used to reduce inflammation, relax airway muscles, and
improve symptoms and lung function
 Inhaled corticosteroids
 Long-acting beta2-agonists
 Leukotriene modifiers

36. Quick relief:
Used in acute episodes.
Generally short-acting beta2agonists.

37. Inhalers and Spacers:
Spacers can help patients who
have difficulty with inhaler use
and can reduce potential for
adverse effects from medication.
Nebulizer:
•Machine produces a mist of the
medication.
•Used for small children or for severe
asthma episodes.
•No evidence that it is more effective than
an inhaler used with a spacer.

38. Reducing Exposure to House Dust Mites
Reducing Exposure to Environmental Tobacco Smoke
Reducing Exposure to Cockroaches
Reducing Exposure to Pets
Reducing Exposure to Mold
Other Asthma Triggers: Air pollution
Trees, grass, and weed pollen

39. Troublesome cough, particularly at night
Awakened by coughing
Coughing or wheezing after physical activity
Breathing problems during particular seasons
Coughing, wheezing, or chest tightness after allergen
exposure
Colds that last more than 10 days
Relief when medication is used
Wheezing sounds during normal breathing
Hyperexpansion of the thorax
Increased nasal secretions or nasal polyps
Atopic dermatitis, eczema, or other allergic skin conditions

40. Chest x-ray :
Lab tests on your blood and sputum (phlegm, mucus)
By forced expiratory volume: in 1 second (FEV1)
TREATMENT OF STATUS ASTHMATICUS:
Life-threatening Acute attack of Severe Asthma needing Immediate
treatment. A High Concentration (40-60%) of O2 is Administered with
high flow rate along with high doses of inhaled Short acting Beta2-
Agonost.

41. Advice and support on stop smoking
Nutritional assessment
Aerobic exercise training
Breathing training with closed lips to improve ventilatory pattern and gas
exchange.
Relaxation techniques
Education about medicines, nutrition, self-management of disease and
lifestyle issues
Psychological support

42. Clinical Pharmacy and Therapeutics: Edited by
Roger Walker
ESSENTIAL OF MEDICAL PHARMACOLOGY
(K.D. Tripathi.)
Pharmacotherapy:A Pathophysiologic Approach
Seventh Edition by Joseph T. DiPiro