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

Drugs for treatment of espiratory diseases Huifang Tang Department of pharmacology Zhejiang University, school of medicine

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

asbestos arlous diseases of Alveoli fill with thick fluid making gas exchange difficult. r respirator system up in lungs, reducing theirs Fibrous connective tissue bu elasticity. Common sympToms Cou sputum Tubercles encapsulate bacteria, and wheezin mucus Alveoli burst and fuse into e inflamed du enlarged air spaces, Surface area acute)or due to an for gas exchange is reduced Asthma irritant(chronic). Coughing brings Airways are inflamed due to up mucus and pus imitation, and bronchioles constrict

Various diseases of respiratory system Common symptoms: cough sputum wheezing

Classification of drugs acting on respiratory system I. Antitussive drugs: 1. Centrally acting: Codeine Peripherally acting: Benzonatate Ⅱ. Mucoactive drugs: Expectorants: Guaifenesin M ucorequlators: Carbocysteine 3. Mucolytics: N-Acetylcysteine 4. Mucokinetic drugs: Ambroxol Il. Antiasthmatic drugs Bronchi ial dilator receptor agonists: Salbuterol eo skylines: Amino ne muscarinic antagonists: Ipratropine Anti-inflammatory drugs sonde isodium 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

A. Antitussives 物理、 感受器(刺激感受器、牵张感 化学一→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. t)in Phhendbbl2015Tun: 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 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

HypertonIc salIne Larynx capsaicin Brady Trachea CItric acld(H+) Nodose Fibers gular C-fbeK HIstam ine Jugular arg cybers s BronchI c-fbers AdenosIne Nodose cybers 2methyl-3-HT RARs PEEP Peripheral AIrways/ Lung Current Opinion in Pharmacology Th distribution and responsiveness of airway afferent subtypes in the guinea pi/"RARs, rapidly adapting receptors:, SARs, slowly adapting receptors Am J Physiol Regul Integr Comp Physiol 2008, 295: R1572-R1584

The distribution and responsiveness of airway afferent subtypes in the guinea pig. RARs, rapidly adapting receptors; SARs, slowly adapting receptors. Am J Physiol Regul Integr Comp Physiol 2008, 295:R1572-R1584

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

Narcotic antitussives Codeine 可待因 HcO CH3 HO

Codeine 可待因 Narcotic Antitussives O N CH3 HO H3CO

Narcotic Antitussives 1. Pharmacological effects suppression of cough (1/4 of morphine) analgesia(1/7-1/10 of morphine) 2. Clinical uses Cough without sputum 3. Adverse effects Respiratory depression(at larger doses) A Addiction Contraindicated in n patients with thick sputum

1. Pharmacological effects suppression of cough (1/4 of morphine) analgesia (1/7~1/10 of morphine) 2. Clinical uses Cough without sputum 3. Adverse effects Respiratory depression (at larger doses) Addiction Contraindicated in patients with thick sputum Narcotic Antitussives