In the treatment of bronchial asthma, instead of focusing on bronchodilatation, emphasis should be placed on both anti-inflammatory and airway reactivity reduction treatments. With the emergence of new perspectives in treatment, the focus of asthma treatment has changed. In the past, the preference for the application of bronchodilators and the adoption of treatments to relieve bronchoconstriction and relieve symptoms necessarily failed to meet the needs of patients. Hormones with anti-inflammatory effects have become the main drugs for the treatment of asthma.
(1) β-agonists
β-agonists have been rated as the drug of choice in the treatment of bronchial asthma and play an important role in the treatment. Their main pharmacological effects are as follows: (1) dilating bronchi; (2) increasing the ciliary clearance capacity of airway mucosa; (3) inhibiting the release of various inflammatory mediators; (4) inhibiting exudative edema; (5) reducing pulmonary hypertension and increasing ventricular ejection fraction, etc. Therefore, they can be used for the treatment of bronchial asthma.
Beta-agonists are divided into three generations.
The first generation of β-agonists: they are characterized by low selectivity and have certain excitatory effects on α, β1 and β2 receptors. The duration of action is short, the applied dose is large, and the side effects of the cardiovascular system are large. Some of the main drugs are as follows.
①Epinephrine: can excite α-receptors and β-receptors, which can produce a calming effect and reduce bronchial mucosal congestion and edema. At the same time, it can make myocardial contraction increase, heart rate accelerate, cardiac blood output increase, blood pressure increase, and basal metabolic rate increase. The effect on bronchial tubes is strong and rapid, but it is short-lived and has large side effects, so it is rarely used clinically.
②Isoprenaline: strong effect on β-receptors. It has almost no effect on α-receptors, and is less used clinically because of its greater excitability to the heart and its tendency to produce drug resistance.
③Isoproterenol: It is selective for β2 receptors of bronchial smooth muscle and can significantly relieve histamine, 5hydroxytryptamine and acetylcholine-induced bronchial asthma, producing a better bronchodilatory effect.
④Clopidone: selective agonism of β2 receptors, with more significant bronchodilator effect and less side effects on the heart. It has good relief effect on histamine and acetylcholine-induced bronchial asthma. It is clinically suitable for the treatment of bronchial asthma and wheezing bronchitis, etc.
Asthma: It mainly acts on β2 receptor and has the effect of poppy alkali-like direct relaxation of bronchial smooth muscle. The strength of its effect on bronchial smooth muscle expansion is 5-10 times that of isoprenaline, and the effect on the cardiovascular central nervous system is smaller. Adverse reactions are less frequent, mainly palpitations, head heaviness, dry mouth, gastrointestinal reactions, etc.
Second-generation β-agonists: characterized by increased selectivity for β2 receptors, enhanced excitatory effects, longer duration of action, and reduced cardiovascular side effects. The commonly used drugs are as follows.
①Salbutamol: a potent β2-receptor agonist with high selectivity. It is one of the most widely used asthma drugs in clinical practice. Its diastolic effect on bronchial smooth muscle is strong and long-lasting, and its effect on cardiovascular and central nervous system is minimal, so it is considered to be a safe and effective asthma drug. It is clinically indicated for bronchial asthma, wheezing bronchitis and bronchospasm. For patients with severe bronchial asthma or asthma persistent state, it can be considered to be administered by static drip.
②Thunderbolt: highly selective excitation of β2 receptors, the diastolic effect on bronchial tubes is 2 times greater than that of ipronin, and it can also inhibit the release of inflammatory biological mediators, reduce mucosal edema, increase the mucosal cilia contouring ability, and rarely cause cardiovascular adverse reactions when applying the recommended dose.
③Lexamethasone: highly selective excitation of β2 receptors, less excitatory to bronchial smooth muscle, but very weak excitatory effect on the heart, longer duration of action, suitable for acute and chronic asthma, adverse effects include palpitations, finger tremors, headache, etc.
④Other: including bimethylphenidate, chaipronine, phenpropynine, pyridine asthma, etc., are all such drugs.
Third-generation β-agonists: they are characterized by higher selectivity for β2 receptors and stronger effects. The adverse effects are reduced and the duration of action is more than 8 hours. The dosage is generally small, at the microgram level. The main products are as follows.
①Aminobiclosporin: It is a potent and highly selective β2 receptor agonist with significant bronchodilator effects and little effect on the cardiovascular system. It can be administered orally, nebulized and rectally and is suitable for the treatment of bronchial asthma, wheezing bronchitis and certain emphysema and other conditions causing bronchospasm. Adverse reactions include transient dizziness, mild tremor, etc., but they are milder than other varieties.
(2) Isoproterenol, tert-butylchlorphenidate, albuterol, formoterol and other drugs belong to this category.
(2) Xanthines
The pharmacological effects of this class of drugs are: ①Diastolic bronchial: achieved by stimulating the release of endogenous catecholamines and inhibiting phosphodiesterase. ② Enhance the contraction of respiratory muscles; ③ Excite the respiratory center; ④ Affect the transport of calcium ions; ⑤ Antagonize the effect of adenosine; ⑥ Anti-inflammatory effect. Therefore, it can be used in the treatment of asthma. The commonly used drugs are.
①Aminophylline: 0.1~0.2mg orally, 3 times daily; the first loading dose of intravenous drug is 5~6mg/kg body weight, then maintained at 0.5~0.7mg/kg body weight?h-1.
②Dihydroxypropyl theophylline (asthma): the drug is neutral in aqueous solution, less irritating to the stomach, easily absorbed, weaker than aminophylline, but reduced cardiovascular side effects, only 1/10 of aminophylline, especially suitable for the elderly. 0.1-0.2mg, 3 times daily.
③Choline: similar to phenazine, with lighter side effects than aminophylline, but weaker than aminophylline. 0.1~0.2mg, 3 times daily.
④Tripropylxanthine: It is a new type of preparation without adenosine antagonism, which is not metabolized by the liver but cleared by the kidney, avoiding large fluctuations in clearance rate, and has no excitatory effect on the center, and is a promising drug.
(3) Anticholinergic drugs
Anticholinergic drugs exert competitive antagonism by competing with acetylcholine for the same binding site on the M receptor, thus reducing bronchial tension and relieving the airway obstruction symptoms of bronchial asthma. Numerous clinical studies have shown that nebulized inhaled anticholinergics in stable asthma exert significant bronchodilatory effects, but their relative efficacy compared to selective β-agonists is currently controversial. Studies of the efficacy of anticholinergics in combination with β-agonists in the treatment of stable asthma have shown overwhelmingly that the efficacy of the combination is not only stronger than that of the respective drugs alone, but also that the maintenance time is significantly longer. These two types of drugs exert airway diastolic effects by different mechanisms, so their efficacy is not dependent on each other, and the combination produces additive effects.
(4) Glucocorticosteroids
The pharmacological effects of glucocorticosteroids include: (1) anti-inflammatory effect; (2) anti-allergic effect; (3) relaxation of airway smooth muscle; (4) prevention of delayed metamorphosis and reduction of bronchial hyperreactivity. Therefore, glucocorticosteroids can be used to prevent and control bronchial asthma. Prednisolone and prednisone are often administered orally at 30 mg per day in adults, with maximum efficacy occurring after several days, and the dosage is reduced and maintained at 5-15 mg. The usual course of treatment is 7 days. Hydrocortisone can be injected, the first dose of 4mg/kg body weight, every 6 hours, generally used for 1 to 3 days, effective after the change to oral. Nebulized inhalation of cortisone dipropionate, de-inflammatory pine, etc., the dose is ≤ 800μg per day.
(5) Anti-allergic drugs
Drugs that interfere with or block every aspect of airway allergic disease can be called anti-allergic drugs, and such drugs are the first-line drugs for asthma control. The commonly used drugs are.
①Sodium cromoglycate: it is a mast cell stabilizer, which can inhibit the release of inflammatory mediators from mast cells, inhibit the activation of eosinophils, neutrophils and alveolar macrophages, and has the inflammatory effect of anti-airway allergic. Long-term treatment may result in significant improvement in lung function. This drug is the safest drug for the treatment of asthma with minimal side effects.
②Ketotifen: pharmacological effects of ketotifen: ① inhibit the synthesis and release of inflammatory mediators; ② antagonize inflammatory mediators; ③ increase the activity of β-receptors and convert them to high affinity state; ④ inhibit the release of intracellular Ca++. The efficiency of clinical application can be as high as 90%, with less side effects and only mild sedative effect in long-term use.
(3) antihistamines: these drugs can antagonize histamine, leukotrienes and platelet-activating factor and prostaglandins and other inflammatory mediators, but also inhibit the release of mast cells, eosinophils, basophils and alveolar macrophages and other inflammatory cells, the drugs commonly used are: benzylphthalazine, terfenadine, cetirizine, breath min and other drugs.
(6) Other drugs: mainly calcium channel blockers, potassium channel activators, inositol phosphate degradation inhibitors and vitamin drugs.