2.  DNase - inhalation (in a spray). By expectorant drugs include marshmallow root, root istoda, licorice root, Terpin hydrate, sodium benzoate Means, used for bronchospasm Under normal circumstances, the bronchial muscle tone is maintained by cholinergic nerve stimulation which results in bronchospastic effect. Sympathetic innervation of the bronchi missing. However, in the bronchi are neinnerviruemye (beta2-adrenergic receptors, which are affected by circulating hell ¬ renalin and input from the outside adrenotropnye substance. Beta2-adrenergic stimulation is accompanied by a bronchodilatory effect.

3.  In the development of bronchospastic conditions, including bronchial asthma ¬ Hoc, there bronchial hyperreactivity to the action of various stimuli that provoke bronchospasm. These include allergens, foreign ¬ infections, chemicals, inhalation of cold air, stress, etc. In the formation of the inflammatory response underlying giperreaktiv ¬ sion bronchi, a major role is played by so-called inflammatory mediators. They are produced in the cells of the bronchial epithelium, in mast cells, macrophages, al ¬ Veolia, in neutrophils, eosinophils, monocytes. Lung mast cells typically contain histamine, adenosine, chemotactic factors for neutrophils and eosinophils. The inflammatory process induces the production of many other copper ¬ ator inflammation - leukotrienes, prostaglandins, thromboxane, a factor ac- tiviruyuschego platelets (PAF).

4.  These substances have BRONCHOSPASTIC action to cause swelling of the bronchial mucosa, increased permeability of blood vessels, promote infiltration of the mucous membrane of leukocytes, ¬ vayut causes hypersecretion of mucus. All this aggravates the course of bronchospasm. Therefore, the tactics of treatment is not only provoke Corrective Actions ¬ ing stimuli (if known), and bronchodilator therapy, but also for pressure ¬ inflammatory process. Based on available data, the drugs used for the treatment of bronchial asthma and other bronchospastic with ¬ states can be represented by the following groups.

5.  I. Funds expand the bronchi (bronchodilators).  1. Substances that stimulate (beta2-adrenergic receptors (salbutamol, fenoterol, terbutaline, izadrin, ortsiprenalina sulfate, epinephrine hydrochloride). 2. M-anticholinergics (atropine sulfate, metacin, ipratropium bromide). 3. Myotropic antispasmodic action (theophylline, aminophylline).  II. Means having anti-inflammatory and bronchodilator activity ¬ sion. 1. Steroid anti-inflammatories (hydrocortisone, dexamethasone, triamcinolone, beclomethasone). 2. Antiallergics (cromolyn sodium, ketotifen). 3. Means, which influence on the system of leukotrienes. A. 5-lipoxygenase inhibitors (zileuton). B. leukotriene receptor blockers (zafirlukast, montelukast).

6.  Of the group of bronchodilators matter of great interest, stimulated ¬ trolling beta2-adrenergic receptors. Currently, with bronchospasm used mainly drugs, WHO ¬ exciting mainly beta2-adrenergic receptors - salbutamol (Ventolin, salben, salgim, Saltos), fenoterol (berotek H). They are much less cause tachycardia than non-selective beta-agonists dei ¬ quences. They are usually used by inhalation. Beta 2-agonists are fast-acting bronchodilators. Furthermore, they contribute to sputum. In recent years, developed a long-acting beta-2 agonists salmeterol (Serevent), formoterol (Foradil), etc. Thus, when inhaled salmeterol bronchodilatory effect persists for about 12 h, whereas it is limited salbutamol 4-6 hours for the treatment of bronchial asthma proposed formulation comprising salmeterol and places with predominantly glucocorticoid ¬ nym action of fluticasone propionate (fliksotid). Such a combination drug called Seretide Multidisc.

7. . In this case, the bronchodilation effect salmoterola combined with anti-inflammatory effects of fluticasone, which is very useful for the effective treatment of bronchial asthma ¬ tion. Introduce the drug using a powder inhaler. Beta 2-agonists can cause tremor, tachycardia, anxiety, Arit ¬ Mia and other side effects. One of the drugs in this group is also izadrin (isoprenaline guide ¬ hydrochloride), which stimulates beta1 and beta2-adrenergic receptors. It is used to eliminate bronchospasm. Prescribe it for this purpose in solutions inhalation. Due to the influence of beta-adrenergic receptors of the heart izadrin can cause increased frequency and heart rate. Blood pressure in this application izadrina practically unchanged.

8.  A somewhat more pronounced tropism for adrenoceptor bronchial region gives ¬ Beta- agonists ortsiprenalina sulfate (alupent). According bronchodilator efficacy, it is similar izadrinu, but over the duration ¬ but. Effect on beta2-and beta1-adrenergic receptors. Orciprenaline administered parenterally, orally, and by inhalation in aerosol form. If bronchospasm often use epinephrine affecting the alpha-and beta (Beta1 and Beta 2)-adrenergic receptors. For subcutaneous administration, it rapidly suppresses bronchial spasms of different etiology, and also reduces the swelling of the mucosa. Operates short. Of the side effects may increase arterial ¬ th pressure, tachycardia, increased cardiac output.

9.  As a sympathomimetic bronchodilator sometimes used ephedrine (alpha-and beta adrenoagonists indirect action). By activity he gives the adrenaline, but it works longer. Usually used as a prophylactic measure. Of the side effects, in addition to the marked adrenaline, there ¬ impact excitation of CNS. If it is largely expressed, it can be reduced using stitching ¬ sedative or hypnotic agents. It should be borne in mind that to ephedrine developed drug dependence.

10.  Thus, one way of dealing with bronchospasm is acti ¬ vation beta 2-adrenoceptor agonist and bronchus associated adenylate cyclase, leading to an increase in intracellular cAMP (this in turn reduces the concentration of calcium ions within the cell) and the lower tone of bronchial smooth muscle. Simultaneously, under the influence of substances Beta-2 activity is reduced Adrenomimeticalkie release from mast cells compounds causing bronchial spasm (histamine, slow reacting substance of anaphylaxis,

11.  Can be used a different principle. Bronchodilator properties are substances that block the cholinergic innervation of the bronchial tubes, espe ¬ cially m-anticholinergics. Thus there is a reduction of the release of mast cell spasmogenic substances. According to ac ¬ ciency in asthma m-holinoblokatory inferior adrenomimetikami. Out of this group of drugs used (especially with bronchospasm neal-lergicheskoy nature associated with increased cholinergic innervation tone) of atropine sulfate, platifillin, metacin and ipratropium bromide, which are non-selective blockers of m-cholinergic receptors. Not ¬ abundance of drugs in this group are to reduce their secretion of bronchial ¬ cial, and other salivary glands, tachycardia, accommodation disturbances (less pronounced when using metatsina).

12.  Pronounced effect was observed when inhaled ipratropium (Atrovent). The action of this drug is slower than that of p-agonists; retain ¬ nyaetsya about 6 hours in the central nervous system does not penetrate (as is a quaternary ammonium compound ¬ Nieve). Ipratropium is also available in combination with fenoterol (such preparation is called berodual H). By bronchodilators from the group of quaternary ammonium compounds, in addition to metatsina and ipratropium, is also a new drug tiotropium.

13.  He acts mainly on the m3 and m1-cholinergic receptors, but more firmly and relatively long ¬ associated with the first. Therefore, this drug is often referred to as pre ¬ property m3 nicotinic acetylcholine receptor blockers. He actively ipratropium and operates more lasting. However, the speed of the effect higher for ipratropium. The maximum effect of tiotropium develops in 1.5-2 hours at ¬ meaningful tiotropium 1 inhalation once daily (in the form of powder in a special inhaler). The main side effects - dry mucous membranes of the oral po ¬ tum.

14.  Bronchiectasis is achieved, in addition to their innervation use of drugs acting directly on smooth muscle bronchioles. Of myotropic antispasmodics for bronchodilator actions use pre ¬ formulations of theophylline, including aminophylline (aminophylline). Latest report ¬ it possible a mixture of theophylline (1,3-theobromine) with 1,2- ethylene diamine. It is noted that high concentrations of theophylline inhibits phosphodiesterase and thereby increases the concentration of cAMP. As in the case of acting beta2-agonists, most accompanied by a decrease in intracellular calcium concentration and relaxation of muscles of bronchi. At one time it was considered the cause of bronchodilator action of theophylline.

15. . However, in the far ¬ shem found that theophylline inhibits phosphodiesterase at concentrations values ​​¬ considerably higher than therapeutic. It has been suggested that, in the range of therapeutic concentrations of bronchodilator action Theophilus ¬ ling associated with the block adenosine receptors bronchioles. A number of authors were also able to show that theophylline prevents the release of histamine from the clouds ¬ cells, the called adenosine. However, this hypothesis is exposed to view, so as to close synthesized compound theophylline (3-propylxanthine), which has potent bronchodilator activity and inhibits adenosine receptors bronchioles. Theophylline also reduces pressure in the pulmonary circulation, improves blood flow to the heart, kidneys and, obviously, in the brain (for vasoconstriction).

16.  It has a mild diuretic effect. Stimulates the activity of myo ¬ infarction, cardiac oxygen demand is on the increase. Has excited ¬ giving effect on the central nervous system. In recent years, theophylline, especially in a long-acting preparations (length 8, 12 and 24 hours) have been widely used for the pro ¬ vention of bronchospasms. On the effectiveness of drugs theophylline comparable ¬ ble with beta-agonists.

17.  However, one should take into account the small therapeutic ¬ ical breadth of theophylline. It is shown that the concentration of toxic substances in the blood of a therapeutic exceed 2-4 times. Therefore dose pre ¬ formulations with caution. Ideally, it is desirable to select the optimal dose, comparing the concentration of the substance in the blood and the severity of the effect. Prolonged use to periodically determine the concentration of theophylline in the plasma, the more the speed of absorption and t, / 2 vary quite widely.

18.  Theophylline is almost completely absorbed from the digestive tract. Metabolized in the liver. Excreted by the kidneys. It should be borne in mind that theophylline passes through the placenta and is excreted in the milk of nursing mothers. Used drugs theophylline inside, rectally and intravenously. In appointing inside they can cause dyspepsia. The irritant effects observed with administration of aminophylline in the rectum. Side effects are quite diverse, and occur relatively frequently. Possible headache, dizziness, nausea, vomiting, delayed urination, Arit ¬ mia, agitation, insomnia, in toxic doses - seizures.

19.  In the treatment of patients with bronchial asthma and other bronchospasm al ¬ lergicheskoy nature, in addition to the true-acting bronchodilators are widely used anti- inflammatory and anti-allergic agents. These medications include corticosteroids. It is shown that they stabilize mast cell membranes and beads coated beta2-adrenergic receptors and provide a direct bronchodilatory action. Important (if not oc ¬ novnoe) is important to have in severe glucocorticoid-protivovos palitelnoy and immunosuppressive activity, which is very favorable ska ¬ is called for bronchial asthma. Glucocorticoids are used in the form of aerosols (beclomethasone dipropionate, fluticasone propionate, budesonide (marketed as a drug benacort (dry powder for inhalation)). ) And into systemic action (dexamethasone, triamcinolone, etc.). The latter two drugs can be used ingalyadionno. If necessary, intravenous hydrocortisone. When changes in ¬ aerosol glucocorticoids may develop candidiasis roto ¬ howling cavity and pharynx, cough.

20.  Of great interest is also a synthetic anti-allergic drug cromolyn sodium (disodium cromoglycate, Intal, kropoz). According to one hypothesis, the principle of its operation is that it blocks occurrences ¬ denie mast cells in calcium ions and stabilizes mast cell membranes and granules. Altogether, this process should inhibit mast cell degranulation and release of these substances spasmogens (histamine, SRS-A, etc.). However, this view is questioned, as cromolyn sodium ¬ turn out a very weak and inconstant effect on mast cells isolated from human lung (salbutamol in these studies was significantly more active). Cromolyn sodium is used to prevent asthma attacks. Enter its inhalation. Similarly with cromolyn sodium drug is nedocromil. It is also anti-allergic drugs ketotifen (zaditen). According to the existing views, it inhibits the release of mediators of allergic ¬ energy from fat cells. It is used to prevent attacks of bronchial asthma ¬ Hoc, as well as hay fever, rhinitis and other allergic re ¬ promotions immediate type. Of the side effects observed sedation, sometimes thrombocytopenia. Taking the drug orally 2 times a day. The action is slow, with a maximum effect observed after 3-4 weeks.

21.  Histamine H,-receptors in bronchial asthma maloeffek ¬ tive. In the treatment of bronchial asthma have occupied important positions Agents acting on the leukotriene ¬ ing system. It is known that leukotrienes are formed from arachidonic acid by the participation of several enzymes. One of the Klu ¬ prong enzymes of this pathway is 5-lipoxygenase. There are selective inhibitors of 5-lipoxygenase inhibitors such as zileuton. Cyclooxygenase this drug is not affected. Therefore, all the effects of zileuton are associated with oppression ¬ tion of the biosynthesis of leukotrienes. Last mainly manifested protivovos ¬ palitelnym effect, as well as the expansion of bronhov.Vvodyat drug inside. It is rapidly absorbed. High fat diet improves ab ¬ sorption of zileuton. He vigorously metabolized in the first pass through the liver (formed glucuronide). The maximum concentration in plasma determined by 1.8-2.5 h A significant proportion (~ 93%) is bound to plasma proteins. Metabolites are distinguished primarily by the kidneys (90 - 95%); t, / 2 = 1-2,3 hours is mostly used in bronchial asthma. Can be used in rheumatoid arthritis, ulcerative colitis. Of the side effects observed fever, myalgia, fatigue, head ¬ tion pain, dizziness, indigestion, etc.

22.  The second group of drugs includes leukotriene receptor blockers. One is zafirlukast which selectively and effectively inhibits relatively long ¬ leukotriene receptors (LTD4, LTE4). Thus there is an anti-inflammatory effect. In bronchial asthma, it is pro ¬ decrease in the permeability of blood vessels, decrease swelling mucous ¬ shell of the bronchi, the suppression of secretion of thick, viscous mucus. At the same time there is a growing bronchioles (block LTD4 receptor). The drug is administered orally (effective and inhalation). Maximum con ¬ centration is determined after 3 hours Accept zafirlukast be fasting since the presence of food in the intestine mass drug absorption is reduced by about 40%. Since blood plasma proteins bind more than 99% of the material. Che ¬ cut penetrates the blood-brain barrier poorly. In the body, the drug is metabolized Institute ¬ intensively. The formed metabolites are allocated com ¬ intestinal (~ 90%) and kidney (~ 10%); t | / 2 ~ 10 h noted that zafirlukast inhibits microsomal enzymes, and therefore influences the metabolism and, therefore, the pharmacokinetics of many other medicaments. The clinical effect is slow (about 1 day).

23.  Therefore, zafirlukast used for prevention and long- term treatment of asthma ¬ Institute. For relief of asthma medication is not suitable ¬. It can be used as a complement to the quick ¬ schim antiasthmatic drugs (beta-agonists, glucocorticoids). Zafirlukast may be appointed in allergic rhinitis. Possible side effects: headache, gastritis, pharyngitis, gastritis, myalgia, arthralgia, etc. By leukotriene receptor blockers is also montelukast (singuler). It is a selective antagonist of leukotriene D4 (LTD4). Zafirlukast also differs from that does not inhibit the microsomal liver enzymes and therefore do not affect the effect of other substances. Entered into, is absorbed quickly. The composition of food does not affect the absorption of montelukast. The drug is extensively metabolized. Provided mainly the intestines; t ~ 2,7-5,5 hours is used for prevention and long-term treatment of bronchial asthma. The drug is well tolerated. Possible adverse effects of headache, dyspepsia, dizziness, skin rashes, etc.

24.  Antagonists are promising and platelet-activating factor, which refers to the mediators of inflammation narrows the bronchi and may contribute to the release of leukotrienes, PG and thromboxane. The first steps of this type of formulations prepared and submitted for clinical trials. Medicines used in acute respiratory failure One of the causes of acute respiratory failure is pulmonary edema. It can develop in diseases of the cardiovascular system, it's time to light ¬ zhenii chemicals in a number of infectious diseases, kidney disease, liver, and brain edema. Even this is not a complete list of possible causes of pulmonary edema suggests that the treatment of this severe disease should be carried out primarily in terms of the main Zabo ¬ ous diseases or the nature of intoxication. However, you can highlight the most important principles of pathogenetic therapy of cardiogenic pulmonary edema and connected ¬ bound thereto hypoxia.

25.  Widespread use in the treatment of pulmonary edema received opioid drugs morphine, fentanyl, Talamonal. One explanation for the effectiveness of opioid analgesics for this condition reduces to the following ¬. They are considered to cause dilation of peripheral arteries and veins, respectively, and decreases venous return to the heart. There is a pererasp ¬ tain blood, which reduces the pressure in the pulmonary circulatory ¬ tion. The result is the positive effect of acute pulmonary edema. To reduce pulmonary edema high blood pressure is one of the main objectives is to reduce the latter. For this purpose, use ganglioblokiruyuschie means (gigrony, pentamine, benzogeksony) vasodilators myotropic action (sodium nitroprusside) and formulations containing alpha-adrenoblokiruyuschey ¬ active surface (eg, phentolamine, small doses of chlorpromazine, Promethazine).

26.  By reducing these drugs blood pressure normalized total hemodynamics, increasing the efficiency of the heart, lowers the pressure in the pulmonary circulation. The latter is particularly important as reducing the hydrostatic pressure of the blood in the pulmonary capillaries prevents the progression of the process and helps reduce of the ongoing OTE ¬ ka lungs. This is due to the fact that extravasation of fluid from the pulmonary capillaries ¬ moat in these conditions is reduced, while its resorption and increased outflow.