作用于呼吸系统的药物——山东大学药理学英文.ppt

1、Drugs Affecting the Respiratory System,anjie Institute of Pharmacology, School of Medicine, Shandong University,introduction,Cough, sputum and Asthma are main symptoms in respiratory systemic diseases. So we are going to learn agents used in therapy of Cough, sputum and Asthma.,Antiasthmatic drugs,A

2、sthma,Asthma is a chronic inflammatory pulmonary disorder that is characterized by reversible obstruction of the airways. Asthma affects 4 to 5% of the whole population.,recurrent dyspnea Shortness of breath Coughing Chest tightness Whistling,Asthma,SYMPTOMS,Asthma,Most people have a mild form of th

3、e disease, with symptoms occurring only occasionally .( e.g, on exposure to allergens or certain pollutants , on exercise, or after a viral infection.),Allergens molds, dust mites, cockroaches, animal dander, pollens, foods Irritants secondhand smoke, strong odors, aerosols, volatile organic compoun

4、ds, ozone, particulate matter,Other Viral respiratory infections Changes in weather (cold air, wind, humidity) Exercise Medication Endocrine factors (menstrual period, pregnancy, thyroid disease),Common,asthma,Triggers,* 5 major indoor asthma triggers,Pathogenesis of asthma,1.allergic reaction (-typ

5、e) : mediate d by IgE antibodies . Symptoms: (1)mediators (HA, PGs) release (2)broncho-constriction (3)vascular leakage.,Pathogenesis of asthma,2.inflammation of airway mucosa: nonspecific bronchial hyper-reactivity to some stimuli (eg. allergen inhalation , or infection with virus.) Neural mechanis

6、m:,Treatment of asthma,Treatment should be directed toward reduction of inflammation, as well as to management of bronchoconstriction.,Classification Branchodilator 1.2 adrenoceptor agonists : salbutamol 2.Theophylline : aminophylline 3.M Receptor blockers: ipratropine Anti-inflamation agents 1.Gluc

7、ocorticoids:beclomethasone 2.inhibitors of leukotirenes(LTs) Anti-hypersensitive agents 1. inhibitors of mediator release : cromolyn sodium,means of administration Drugs can be delivered to the lungs by inhalation, oral, or injection. Inhalation is often preferred because the drug is delivered direc

8、tly to the target tissue and is effective in doses that do not cause significant systemic side effects.,Antiasthmatic Drugs,The drugs most commonly used drugs for management of asthma are adrenoceptor agonists (used as “relievers” or broncho-dilators ) and inhaled corticosteroids (used as “controlle

9、rs” or anti-inflamatory agents),Bronchodilators,The major drugs used to treat bronchospasm are the 2- adrenoceptor agonists and the theophylline.,adrenoline receptor agonists,adrenaline,pharmacological actions: AD is a nonselective adrenoceptor agonist which can activate all of the , -receptors nons

10、electively., mechanism of anti-asthma actions,1. activate 2-R ACcAMPPKA Ca2+ relaxation of airway smooth muscle 2. activate -Rvascular constriction of bronchial mucosaedema lightened airflow improved 3. inhibit mast cell degranulation release of alergic mediators decreased,clinical use:,S.C(subcutan

11、ous) : acute attacks of asthma side effects: stimulates1 as well as2 receptors, can result in cardiac adverse reactions (eg. tachycardia, arrhythmias),Ephedrine, characteristics (VS AD): slow onset; moderate effect; long duration; vasoconstriction and CNS excitation. clinical use The oldest agents u

12、sed to treat asthma, and can be used in prevention and treatment of mild asthma.,Isoprenaline (Isop),was introduced in the 1940s as a pure -agonist. anti-asthmatic action: potent , quick-onset used in acute asthma severe toxicity on heart: arrythmia,Selective2- R agonists,The most widely used adreno

13、ceptor agonist for the treatment of asthma at the present time . They are effective after inhaled or oral administration and have a long duration of action and significant 2 selectivity.,Selective2- R agonists,Salbutamol(沙丁胺醇), p.o. inhale，ivd Clenbuterol(克伦特罗）, potent effect Terbutaline (特布他林) p.o.

14、 s.c. long duration formaterol(福莫特罗), sameterol(沙美特罗) : long duration, also inhibit release of inflammatory mediator. Mainly used in chronic asthma and Chronic obstructive lung disease. Bambuterol(班布特罗) P.O.,Selective2- R agonists,Clinical use acute attacks of asthma. interact with inhaled corticost

15、eroids to improve asthma control. Adverse effects: cardiac reaction skeletal muscle tremor (2- R) metabolic disorder,Theophylline,aminophylline(氨茶碱), choline theophylline(胆茶碱), glyphylline(甘油茶碱, 喘定), Effects:,relaxation of smooth muscle cardiac stimulation CNS stimulation Excitation of skeletal musc

16、le diuresis, Mechanism,1) PDE ( phosphodiesterase ) 2) Release of CA (catecholamine) 3) Block adenosine (a bronchoconstrictor) 4) Anti-inflammatory effect,Therapeutic uses,Chronic asthma Chronic obstructive lung disease,Theophylline, adverse reactions: gastrointestinal distress CNS stimulation Cardi

17、ovescular reaction: arrythmia, BP Acute nephridial failure,3. M-receptor blocker : ipratropium(异丙阿托品) Slow onset Oxitropium (氧托品) Tiotropium (泰乌托品)： potent effect, long duation,Anti-inflammatory steroids,Glucocorticoids Most effective anti-inflamatory drugs Used in continuous and severe asthma attac

18、k,Glucocorticoids,Effect : effective in improving all index of asthma control and can improve quality of life. (1) reduce bronchial reactivity; (2) increase airway caliber; (3) reduce the frequency of asthma ecurrence,Mechanisms:,1) reduce microvascular leakage. 2) inhibit influx of inflammatory cel

19、ls into the lungs. 3) inhibit of production of inflammatory cytokines. 4) increase the effect of -R agonists,Beclomethasone（倍氯米松）,Characteristics: 1) inhaled: potent local anti-inflammatory action (500 times than Dex). 2)far fewer systemic adverse reaction 3) slow onset, used in prevention of attack

20、 of moderate or severe asthma flunisolide(氟尼缩松) , budesonide(布地萘德，布的松),leukotrienes (LTs) pathway inhibitors,LTs: LTC4 and LTD4: inflimatory reaction increased bronchial reactivity mucosal edema mucus hypersecretion,two approaches: 1) inhibition of 5-lipoxygenase: zileuton(齐留通) 2) LTD4 -receptor ant

21、agonists: zafirlukast(扎鲁司特), montelukast(孟鲁司特) Principle advantage can be taken orally Clinical use : all kinds of asthma , especially aspirin-induced asthma.,Drugs stabilizing cellular membrane, Sodium cromoglycate,Mechanism of action: stabilizing cellular membrane 1)on mast cell: inhibits the earl

22、y response to antigen challenge. 2) on eosinophils: inhibit the inflammatory response to inhalation of allergens. 3) inhibit sensory nerve endings,Clinical use:,pretreatment of asthma caused by antigen inhalation, by exercise, by aspirin, etc. administrated shortly before exercise or before unavoida

23、ble exposure to an allergen. Adverse reactions: throat irritation,Nadocrimil sodium(奈多罗米钠) Ketotifen(酮替芬),Antitussives,Overview,Coughing is a protective mechanism through which foreign materials and secretions are cleared from the respiratory tract. But severe and prolonged coughing can be painful a

24、nd exhausting.,Overiew,Some drugs act at one or more sites within the respiratory tract; others act at the cough center to inhibit activation of the efferent limb of the response.,Classification Central antitussives Dependence : Codeine（可待因） , Dihydrocodeine（二氢可待因 ） Nondependence: Dextromethorpham, Cloperastine, Pentoxyverine Peripheral antitussives: Benzonatate（苯佐那酯）, narcotin(那可丁）,Central anti