浙江大学医学院《药理学 Pharmacology》课程教学资源（PPT课件）治疗呼吸系统疾病的药物 Drugs for treatment of respiratory diseases

ZheJiang University Drugs for treatment of respirato ry diseases Huifang Department of pharmacolog Zhejiang University, school medicin inghuifang@ zju.edu Research building C4

Drugs for treatment of respiratory diseases Huifang Tang Department of pharmacology Zhejiang University, school of medicine tanghuifang@zju.edu.cn Research building C422

Classification of drugs acting on respiratory system I. Antitussive drugs: Centrally acting: Codeine Peripherally acting: Benzonatate Ⅱ. Mucoactive drugs Expectorants: Guaifenesin Mucorequlators: Carbocysteine 3. Mucolytics: N-Acetylcysteine Mucokinetic drugs: Ambroxol II. Antiasthmatic drugs 1.B ronchial dilators receptor agonists: Salbuterol theophyllines Aminophylline muscarinic antagonists: Ipratropine nti-inflammatory drugs glucocorticosteroids:. Budesonide mediator release inhibitors Disodium cromoglycate

Ⅰ. Antitussive drugs: 1. Centrally acting: Codeine 2. Peripherally acting: Benzonatate Ⅱ. Mucoactive drugs : 1. Expectorants: Guaifenesin 2. Mucoregulators:Carbocysteine 3. Mucolytics: N-Acetylcysteine 4. Mucokinetic drugs: Ambroxol Ⅲ. Antiasthmatic drugs: 1. Bronchial dilators (1) receptor agonists: Salbuterol (2)theophyllines: Aminophylline (3)muscarinic antagonists: Ipratropine 2. Anti-inflammatory drugs (1)glucocorticosteroids: Budesonide (2)mediator release inhibitors: Disodium cromoglycate Classification of drugs acting on respiratory system

oASAntitussives 物理 感受器(刺激感受器、牵张感 化学 受器等) 刺激 传入神经(迷走、喉上神经) 咳嗽中枢(延髓) 传出神经(迷走、喉返、膈神经) 效应器(声门、 咳嗽反射 呼气肌) 咳嗽反射示意图

物 理 、 化学 刺激 感受器（刺激感受器、牵张感 受器等） 传入神经（迷走、喉上神经） 咳嗽中枢（延髓） 传出神经（迷走、喉返、膈神经） 效应器（声门、 呼气肌） 咳嗽反射 咳嗽反射示意图 A. Antitussives

Likely Etiologies of Cough Based on Duration Acute(<3 weeks) Acute viral upper respiratory tract infection (common cold Subacute (3-8 weeks) Post-viral(post-infectious Bordetella pertussis(whooping cough) Chronic(8 weeks )* Upper airway cough syndrome(postnasal drip syndrome; rhinitis Conditions associated with eosinophilic airway inflammation Asthma Non-asthmatic eosinophilic bronchitis Gastroesophageal reflux disease(GERD) Acid reflux Non-acid, or weakly-acid, reflux Occupational/ Environmental Unexplained in patients who are not smokers, have no active pulmonary disease evident on radiographic imaging, and not currently receiving angiotensin converting-enzyme(ACE)inhibitors Current Opinion in Pharmacology Clinical perspective- cough: an unmet need. Curr Opin pharmacoL. 2015 Jun: 22: 24-8

Clinical perspective - cough: an unmet need. Curr Opin Pharmacol. 2015 Jun;22:24-8

Multiple vagal afferent nerve subtypes innervate the airways and lungs NK receptor antagonists GABA-B agonists o-agc u-agonists NMDA glutamate antagonists Cortical neurons Tractus Placebo Solitarius CNS Brainstem channel blockers afferent neurons ′ otor neurons Respiratory Musdes Na1.7 blockers TRPV1 antagonists ungs RSD931 TRPA1 antagonists TRaNt Cough S Centers As-fibers Bronchoconstriction Oedema Environmental imtants: SO, Ozone, Toluene Disocyanat Mucus secretion Inflammation Antitussive drugs--past, present, and future. Pharmacol Rev. 2014 Mar 26: 66(2): 468-512

Antitussive drugs--past, present, and future. Pharmacol Rev. 2014 Mar 26;66(2):468-512. Multiple vagal afferent nerve subtypes innervate the airways and lungs

A. Antitussives Central antitussives Narcotic drugs: codeine可待因 pholcodine福尔可定 Drotebanol羟蒂巴酚 Non-Narcotic drugs: dextromethorphan右美沙芬 pentoxyverine喷托维林(咳必清) Peripheral antitussives benzonatate苯佐那酯

Central antitussives Narcotic drugs: codeine 可待因 pholcodine 福尔可定 Drotebanol 羟蒂巴酚 Non-Narcotic drugs: dextromethorphan 右美沙芬 pentoxyverine 喷托维林(咳必清) Peripheral antitussives benzonatate 苯佐那酯 A. Antitussives

o Narcotic Antitussives Codeine 可待因 HacO HO CODM NCH NCH3 H H HO HO Codeine Morphine Clinical use: Severe cough without sputum, such as cough induced by tumor pleurisy胸膜炎) with pain

Codeine 可待因 Clinical use: Severe cough without sputum, such as cough induced by tumor, pleurisy(胸膜炎) with pain Narcotic Antitussives

oo Narcotic Antitussives Name cough suppressant analgesic dependence effects effects morphine 4 10 10 Codeine(可待因) Dihydrocodeine 1.5 1.5 (双氢可待因) Drotebanol|(羟蒂巴酚) 10 Pholcodine(福尔可定) less Clinical use: Severe cough without sputum

Narcotic Antitussives Name cough suppressant effects analgesic effects dependence morphine 4 10 10 Codeine (可待因) 1 1 1 Dihydrocodeine (双氢可待因) 1.5 1.5 0 Drotebanol（羟蒂巴酚） 10 <10 Pholcodine（福尔可定） 0 less Clinical use: Severe cough without sputum

o Non-Narcotic Antitussives Dextromethorphan(右美沙芬,DXM CH, O I3C0 -CP.3 N—CH HO Dextromethorphan Codeine

Dextromethorphan(右美沙芬， DXM) O N CH3 HO H3CO Codeine Dextromethorphan Non-Narcotic Antitussives

Metabolism of dextromethorphan CY3PA HO 3-methoxymorphinan Dextromethorphan (3-甲氧基吗啡喃) H CY2PD CY3PA 3-hydroxymorphinan 3-hydroxymorphinan H (3-羟基吗啡喃) CH3 dextrorphan(右啡烷) Antitussive drugs--past, present, and future. _ Pharmacol rev. 2014 Mar 26: 66(2): 468-512

Antitussive drugs--past, present, and future. Pharmacol Rev. 2014 Mar 26;66(2):468-512. Metabolism of dextromethorphan. dextrorphan(右啡烷) 3-methoxymorphinan (3-甲氧基吗啡喃) 3-hydroxymorphinan (3-羟基吗啡喃)