Bronchodilators (??????)

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Bronchodilators(??????)

• Huifang Tang (???)
• Department of Pharmacology
• Zhejiang university, school of Medicine
• tanghuifang_at_zju.edu.cn

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Drugs acting on respiratory system

• Cough antitussive drugs
• centrally acting
• peripherally acting
• Sputum expectorant drugs
• sputum-diluting drugs
• mucolytic drugs
• Asthma antiasthmatic drugs
• Bronchodilators
• ? receptor
  agonists
• theophyllines
• muscarinic
  antagonists
• Anti-inflammatory drugs
• 
  glucocorticosteroids
• mediator release
  inhibitors

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

• ? Receptor agonists
• Non-selectiveadrenaline, isoprenaline
• ?2-selective
• moderate-acting salbutamol, terbutaline
• long-acting salmeterol, formoterol
• Theophyllines aminophylline
• Muscarinic antagonists ipratropium bromide

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1. ? receptor agonists
non-selectivity
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• ?2 receptor selective agonists

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Bronchial dilators

• Salbuterol ????
• 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.)

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Selectivity of ?2 agonists
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Bronchial dilators
?2 receptor selective agonists Long-acting
Formoterol ????
Salmeterol ????
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1. ? receptor agonists
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Bronchial dilators

• Theophyllines

Aminophylline ???
Theophyllines One type of xanthine
derivatives (?????????)
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Bronchial dilators

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

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Bronchial dilators

• 2. Clinical uses
• Bronchial asthma (p.o., i.v.)
• 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

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• 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.

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Bronchial dilators

• Muscarinic antagonists
• M receptor blocking

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Bronchial dilators

• Muscarinic antagonists
• M receptor blocking

Ipratropine ?????,????
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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.
• 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.

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Clinical Use and Toxicity

• Ipratropium and tiotropium are useful in one
  third to two thirds of asthmatic patients ß2
  agonists are effective in almost all.
• For acute bronchospasm, therefore, the ß 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 ß agonists.

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Novel class of Brochodilators
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Aerosol inhalation
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???? ???
Spacer used for aerosol inhalation
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Spacer will aid patients to inhale the
aerosolized drugs easier Outcome of different
sized particles gt 10µm mouth and oropharynx lt
0.5µm inhaled to the alveoli and subsequently
exhaled without being deposited in the
lung 1-5µm the most effective
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Reference
Pharmacology and therapeutics of bronchodilators.
Cazzola M, Page CP, Calzetta L, Matera MG.
Pharmacol Rev. 2012 Jul64(3)450-504. doi
10.1124/pr.111.004580. Review.