1. Antitussives, expectorants, and
antiasmatic drugs
Ximei Wu
Dept. of pharmacology,
ZJUMS

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

4. 1. Antitussives

5. Centrally acting Peripherally acting Addictive drugs: codeine 可待因
Non-addictive drugs:
dextromethorphan 右美沙芬
pentoxyverine 喷托维林(咳必清)
Peripherally acting
benzonatate 苯佐那酯

7. Codeine 可待因

8. 1. Pharmacological effects suppression of cough
analgesia
2. Clinical uses
Cough without sputum
3. Adverse effects
Respiratory depression (at larger doses)
Addiction
Contraindicated in patients with thick sputum

9. Dextromethorphan 右美沙芬

10. 1. Pharmacological effects
suppression of cough
muscarinic and NMDA receptor antagonism
2. Clinical uses
Upper respiratory infection, cough without sputum
3. Adverse effects
Atropine-like side effects
Contraindicated in patients with glaucoma,
pregnancy (< 3 m), psychotic disorders, etc.

11. Pentoxyverine
喷托维林(咳必清)

12. Pharmacological effects
Suppression of cough
Muscarinic antagonism and local
anesthetic effects
Uses and adverse effects are similar to
dextromethorphan

13. Benzonatate
苯佐那酯

14. Pharmacological effects
Peripherally acting
Blocking cough reflex
Local anesthetic effects
CNS depression

15. 2. Expectorants

16. Sputum-diluting drugs
Stimulating bronchial secretion
Amonium chloride 氯化铵
Potassium iodide 碘化钾
Mucolytic drugs
Bromhexine 溴己新
Ambroxol 氨溴索
Acetylcysteine 乙酰半胱氨酸
Methylcysteine 美司坦
Carbocisteine 羧甲司坦
Mesna 美司钠

17. Antiasthmatic drugs

18. Asthma
Asthma 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 airway smooth muscle, mucosal thickening from edema and cellular infiltration, and inspiration in the airway lumen of abnormally thick, viscid plugs of mucus.

20. Asthma
Symptom: dyspnea, wheezing, stridor, coughing, an inability for physical exertion. The cough may sometimes produce clear sputum.
Between episodes, 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.

22. non-immunological stimuli Wheezing (asthmatic symptoms)
Immunological and
non-immunological stimuli
inflammation
bronchoconstriction
2 receptor agonists
Theophylline
muscerinic antagonists
glucocorticosteroids
disodium cromoglycate
Airway hyperresponsiveness
Wheezing (asthmatic symptoms)

23. 1. Bronchial dilators  Receptor agonists Theophyllines: aminophylline
Non-selective：adrenaline, isoprotererol
2-selective: moderate-acting: salbutamol, terbutaline
long-acting: salmeterol, formoterol
Theophyllines: aminophylline
Muscarinic antagonists: ipratropine

24. 2. Anti-inflammatory drugs
Glucocorticosteroids:
Systemic: hydrocortisone, dexamethasone
Inhalation: beclomethasone, budesonide
Inhibitors of mediator release:
cromolyn sodium, nedocromil

25. Bronchial dilators Salbuterol 沙丁胺醇 Terbutaline 特布他林
2 receptor selective agonists
Salbuterol
沙丁胺醇
Terbutaline
特布他林

26. 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.)

27. Selectivity of 2 agonists

28. Aerosol inhalation
less systemic toxicity

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

30. Spacer will aid patients inhale the aerosolized drugs easier

31. 2 receptor selective agonists
long-acting
Formoterol
Salmeterol

32. Bronchial dilators
Theophyllines
Aminophylline

33. Theophyllines 1. Pharmacological effects Bronchus dilation
Inhibiting phosphodiesterase;
Blocking adenosine receptors;
Increasing catecholamine release;
Immunomodulation;
Increasing respiratory muscle contractility;
CNS stimulation, diuretic, gastric acid secretion, etc.

34. Theophyllines 2. Clinical uses 3. Adverse effects
Bronchial asthma (p.o., i.v.)
Others: acute pulmonary edema, etc.
3. Adverse effects
GI reactions
CNS stimulation
Acute toxication ( i.v. injection too rapidly )
tachycarida, arrhythmia, seizure, coma, death

35. Muscarinic antagonists
Bronchial dilators
Muscarinic antagonists
Ipratropine

36. Relaxing bronchial smooth muscles
No effect on sputum secretion
Replaced with or combined with 2 receptor selective agonists

37. Glucocorticosteroids
Systemic (adverse effect):
hydrocortisone
prednisone
dexamethasone
Inhalation:
beclomethasone dipropionate
budesonide
triamcinolone acetonide
fluticasone propionate
flunisolide

38. Beclomethasone dipropionate

39. Beclomethasone dipropionate
1. Pharmacological effects (Antiinflammation)
Inhibiting inflammatory cell activities,
Antibody production, mediator release,
Inhibit increased responsiveness of the trachea and bronchi
2. Clinical uses
As first-line drugs, currently
Controlling chronic symptoms
Ineffective for acute symptoms

40. Adverse effects Systemic effects
Local: oropharyngeal candidiasis－using spacer
Systemic effects
a) Hypercorticism-like syndrome: central obesity
(moon face, buffalo hump, etc.); hypertension;
glycosuria, hypokalemia; etc.
b) Increasing susceptibility to infections
c) Ingestive system: peptic ulcers, etc.
d) Cardiovascular system: hypertension,
arteriosclerosis
e) Myopathy and osteoporosis: vertebral
compression fractures, spontaneous fractures,
especially in postmenopausal women
f) Adrenal suppression

41. Disodium cromoglycate ( cromolyn )
Inhibitors of mediator release
Disodium cromoglycate ( cromolyn )

42. Disodium cromoglycate
1. Pharmacological effects
Inhibiting mediator release from mast or other cells
Inhibiting sensory neuropeptide release and non-specific stimulus induced bronchus contraction
2. Clinical uses (only inhalation)
Prevention of allergic asthma
Acting slowly (2-4 weeks)
3. Adverse effects
Oropharyngeal irritation

44. Other inhibitors of mediator release
Nedocromil sodium: GI effect
Tranilast
Ketotifen (H1 receptor antagonist)

45. Leukotriene pathway inhibitors
Airways
LTC4, LTD4, LTE4----bronchoconstrictors, increase microvascular permeability, mucus secretion
LTB4----chemoattractant for neutrophils
Leukotriene pathway inhibitors
CysLT1 receptor antagonist (zafirlukast):
for mild or moderate asthma, but not use alone
for acute asthma
5-LOX inhibitor (zileuton)