Asthma

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 2010 Smt Cengage Padalia Asst. Prof. Dept of Pharmacology, Delmar,N. M. Learning Pharmacy College, Ahmedabad2
Asthma is a chronic 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 2010 Smt Cengage Padalia Asst. Prof. Dept of Pharmacology, Delmar,N. M. Learning Pharmacy College, Ahmedabad3
Immediate phase
Eliciting agent: Allergen or Non-specific stimulus Mast cells, Mononuclear cells Spasmogens cysLTs, H, PGD2
Late phase
Infiltration of cytokineReleasing Th2 cells, & monocytes, & activation of inflammatory cells, particularly eosinophils
Mediators e.g. cysLTs, NO
Chemotaxins, chemokines
Epithelial damage Airway inflammation Airway hyper-reactivity
Bronchospasm
Bronchospasm,Wheezing, coughing
Allergens T lymphocytes activated & secrete lymphokines Lymphokines activates eosinophils & secrete mediators & damaging proteins
Mediators potentiate inflammation & damage epithelium Enhancing BHR
Hypoxemia Airway Inflammation Acute Chronic Bronchospasm
Hypersecretion production Cough Wheezing Dyspnoea
Acute severe asthma: Upright position, Cant complete sentences in one breath, Tachypnea > 25/min, Tachycardia > 110/min, PEF < 50% of pred or best, Prolonged expiration, Breath sounds decreased, Inspiratory and expiratory rhonchi, Cough
Chronic asthma: Dyspnoea on exertion, wheeze, chest tightness and cough on daily basis, usually at night and early morning; productive cough (mucoid sputum), recurrent respiratory infection, expiratory rhonchi throughout and accentuated on forced expiration.
1) Spirometer In asthma, the following results may be obtained on spirometry:

Sr.no 1 Normal spirometry Interpretation Asthma in remission or asthma under control Airflow obstruction present (can be graded based on amount of reduction) Significantly reversible airflow obstruction
FEV1 <80% FVC FEV1 increase by 15% or more than 200 mL after bronchodilator
By Jitendra Bhangale 10 2010 Smt Cengage Padalia Asst. Prof. Dept of Pharmacology, Delmar,N. M. Learning Pharmacy College, Ahmedabad
2) Peak Expiratory Flow Rate:
Mini Wright's peak flow meter
Chest X-Ray Allergy Tests
Clinical features before treatment Symptoms STEP 4 Severe Persistent STEP 3 Moderate Persistent STEP 2 Mild Persistent STEP 1 Mild Intermitte nt Quick relief all patients Continuous, Limited physical activity Night time symptoms Frequent PEF 60% predicted Variability >30% Daily medications High dose inhaled CS & LA A Low to medium dose CS & LA A Alternative:-LA or theophylline Low dose CS
Daily
>time/weak
>60%-<80% predicted Variability >30%
1 time a week But <1 time a day < 1 time a week Asymptomatic & Normal PEF betw attacks
>2 times a months
80% predicted Variability 20-30 %
2 times a months
80% predicted Variability <20%
No daily medication needed.
Short acting bronchodilator Use of short acting 2 agonists

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Initial assessment History, physical examination, PEFR Initial therapy Inhaled 2 agonist.o2 if needed Incomplete/ poor response
Good response
Respiratory failure
Observe for at least 1 hr If stable Discharge to home
Add systemic corticosteroids Admit to ICU
Good response Discharge
Poor response Admit to hospital
SR.NO. I a b c II a b c d e III a b IV
DEVICE Metered dose Inhaler (MDI) CFC MDI HFA MDI Autohaler MDI Dry powder Inhaler (DPI) Rotahaler Terbuhaler Diskus Aerolizer Twisthaler Nebulizer Jet Nebulizer Ultrasonic Nebulizer Spacer Devices
DRUGS
All classes Albuterol Beclomethasone Pirbuterol
Albuterol Budesonide Fluticasone Salmeterol Fluticasone/salmeterol Formoterol mometasone
All classes except long acting 2agonists Cromolyn solution Short acting 2-agonist solution
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I) a.
b)
c)
Bronchodilators II) Leukotriene antagonists Sympathomimetics Montelukast Adrenaline Zafirlukast Ephedrine Zileuton Salbutamol III) Mast cell stabilizers Terbutaline Sodium cromoglycate Bambuterol Nedocromil Salmeterol Ketotifen Formoterol IV) Corticosteroids Methylxanthines Systemic Theophyline Hydrocortisone Aminophylline Prednisoloneetc Choline theophyline Inhalational Hydroxyethyl theophylline Beclomethasone dipropionate Anticholinergics Budesonide Atropine methnitrate Fluticasone propionate Ipratropium bromide 19 2010 Tiotropium bromide Delmar, Cengage Learning flunisolide
Therapeutic action of 2 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
Adverse effect Muscle tremor due to skeletal muscle -receptors Tachycardia and palpitations due to reflex cardiac stimulation secondary to peripheral vasodilation, stimulation of myocardial 1 receptors Metabolic effects: increased FFA, glucose, lactate after large systemic doses Hypokalemia (due to stimulation of K+ entry into skeletal muscle
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
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
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
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
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 -adrenergic responsiveness Delivery Aerosol Oral or IV for severe episodes: prednisone
Side Effects of Inhaled 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
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
Action of PDE4 inhibitors

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)
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.
THANK YOU
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Asthma

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By- Jitendra Bhangale Assistant Professor & Head, Department of Pharmacology, Smt N. M.

Padalia Pharmacy College, Ahmedabad

Introduction Etiology Pathophysiology Symptoms Diagnosis Management References

Mediators e.g. cysLTs, NO

Epithelial damage Airway inflammation Airway hyper-reactivity

Mediators potentiate inflammation & damage epithelium Enhancing BHR

Hypoxemia Airway Inflammation Acute Chronic Bronchospasm

Hypersecretion production Cough Wheezing Dyspnoea

1) Spirometer In asthma, the following results may be obtained on spirometry:

2) Peak Expiratory Flow Rate:

Mini Wright's peak flow meter

Chest X-Ray Allergy Tests

>60%-<80% predicted Variability >30%

>2 times a months

80% predicted Variability 20-30 %

80% predicted Variability <20%

No daily medication needed.

Short acting bronchodilator Use of short acting 2 agonists

Observe for at least 1 hr If stable Discharge to home

Add systemic corticosteroids Admit to ICU

Good response Discharge

Poor response Admit to hospital

All classes Albuterol Beclomethasone Pirbuterol

Albuterol Budesonide Fluticasone Salmeterol Fluticasone/salmeterol Formoterol mometasone

Side Effects of Inhaled Preparations Dysphonia

Action of PDE4 inhibitors

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