pharmacothrapy of asthma.pptxBronchial asthma is a chronic respiratory disease characterized by inflammation and narrowing of airways in the lungs, which cause difficulty in breathing.

pharmacotherpy of asthma M pharm 2nd sem.
Bronchial asthma is a chronic respiratory disease characterized by inflammation and narrowing of airways in the lungs, which cause difficulty in breathing.
Symptoms can include coughing, wheezing, shortness of breath and chest tightness. These symptoms can be mild or severe and can come and go over time.

Although asthma can be a serious condition, it can be managed with the right treatment.

Asthma affected an estimated 262 million people in 2019 (1) and caused 455 000 deaths.

1. Prepared by, Abhishek Kumar Gupta M.Pharm , 2ndSem. Department of Pharmacology ISF College of Pharmacy, Punjab [email protected] Pharmacotherapy for Asthma 1

2. CONTENT Sl.No. Title 1. Introduction to Asthma 2. Clinical feature 3. Risk factor 4. Classification and types of asthma 5. Inflammation and asthma symptoms 6. pathophysiology 7. Diagnosis of asthma 8. Drugs for treatment of asthma 9.  Bronchodilators 10. Corticosteroids 14. References 2

3. 3 OBSTRUCTIVE VS RESTRICTIVE PULMONARY DISEASE Obstructive Restrictive Characterized by an increase in resistance to air flow due to partial or complete obstruction Characterized by reduced expression of lung parenchyma accompanied by decreased total lung capacity Total lung capacity normal Total lung capacity normal decreased Asthma, chronic bronchitis, emphysema, and small- airway disease pulmonary fibrosis Can not out air Can not in air

4. Symptoms can include coughing, wheezing, shortness of breath and chest tightness. These symptoms can be mild or severe and can come and go over time. Although asthma can be a serious condition, it can be managed with the right treatment. Asthma affected an estimated 262 million people in 2019 (1) and caused 455 000 deaths . Bronchial asthma is a chroni c respiratory disease characterized by inflammation and narrowing of airways in the lungs, which cause difficulty in breathing. INTRODUCTION 4

5. CLINICAL FEATURES 5 Recurrent episodes characterized by : - Breathlessness Wheezing Coughing – especially at night or early morning Tightness chest Hyperinflation Increased mucus production TRIGGERS Allergens Respiratory tract infection Exercise Cold air Stress Drug aspirin

6. Endogenous Atopy Genetic predisposition Obesity Early infection Environmental Indoor allergens Outdoor allergens Occupation sensitizers Passive smoking 6 RISK FACTORS

7. 7 Atopic (extrinsic) Predisposition towards hyper reaction to normal allergen Atopic are those patients who have familiar inherited disposition towards reacting to normal allergen External allergen may be dust, cat, dog, etc Non atopic (intrinsic) Not allergic Aspirin Exercise Stress Cold Occupational toxin inhalation eg - toluene Types of asthma according to causes clinical classification of asthma Intermittent Chronic Twice a week Go away within few minute More then twice a week Duration more then a day More then twice a week Duration more then a day

8. 8 Allergens Sensitizers Viruses Air pollution Airway inflammation INFLAMATION AND ASTHMA SYMPTOMS Symptoms Cough wheezing Chest tightness Dyspnea Airway hyperresponsiveness Effects Bronchospasm Plasma exudation Mucus secretion Structural change Triggers Allergens Exercise Cold air So 2 particulates Sensory nerve activation

9. 9 PATHOPHYSIOLOGY Fig- A & B, Comparison of a normal bronchus with that in a person with asthma. Note the accumulation of mucus in the bronchial lumen resulting from an increase in the number of mucus secreting goblet cells in the mucosa and hypertrophy of submucosal gland. In addition, there is intense chronic inflammation due to recruitment of eosinophils, macrophages and other inflammatory cells.

10. 10 PATHOPHYSIOLOGY Inhaled allergen binds with dendritic cell and stimulate TH2 cells. TH2 cell secrete cytokines that promote allergic inflammation and stimulate B cells to produce IgE and other antibodies. TH2 cells IL-4 IL-5 IL-13 Stimulate the production of IgE by B cell Stimulate mucus secretion and promotes IgE production by B cell Activate required eosinophil cytokines

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12. 12 Diagnosis Clinical and occupational history Diagnostic test Non- specific Specific 1.Lung function assessment Monitoring peak expiratory flow Serial spirometry's with reversibility test if air flow obstruction Methacholine/histamine challenge test if normal lung function 2. FeNO measurement 3.Sputum eosinophil count Skin prick tests Serum-specific IgE Specific inhalation challenge Basophil activation test DIAGNOSIS OF ASTHMA

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15. 15 BRONCHODILATORS Bronchodilator are drug that relax constricted airway smooth muscle and cause immediate reversal of airway obstruction in asthma. There are mainly three classes of bronchodilators are in current clinical use: β 2 Adrenergic agonists (sympathomimetics) Theophylline (a methylxanthine) Anticholinergic agents (muscarinic receptor antagonist) β 2 Adrenergic agonists (sympathomimetics) :- Inhaled β 2 agonists are the bronchodilator treatment of choice in asthma because they are most effective bronchodilator and have minimal side effect.

16. 16 CLASSIFICATION OF β2 AGONISTS β2 Agonist SABA(short acting) LABA(Long acting) Ultra LABA Salbutamol Terbutaline Levalbuterol Fenoterol metaproterenol Indacaterol (as not approved for asthma) Salmeterol Formoterol

17. 17 Activation of β2 receptors ( β2 AR) results in activation of AC via Gs' leading to an increase in intracellular cAMP and activation of PKA. PKA phosphorylates a variety of target substrates, resulting in opening of Ca2+-activated K+ channels ( KCa ), thereby facilitating hyperpolarization, decreased PI hydrolysis, increased Na+/Ca2+ exchange, increased Na+, Ca2+-ATPase activity, and decreased myosin light chain kinase (MLCK) activity and increased myosin light chain (MLC) phosphatase. β2 Receptors may also couple to KCa via Gs . PDE, cyclic nucleotide phosphodiesterase. MECHANISM OF ACTION OF β2 AGONISTS

18. 18 Therapeutic uses: Side effects: Dilation of airway in asthma, chronic bronchitis, & emphysema Mild to moderate cases of asthma Adjunct therapy for the relief of pulmonary edema . Nausea, vomiting, anorexia Gastroesophageal reflux during sleep Sinus tachycardia, extra systolic palpitations, ventricular dysrhythmias Transient increased urination.

19. 19 LEUKOTRIENE ANTAGONISTS An Leukotriene antagonists is a drug which functions as a leukotriene- related enzyme inhibitor (arachidonate 5-lipoxygenase) or leukotriene receptor antagonist and consequently opposes the function of these inflammatory mediators; leukotrienes are produced by the immune system. Leukotriene receptor antagonists, such as montelukast, zafirlukast can be used to treat these diseases. They are less effective than corticosteroids for treating asthma, but more effective for treating certain mast cell disorders. Μ.Ο.Α: Montelukast ,zafirlukast are competitively prevent the bronchoconstrictor effects of leukotrienes By blocking their receptor Prevent leukotrienes from attaching to receptor on cells in the lungs and in circulation Blocking the inflammation in the lungs.

20. 20 Side effects: Headache Stomach pain, heartburn, upset stomach, nausea, diarrhea, Tooth pain Tired feeling Fever, stuffy nose, sore throat, cough, hoarseness Mild rash. Uses: Prophylaxis and chronic treatment of asthma.

21. 21 CORTICOSTEROIDS Are not bronchodilators Given as prophylactic medications, used alone or combined with beta-agonists Mechanism of action Inhibition of phospholipase A2 ↓prostaglandin and leukotrienes- Mast cell stabilization →↓ histamine release- Upregulation of ẞ2 receptors

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23. Route of administration . Inhalation Budesonide, Fluticasone, Beclomethasone Less side effects Oral Prednisolone Parenteral Hydrocortisone, Methylprednisolone Status asthmaticus (IV infusion) Side effects of systemic corticosteroids Adrenal suppression Growth retardation in children Osteoporosis Fluid retention, weight gain, hypertension Hyperglycemia Susceptibility to infections Glaucoma Cataract Fat distribution, wasting of the muscles Psychosis 23

24. 1. Goodman and Gilman’s ,The Pharmacological Basis of Therapeutics (12 th edition) 2. Rang and Dale’s Pharmacology,6 th edition published in 2012. 3.A complete Textbook of Medical Pharmacology by S.K Srivastava. 4. https://youtu.be/oNnuGtxZzgc?si=DKVkm_gCBEl77pnO . 5. https://image.slidesharecdn.com/bronchialasthma-drugsandstatusasthmaticus REFERENCE 24

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