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BronchodilatorsBronchodilators((支气管扩张药支气管扩张药 ))
Huifang Tang (汤慧芳 )Department of PharmacologyZhejiang university, school of
Drugs acting on respiratory systemCough Cough antitussive drugsantitussive drugs centrally actingcentrally acting peripherally actingperipherally actingSputumSputum expectorant drugs expectorant drugs sputum-diluting drugssputum-diluting drugs mucolytic drugsmucolytic drugsAsthmaAsthma antiasthmatic drugs antiasthmatic drugs BBronchodilatorsronchodilators receptor agonistsreceptor agonists theophyllinestheophyllines muscarinic antagonistsmuscarinic antagonists AAnti-inflammatory drugsnti-inflammatory drugs glucocorticosteroidsglucocorticosteroids mediator release mediator release
inhibitorsinhibitors
Antiasthmatic drugs
Airway Airway inflammationinflammation
bronchoconstrictibronchoconstrictionon
Airway hyperresponsiveness
Immunological and non-Immunological and non-immunological stimuliimmunological stimuli
Wheezing (asthmatic symptoms)
glucocorticosteroids
Disodium cromoglycate
Leukotriene modifiers
2 receptor agonists
Theophylline
Muscerinic antagonists
BronchodilatorsBronchodilators
Receptor agonistsReceptor agonists
Non-selectiveNon-selective :: adrenaline, adrenaline,
isoprenalineisoprenaline
22-selective: -selective:
moderate-acting:moderate-acting: salbutamol, salbutamol,
terbutalineterbutaline
long-acting:long-acting: salmeterol, formoterolsalmeterol, formoterol
Theophyllines:Theophyllines: aminophyllineaminophylline
Muscarinic antagonists:Muscarinic antagonists: ipratropium ipratropium
bromidebromide
1. 1. receptor agonists receptor agonists
去甲肾上腺素去甲肾上腺素
异丙肾上腺素异丙肾上腺素
沙丁胺醇沙丁胺醇
福莫特罗福莫特罗
肾上腺素肾上腺素
non-selectivity non-selectivity
22 receptor selective agonists receptor selective agonists
Salbuterol Salbuterol 沙丁胺醇沙丁胺醇
1. 1. Pharmacological effectsPharmacological effects Relaxing bronchial smooth musclesRelaxing bronchial smooth muscles
2. 2. Clinical usesClinical uses Controlling asthmatic symptomsControlling asthmatic symptoms
Given by Given by inhalationinhalation, oral or injection, oral or injection
3. 3. Adverse effectsAdverse effects Skeletal muscle tremorSkeletal muscle tremor
Cardiac stimulation (larger doses)Cardiac stimulation (larger doses)
Dysfunction of metabolism Dysfunction of metabolism (hypokalemia, (hypokalemia, etcetc.).)
Bronchial dilators
Selectivity of Selectivity of 22 agonistsagonists
22 receptor selective agonists receptor selective agonists ::
LLong-actingong-acting
Salmeterol Salmeterol 沙美特沙美特罗罗
Formoterol Formoterol 福莫特福莫特罗罗
Bronchial dilators
1. 1. receptor agonists receptor agonists
维兰特罗奥达特罗茚达特罗
TheophyllinesTheophyllines
Aminophylline 氨茶碱
N
N N
NH3C H
CH2NH2
2H2OCH2NH2
O
O
CH3--
--
--
--
2
. .
Theophyllines:Theophyllines:
One type of xanthine derivatives (One type of xanthine derivatives ( 甲基黄嘌呤类衍生甲基黄嘌呤类衍生物物 ))
Bronchial dilatorsBronchial dilators
1. Pharmacological effects1. Pharmacological effects
Inhibiting phosphodiesterase(PDE); Inhibiting phosphodiesterase(PDE);
Blocking adenosine receptors;Blocking adenosine receptors;
Increasing catecholamine release;Increasing catecholamine release;
Immunomodulation;Immunomodulation;
Increasing contractilityIncreasing contractility of of respiratory respiratory
muscle(diaphragm muscle);muscle(diaphragm muscle);
Diuretic, Diuretic,
CNS stimulation,CNS stimulation,
Gastric acid secretion, etc.Gastric acid secretion, etc.
Bronchial dilators
2. 2. Clinical usesClinical uses Bronchial asthma (Bronchial asthma (p.o.p.o., , i.v.i.v.))
Others: Others: acute pulmonary edema, acute pulmonary edema, etc.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;
Bronchial dilators
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.
Muscarinic antagonists—— M receptor blocking
Bronchial dilators
Muscarinic antagonists
—— M receptor blockingIpratropine 异丙托溴铵,异丙托
品O
C
CH2
CH2 CH2
C6H5CHOCH
CH3
CH3
CH
NCH3
CH
OH
(CH3)2CH
Bronchial dilators
Mechanism of Action and EffectsMechanism of Action and Effects
When given by aerosol, ipratropium and When given by aerosol, ipratropium and tiotropium competitively block muscarinic tiotropium competitively block muscarinic receptors in the airways and effectively receptors in the airways and effectively prevent bronchoconstriction mediated by prevent bronchoconstriction mediated by vagal dischargevagal discharge.
Muscarinic antagonists reverse Muscarinic antagonists reverse bronchoconstriction in some asthma bronchoconstriction in some asthma patients patients (especially children) (especially children) and in many and in many patients with COPD. patients with COPD.
They have no effect on the chronic They have no effect on the chronic inflammatory aspects of asthma.inflammatory aspects of asthma.
Clinical Use and ToxicityClinical Use and Toxicity
Ipratropium and tiotropium are useful in Ipratropium and tiotropium are useful in one third to two thirds of asthmatic one third to two thirds of asthmatic patients; β2 agonists are effective in patients; β2 agonists are effective in almost all. almost all.
For acute bronchospasm, therefore, the For acute bronchospasm, therefore, the β agonists are usually preferred.β agonists are usually preferred.
However, in COPD, which is often However, in COPD, which is often associated with acute episodes of associated with acute episodes of bronchospasm, the antimuscarinic bronchospasm, the antimuscarinic agents may be more effective and less agents may be more effective and less toxic than β agonists.toxic than β agonists.
Novel class of BrochodilatorsNovel class of Brochodilators
Aerosol Aerosol inhalatioinhalatio
nn
Spacer used for aerosol Spacer used for aerosol inhalationinhalation
定量手控定量手控
气雾器气雾器
Spacer will aid Spacer will aid patients to inhale patients to inhale the aerosolized the aerosolized drugs easierdrugs easier
Outcome of different sized Outcome of different sized particles:particles:
> 10μm: mouth and > 10μm: mouth and oropharynxoropharynx
< 0.5μm: inhaled to the < 0.5μm: inhaled to the alveoli and subsequently alveoli and subsequently exhaled without being exhaled without being deposited in the lungdeposited in the lung
1-5μm: the most effective1-5μm: the most effective
Reference
Pharmacology and therapeutics of bronchodilators.Cazzola M, Page CP, Calzetta L, Matera MG. Pharmacol Rev. 2012 Jul;64(3):450-504. doi: 10.1124/pr.111.004580. Review.