RESPIRATORY SYSTEM - PHARMACOLOGY

DRUGS USED IN THE TREATMENT OF BRONCHIAL ASTHMA AND COPD
Characterized by hyper responsiveness of bronchial smooth muscle to a variety of stimuli”

Resulting in:

Narrowing of air ways
Increased secretion
Mucosal edema
Mucus plugging

1. DRUGS USED IN THE TREATMENT OF BRONCHIAL ASTHMA & COPD Respiratory system - PHARMACOLOGY PREPARED BY GOWTHAMRAJ SAKTHIVEL M.Pharm ., Department of Pharmacognosy .

2. TREATMENT OF BRONCHIAL ASTHMA BRONCHIAL ASTHMA: “Characterized by hyper responsiveness of bronchial smooth muscle to a variety of stimuli” Resulting in: Narrowing of air ways Increased secretion Mucosal edema Mucus plugging

3. BRONCHIAL ASTHMA: INFECTION, POLLUTION, EXERCISE, COLD AIR EXPOSURE ANTIGEN: ANTIBODE REACTION ( IgE antibody) DEGRANULATION OF MAST CELL RELEASE OF INFLAMMATORY MEDIATORS like HISTAMINE, LTs, INFLAMMATION IN THE AIR WAYS NARROWING OF AIRWAY BREATHING DIFFICULTY, WHEEZING, COUGH (symptoms) BRONCHIAL ASTHMA

4. I.BRANCHODILATORS: β2 SYMPATHOMIMETICS SALBUTAMOL TERBUTALINE BAMBUTEROL SALMETEROL EPHEDRINE METHYLXANTHINES THEOPHYLLINE AMINOPHYLLINE HYDROXY THEOPHYLLINE ANTI CHOLONERGICS IPRATROPIUM BROMIDE TIOTROPIUM BROMIDE II.LEUKOTRIENE ANTAGONISTS: MONTELUKAST, ZAFIRLUKAST. III.MAST CELL STABILIZERS SODIUM CROMOGLYCATE, KETOTIFEN. IV.CORTICOSTEROIDS A. SYSTEMIC: HYDROCORTISONE, PREDNISOLONE B. INHALATIONAL: BECLOMETHASONE DIPROPIONATE, BUDESONIDE, FLUTICASONE PROPIONATE, FLUNISOLIDE, CICLESONIDE. V. ANTI-IGE ANTIBODY OMALIZUMAB CLASSIFICATION OF DRUGS

5. BRANCHODILATORS: β2 SYMPATHOMIMETICS Fastest acting bronchodilator when inhaled ADRENERGIC DRUG ACTS ON β2 RECEPTOR BRANCHODILATATION Should be used cautiously in HYPERTENSIVE PATIENTS, ISH DISEASE PATIENTS

6. SALBUTAMOL Highly selective β2 agonist Inhaled salbutamol produce branchodilatation with in 5 mins Duration of action 2-4 hrs Used to abort or to terminate asthmatic attack It cannot be used for prophylaxis MECHANISM OF ACTION SALBUTAMOL BINDS TO β 2 RECEPTOR PRESENT IN THE BRONCHIAL SMOOTH MUSCLE STIMULATION OF β 2 RECEPTOR INCREASE IN THE FORMATION OF CYCLIC AMP (CAMP) RELAXATION OF SMOOTH MUSCLE RELIEF FROM THE ASTHMATIC ATTACK

7. PHARMACOKINETICS: Administered by inhalation and injection Oral route is not preferred - Due to pre systemic metabolism in gut wall Oral bio availability is 50% Acts for 4 hours Oral route is used when the patients who cannot currently use in- halars ADR: Muscle tremors Palpitation Restlessness Nervousness Throat irritation USES: Used in terminating the attack of asthma

8. METHYXANTHINES Extensively used in asthma Cannot be used as first line drug THEOPHYLLINE One of the naturally occuring methylated xanthine alkaloids Relatively weak bronchodilator Effective when adrenaline fails to relieve acute attack MECHANISM OF ACTION: ATP ADENYLYL CYCLASE CYCLIC AMP THEPHYLLINE (blocks) PHOSPHODIESTERASE 5- AMP Increase in cyclic AMP level Vasodilatation Reduces the asthmatic attack

9. PHARMACOKINETICS: Well absorbed orally Distributed in all tissues Crosses the placenta and secreted in milk Metabolized in liver by demethylation & oxidation Excreted in urine ADR: Gastric pain Head ache Tremors Vomiting Hypotension Convulsion Death USES: Bronchial asthma & COPD

10. ANTI-CHOLINERGICS IPRATROPIUM BROMIDE: Brancho dilatation by blocking the M3 receptor When it is combined with sympathomimetics produce most effective activity MECHANISM OF ACTION: IPRATROPIUM BROMIDE BINDS & BLOCKS THE M3 RECEPTOR PRESENT IN THE LARGER AIRWAYS OF LUNGS PREVENTS THE CONTRACTION OF LARGER AIRWAYS OF LUNGS DILATATION RELIEF FROM ASTHMATIC ATTACK LEUKOTRIENE ANTAGONISTS cystenyl leukotrienes (LT-C4/D4) are important mediators of bronchial asthma, Two antagonist drugs were developed for the treatment of asthma Eg : Montelukast and Zafirlukast

11. MONTELUKAST AND ZAFIRLUKAST Montelukast and zafirlukast are indicated for prophylactic therapy of mild-to-moderate asthma as alternatives to inhaled glucocorticoids The efficacy is low They are very safe drugs In severe asthma, they have additive effect with inhaled steroids They are not to be used for terminating asthma episodes. LT1 antagonists are modestly effective in aspirin-induced asthma and exercise induced asthma, but are of no value in COPD. MECHANISM OF ACTION: Montelukast and Zafirlukast They competitively antagonize LT1 receptor Decreases the LT1 receptor mediated bronchoconstriction, airway mucus secretion Broncho dilatation, suppression of bronchial inflammation Improvement from asthmatic attack

12. PHARMACOKINETICS: They are well absorbed orally, Highly plasma protein bound Metabolized by CYP2C9 The plasma t½ of montelukast is 3–6 hours & zafirlukast is 8–12 hours. ADR: Produce few side effects: headache and rashes. Eosinophilia and neuropathy are infrequent. Few cases: Churg -Strauss syndrome ( vasculitis with eosinophilia).

13. MAST CELL STABILIZERS Eg:Sodium cromoglycate ( Cromolyn sod) It is a synthetic chromone derivative It is not a bronchodilator and does not antagonize constrictor action of histamine, ACh , LTs I t is ineffective if given during an asthmatic attack. Bronchospasm induced by allergens, irritants, cold air and exercise may be attenuated. MECHANISM OF ACTION: Mast cells are cells found in connective tissues including the airways Mast cells release histamine and other inflammatory substances in response to allergens The process of releasing inflammatory mediators by mast cells is referred to as "degranulation." [ Sodium cromoglycate ] Inhibits mast cell degranulation Blocking the release of inflammatory mediators (histamine, LTs, PAF, interleukins, etc ) Decreases the cellular inflammatory response; bronchial hyperactivity Anti asthmatic activity

14. PHARMACOKINETICS: It is not absorbed orally. It is administered as an aerosol through metered dose Inhaler delivering 1 mg per dose: 2 puffs 4 times a day. Only a small fraction of the inhaled drug is absorbed systemically Rapidly excreted unchanged in urine and bile. ADVERSE EFFECTS: Bronchospasm, Throat irritation Cough Uses Bronchial asthma Allergic rhinitis Allergic conjunctivitis

15. CORTICOSTEROIDS Glucocorticoids are not bronchodilators. They reduces bronchial hyperreactivity , mucosal edema Corticosteroids afford more complete and sustained symptomatic relief than bronchodilators or cromoglycate ; Improve airflow; reduce asthma, retarding disease progression. Also increase airway smooth muscle responsiveness to β 2 agonists Inhaled corticosteroids have thus markedly changed the outlook on asthma therapy. Long-term systemic steroid therapy may be worse than asthma itself SYSTEMIC STEROID THERAPY Systemic steroid therapy can be used in the following situations Severe chronic asthma: It is not controlled by bronchodilators and inhaled steroids, or when there are frequent recurrences of increasing severity Shall be treated with prednisolone 20–60 mg daily Dose reduction after 1–2 weeks of good control Then the patient can be shifted to inhaled steroid. (ii) Status asthmaticus /acute asthma exacerbation: When asthma attack not responding to intensive bronchodilator therapy: Treatment shall be start with high dose of a rapidly acting i.v. glucocorticoid which generally acts in 6–24 hours, Patients to be shifted to oral therapy for 5–7 days and then discontinue abruptly or taper rapidly.

16. (iii) COPD A short course (1–3 week) of oral glucocorticoid May benefit some patients of COPD during an exacerbation. INHALED STEROIDS: These are glucocorticoids with high topical and low systemic activity (due to poor absorption and/or marked first pass metabolism). Beclomethasone dipropionate , Budesonide Fluticasone Ciclesonide is a later addition. Inhaled steroids suppress bronchial inflammation, increase peak expiratory flow rate, reduce need for rescue β2-agonist inhalations and prevent episodes of acute asthma. They have no role during an acute attack or in status asthmaticus . Peak effect is seen after 4–7 days of instituting inhaled steroids and benefit persists for a few weeks after discontinuation.

17. ANTI- IgE ANTIBODY OMALIZUMAB It is a humanized monoclonal antibody against IgE . Administered s.c. It neutralizes free IgE in circulation without activating mast cells and other inflammatory cells. It is very expensive Use is reserved for resistant asthma patients with positive Skin tests or raised IgE levels who require frequent hospitalization.

18. COPD Chronic Obstructive Pulmonary Disease (COPD) It is a chronic disease of the lungs that damages both the airways and the lung tissue, making it difficult to breathe. A person with COPD may have obstructive bronchiolitis, emphysema, or a combination of both conditions. People with COPD often use several kinds of medicines to help control symptoms. There is no cure; medicines can help improve your quality of life The goals of effective COPD management are to: Prevent disease progression Relieve symptoms Improve exercise tolerance Improve health status Prevent and treat complications Prevent and treat exacerbations Reduce mortality The most common medications for treating chronic obstructive pulmonary disease (COPD) are

19. BRONCHODILATORS AND STEROIDS Both make breathing easier, but do this in different ways. I.BRONCHODILATORS β2 SYMPATHOMIMETICS SALBUTAMOL TERBUTALINE BAMBUTEROL SALMETEROL EPHEDRINE METHYLXANTHINES THEOPHYLLINE AMINOPHYLLINE HYDROXY THEOPHYLLINE ANTI CHOLONERGICS IPRATROPIUM BROMIDE TIOTROPIUM BROMIDE II.CORTICOSTEROIDS SYSTEMIC : HYDROCORTISONE , PREDNISOLONE INHALATIONAL : BECLOMETHASONE DIPROPIONATE , BUDESONIDE, FLUTICASONE PROPIONATE , FLUNISOLIDE, III.ROFLUMILAST It have not been mentioned have not as yet been proven to be effective in the treatment of COPD. It is a new medication that may decrease the number of exacerbations IV . AZITHROMYCIN Long-term use may decrease the number of exacerbations V.OTHER MEDICATIONS Antibiotics for bacterial infection, M ucolytics to thin mucus (phlegm or sputum), Oxygen to treat low oxygen levels CLASSIFICATION OF DRUGS

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