Bronchodilators ( 支气管扩张药 ) Huifang Tang ( 汤慧芳 ) Department of Pharmacology Zhejiang university, school of Medicine

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

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

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

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

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

Selectivity of  2 agonists

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

1.  receptor agonists 维兰特罗 奥达特罗 茚达特罗

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

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

2. Clinical uses Bronchial asthma (p.o., i.v.) Bronchial asthma (p.o., i.v.) Others: acute pulmonary edema, etc. 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; Bronchial dilators

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.

§Muscarinic antagonists —— M receptor blocking Bronchial dilators

§Muscarinic antagonists —— M receptor blocking Ipratropine 异丙托溴铵，异丙托品 Bronchial dilators

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  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.

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.

Novel class of Brochodilators

Aerosol inhalation

Spacer used for aerosol inhalation 定量手控气雾器

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

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