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BRONCHIAL ASTHMA
Bronchial asthma: Bronchial asthma is characterized by chronic airway inflammation and increased airway hyper-responsiveness leading to symptoms of wheeze, cough, chest tightness and dyspnoea. It is characterized functionally by the presence of airflow obstruction which is variable over periods of time, or is reversible with treatment. Cardinal features of bronchial asthma: 1. Recurrent episodes of wheezing, chest tightness, breathlessness and cough. 2. Vesicular breath sound with prolonged expiration. 3. Widespread high-pitched polyphonic expiratory wheezes. Pathophysiology: The bronchi become hyperactive as a result of a persistent inflammatory process or response to a number of stimuli which include biological agents, e.g., allergen, viruses, and environmental chemicals such as ozone. Inflammatory mediators are liberated from mast cell, eosinophil, neutrophil, monocyte and macrophage. Some mediators are: i) Preformed: Histamine ii) Others are formed after cell activation (PGD2, LT, PAF) Produce mucosal edema and cause damage to the ciliated epithelium Breaching of protective epithelial barrier Hypersensitivity Wheezing, breathlessness Main path physiological features:
i) Reversible bronchoconstriction increase resistance to air flow for smooth muscle contraction. ii) Bronchial inflammation mucosal thickening from oedema and cellular infiltration. iii) Bronchial hyper-reactivity. iv) Bronchial mucosal hyper secretion leads to blocking of airway lumen by abnormal thick viscid mucous plug.
As a result there is decrease efficiency with which air is carried to and from alveoli. Types of asthma: A) Aetilogical: i. Extrimsic/atopic/early onset asthma: When a definite external cause can be identified. ii. Intrinsic/cryptogenic/non-atopic/late onset asthma: When no causative agent can be identified. B) Clinical: i. Episodic asthma
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Allergen
o Viral infection o Emotional status o Exercise o Chemicals- Ozone (O3), SO2 o Occupation o Drugs- blocker, NSAID, Aspirin o Environment- Cold air, dust, mite, tobacco smoke, pollens, animal dander
Synthetic: Aminophylline b.Propyl-xanthine derivative: Enprophylline o Ipratropium bromide Systemic: Prednisolone (Oral) Hydrocortisone (IV)
Topical or inhalation: Beclomethasone Fluticasone Budesonide o Sodium chromoglycate o Nedocromyl sodium o Ketotifen o Azalastin o Zileutin
Mast cell stabilizer Anti-histamine(3) Newer dugs o Leukotriene synthesis inhibitoro Leukotriene receptor antagonistso Anti IgE monoclonal antibody therapy-
Approaches to treatment:
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Step I :Short acting 2 agonist Step II : Low dose steroid inhaler, or, Other anti-inflammatory agent High dose steroid inhaler, or, Low dose steroid inhaler +
High dose steroid inhaler + Regular bronchodilator / Ipratropium bromide / Methylxanthine / LT pathway inhibitor Step V : Addition of best of 4 + Regular steroid therapy (oral
prednisolone).
Status asthmaticus/Acute severe asthma: Acute severe asthma is an acute medical emergency characterized by severe wheeze, breathlessness to such extent that the pt. cannot speak, tachycardia, central cyanosis and sometimes pulsus paradoxes may develop. Pt. must be hospitalized immediately. Mx of acute severe asthma: i) ii) iii) iv) Immediate hospitalization Propped up position O2 inhalation: High flow (60%) Nebulization with Salbutamol or terbutaline Ipratropium bromide Normal saline Every 20 min for 3 doses. v) Prednisolone 30-60 mg orally or Hydrocortisone 200 mg i.v. 6 hourly for 2-3 days vi) If not improved, Inj. Aminophylline by slow infusion Loading dose 5 mg/kg Continuous infusion 0.5 mg/kg/hour vii) If not improved, refer the patient to ICU. But if ICU is not available Inj. Magnesium sulphate. Rx of chronic asthma:
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Rx. Shorter acting 2 agonist in inhalation form during bronchoconstriction. It is not regularly taken. 2. Moderate asthma: More than 2 broncho constriction episodes in a week.
Rx. Long acting 2 agonist (Salmetarol) Inhaled chromolyn Inhaled glucocorticoid 3. Severe asthma: Daily bronchoconstrictive episodes.
Rx. Long acting 2 agonist Chromolyn inhalation Inhaled glucocorticoid Theophylline Oral glucocorticoid- Prednisolone
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Relief of asthma 2) It increases mucocilliary function & clears mucous. It decreases capillary permeability. Preparation and doses: Oral tablet: 2-4 mg four times daily Aerosol: 1-2 puffs 4-6 hour interval 90 gm/puff (each inhalation) IM/IV form Advantage of inhaled salbutamol: Drugs are directly delivered to the site of action. So minimum systemic absorption. Selective stimulation of pulmonary 2 receptor. Rapid onset of action i.e. within 15 min. Long duration of action (4-6 hour) Minimum toxic effect and unwanted cardiovascular effects are less Less dose required Suitable for acute asthma Disadvantage of oral route: Undergoes first pass metabolism. So, dose requirement is high and therapeutic effect. Delayed onset of action More toxic effect Not suitable for acute asthma
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Xanthine Derivatives
Mechanism of action: Theophylline/Aminophylline High concentration Inhibit Phosphodiesterase enzyme (PDE) No conversion of cAMP to 5AMP Increase cAMP accumulation Relaxation of bronchial smooth muscle Bronchodilation Low concentration Inhibit adenosine receptor Inhibit antigen induced release of histamine Prevent brochoconstriction
Relief of asthma Indication: i. ii. iii. iv. v. vi. Secondary drug in both acute and chronic asthma Congestive cardiac failure Emergency heart failure with asthma Migraine Ordinary headache Apnoea in preterm baby.
Q. Briefly discuss the advantages and disadvantages of Aminophylline in the treatment of bronchial asthma. Ans: Advantages of Aminophylline: 6
Side effect: I. CNS: II. CVS: Insomnia Headache Dizziness Severe restlessness Agitation
III. Others: Nausea Vomiting Mild diuresis Contraindication (C/I): I. Cardiac or liver failure II. Peptic ulcer III. Pregnancy Type of asthma and Aminophylline: 1) Acute asthma:
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3.Onset of action 4.Duration of action 5.Usual form 6.Cardio toxic effect 7.CNS toxicity 8.Action on GFR 9.TI 10.In acute asthma 11.Drug of choice for 12.Caution during administration
Corticosteroids in Asthma
Mechanism of action of corticosteroids in asthma: The most important action of corticosteroids in asthmatic patient is inhibition of the lymphocytic, eosinophilic mucosal inflammatory reactions in
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Arachidonic acid Lipo-oxygenase pathway Synthesis of Leukotriene, PAF (Bronchoconstrictor) Role of glucocorticoids in asthma: 1. Anti-inflammatory action: a) Regulation of cytokine and chemokine production b) Inhibition of synthesis of arachidonic acid metabolites (LT, PG & PAF) Decrease bronchial hyper-reactivity c) Marked inhibition in accumulating basophil, eosinophil & other leukocytes in lung tissue d) Decrease capillary permeability Decrease bronchial oedema and congestion. e) Reduce inflammation by relieving mucosal oedema. Cyclo-oxygenase pathway Synthesis of PG (Inflammatory mediator)
2. Permissive action: Potentiate the action of adrenaline Increase cAMP Bronchodilation. Ultimately there is limitation of inflammatory process & inhibition of immune responses; thus reduce the asthmatic attack. Adverse effects: A. Due to inhalation: i) Oropharyngeal candidiasis ii) Dryness of mouth iii) Hoarseness of voice B. Due to systemic absorption: i) Hypertension ii) Aggravation of peptic ulcer disease iii) Osteoporosis iv) Weight gain v) Impaired glucose control in DM vi) Susceptibility to infection vii) CNS depression Corticosteroids in asthma: Acute asthma: Immediately:
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Chronic asthma: Mild to moderate: Beclomethasone dipropionate, Budesonide or fluticasone propionate inhalation 800-2000 mg Severe: Inhaled (800-2000mg) plus Tab. Prednisolone 30-60mg/day Comparison of Salbutamol with Beclomethasone: Both Salbutamol & Beclomethasone are used in the treatment of asthma but they differ in the following pointsTraits 1.Group 2. Mechanism of action 3.Onset of action 4.Adverse effect Salbutamol 2 agonist It relaxes the smooth muscle of airway causing bronchodilation Rapid relief of symptoms. So suitable in emergency management Fine tremor, tachycardia, hypokalaemia etc Beclomethasone Steroid It reduces the number & activity of cells involved in airway inflammation Slow onset of action. So not suitable in emergency management Hoarseness of voice, oral candidiasis, rarely rash
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