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VARA LAKSHMI M.PHARM HINDU COLLEGE OF PHARMACY, AMARAVATHI ROAD , GUNTUR-522002 ANTI ASTHMA DRUGSWhat is ASTHMA: What is ASTHMA Bronchial asthma is characterised by hyperresponsiveness of tracheobronchial smooth muscle to a variety of stimuli, resulting in narrowing of air tubes,often accompained by increased secretion, mucosal edema and mucus plugging. Symptoms include dyspnoea,wheezing , cough . TYPES OF ASTHMA: TYPES OF ASTHMA Asthma associated with specific allergic reaction. Asthma not associated with known allergy. Asthma associated with chronic obstructive pulmonary disease. Exercise-induced asthma → some patients develop wheeze that regular follows with in a few minutes of exercise .CLASSIFICATION OF DRUGS : CLASSIFICATION OF DRUGS a)BRONCHODILATORS: 1.Selective β 2 Agonists Salbutamol , T erbutaline, Remiterol, Fenoterol, Salmeterol , Formoterol , Bambuterol. 2. Non Selective Sympathmimetics Epinephrine, Ephedrine , Isoprenaline Orciprenaline, Isoetharine 3.Anti cholinergics Ipratropium, Oxitropium , Tiotropium. 4.Methyl xanthines Theophylline, Aminophylline Diprophylline, Choline theophyllinatePowerPoint Presentation: b)Corticosteroids 1.Oral: Prednisone, Methyl Prednisolone 2.parenteral: Methyl prednisolone hydro cortisone 3.Inhalational:- Beclomethasone Triamcilone Budesonide c)MAST CELL STABILISERS: Sodium Cromoglycate (Cromolyn sodium) Nedocromil Ketotifen d)LEUKOTRIENE MODULATORS 1.5-Lipoxygenase inhibitors: Zileuton 2.LTD4-receptor antagonists: Zafirlukast Montelukast e)MONOCLONAL ANTI- Ig E Anti Body: Omalizumab f)Miscellaneous: 1. Nitric oxide donors 2.Calcium channel Blockers: Nifedipne , Verapamil .Bronchodilators: Beta-Agonists : Bronchodilators: Beta-Agonists Three types Nonselective adrenergics Stimulate alpha-, beta 1 - (cardiac), and beta 2 - (respiratory) receptors Example: Epinephrine When injected S.C., an effective and rapid bronchodilation. Nonselective beta adrenergics Stimulate both beta 1 - and beta 2 -receptors Example: Isoproterenol Selective beta 2 drugs Stimulate only beta 2 -receptors Example: SalbutamolBRONCHODILATORS:: BRONCHODILATORS: Relief of bronchospasm related to asthma,bronchitis , and other pulmonary diseases Useful in treatment of acute attacks as well as prevention. Beta-Agonists Large group, sympathomimetics Used during acute phase of asthmatic attacks Quickly reduce airway constriction and restore normal airflow Stimulate beta 2 -adrenergic receptors throughout the lungsBeta-Agonists: Side Effects: Beta-Agonists: Side Effects Beta 2 (salbutamol) Hypotension OR hypertension Vascular headaches Tremor Contraindicated: clients with allergies, tachyarythmias, severe cardiac disease Anti cholinergics Mechanism of Action : Anti cholinergics Mechanism of Action Acetylcholine (ACh) causes bronchial constriction and narrowing of the airways Anticholinergics bind to the ACh receptors, preventing ACh from binding Result: bronchoconstriction is prevented, airways dilateAnticholinergics: Anticholinergics Atrovent (Ipratropium bromide) is the only anticholinergic used for respiratory disease Slow and prolonged action Used to prevent bronchoconstriction NOT used for acute asthma exacerbations! Combivent (Salbutamol / Ipratroprium). Side effects: Dry mouth or throat Gastrointestinal distress Headache Coughing Anxiety Xanthine Derivatives: Xanthine Derivatives Plant alkaloids: Caffeine , Theobromine , and Theophylline Only Theophylline is used as a bronchodilator Examples: Aminophylline TheophyllineXanthine Derivatives: Drug Effects: Xanthine Derivatives: Drug Effects Cause bronchodilation by relaxing smooth muscles of the airways Result: relief of bronchospasm and greater airflow into and out of the lungs Also cause CNS stimulation Slow onset action and are mostly used for prevention Aminophylline(Status asthmaticus ) Also cause cardiovascular stimulation: increased force of contraction and increased HR, resulting in increased cardiac output and increased blood flow to the kidneys (diuretic effect)Xanthine Derivatives: (cont’d) : Xanthine Derivatives : (cont’d) Dilation of airways in asthmas, chronic bronchitis, and emphysema Mild to moderate cases of acute asthma Adjunct agent in the management of COPD Side Effects: Nausea, vomiting, anorexia Gastroesophageal reflux during sleep Sinus tachycardia, extrasystole, palpitations, ventricular dysrhythmias Transient increased urinationCorticosteroids : Corticosteroids Actions of corticosteroids : They enhance β 2-adrenergic receptor response by up- regulating the β 2- receptor in lung cells and leukocyte They inhibit the release of prostaglandins and leukotrienes They produce eosinopenia which prevents cytotoxic effects of the mediators released from eosinophils They inhibit the formation and release of cytokines and chemical mediatorsAerosol corticosteroids: Aerosol corticosteroids Aerosol corticosteroids such as: Beclomethasone, Triamcinolone, Budesonide, & Flunisolide are least absorbed in to systemic circulation (on inhalation). Produce minimal systemic side effect. Most suitable for long –term treatment of asthma(along with β 2 -Agonist aerosol). Side effect: → dryness of mouth, → voice change and oral candidiasis (preventable by oral rinsing)Oral corticosteroids: Oral corticosteroids Many patients are treated with oral corticosteroids for a period of 7-10 days to suppress symptoms & to prevent relapse. Commonly used drugs include , Prednisone, Prednisolone, and methyl Prednisolone. Prednisone is a Prodrug & is converted to Prednisolone in liver.Parenteral corticosteroids: Parenteral corticosteroids These may be used in severe acute asthma . Dose can be adjusted to clinical need. Generally used drugs are hydrocortisone and methylprednisoloneMast Cell Stabilizers:: Mast Cell Stabilizers : Adjuncts to the overall management of asthma Used solely for prophylaxis, NOT for acute asthma attacks Used to prevent exercise-induced bronchospasm Used to prevent bronchospasm associated with exposure to known precipitating factors, such as cold, dry air or allergens For prophylactic use only Contraindicated for acute exacerbations Not recommended for children younger than age 5 Therapeutic effects may not be seen for up to 4 weeks Side Effects Coughing Taste changes Dizziness Headache Sore throat Rhinitis BronchospasmAntileukotrienes: Antileukotrienes Also called leukotriene receptor antagonists (LRTAs) Newer class of asthma medications Currently available agents: 1.Montelukast 2.Zafirlukast:Antileukotrienes (cont’d): Antileukotrienes (cont’d) Zafirlukast: Is rapidly absorbed after oral administration but bioavailability decreases after food . Hence it is administered 2hrs before meals. It is metabolized by liver ,& inhibit the metabolism of Warfarin. Adverse effect include GIT distress and headacheAntileukotrienes: Mechanism of Action: Antileukotrienes: Mechanism of Action Leukotrienes are substances released when a trigger, such as cat hair or dust, starts a series of chemical reactions in the body Leukotrienes cause inflammation, bronchoconstriction, and mucus production Result: coughing, wheezing, shortness of breathAntileukotrienes: Mechanism of Action (cont’d): Antileukotrienes: Mechanism of Action (cont’d) Antileukotriene agents prevent leukotrienes from attaching to receptors on cells in the lungs and in circulation. Inflammation in the lungs is blocked, and asthma symptoms are relieved.Antileukotrienes: Drug Effects: Antileukotrienes: Drug Effects By blocking leukotrienes: Prevent smooth muscle contraction of the bronchial airways Decrease mucus secretion Prevent vascular permeability Decrease neutrophil and leukocyte infiltration to the lungs, preventing inflammationLEUKOTRIENE MODULATORS : LEUKOTRIENE MODULATORS Zileuton is given orally 6 hrly intervals and is well absorbed from GIT . Side effect: hepato toxicity, headache nausea and GIT distress may also occur. It inhibits the metabolism of theophylline & warfarin . Montelukast: administered once daily (usually in the evening ). It can be used in children above 5years of age .Calcium channel Blockers: : Calcium channel Blockers: Bronchoconstriction ultimately involves some degree of movement of Ca 2+ into the cells. Hence , It is expected that inhalation of Ca 2+ channel blockers such as nifedipine and verapamil sholud provide relief in bronchial asthma . But their bronchodilatory effects are much less than salbutamol.MONOCLONAL ANTI-Ig E Anti Body: MONOCLONAL ANTI- Ig E Anti Body 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 & other inflammatory cells.TREATMENT OF STATUS ASTHMATICUS: TREATMENT OF STATUS ASTHMATICUS It is a potentially life –threatening acute attack of severe asthma needing immediate treatment . A high concentration (40-60%) of O 2 is administered with high flow rate along with high doses of inhaled short acting β 2 -agonist . Simultaneously ,high dose of systemic corticosteroids are also needed Example 30-60 mg of prednisolone by mouth or 200 ml of hydrocortisone intravenously. If situation is life threatening 0.5 mg of Ipratropium can also be added through inhalationPowerPoint Presentation: Reference RANG N DALE’S PHARMACOLOGY Page no:356-367 ESSENTIAL OF MEDICAL PHARMACOLOGY by K.D TRIPATHI Page no:213-227 PHARMACOLOGY AND PHARMACOTHERAPEUTICS by R.S.SATOSKAR Page no : 352, 369 - LIPPINCOTT’S PHARMACOLOGY Page no:319-328 PRINCIPLES OF PHARMACOLOGY by HL.SHARMA and KK.SHARMA page no:658-666.PowerPoint Presentation: THANK U You do not have the permission to view this presentation. In order to view it, please contact the author of the presentation.