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Asthma by jitendra bhangale
1) Asthma is a chronic inflammatory disease of the airways characterized by recurrent episodes of wheezing, breathlessness, chest tightness, and coughing. 2) The inflammation is caused by a variety of inflammatory cells like mast cells, eosinophils, and T lymphocytes which release mediators that cause bronchoconstriction and airway hyperresponsiveness. 3) Symptoms of asthma include wheezing, coughing, chest tightness, and shortness of breath. Diagnosis involves lung function tests and demonstration of improvement after bronchodilator treatment.
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Asthma by jitendra bhangale
- 1. 7/19/2012 By- Jitendra Bhangale Assistant Professor & Head, Department of Pharmacology, Smt N. M. Padalia Pharmacy College, Ahmedabad 1 © 2010 Delmar, Cengage Learning Introduction Etiology Pathophysiology Symptoms Diagnosis Management References By Jitendra Bhangale Asst. Prof. Dept of Pharmacology, Delmar, Cengage Learning Pharmacy College, Ahmedabad2 © 2010 Smt N. M. Padalia 1
- 2. 7/19/2012 Asthma is achronic inflammatory disorder of the airways in which many cells and cellular elements play a role, in particular, mast cells, eosinophils, T lymphocytes, macrophages, neutrophils, and epithelial cells. In susceptible individuals, this inflammation causes recurrent episodes of wheezing, breathlessness, chest tightness, and coughing, particularly at night or in the early morning. The inflammation also causes an associated increase in the existing bronchial hyperresponsiveness to a variety of stimuli. By Jitendra Bhangale Asst. Prof. Dept of Pharmacology, Delmar, Cengage Learning Pharmacy College, Ahmedabad3 © 2010 Smt N. M. Padalia By Jitendra Bhangale Asst. Prof. Dept of Pharmacology, Delmar, Cengage Learning Pharmacy College, Ahmedabad4 © 2010 Smt N. M. Padalia 2
- 3. 7/19/2012 Immediatephase Late phase Infiltration of cytokine- Eliciting agent: Releasing Th2 cells, Allergen or & monocytes, & activation of Non-specific stimulus inflammatory cells, particularly eosinophils Mast cells, Mononuclear cells Mediators e.g. cysLTs, NO Spasmogens Epithelial damage Chemotaxins, cysLTs, Airway chemokines H, PGD2 inflammation Airway hyper-reactivity Bronchospasm Bronchospasm,Wheezing, coughing By Jitendra Bhangale Asst. Prof. Dept of Pharmacology, Delmar, Cengage Learning Pharmacy College, Ahmedabad5 © 2010 Smt N. M. Padalia Allergens T lymphocytes activated & secrete lymphokines Lymphokines activates eosinophils & secrete mediators & damaging proteins Mediators potentiate inflammation & damage epithelium Enhancing BHR By Jitendra Bhangale Asst. Prof. Dept of Pharmacology, Delmar, Cengage Learning Pharmacy College, Ahmedabad6 © 2010 Smt N. M. Padalia 3
- 4. 7/19/2012 Hypoxemia Hypersecretion production Airway Inflammation Cough Acute Chronic Wheezing Bronchospasm Dyspnoea By Jitendra Bhangale Asst. Prof. Dept of Pharmacology, Delmar, Cengage Learning Pharmacy College, Ahmedabad7 © 2010 Smt N. M. Padalia By Jitendra Bhangale Asst. Prof. Dept of Pharmacology, Delmar, Cengage Learning Pharmacy College, Ahmedabad8 © 2010 Smt N. M. Padalia 4
- 5. 7/19/2012 Chronic asthma: Acute severe asthma: Dyspnoea on exertion, Upright position, wheeze, Can’t complete sentences in one chest tightness and cough on breath, daily basis, usually at night Tachypnea > 25/min, and early morning; Tachycardia > 110/min, productive cough (mucoid PEF < 50% of pred or best, sputum), Prolonged expiration, recurrent respiratory infection, Breath sounds decreased, expiratory rhonchi throughout Inspiratory and expiratory rhonchi, and accentuated on forced expiration. Cough By Jitendra Bhangale Asst. Prof. Dept of Pharmacology, Delmar, Cengage Learning Pharmacy College, Ahmedabad9 © 2010 Smt N. M. Padalia 1) Spirometer In asthma, the following results may be obtained on spirometry: Sr.no Interpretation Asthma in remission or 1 Normal spirometry asthma under control Airflow obstruction present (can be graded 2 FEV1 <80% FVC based on amount of reduction) FEV1 increase by 15% or more Significantly reversible 3 than 200 mL after bronchodilator airflow obstruction By Jitendra Bhangale 10 Asst. Prof. Dept of Pharmacology, Delmar, Cengage Learning Pharmacy College, Ahmedabad © 2010 Smt N. M. Padalia 5
- 6. 7/19/2012 2) Peak ExpiratoryFlow Rate: Mini Wright's peak flow meter By Jitendra Bhangale 11 Asst. Prof. Dept of Pharmacology, Delmar, Cengage Learning Pharmacy College, Ahmedabad © 2010 Smt N. M. Padalia Chest X-Ray Allergy Tests By Jitendra Bhangale 12 Asst. Prof. Dept of Pharmacology, Delmar, Cengage Learning Pharmacy College, Ahmedabad © 2010 Smt N. M. Padalia 6
- 7. 7/19/2012 By Jitendra Bhangale 13 Asst. Prof. Dept of Pharmacology, Delmar, Cengage Learning Pharmacy College, Ahmedabad © 2010 Smt N. M. Padalia Clinical features before treatment Night time Daily Symptoms PEF symptoms medications STEP 4 Continuous, ≤60% predicted High dose inhaled Severe Limited physical Frequent Variability >30% CS & LAβA Persistent activity Low to medium STEP 3 >60%-<80% predicted dose CS & LAβA Moderate Daily >time/weak Variability >30% Alternative:-LA or Persistent theophylline STEP 2 ≥1 time a week >2 times a ≥80% predicted Mild Low dose CS But <1 time a day months Variability 20-30 % Persistent STEP 1 < 1 time a week No daily Mild Asymptomatic & ≤2 times a ≥80% predicted medication Intermitte Normal PEF betw months Variability <20% needed. nt attacks Quick relief Short acting bronchodilator all patients Use of short acting β2 agonists 14 © 2010 Delmar, Cengage Learning 7
- 8. 7/19/2012 Initial assessment History, physical examination, PEFR Initial therapy Inhaled β2 agonist.o2 if needed Incomplete/ poor response Good response Respiratory failure Add systemic corticosteroids Observe for at least 1 hr Admit to ICU If stable Good response Poor response Discharge to home Discharge Admit to hospital By Jitendra Bhangale 15 Asst. Prof. Dept of Pharmacology, Delmar, Cengage Learning Pharmacy College, Ahmedabad © 2010 Smt N. M. Padalia By Jitendra Bhangale 16 Asst. Prof. Dept of Pharmacology, Delmar, Cengage Learning Pharmacy College, Ahmedabad © 2010 Smt N. M. Padalia 8
- 9. 7/19/2012 SR.NO. DEVICE DRUGS I Metered dose Inhaler (MDI) a CFC MDI All classes b HFA MDI Albuterol c Autohaler MDI Beclomethasone Pirbuterol II Dry powder Inhaler (DPI) a Rotahaler Albuterol b Terbuhaler Budesonide Fluticasone c Diskus Salmeterol Fluticasone/salmeterol d Aerolizer Formoterol e Twisthaler mometasone III Nebulizer All classes except long acting β2- a Jet Nebulizer agonists Cromolyn solution b Ultrasonic Nebulizer Short acting β2-agonist solution IV Spacer Devices 17 © 2010 Delmar, Cengage Learning By Jitendra Bhangale 18 Asst. Prof. Dept of Pharmacology, Delmar, Cengage Learning Pharmacy College, Ahmedabad © 2010 Smt N. M. Padalia 9
- 10. 7/19/2012 I) Bronchodilators II) Leukotriene antagonists a. Sympathomimetics Montelukast Adrenaline Zafirlukast Ephedrine Zileuton Salbutamol III) Mast cell stabilizers Terbutaline Sodium cromoglycate Bambuterol Nedocromil Salmeterol Ketotifen Formoterol IV) Corticosteroids b) Methylxanthines Systemic Theophyline Hydrocortisone Aminophylline Prednisolone…etc Choline theophyline • Inhalational Hydroxyethyl theophylline Beclomethasone c) Anticholinergics dipropionate Atropine methnitrate Budesonide Ipratropium bromide Fluticasone propionate flunisolide 19 Tiotropium bromide Delmar, Cengage Learning © 2010 Therapeutic action of β2 agonists:- Relax contracted bronchial smooth muscle Prevent bronchial smooth muscle contraction by various stimuli Increase mucous clearance Prevent mast cell mediator release Prevent edema induced by histamine, etc. by preventing increase in endothelial permeability Delivery By Aerosol: mild to moderately severe asthma only often used in conjunction with other drugs; e.g. to promote better delivery of cromolyn or corticosteroids to the distal airways. Systemically: available orally and for injection By Jitendra Bhangale 20 Asst. Prof. Dept of Pharmacology, Delmar, Cengage Learning Pharmacy College, Ahmedabad © 2010 Smt N. M. Padalia 10
- 11. 7/19/2012 Adverse effect Muscle tremor due to skeletal muscle β-receptors Tachycardia and palpitations due to reflex cardiac stimulation secondary to peripheral vasodilation, stimulation of myocardial β1 receptors Metabolic effects: increased FFA, glucose, lactate after large systemic doses Hypokalemia (due to stimulation of K+ entry into skeletal muscle By Jitendra Bhangale 21 Asst. Prof. Dept of Pharmacology, Delmar, Cengage Learning Pharmacy College, Ahmedabad © 2010 Smt N. M. Padalia Major therapeutic actions Relaxes bronchial smooth muscle Decreases mast cell mediator release Increases mucocilliary clearance Mechanisms of action Inhibition of phosphodiesterases Increase intracellular cAMP Adenosine receptor antagonism Adenosine causes bronchoconstriction in asthmatics Bronchoconstriction prevented by theophylline at therapeutic concentrations Other Increased epinephrine secretion form adrenal medulla; increase small and cannot account for the bronchodilation Antagonizes some prostaglandins in smooth muscle By Jitendra Bhangale 22 Asst. Prof. Dept of Pharmacology, Delmar, Cengage Learning Pharmacy College, Ahmedabad © 2010 Smt N. M. Padalia 11
- 12. 7/19/2012 Delivery Ineffective by inhalation;requires build-up of effective plasma concentration Intravenous; for severe acute asthma only Side effects of Methylxanthine Nausea Vommiting Headache Restlessness Increased acid secretion Diuresis Convulsions Cardiac arrhythmias CNS stimulation By Jitendra Bhangale 23 Asst. Prof. Dept of Pharmacology, Delmar, Cengage Learning Pharmacy College, Ahmedabad © 2010 Smt N. M. Padalia Mechanism of Action Mast cell stabilization Inhibition of degranulation by a variety of stimuli, including cell-bound IgE allergen Interactions Inhibition of leukotriene production Above actions due to blockage of calcium influx into mast cells No bronchodilator or antihistamine activity By Jitendra Bhangale 24 Asst. Prof. Dept of Pharmacology, Delmar, Cengage Learning Pharmacy College, Ahmedabad © 2010 Smt N. M. Padalia 12
- 13. 7/19/2012 Delivery Less than 1% of an oral dose of cromolyn is absorbed, so therapeutic effects are achieved through local administration via inhalation: In 4% solution - By aerosol spray or nebulizer Powdered drug - as capsules to use in powered turbo-inhaler or as a metered dose Inhaler Adverse reactions: Bronchospasm, Cough, Laryngeal edema, Joint swelling or pain Headache Rash, Nausea By Jitendra Bhangale 25 Asst. Prof. Dept of Pharmacology, Delmar, Cengage Learning Pharmacy College, Ahmedabad © 2010 Smt N. M. Padalia Mechanisms of action due to anti-inflammatory properties Reduces number and activity of inflammatory cells in airways Inhibits release of arachidonic acid metabolites Prevents increased vascular permeability Suppresses IgE binding Increases β-adrenergic responsiveness Delivery Aerosol Oral or IV for severe episodes: prednisone By Jitendra Bhangale 26 Asst. Prof. Dept of Pharmacology, Delmar, Cengage Learning Pharmacy College, Ahmedabad © 2010 Smt N. M. Padalia 13
- 14. 7/19/2012 Side Effects ofInhaled Preparations Dysphonia Oropharyngeal candidiasis Both can be reduced by mouth rinsing with water after administration and through use of appropriate spacers with the inhaler to avoid oral deposition By Jitendra Bhangale 27 Asst. Prof. Dept of Pharmacology, Delmar, Cengage Learning Pharmacy College, Ahmedabad © 2010 Smt N. M. Padalia PDE4 inhibitors Inhaled ciclosporin A Monoclonal antibodies against IgE, CD4 cells, and Th2 cytokines (e.g., interleukin 4 and 5) More specific immunotherapy Antagonists to chemokines, adhesion molecules, proinflammatory cytokines, tumour necrosis factor , interleukin 1 Antisense oligonucleotides and gene therapy Inhibitory cytokines interleukin 10 By Jitendra Bhangale 28 Asst. Prof. Dept of Pharmacology, Delmar, Cengage Learning Pharmacy College, Ahmedabad © 2010 Smt N. M. Padalia 14
- 15. 7/19/2012 Action of PDE4inhibitors Relax airway smooth muscle Reduce bronchoconstriction Decrease oedema Reduce secretion of inflammatory mediators, such as histamine, leukotrine and chemokines (IL-4, IL5) Block leukocyte adhesion to vascular endothelial cells Block generation of oxygen derived free radicals E.g.. Roflumilast (Altana pharma) Cilomilast (GSK) S-5751 (Shionogi) By Jitendra Bhangale 29 Asst. Prof. Dept of Pharmacology, Delmar, Cengage Learning Pharmacy College, Ahmedabad © 2010 Smt N. M. Padalia Mechanism of action:- Monoclonal antibodies blocks the attachment of the IgE to the Fc receptors on mast cells and basophils and the subsequent release of histamine by those cells upon exposure to allergen. By Jitendra Bhangale 30 Asst. Prof. Dept of Pharmacology, Delmar, Cengage Learning Pharmacy College, Ahmedabad © 2010 Smt N. M. Padalia 15
- 16. 7/19/2012 Thank you 31 © 2010 Delmar, Cengage Learning 16