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1、Antitussives, expectorants, and antiasmatic drugsXimei Wu M.D., Ph.D.Dept. of pharmacology,ZJUMSDrugs acting on respiratory system Cough Cough antitussive drugsantitussive drugs centrally actingcentrally acting peripherally acting peripherally acting SputumSputum expectorant drugs expectorant drugs
2、sputum-diluting drugssputum-diluting drugs mucolytic drugs mucolytic drugs AsthmaAsthma antiasthmatic drugs antiasthmatic drugs bronchial dilatorsbronchial dilators receptor agonists receptor agonists theophyllines theophyllines muscarinic antagonists muscarinic antagonists anti-inflammatory drugs a
3、nti-inflammatory drugs glucocorticosteroidsglucocorticosteroids mediator release inhibitors mediator release inhibitors1. AntitussivesCentrally acting Addictive drugs: Addictive drugs: codeine codeine 可待因可待因可待因可待因 Non-addictive drugs: Non-addictive drugs: dextromethorphan dextromethorphan 右美沙芬右美沙芬右美
4、沙芬右美沙芬 pentoxyverine pentoxyverine 喷托维林喷托维林喷托维林喷托维林( (咳必清咳必清咳必清咳必清) )Peripherally acting benzonatate benzonatate 苯佐那酯苯佐那酯苯佐那酯苯佐那酯Codeine 可待因可待因1. 1. Pharmacological effectsPharmacological effects supression of coughsupression of cough analgesia analgesia2. 2. Clinical usesClinical uses Cough without
5、 sputumCough without sputum3. 3. Adverse effectsAdverse effects Respiratory depression (at larger doses)Respiratory depression (at larger doses) Addiction Addiction Contraindicated in patients with thick sputumContraindicated in patients with thick sputumDextromethorphan 右美沙芬右美沙芬1. 1. Pharmacologica
6、l effectsPharmacological effects supression of cough supression of cough muscarinic and NMDA receptor antagonism muscarinic and NMDA receptor antagonism2. 2. Clinical usesClinical uses Upper respiratory infection, cough without sputum Upper respiratory infection, cough without sputum3. 3. Adverse ef
7、fectsAdverse effects Atropine-like side effects Atropine-like side effects Contraindicated in patients with glaucoma, Contraindicated in patients with glaucoma, pregnancy ( 3 m), psychotic disorders, pregnancy ( 3 m), psychotic disorders, etc.etc. Pentoxyverine喷托维林喷托维林(咳必清咳必清) Pharmacological effect
8、s Supression of coughSupression of cough Muscarinic antagonism and local Muscarinic antagonism and local anesthetic effects anesthetic effects Uses and adverse effects are similar to Uses and adverse effects are similar to dextromethorphan dextromethorphanBenzonatate苯佐那酯苯佐那酯Pharmacological effects P
9、eripherally actingPeripherally acting Blocking cough reflex Blocking cough reflex Local anesthetic effectsLocal anesthetic effects CNS depressionCNS depression2. ExpectorantsSputum-diluting drugsStimulating bronchial secretionStimulating bronchial secretion Amonium chloride Amonium chloride 氯化铵氯化铵氯化
10、铵氯化铵 Potassium iodide Potassium iodide 碘化钾碘化钾碘化钾碘化钾Mucolytic drugs Bromhexine Bromhexine 溴己新溴己新溴己新溴己新 Ambroxol Ambroxol 氨溴索氨溴索氨溴索氨溴索 Acetylcysteine Acetylcysteine 乙酰半胱氨酸乙酰半胱氨酸乙酰半胱氨酸乙酰半胱氨酸 Methylcysteine Methylcysteine 美司坦美司坦美司坦美司坦 Carbocisteine Carbocisteine 羧甲司坦羧甲司坦羧甲司坦羧甲司坦 Mesna Mesna 美司钠美司钠美司钠美司钠
11、3. Antiasthmatic drugsAsthmaAsthma is physiologically characterized by increased responsiveness of the trachea and bronchi to various stimuli and by widespread narrowing of the airways that changes in severity either spontaneously or as a result of therapy.Its pathologic features are contraction of
12、airway smooth muscle, mucosal thickening from edema and cellular infiltration, and inspissation in the airway lumen of abnormally thick, viscid plugs of mucus.Symptom: dyspnea, wheezing, stridor, coughing, an inability for physical exertion. The cough may sometimes produce clear sputum. Between epis
13、odes, most patients feel well but can have mild symptoms and they may remain short of breath after exercise for longer periods of time than the unaffected individual. AsthmainflammationinflammationbronchoconstrictionbronchoconstrictionAirway hyperresponsivenessAirway hyperresponsiveness Immunologica
14、l and Immunological and non-immunological stimuli non-immunological stimuliWheezing (asthmatic Wheezing (asthmatic symptoms)symptoms)glucocorticosteroidsglucocorticosteroidsdisodium cromoglycate disodium cromoglycate 2 2 receptor agonistsreceptor agonistsTheophyllineTheophyllinemuscerinic antagonist
15、smuscerinic antagonists Receptor agonists Receptor agonists Non-selective Non-selective：adrenaline, isoprotereroladrenaline, isoprotererol 2 2-selective: -selective: moderate-acting:moderate-acting: salbutamol, terbutalinesalbutamol, terbutaline long-acting:long-acting: salmeterol, formoterolsalmete
16、rol, formoterolTheophyllines:Theophyllines: aminophyllineaminophyllineMuscarinic antagonists:Muscarinic antagonists: ipratropine ipratropine 1. Bronchial dilatorsGlucocorticosteroids:Glucocorticosteroids: Systemic: Systemic: hydrocortisone, dexamethasonehydrocortisone, dexamethasone Inhalation: Inha
17、lation: beclomethasone, budesonidebeclomethasone, budesonideInhibitors of mediator release: Inhibitors of mediator release: cromolyn sodium, nedocromil cromolyn sodium, nedocromil2. Anti-inflammatory drugsBronchial dilators 2 receptor selective agonistsSalbuterolSalbuterol沙丁胺醇沙丁胺醇沙丁胺醇沙丁胺醇Terbutaline
18、Terbutaline特布他林特布他林特布他林特布他林1. 1. Pharmacological effectsPharmacological effects Relaxing bronchial smooth musclesRelaxing bronchial smooth muscles2. 2. Clinical usesClinical uses Controlling asthmatic symptomsControlling asthmatic symptoms Given by Given by inhalationinhalation, oral or injection, o
19、ral or injection3. 3. Adverse effectsAdverse effects Skeletal muscle tremorSkeletal muscle tremor Cardiac stimulation (larger doses) Cardiac stimulation (larger doses) Dysfunction of metabolism (hypokalemia, etc.) Dysfunction of metabolism (hypokalemia, etc.)Salbuterol 沙丁胺醇沙丁胺醇Selectivity of Selecti
20、vity of 2 2 agonistsagonistsAerosol inhalationless systemic toxicitySpacer used for aerosol inhalation定量手控定量手控定量手控定量手控气雾器气雾器气雾器气雾器Spacer will aid patients Spacer will aid patients inhale the aerosolized inhale the aerosolized drugs easierdrugs easier 2 receptor selective agonistslong-actingSalmetero
21、lSalmeterolFormoterolFormoterol Theophyllines AminophyllineBronchial dilators1. Pharmacological effectsBronchus dilationBronchus dilation Inhibiting phosphodiesterase; Inhibiting phosphodiesterase; Blocking adenosine receptors; Blocking adenosine receptors; Increasing catecholamine release; Increasi
22、ng catecholamine release;Immunomodulation;Immunomodulation;Increasing respiratory muscle contractility;Increasing respiratory muscle contractility;CNS stimulation, diuretic, gastric acid CNS stimulation, diuretic, gastric acid secretion, etc.secretion, etc.Theophyllines2. 2. Clinical usesClinical us
23、es Bronchial asthma ( Bronchial asthma (p.o.p.o., , i.v.i.v.) ) Others: Others: acute pulmonary edema, acute pulmonary edema, etc.etc.3. 3. Adverse effectsAdverse effects GI reactions GI reactions CNS stimulation CNS stimulation Acute toxication ( Acute toxication ( i.vi.v. injection too rapidly ).
24、injection too rapidly ) tachycarida, arrhythmia, seizure, coma, death tachycarida, arrhythmia, seizure, coma, deathTheophyllines Muscarinic antagonistsIpratropineBronchial dilatorsRelaxing bronchial smooth musclesNo effect on sputum secretionReplaced with or combined with 2 receptor selective agonis
25、ts Systemic (adverse effect): hydrocortisonehydrocortisone prednisone prednisone dexamethasone dexamethasone Inhalation: beclomethasone dipropionatebeclomethasone dipropionate budesonide budesonide triamcinolone acetonide triamcinolone acetonide fluticasone propionate fluticasone propionate flunisol
26、ide flunisolideGlucocorticosteroids Beclomethasone dipropionate 1. 1. Pharmacological effects Pharmacological effects ( (Antiinflammation)Antiinflammation) Inhibiting inflammatory cell activities, Inhibiting inflammatory cell activities, Antibody production, mediator release, Antibody production, me
27、diator release, Inhibit increased responsiveness of the trachea and Inhibit increased responsiveness of the trachea and bronchibronchi 2. 2. Clinical usesClinical uses As first-line drugs, currently As first-line drugs, currently Controlling chronic symptoms Controlling chronic symptoms Ineffective
28、for acute symptoms Ineffective for acute symptoms Beclomethasone dipropionateBeclomethasone dipropionateAdverse effects Local: oropharyngeal candidiasisoropharyngeal candidiasisusing spacerusing spacer Systemic effects Systemic effects a) Hypercorticism-like syndrome: central obesity a) Hypercortici
29、sm-like syndrome: central obesity (moon face, buffalo hump, etc.); hypertension; (moon face, buffalo hump, etc.); hypertension; glycosuria, hypokalemia; glycosuria, hypokalemia; etcetc. . b) Increasing susceptibility to infectionsb) Increasing susceptibility to infections c) Ingestive system: peptic
30、 ulcers, c) Ingestive system: peptic ulcers, etcetc. . d) Cardiovascular system: hypertension, d) Cardiovascular system: hypertension, arteriosclerosis arteriosclerosis e) Myopathy and osteoporosis: vertebral e) Myopathy and osteoporosis: vertebral compression fractures, spontaneous fractures, compr
31、ession fractures, spontaneous fractures, especially in postmenopausal women especially in postmenopausal women f) Adrenal suppressionf) Adrenal suppressionInhibitors of mediator releaseDisodium cromoglycate ( cromolyn )( cromolyn )1. 1. Pharmacological effectsPharmacological effects Inhibiting media
32、tor release from mast or other cellsInhibiting mediator release from mast or other cells Inhibiting sensory neuropeptide release and non-Inhibiting sensory neuropeptide release and non-specifical stimulus induced bronchus contractionspecifical stimulus induced bronchus contraction2. 2. Clinical uses
33、 (only inhalation)Clinical uses (only inhalation) Prevention of allergic asthmaPrevention of allergic asthma Acting slowly (2-4 weeks) Acting slowly (2-4 weeks)3. 3. Adverse effectsAdverse effects Oropharyngeal irritationOropharyngeal irritationDisodium cromoglycateOther inhibitors of mediator relea
34、se Nedocromil sodium: GI effectTranilastKetotifen (H1 receptor antagonist) Leukotriene pathway inhibitorsAirways LTC4, LTD4, LTE4-bronchoconstrictors, increase microvascular permeability, mucus secretion LTB4-chemoattractant for neutrophilsLeukotriene pathway inhibitors CysLT1 receptor antagonist (zafirlukast): for mild or moderate asthma, but not use alonefor acute asthma 5-LOX inhibitor (zileuton)
