Bronchodilators (支气管扩张药)

1. Bronchodilators(支气管扩张药) Huifang Tang (汤慧芳) Department of Pharmacology Zhejiang university, school of Medicine tanghuifang@zju.edu.cn

2. Drugs acting on respiratory system Cough antitussive drugs centrally acting peripherally acting Sputum expectorant drugs sputum-diluting drugs mucolytic drugs Asthma antiasthmatic drugs Bronchodilators  receptor agonists theophyllines muscarinic antagonists Anti-inflammatory drugs glucocorticosteroids mediator release inhibitors

4. Antiasthmatic drugs Immunological and non-immunological stimuli Airway inflammation bronchoconstriction 2 receptor agonists Theophylline Muscerinic antagonists glucocorticosteroids Disodium cromoglycate Leukotriene modifiers Airway hyperresponsiveness Wheezing (asthmatic symptoms)

7. Bronchodilators •  Receptor agonists • Non-selective：adrenaline, isoprenaline • 2-selective: • moderate-acting:salbutamol, terbutaline • long-acting:salmeterol, formoterol • Theophyllines:aminophylline • Muscarinic antagonists:ipratropium bromide

9. 1.  receptor agonists non-selectivity 去甲肾上腺素 肾上腺素 异丙肾上腺素 • 2 receptor selective agonists 沙丁胺醇 福莫特罗

11. Bronchial dilators Salbuterol 沙丁胺醇 1. Pharmacological effects Relaxing bronchial smooth muscles 2. Clinical uses Controlling asthmatic symptoms Given by inhalation, oral or injection 3. Adverse effects Skeletal muscle tremor Cardiac stimulation (larger doses) Dysfunction of metabolism (hypokalemia, etc.)

13. Selectivity of 2agonists

14. Bronchial dilators 2 receptor selective agonists： Long-acting Formoterol 福莫特罗 Salmeterol 沙美特罗

16. 1.  receptor agonists 茚达特罗 奥达特罗 维兰特罗

17. Bronchial dilators • Theophyllines Aminophylline 氨茶碱 Theophyllines: One type of xanthine derivatives (甲基黄嘌呤类衍生物)

19. Bronchial dilators • 1. Pharmacological effects • Inhibiting phosphodiesterase(PDE); • Blocking adenosine receptors; • Increasing catecholamine release; • Immunomodulation; • Increasing contractility of respiratory muscle(diaphragm muscle); • Diuretic, • CNS stimulation, • Gastric acid secretion, etc.

20. Bronchial dilators 2. Clinical uses Bronchial asthma (p.o., i.v.) Others: acute pulmonary edema, etc. • Slow-release theophylline (for control of nocturnal asthma) is the most commonly used methylxanthine. • Aminophylline • pentoxifylline, is promoted as a remedy for intermittent claudication;

21. Common adverse effects: • Gastrointestinal distress, tremor, and insomnia. • Severe nausea and vomiting, hypotension, cardiac arrhythmias, Seizures • Very large overdoses (eg, in suicide attempts) are potentially lethal because of arrhythmias and seizures. • Beta blockers are useful in reversing severe cardiovascular toxicity from theophylline.

22. Bronchial dilators • Muscarinic antagonists —— M receptor blocking

23. Bronchial dilators • Muscarinic antagonists —— M receptor blocking Ipratropine异丙托溴铵，异丙托品

24. Mechanism of Action and Effects When given by aerosol, ipratropium and tiotropium competitively block muscarinic receptors in the airways and effectively prevent bronchoconstriction mediated by vagal discharge. Muscarinic antagonists reverse bronchoconstriction in some asthma patients (especially children) and in many patients with COPD. They have no effect on the chronic inflammatory aspects of asthma.

25. Clinical Use and Toxicity Ipratropium and tiotropium are useful in one third to two thirds of asthmatic patients; β2 agonists are effective in almost all. For acute bronchospasm, therefore, the β agonists are usually preferred. However, in COPD, which is often associated with acute episodes of bronchospasm, the antimuscarinic agents may be more effective and less toxic than β agonists.

26. Novel class of Brochodilators

27. Aerosol inhalation

28. 定量手控 气雾器 Spacer used for aerosol inhalation

29. Spacer will aid patients to inhale the aerosolized drugs easier Outcome of different sized particles: > 10μm: mouth and oropharynx < 0.5μm: inhaled to the alveoli and subsequently exhaled without being deposited in the lung 1-5μm: the most effective

30. Reference Pharmacology and therapeutics of bronchodilators. Cazzola M, Page CP, Calzetta L, Matera MG. Pharmacol Rev. 2012 Jul;64(3):450-504. doi: 10.1124/pr.111.004580. Review.