Anti-asthmatics Asthma : is physiologically characterized by increased responsiveness of trachea and bronchi to various stimuli and by widespread narrowing of the airways.

 The mechanisms underlying bronchial hyperreactivity are somehow related to inflammation of airway mucosa.  The agents that increase bronchial reactivity, such as ozone exposure, allergen inhalation, and infection with respiratory viruses, also cause airway inflammation.

 Its pathologic characters are contraction of airway smooth muscle, mucosal thickening from edema and cellular infiltration, and inspissation in the airway lumen of abnormally thick, viscid plugs of mucus.  The products of cells in the airways, such as eosinophil, lymphocytes, macrophages, mast cells, sensory nerves, and epithelial cells, have been shown to alter airway smooth muscle function.

 Asthma therapies are divided into two categories: short-term relievers and long- term controllers.  short-term relievers: β-adrenoceptor stimulants, theophylline, antimuscarinic agents.  long-term controllers: anti-inflammatory agents, inhibitor of mast cell degranulation.

Ⅰ. Adrenoceptor agonists //mechanism 1. Stimulation of β 2 receptor in bronchial smooth muscle cell mb →cAMP →Ca 2+ ↓ →SM relaxation. 2. Also activateβreceptor on mast cell mb., thus used in prophylaxis of allergic asthma.

3. Stimulation of αreceptor in bronchial vessels contraction of vascular smooth muscle edema. 4. The density of β receptor will decrease after prolonged treatment.

Adrenaline/epinephrine Adrenaline/epinephrine ( 肾上腺素 ): //agonist of α and β receptor //adverse effect of cardiovascular system usually occurs thereby less usable //s.c. injection Ephedrine （麻黄碱） Ephedrine （麻黄碱） //orally administered //similar action to Adr. //less usable for central excitation

Isoproterenol （异丙肾上腺素） //agonist of β 1 &β 2 receptor //no action on α receptor //used for acute attack of bronchoasthma by inspiration route //orally ineffective //involved in adverse effect of β 1 receptor excitation.

 Selectively β 2 receptor agonist Salbutamol ( 沙丁胺醇，舒喘灵 ) Terbutaline （特布他林，博利康尼） Clenbuterol （克仑特罗） Clenbuterol （克仑特罗） The β 2 -Selective adrenoceptor agonist drugs are the most widely used sympathomimetics for the treatment of asthma at the present time.

//Mechanism : Air way smooth muscle has little sympathetic nervous supply but contain lots of ß 2 -adrenoceptors that respond to circulating adrenaline. The stimulation of ß 2 -receptors leads to a rise in intracellular cAMP levels and the subsequent bronchial smooth muscle relaxation

 They are effective after inhaled or oral administration and have a long duration of action and significant β 2 selectivity.  Given by inhalation, these agents cause bronchodilation equivalent to that produced by isoproterenol.

ß 2 -adrenoceptor agonist may also help to prevent the activation of mast cell to prevent the activation of mast cell in a minor degree. in a minor degree. Modern selective ß 2 -receptor agonists are potent bronchodilators and have are potent bronchodilators and have very few ß 1 -stimulating properties. very few ß 1 -stimulating properties.

Route of administration //Route of administration : usually delivered via a metered dose inhaler with immediate effect orally used in children iv used for acute-care. S.C. (terbutaline) Adverse effect //Adverse effect : cardiac arrhythmias tolerance to ß agonist hypoxemia

Ⅱ. Theophylline : derivatives of methylxanthine The importance of theophylline as a therapeutic agent in the treatment of asthma has waned. The importance of theophylline as a therapeutic agent in the treatment of asthma has waned. But theophylline's very low cost is important advantage for economically disadvantaged patients. But theophylline's very low cost is important advantage for economically disadvantaged patients.

They are divided into two types : 1. Salt complex : increased water solubility without augmentation of pharmacological action, such as : aminophylline （氨茶碱） choline theophylline （胆茶碱）

2. Agent of delayed release : small fluctuation of blood concentration after oral administration thus used for nocturnal attact of asthma protheo ( 优喘平）

//Mechanism : Anti-inflammation inhibit activity of PDE cAMP Ca 2+ bronchial relaxation increase the release of NA, Adr inhibition the cell surface receptor of adenosine interfere with the transportation of Ca 2+

//pharmacodynamics  The bronchodilation is the major therapeutic action in asthma.  Potent effects in improving contractility and in reversing fatigue of diaphragm in patients with chronic obstructive lung diseases.  Direct positive chronotropic and inotropic effects on the heart.  In large doses, these agents also relax vascular smooth muscle.

//Administration route : orally effective but different from adrenergic agent for metabolism by P 450 enzyme system //Indications : Bronchial asthma (+βreceptor agonist) Chronic obstructive lung diseases Cardiogenic asthma Sleep apenea syndrom

//Adverse effect : it has a narrow therapeutic window and its therapeutic and toxic effects are related to its plasma concentration. <20mg/L : nausea, vomiting, headache, anxiety, abdominal discomfort 20-40mg/L: arrhythmia

Ⅲ. Muscarinic antagonist : Ipratropium bromide ( 异丙托溴铵 ) Ipratropine( 异丙托品 ) //Mehanism : act by blocking muscarinic receptors esp. the M 3 subtype, which responds to this parasympathetic bronchial constrictor tone.

//Route of administration : metered dose inhaler //Indication : used as adjuncts to ß 2 -adrenoceptor agonist in treatment of asthma and more effective in vagus-induced asthma. //Therapeutic note : synergism when administered with ß 2 -adrenoceptor agonist.

Ⅳ. Anti-inflammatory drug Glucocorticoids include : beclomethasone ( 倍氯米松 ) budesonide （布地奈德） //Mechanism : depress the inflammatory response in bronchial mucosa thus diminish bronchial hyperresponsiveness.

 Anti-inflammatory effect  Immunosuppressive effect  Increase the response to catecholamines  Inhibit the activity of PDE  Adenoceptor-upregulation

//Route of administration : orally i.v used for : severe asthma status asthmaticus metered dose inhaler //Indications : Because of the efficacy and safety of inhaled corticosteroids, they are now routinely prescribed for patients who require more than occasional inhalations of β agonist for relief of symptom.

// Adverse effect:  Oropharyngeal candidiasis it can be reduced by having patients gargle water and spit after each inhaled treatment.  Hoarseness

Ⅴ. Anti-allergic agents i.e. mast-cell-stabilizers cromolyn sodium ( 色甘酸钠 ) //Mechanism : They appear to stabilize antigen-sensitized mast cell by reducing calcium influx and subsequent release of inflammatory mediators.

 On mast cells, for inhibition of the early response to antigen challenge  On eosinophils, for inhibition of the inflammatory response to inhalation of allergens

// Route of administration : metered dose inhaler of cromoly sodium // Indications : pretreatment with cromolyn blocks the bronchoconstriction caused by antigen inhalation,by exercise, by aspirin, and by a variety of cause of occupational asthma.

// Adverse effect  Throat irritation  Cough  Mouth dryness  Chest tightness and so forth