Lecture 2 anti-asthmatics Part-2

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Pharmacology of Respiratory sytem-Part 2

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Anti-Asthmatics Ms. Seema Thakur Associate Professor Faculty of Pharmaceutical Sciences PCTE Group of Institutes

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Content • Bronchodilators – Anticholinergics • Leukotriene antagonist • Mast cell stabilizers • Corticosteroids – Systemic – Inhalational

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ANTICHOLINERGICS • Atropinic drugs causes bronchodilatation by blocking cholinergic constrictor tone M 3 receptors • Acting on larger airways Vagal innervation • Less efficacious than sympathomimetics but add to their response • Best suites for regular prophylactic use than for control of an acute attack

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MAST CELL STABILIZERS Sodium cromoglycate cromolyn sodium • Synthetic chromone derivative that inhibits degranulation of mast cells by trigger stimuli • Prevention of release of pro-asthmatic mediators like histamine LTs PAF leukotrienes • Long term treatment decreases proinflammatory response • Inhibit chemotaxis of inflammatory cells • Inhibit bronhial hyperreactivity allergen induced bronchospasm • It is not a bronchodilator and doesnot block constrictor action of histamine →→ therefore ineffective during asthmatic attack

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USES • Bronchial asthma • Allergic rhinitis • Allergic conjunctivitis ADVERSE EFFECTS • Bronchospasm throat irritation cough in some patients • Rarely nasal congestion headache dizziness arthralgia rashes dysuria

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CORTICOSTEROIDS • Are not bronchodilators benefit by reducing bronchial hyperreactivity • Also reduce mucosal edema and suppress inflammatory response to AG-AB reaction or other trigger stimuli • Restore responsiveness to sympathomimetics once if resistance develops to them • Corticosteroids offer more complete and sustained symptomatic relief than bronchodilators or cromoglycate -- long term treatment has side-effects:

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SIDE-EFFECTS 1. Cushing habitus: characteristic appearance of rounded face narrow mouth obesity of trunk 2. Fragile skin purple striations –typically on thighs and lower abdomen hirsutism 3. Hyperglycemia may be glycosuria precipitation of diabetes 4. Muscular weakness proximal myopathy shoulder arms pelvis thighs 5. Susceptibility to infections opportunistic infections with low grade pathogens 6. Delayed healing of wounds and infections 7. Peptic ulcerations associated with bleeding and slight perforations 8. Osteoporosis esp. in vertebrae and flat spongy bones 9. Glaucoma 10. Growth retardation in children 11. Psychatric disturbances mild euphoria nervousness decreased sleep mood changes 12. Supression of hypothalamo-pituitary-adrenal axis HPA 13. Stoppage of exogenous steroid precipitate withdrawal syndrome – malaise fever weakness myalgia

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LEUKOTRIENE ANTAGONISTS • LTC4/D4 are important mediators of asthma • Zileuton is 5-LOX inhibitor • Montelukast an zafirlukast antagonise cysLT1 receptor mediated bronchoconstriction increased vascular permeability and recruitment of eosinophils • Lung function also show improvement • Are indicated for prophylactic therapy for mild to moderate asthma • In severe asthma these permit reduction in steroid dose • Are very safe drugs • Side-effects: headache rashes eosinophilia neuropathy • T1/2 of montelukast: 3-6 hrs zafirlukast: 8-12 hrs

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Anti-IgE Antibody Omalizumab • Humanized monoclonal antibody against IgE • Administered i.v or s.c • Used in severe extrinsic asthma • Very expensive • Reserved for resistant asthma patients with positive skin test • Raised IgE levels who require frequent hospitalization

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Status Asthmatics • Hydrocortisone hemisuccinate 100mg i.v. stat followed by 100-200 mg 4-8 hourly infusion: may take upto 6 hrs to act • Nebulized salbutamol 2.5-5 mg + ipratropium bromide 0.5 mg intermittent inhalation driven by O2 • High flow humidified oxygen inhalation • Salbutamol/ terbutaline 0.4 mg i.m/s.c may be added • Intubation and mechanical ventilation if needed • Treat chest infection with intensive antibiotic therapy • Correct dehydration acidosis with saline + Sod. bicarbonate/lactate infusion

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Case study A 60-year-old male patient of moderately severe chronic obstructive pulmonary disease COPD with FEV1 45 of predicted who has quit smoking for the last 5 years and is maintained on—Ipratropium br. 20 μg/puff metered dose inhaler 2 puffs 3 times a day and Theophylline 400 mg SR tab. twice a day developed sore throat and fever. He was prescribed — Tab Erythromycin 250 mg one tab 4 times a day for 5 days Tab Paracetamol 500 mg 3 times a day till fever persists. After 3 days he presented with pain in epigastrium restlessness irritability inability to sleep palpitation tremor of fingers and hand and had vomited twice. His fever had subsided and throat was better. a What could be the reason for his recent illness b Could this illness be prevented if so how

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Case study A 60-year-old male patient of moderately severe chronic obstructive pulmonary disease COPD with FEV1 45 of predicted who has quit smoking for the last 5 years and is maintained on—Ipratropium br. 20 μg/puff metered dose inhaler 2 puffs 3 times a day and Theophylline 400 mg SR tab. twice a day developed sore throat and fever. He was prescribed — Tab Erythromycin 250 mg one tab 4 times a day for 5 days Tab Paracetamol 500 mg 3 times a day till fever persists. After 3 days he presented with pain in epigastrium restlessness irritability inability to sleep palpitation tremor of fingers and hand and had vomited twice. His fever had subsided and throat was better. a What could be the reason for his recent illness b Could this illness be prevented if so how

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