Over the past 10 years, long-acting β2-agonists have taken a leading place in international standards treatments bronchial asthma and chronic obstructive pulmonary disease. If in the first version of the Global Strategy for Bronchial Asthma these drugs were assigned the role of second-line agents, then in the new version of GINA 2002 β 2-agonists long acting are considered as an alternative to increasing daily doses of inhaled glucocorticosteroids if the patient’s response to anti-inflammatory therapy is insufficient and it is impossible to control bronchial asthma. In this case, the administration of long-acting β2-agonists should always precede the next increase in the daily dose of inhaled glucocorticosteroids. This is due to the fact that the inclusion of long-acting β 2 -agonists in the treatment regimen with inhaled glucocorticosteroids for uncontrolled bronchial asthma is more effective than simply increasing the daily dose of inhaled glucocorticosteroids by 2 times or more. However, long-term therapy with long-acting β2-agonists does not appear to affect persistent inflammation in asthma, and therefore their use should always be combined with the administration of inhaled glucocorticosteroids.
Long-acting inhaled β2-agonists include salmeterol and formoterol (more than 12 hours). The effect of most short-acting inhaled β 2 -agonists lasts from 4 to 6 hours. Salmeterol, like formoterol, relaxes bronchial smooth muscle, increases mucocillar clearance, reduces vascular permeability and can affect the release of mediators from mast cells and basophils. A study of biopsy specimens shows that when treated with long-acting inhaled β 2 -agonists, signs of chronic inflammation in the respiratory tract in patients with bronchial asthma do not increase; in fact, with long-term use of these drugs, even a small anti-inflammatory effect is noted. In addition, salmeterol also provides long-term (more than 12 hours) protection against factors leading to bronchoconstriction. Formoterol is a full β 2 -receptor agonist, while salmeterol is a partial agonist, but the clinical significance of these differences is unclear. Formoterol has a faster onset of action than salmeterol, making it more suitable for both symptom management and prevention, although its effectiveness and safety as a rescue treatment requires further study.
Salmeterol (in particular salmeter, Dr. Reddy's Laboratories) exhibits higher specificity for β 2 receptors compared to other sympathomimetics. The bronchodilatory effect of the drug appears 10-20 minutes after inhalation. Forced expiratory volume in 1 s (FEV 1) increases within 180 minutes, and the clinically significant bronchodilator effect persists for 12 hours. The lipophilicity of salmeterol is 10,000 times higher than that of salbutamol, which promotes rapid penetration of the drug into cell membranes. Salmeterol has a stabilizing effect on mast cells, inhibits their release of histamine , reduces the permeability of pulmonary capillaries to a greater extent than inhaled glucocorticosteroids, reduces the production of cytokines by T lymphocytes, suppresses IgE-dependent synthesis of TNF-α and the release of leukotriene C 4 and prostaglandin D.
In most patients with bronchial asthma, it is possible to achieve control of symptoms when prescribing the drug 50 mcg 2 times a day. A large randomized trial showed that taking salmeterol for 12 weeks was associated with an increase in peak expiratory flow (PEF) in the morning by 7.1% compared to baseline (p< 0,001). При этом число дней без симптомов возросло с 35 до 67%. На 20% увеличилось количество ночей без приступов удушья, использование сальбутамола сократилось более чем в 3 раза. Применение сальметерола 2 раза в сутки более эффективно, чем 4-кратное ежедневное использование симпатомиметиков короткого действия, особенно при бронхиальной астме физического усилия.
In persons with chronic obstructive pulmonary disease, salmeterol is usually prescribed at a daily dose of 50 mcg 2 times. The results of 3 large randomized placebo-controlled studies revealed a significant decrease in the severity of symptoms of the disease and an improvement in FEV 1. There were no signs of tolerance to the drug during the study, and the frequency of exacerbations did not differ from that in the placebo group. However, the significant improvement in the quality of life when taking salmeterol makes it possible to consider its inclusion in the treatment regimen for patients with chronic obstructive pulmonary disease.
Due to the relatively slowly developing effect, salmeterol is not recommended for use to relieve acute symptoms of bronchial asthma; in this case, inhaled short-acting bronchodilators are preferable. When prescribing salmeterol twice a day (morning and evening), the physician should additionally provide the patient with a short-acting β2-agonist inhaler to treat acutely developing symptoms in parallel with the constant use of salmeterol.
Increasing frequency of taking bronchodilators, in particular inhaled forms of short-acting β 2 -agonists, reduces the curability of bronchial asthma. The patient should be warned about the need to seek medical care in case of a decrease in the effectiveness of prescribed short-acting bronchodilators or to increase the frequency of dosing of the drug. In this situation, an examination is necessary, after which recommendations are made to intensify anti-inflammatory therapy (for example, higher doses of corticosteroids in the form of inhalations or orally). Increasing the daily dose of salmeterol in this case is not justified.
Salmeterol should not be taken more than 2 times a day (morning and evening) at the recommended dose (two inhalations). Taking large doses of salmeterol by inhalation or oral form (12-20 times the recommended dose) will lead to a clinically significant prolongation of the QT interval, which means the onset of ventricular arrhythmias. At recommended doses, salmeterol has no effect on the cardiovascular system. Disorders of cardiovascular and central functions nervous systems Caused by all sympathomimetic drugs (increased blood pressure, tachycardia, agitation, ECG changes) are observed in rare cases after taking salmeterol. Such effects are uncommon, and if they occur, the drug should be discontinued. However, salmeterol, like all sympathomimetics, is prescribed with caution to patients with cardiovascular disorders, especially coronary insufficiency, arrhythmias, and hypertension; persons with convulsive syndrome, thyrotoxicosis, inadequate response to sympathomimetic drugs.
Salmeterol cannot be used as a substitute for inhaled or oral corticosteroids, or sodium cromoglycate, and the patient should be warned not to stop taking these drugs, even if salmeterol provides greater relief.
Inhalation of salmeterol may be complicated by acute hypersensitivity in the form of paradoxical bronchospasm, angioedema, urticaria, rash, hypotension, collaptoid reaction and symptoms of laryngospasm, irritation or laryngeal edema, leading to stridor and asphyxia. Due to the fact that bronchospasm is a life-threatening condition, the patient must be warned about the possible discontinuation of the drug and the appointment of alternative treatment.
Conducted multicenter studies prove the high effectiveness of long-acting β 2 agonists. The emergence of these drugs has significantly changed approaches to the treatment of broncho-obstructive diseases. The inclusion of salmeter in drug treatment regimens will significantly improve the results of long-term basic therapy of chronic broncho-obstructive pathology, especially since the drug has advantages not only in terms of effectiveness and safety, but also cost.
(Lapteva I. M. Research Institute of Pulmonology and Phthisiology of the Ministry of Health of the Republic of Belarus. Published: "Medical Panorama" No. 10, November 2004)
The group of bronchodilators includes sympathomimetics (beta 2-agonists), anticholinergics (M-anticholinergics), methylxanthines (theophyllines).
Beta-2 agonists are divided into short-acting and long-acting drugs based on their duration of action.
Short-acting beta-2 agonists are the most effective bronchodilators for relieving symptoms (wheezing, chest tightness, and cough) and providing emergency assistance. They are able to quickly expand narrowed bronchi. When used inhaled, the bronchodilator effect occurs within 5-10 minutes. They are prescribed no more than 4 times a day.
The effect of long-acting beta-2 agonists occurs later. In this connection, these drugs are not intended to relieve attacks of bronchospasm, but can be recommended for longer-term continuous therapy in order to prevent attacks of suffocation and exacerbation of the disease, and are also an alternative to increasing doses of inhaled GCS. The downside is that patients taking these drugs are forced to carry a fast-acting inhaled corticosteroid at all times in case the beta-2 agonist prophylaxis fails and they develop breathing problems. These medications may be used as adjunctive therapy for moderate to severe asthma. However, opinions regarding the advisability of long-term use of long-acting sympathomimetics are quite controversial. Some researchers believe that permanent use such drugs for a long time can worsen the prognosis during the course of the disease itself, others fear a faster development of tachyphylaxis, but this is not clear and requires further study. The main requirements for modern sympathomimetic drugs are their high efficiency and selectivity. The side effects on the cardiovascular system of such drugs are reduced to a minimum. The main disadvantage of most beta-2 agonists is their short duration of action (4–6 hours), requiring frequent use throughout the day, and low concentrations of the drug in the blood at night.
Comparative characteristics of the main beta-2-agonist drugs are presented in Table 2.
Comparative characteristics of the main beta-2 agonists used in the treatment of bronchial asthma.
M-anticholinergics (anticholinergics) are not first-line drugs for the treatment of exacerbation of asthma; their effectiveness in asthma is inferior to sympathomimetics. Anticholinergic drugs have a number of effects that make their use difficult: they cause dryness of the mucous membranes of the nasopharynx and upper respiratory tract, reduce the secretion of bronchial glands and the mobility of epithelial cilia, that is, they inhibit the evacuation function of the bronchi, increase the number of heartbeats, stimulate pupil dilation, and redness of the skin. Therefore, with a stable course of asthma, anticholinergic drugs occupy a more modest place compared to beta-2 agonists. In Russia, the most common anticholinergic drug is ipratropium bromide (Atrovent®). The advantages of this drug are that it has a longer action than sympathomimetics, the total duration of its action is approximately, the onset of action is observed after 5 minutes, and the peak of action occurs after 1.5 hours.
Cholinergic drugs are mainly used:
If signs of bronchitis predominate,
For “cough asthma” (cough as the equivalent of an asthma attack),
With bronchial obstruction provoked by physical activity, cold, inhalation of dust, gases;
In case of broncho-obstructive syndrome with severe bronchorrhea (“wet asthma”),
In patients with asthma with contraindications to the use of beta-2 adrenergic stimulants;
In case of psychogenic asthma and hormonal characteristics (premenstrual asthma, combination of asthma with thyrotoxicosis), the use of a complex of anticholinergic and sedatives has an advantage compared to beta-2-adrenergic agonists;
For nocturnal asthma,
For asthma induced by atmospheric pollutants and chemical irritants,
In some cases, anticholinergics are used in combination with beta-2 agonists. However, combination drugs are rarely used in the treatment of asthma, because Treatment with standard drugs, such as beta-2 agonists or ipratropium bromide, is more effective and allows for selective dosing of each drug. The advantage is that this combination is synergistic and reduces the risk side effects constituent components. Combination therapy also leads to a greater bronchodilator effect compared to monotherapy and can significantly increase its duration. The main combination drugs of ipratropium with beta-2 agonists are ipratropium/fenoterol (Berodual®) and ipratropium/salbutamol (Combivent®). These drugs are mainly used as part of complex therapy for severe attacks of suffocation - inhalation through a nebulizer.
Among methylxanthines, theophylline and aminophylline are used in the treatment of bronchial asthma.
Due to a number of adverse side effects that can occur with overdose of these drugs, monitoring of theophylline blood concentrations is required. Aminophylline (a mixture of theophylline and ethylenediamine, which is 20 times more soluble than theophylline itself) is administered intravenously very slowly (at least 20 minutes). Intravenous aminophylline plays an important role in the relief of severe asthma attacks that are tolerant to nebulized forms of beta-2 agonists. Aminophylline is also used in patients with heart failure when it is combined with asthma or bronchitis, and with hypertension of the pulmonary circulation. In the body, aminophylline releases free theophylline.
Modern beta-2-adrenomimetic drugs and anti-inflammatory drugs have “displaced” theophylline drugs in the treatment of asthma. Indications for primary use in asthma are:
In the attacking period of asthma, in the form of a course of intravenous drip infusions of 5-10 ml of a 2.4% solution together with potassium preparations and (if indicated) corticosteroids in saline solution;
Extended-release theophylline preparations with individual dose selection (from 0.1 to 0.5 g) are effective for the treatment of nocturnal asthma attacks;
In chronic asthma, the use of long-acting theophylline preparations can significantly reduce the dose of beta-2 adrenergic agonists and reduce the severity of asthma symptoms.
You can find an analysis of the market for bronchodilator drugs in the report of the Academy of Industrial Market Studies “Russian market of drugs for the treatment of bronchial asthma.”
Academy of Industrial Market Conditions
Medicines
Expectorant stimulants
Reflex acting drugs
These include preparations of thermopsis, istoda, marshmallow, licorice, coltsfoot. When taken orally, drugs of this group have a moderate irritant effect on the stomach receptors, which reflexively increases the secretion of the salivary glands and bronchial mucous glands. The effect of these drugs is short-lived, so frequent, small doses are necessary (every 2-4 hours). Expectorants include copious alkaline drinks, infusions and decoctions of marshmallow and thermopsis - up to 10 times a day. Expectorants are used both during exacerbation of the disease and during remission.
Resorptive drugs: sodium and potassium iodide, sodium bicarbonate and other salt preparations. They increase bronchial secretion, cause dilution of bronchial secretions and thereby facilitate expectoration.
Tablets and dragees of 8, 12, 16 mg. Medicine in a bottle.
Syrup. Solution for oral use. Adults are prescribed 8-16 mg 4 times a day.
8 mg tablets, 100 pieces per package. Solution for oral use. Elixir. Prescribe 8-16 mg 4 times a day.
Tablets 30 mg 20 pieces per package. Retard capsules 75 mg, 10 and 20 pieces per package. Solution for oral use, 40 and 100 ml in bottles. Syrup 100 ml in bottles. The usual daily dose of the drug in tablets is 60 mg. Take 1 tablet 2-3 times a day with food, with a small amount of liquid. Extended-release capsules (retard capsules) are prescribed 1 piece in the morning. The solution is prescribed in 4 ml 3 times a day for the first 2-3 days, and then 2 ml 3 times a day. The drug in the form of syrup is recommended for adults in the first 2-3 days, 10 ml 3 times a day, and then 5 ml 3 times a day.
Tablets 30 mg 50 pieces per package. Syrup 100 ml in bottles. Prescribe 30 mg 2-3 times a day.
There are also a large number of combination drugs: Doctor IOM, broncholitin, bronchicum, etc.
Currently, a drug has appeared that has both an anti-inflammatory and bronchodilator effect. This drug is called erespal (fenspiride). When treated with Erespal, the degree of airway obstruction decreases, the amount of mucus produced decreases, which is associated with both a decrease in the formation and a decrease in secretion, that is, the drug acts in terms of reducing excess mucus production. Available in 80 mg tablets (30 tablets per pack). The drug is prescribed 2-3 tablets per day.
Aerosol therapy with phytoncides and antiseptics can be carried out using ultrasonic inhalers, which create homogeneous aerosols with optimal particle size that penetrate to the peripheral parts bronchial tree. The use of drugs in the form of aerosols ensures their high local concentration and uniform distribution of the drug in the bronchial tree. Using aerosols, you can inhale the antiseptics furatsilin, rivanol, chlorophyllipt, onion or garlic juice (diluted with a 0.25% solution of novocaine in a ratio of 1:30), fir infusion, lingonberry leaf condensate, dioxidine. After aerosol therapy, postural drainage and vibration massage are performed.
During periods of remission of chronic bronchitis, secondary prevention measures are carried out aimed at preventing exacerbations. The most preferred and safest route of drug administration is inhalation, which usually does not cause serious side effects. With this method of administration, the bronchodilator drug enters directly into the bronchi. There is a wide variety of inhalers, and metered dose inhalers are the most common.
To ensure maximum impact medicinal product deep into the respiratory tract, it is very important to use the metered dose inhaler correctly.
The technique for using the inhaler is as follows:
Shake the inhaler (to obtain an aerosol of uniform particle size); remove the protective cap (many patients forget to do this); tilt your head back a little (to slightly straighten the upper respiratory tract and ensure free flow of medicine into the bronchi); turn the inhaler upside down (the mouthpiece should be down); exhale completely.
Starting to inhale, press the bottom of the inhaler and inhale the medicine deeply (make only one press on the bottom of the can). Hold your breath for 5-10 seconds (so that the medicine settles on the wall of the bronchi). Exhale calmly. If necessary, repeat the manipulation.
It is important to understand that despite feeling well, regular treatment is necessary. This is due to the fact that the progression of the process occurs imperceptibly, gradually, over many years. Therefore, when a patient experiences pronounced changes in well-being (shortness of breath with little physical exertion and at rest), the process of changes in the bronchi is already significantly expressed. Therefore, in order to stop the progression of the process, it is necessary to begin treatment as early as possible, that is, immediately from the moment of diagnosis.
Another point that I would like to draw attention to is that the treatment of chronic obstructive bronchitis is not a matter of temporarily reducing shortness of breath, or episodic, course treatment with any drug. Treatment of the disease is therapy carried out regularly over many months and years. This is the only way to slow down the rate of progression of the disease and maintain satisfactory health and good physical activity for a long time.
Since narrowing of the bronchi plays a major role in the development and progression of chronic obstructive bronchitis, drugs that dilate the bronchi are mainly used for the permanent treatment of the disease. An ideal bronchodilator drug for the treatment of chronic obstructive bronchitis should meet the following requirements: high efficiency; minimal number and severity of adverse reactions; maintaining effectiveness despite long-term use.
Today, inhaled anticholinergic drugs best meet these requirements. They act mainly on large bronchi. Drugs in this group are characterized by a pronounced bronchodilator effect and a minimal number of side effects. These include Atrovent, Troventol, Truvent.
These drugs do not cause tremor (shaking) and do not affect the cardiovascular system. Treatment with Atrovent usually begins with 2 inhalations 4 times a day. A decrease in bronchial obstruction and, therefore, an improvement in well-being occurs no earlier than 7-10 days after the start of therapy. It is possible to increase the dose of the drug by one breath per day. Drugs in this group are used for basic long-term bronchodilator therapy. It is preferable to use a metered dose inhaler with a spacer.
Metered aerosol. 300 doses of 20 mcg.
Inhaled short-acting B-2-agonists
They also have a bronchodilator effect. These drugs are less effective for chronic obstructive bronchitis than anticholinergics. It is recommended to use drugs in this group no more than 3-4 times a day or as a prophylaxis before physical activity. The combined use of short-acting inhaled beta-2 agonists in patients with chronic obstructive bronchitis is more effective than therapy with bronchodilator drugs of the same group.
Caution is required when using beta-2 agonist drugs in elderly people, especially in the presence of cardiovascular diseases.
Side effects: possible trembling of the hands, internal tremors, tension, palpitations, nausea, vomiting.
The most common drugs in this group are the following.
Berotec (fenoterol). Metered aerosol for inhalation. 300 inhalation doses of 200 mcg.
Berotek-100 (fenoterol). (Boehringer Ingelheim, Germany). Metered aerosol containing a lower dose of the drug, mcg.
Metered aerosol of 100 mcg per dose.
Ventolin (salbutamol). Aerosol inhaler 100 mcg per dose.
There is a drug that is a combination of drugs from these two groups.
Berodual (20 mcg ipratropium bromide + 50 mcg fenoterol). The two bronchodilators contained in Berodual have a stronger effect in combination than each of them individually. If combined treatment with inhaled anticholinergics and short-acting beta-2 agonists is ineffective, your doctor may recommend another group of drugs.
The main representative of the methylxanthines group is theophylline. It has a weaker bronchodilator effect compared to inhaled anticholinergics and beta-2 agonists. However, in addition to the bronchodilator effect, drugs in this group have a number of other properties: they prevent or reduce fatigue of the respiratory muscles; activate the motor ability of the ciliated epithelium; stimulate breathing.
Side effects: irritation of the gastric mucosa, pain in the epigastric region, nausea, vomiting, diarrhea, agitation, insomnia, anxiety, headache, trembling, rapid heartbeat, arrhythmias, decreased blood pressure.
Of the theophylline group of drugs, its extended forms are of greatest interest.
There are a large number of drugs offered in this group. They are prescribed by a doctor. The dose and treatment regimen depend on the severity of the disease and some other individual factors.
First generation drugs (taken 2 times a day)
Tablets, 0.3 g. 50 pieces per package.
Slow fillin. Tablets of 0.1 and 0.2 g. 100 pieces per package.
Retard capsules of 0.1, 0.2, 0.3 g. 20, 60 and 100 pieces per package.
Capsules of 0.125 and 0.25 g. 40 pieces per pack.
Tablets of 0.2 and 0.3 g. 100 pieces per package.
II generation drugs (taken once a day)
Retard capsules of 0.375 and 0.25 g. 20, 50, 100 pieces per package.
Another group of drugs that can be recommended to be taken as basic therapy are glucocorticosteroids. In chronic obstructive bronchitis, they are prescribed in cases where airway obstruction remains severe and causes disability despite smoking cessation and optimal bronchodilator therapy. The doctor usually prescribes these drugs in tablet form against the background of ongoing therapy with bronchodilators. The most common of this group is prednisolone.
All of the above drugs belong to basic therapy, that is, when prescribed, they should be taken regularly for a long time. Only in this case can you count on the success of therapy. We would like to once again emphasize the need to stop smoking as one of the factors that significantly aggravates the condition and accelerates the progression of the disease.
For chronic bronchitis, methods are used to increase the body's nonspecific resistance. For this purpose, adaptogens are used - eleutherococcus extract 40 drops 3 times a day, ginseng tincture 30 drops 3 times a day, tinctures of aralia, Rhodiola rosea, pantocrine in the same doses, saparal 0.05 g 3 times a day. The effect of these drugs is multifaceted: they have a positive effect on the functioning of the immune system, metabolic processes, and increase the body’s resistance to adverse environmental influences and the influence of infectious factors.
Source: Encyclopedia of Traditional and Alternative Medicine
Treatment and prevention
quickly affect bronchial obstruction, improving the well-being of patients in short time. With long-term use of β2-agonists, resistance to them develops; after a break in taking the drugs, their bronchodilator effect is restored. A decrease in the effectiveness of β2-adrenergic stimulants and, as a consequence, deterioration of bronchial obstruction are associated with desensitization of β2-adrenergic receptors and a decrease in their density due to prolonged exposure to agonists, as well as with the development of “rebound syndrome”, characterized by severe bronchospasm. “Rebound syndrome” is caused by blockade of b2-adrenergic receptors of the bronchi by metabolic products and disruption of the drainage function of the bronchial tree due to the development of “pulmonary closure” syndrome. Contraindications to the use of β2-agonists in COPD are hypersensitivity to any component of the drug, tachyarrhythmias, heart defects, aortic stenosis, hypertrophic cardiomyopathy, decompensated diabetes mellitus, thyrotoxicosis, glaucoma, threatened abortion. This group of drugs should be used especially carefully in elderly patients with concomitant heart pathology.
Features of short-acting (salbutamol, fenoterol) and long-acting (formoterol, salmeterol) b2-agonists.
Metered dose inhaler 100 mcg/inhalation dose kg/6-8 hours (maximum kg per day) Diskhalermkg/blistermkg/6-8 hours (maximum 1600 µg/day Nebulizer 2.5-5.0 mg every 6 hours
The most common side effects: Tremor Headache Agitation Hypotension Hot flashes Hypokalemia Tachycardia Dizziness
Metered dose inhaler 100 mcg/inhalation dose kg/6-8 hours (maximum kg per day) Nebulizer 0.5-1.25 mg every 6 hours
Onset of action: 5-10 min Maximum effect: min Duration of effect: 3-6 h
Monitoring side effects Symptom analysis Blood pressure control Heart rate control Electrolyte control
12 mcg/capsule 12 mcg/12 hours (maximum 48 mcg/day)
Onset of action: min Duration of effect: 12 h
Metered dose inhaler 25 mcg/inhalation dose kg/12 hours (maximum 100 mcg/24 hours) Diskhaler 50 mcg/blister 50 mcg/12 hours Discus 50 mcg/inhalation dose 50 mcg/12 hours
Onset of action: 10-2 minutes Duration of effect: 12 hours
added to therapy when the first two groups of drugs are insufficiently effective, they reduce systemic pulmonary hypertension and enhance the work of the respiratory muscles.
These drugs have pronounced anti-inflammatory activity, although in patients with COPD it is significantly less pronounced than in patients with asthma. Short (10-14 days) courses of systemic steroids are used to treat exacerbations of COPD. Long-term use of these drugs is not recommended due to the risk of side effects (myopathy, osteoporosis, etc.).
It has been shown that they have no effect on the progressive decrease in bronchial obstruction in patients with COPD. Their high doses (for example, fluticasone propionate 1000 mcg/day) can improve the quality of life of patients and reduce the frequency of exacerbations of severe and extremely severe COPD.
The reasons for the relative steroid resistance of airway inflammation in COPD are the subject of intense research. This may be due to the fact that corticosteroids increase the lifespan of neutrophils by inhibiting their apoptosis. The molecular mechanisms underlying resistance to glucocorticoids are not well understood. There have been reports of a decrease in the activity of histone deacetylase, which is a target for the action of steroids, under the influence of smoking and free radicals, which may reduce the inhibitory effect of glucocorticoids on the transcription of “inflammatory” genes and weaken their anti-inflammatory effect.
SYNDROMES AND EMERGENCY DISEASES OF THE RESPIRATORY ORGANS.
5.1 EXacERBATION OF BRONCHIAL ASTHMA
Bronchial asthma is a disease based on chronic allergic inflammation and bronchial hyperreactivity, clinically manifested by bronchial obstruction that changes over time. Repeated episodes of obsessive nonproductive cough, especially at night and/or early morning, are symptoms of widespread but variable bronchial obstruction, partially reversible spontaneously or disappearing with treatment.
There are 4 known mechanisms of airway obstruction:
Smooth muscle spasm;
Swelling of the mucous membrane of the respiratory tract;
Hypersecretion with the formation of mucus plugs;
Sclerosis of the bronchial wall with long-term and severe course of the disease.
Thus, asthma is a chronic, allergic inflammation of the airways, leading to bronchial hyperreactivity, obstruction due to bronchoconstriction, mucosal edema and obstruction with viscous secretions, clinically manifested by respiratory symptoms.
Diagnostic criteria for asthma
Diagnosis of asthma on prehospital stage diagnosed on the basis of complaints, medical history and clinical examination.
1. Complaints and medical history.
The presence of attacks of suffocation or shortness of breath, the appearance of wheezing, coughing and their disappearance spontaneously or after the use of bronchodilators and anti-inflammatory drugs. The relationship of these symptoms with risk factors for asthma (see risk factors for asthma). The patient or his relatives have a history of established asthma or other allergic diseases.
2. Clinical examination.
Forced position, participation of auxiliary respiratory muscles in the act of breathing, dry wheezing that can be heard at a distance and/or upon auscultation over the lungs.
If (including the patient) a peak flow meter or spirometer is recorded, significant broncho-obstruction is recorded - forced expiratory volume in 1 second (FEV1) or peak expiratory flow (PEF) less than 80% of the proper or normal values.
Criteria for exacerbation of asthma
Exacerbation of BA can occur in the form of an acute attack or a protracted state of bronchial obstruction.
An attack of asthma is an acutely developed and/or progressively worsening expiratory suffocation, difficulty and/or wheezing, spasmodic cough, or a combination of these symptoms, with a sharp decrease in the peak expiratory flow rate.
An exacerbation in the form of a protracted state of bronchial obstruction is characterized by long-term (days, weeks, months) difficulty breathing, with a clinically pronounced bronchial obstruction syndrome, against the background of which acute attacks of BA of varying severity may recur.
Exacerbations of bronchial asthma are the leading cause of ambulance calls and hospitalization of patients.
Assessment of asthma exacerbation is carried out based on clinical signs and (if a peak flow meter is available) functional respiratory tests. The severity of the exacerbation can be mild, moderate, severe and in the form of status asthmaticus.
Table 1. Classification of severity of exacerbation of asthma *.
Sharply reduced, forced position
Sharply reduced or absent
Unchanged, sometimes agitated
Excitement, fear, “breathing panic”
Confusion, coma
Limited, speaks isolated phrases
Normal respiratory rate in awake children (RR per minute)
Normal or increased up to 30% of normal
Severe expiratory dyspnea. More than 30-50% of normal
Severe expiratory shortness of breath more than 50% of normal
Tachypnea or bradypnea
Involvement of accessory respiratory muscles;
jugular fossa retraction
Not pronounced
Paradoxical thoraco-abdominal breathing
Breathing during auscultation
Wheezing, usually at the end of expiration
Severe wheezing on inhalation and exhalation or mosaic breathing
Severe whistling or weakening of conduction
Absence of breathing sounds, “silent lung”
Normal heart rate in awake children (bpm)
PSV** (% of normal or best individual indicator)
Frequency of bronchodilator use in recent years
Not used or low/moderate doses used. Efficiency is insufficient, the need has increased compared to the individual norm
High doses were used.
* - The severity of an exacerbation is indicated by the presence of at least several parameters
** - PSV - used in adults and children over 5 years old
***-Currently it is determined mainly in the hospital
Table 2. Standards for function indicators external respiration in children
The tactics of prehospital therapy are completely determined by the severity of the exacerbation of asthma, therefore, when formulating a diagnosis by the doctor of the SS and NMP, it is necessary to indicate the severity of the exacerbation of asthma.
The doctor’s tactics when treating an attack of bronchial asthma have several general principles:
During the examination, the doctor must use clinical data to assess the severity of the exacerbation and determine the PEF (if a peak flow meter is available).
If possible, limit contact with causative allergens or triggers.
Based on the medical history, clarify the previous treatment:
bronchospasmolytic drugs, routes of administration; doses and frequency of administration;
time of last medication intake; whether the patient receives systemic corticosteroids, in what doses.
Rule out complications (eg, pneumonia, atelectasis, pneumothorax, or pneumomediastinum).
Provide emergency assistance depending on the severity of the attack.
Assess the effect of therapy (shortness of breath, heart rate, blood pressure. Increase in PEF>15%).
Choice of drug, dose and route of administration
Modern care for patients with exacerbation of asthma involves the use of only the following groups of drugs:
1. Selective short-acting beta-2 adrenergic receptor agonists (salbutamol, fenoterol).
2. Anticholinergic drugs (ipratropium bromide); their combination drug berodual (fenoterol + ipratropium bromide).
Short-acting selective beta-2 agonists.
These drugs, having a bronchospasmolytic effect, are first-line drugs in the treatment of asthma attacks.
SALBUTAMOL (ventolin, salben, ventolin nebulas and 0.1% salgim solution for nebulizer therapy) is a selective beta-2 adrenergic receptor agonist.
The bronchodilator effect of salbutamol occurs within 4-5 minutes. The effect of the drug gradually increases to its maximum in minutes. The half-life is 3-4 hours and the duration of action is 4-5 hours.
Mode of application : Using a nebulizer, 2.5 ml nebulas containing 2.5 mg of salbutamol sulfate in saline solution. 1-2 nebulas (2.5 - 5.0 mg) are prescribed for inhalation, undiluted. If there is no improvement, repeat inhalations of salbutamol 2.5 mg every 20 minutes for an hour. In addition, the drug is used in the form of a MDI (spacer), spacer or dischaler (100 mcg per inhalation, 1-2 puffs) or cyclohailer (200 mcg per inhalation, 1 puff).
FENOTEROL (Berotec) and Berotec solution for nebulizer therapy is a short-acting selective beta-2 agonist. The bronchodilator effect occurs within 3-4 minutes and reaches its maximum effect by 45 minutes. The half-life is 3-4 hours, and the duration of action of fenoterol is 5-6 hours.
Mode of application: Using a nebulizer - 0.5-1.5 ml of fenoterol solution in saline solution for 5-10 minutes. If there is no improvement, repeat inhalations of the same dose of the drug every 20 minutes. Children 0.5 -1.0 ml (10-20 drops) per 1 inhalation. Berotec is also used in the form of a MDI (100 mcg in 1-2 puffs).
Side effects. When using beta-2 agonists, hand tremors, agitation, headache, compensatory increase in heart rate, cardiac arrhythmias, and arterial hypertension are possible. Side effects are more expected in patients with diseases of the cardiovascular system, in older age groups and in children; with repeated use of a bronchospasmolytic, depend on the dose and route of administration of the drug.
Relative contraindications to the use of inhaled beta-2 agonists - thyrotoxicosis, heart defects, tachyarrhythmia and severe tachycardia, acute coronary pathology, decompensated diabetes mellitus, increased sensitivity to beta-adrenergic agonists.
IPRATROPIUM BROMIDE (atrovent) is an anticholinergic drug with very low (no more than 10%) bioavailability, which makes the drug well tolerated. Ipratropium bromide is used in cases of ineffectiveness of beta-2-agonists, as an additional agent to enhance their bronchodilator effect, in case of individual intolerance to beta-2-agonists, and in patients with chronic bronchitis.
Mode of application: Inhalation - using a nebulizer - 1.0 - 2.0 ml (0.25 - 0.5 mg). If necessary, repeat after a minute. Using a pMDI or a spacer.
BERODUAL is a combined bronchospasmolytic drug containing two bronchodilators fenoterol and ipratropium bromide. One dose of Berodual contains 0.05 mg of fenoterol and 0.02 mg of ipratropium bromide.
Mode of application: Using a nebulizer, to relieve an attack, inhale a solution of Berodual 1-4 ml in physiological solution for 5-10 minutes. If improvement does not occur, repeat inhalation after 20 minutes. The dose of the drug is diluted in saline solution. Using DAI, if necessary, after 5 minutes - 2 more doses, subsequent inhalation should be carried out no earlier than after 2 hours.
severe and life-threatening exacerbation of asthma
relief of an attack of suffocation in a patient with a hormonally dependent form of asthma
anamnestic indications of the need to use glucocorticoids to relieve exacerbation of asthma in the past.
Side effects: arterial hypertension, agitation, arrhythmia, ulcerative bleeding
Contraindications: Peptic ulcer of the stomach and duodenum, severe arterial hypertension, renal failure.
PREDNISOONE is a dehydrogenated analogue of hydrocortisone and belongs to the synthetic glucocorticosteroid hormones. The half-life is 2-4 hours, the duration of action is hours. It is administered parenterally to adults at a dose of at least 60 mg, to children - parenterally or orally at 1-2 mg/kg.
METHYLPREDNISOLONE (solumedrol, metypred) A non-halogen derivative of prednisolone, which has greater anti-inflammatory activity (5 mg prednisolone is equivalent to 4 mg methylprednisolone) and significantly less mineralocorticoid activity.
The drug is characterized by a short half-life, like prednisolone, and weaker stimulation of the psyche and appetite. For the treatment of exacerbations of bronchial asthma, it is used like prednisolone, but in smaller doses (at the rate of methylprednisolone-prednisolone as 4: 5).
Inhaled glucocorticoids (budesonide) may be effective. It is advisable to use inhaled glucocorticoids through a nebulizer.
BUDESONIDE (pulmicort) - suspension for nebulizer in plastic containers 0.25-0.5 mg (2 ml).
During biotransformation of budesonide in the liver, it forms metabolites with low glucocorticosteroid activity.
Pulmicort nebulizer suspension can be diluted with saline and also mixed with solutions of salbutamol and ipratropium bromide. Dose for adults - 0.5 mg (2 ml), for children - 0.5 mg (1 ml) twice every 30 minutes.
EUPHYLLINE is a combination of theophylline (80%), which determines the pharmacodynamics of the drug, and ethylenediamine (20%), which determines its solubility. The mechanisms of the bronchodilator action of theophylline are well known.
When providing emergency care, the drug is administered intravenously, and the effect begins immediately and lasts up to 6-7 hours. Theophylline is characterized by a narrow therapeutic range, i.e. Even with a slight overdose of the drug, side effects may develop. Half-life in adults hours. About 90% of the administered drug is metabolized in the liver, metabolites and unchanged drug (7-13%) are excreted in the urine through the kidneys. In adolescents and smokers, the metabolism of theophylline is accelerated, which may require an increase in the drug dose and infusion rate. Liver dysfunction, congestive heart failure and old age, on the contrary, slow down the metabolism of the drug, increase the risk of side effects and necessitate the need to reduce the dose and reduce the rate of intravenous infusion of aminophylline.
Indications for use in asthma:
relief of an asthma attack in the absence of inhaled drugs or how additional therapy with severe or life-threatening exacerbation of asthma.
from the cardiovascular system - decreased blood pressure, palpitations, cardiac arrhythmias, cardialgia
from the gastrointestinal tract - nausea, vomiting, diarrhea;
from the central nervous system - headache, dizziness, tremor, convulsions.
Interaction (see Table 3)
the drug is incompatible with glucose solution.
Dose in children: 4.5-5 mg/kg intravenously (administered over a period of minutes) per ml of saline solution.
The goal of nebulizer therapy is to deliver a therapeutic dose of the drug in aerosol form directly into the patient’s bronchi and obtain a pharmacodynamic response in a short period of time (5-10 minutes).
Nebulizer therapy is carried out using a special device, consisting of the nebulizer itself and a compressor, creating a flow of particles 2-5 microns in size at a speed of at least 4 l/min.
The word "nebulizer" comes from the Latin word nebula, which means mist. A nebulizer is a device for converting liquid into an aerosol with particularly fine particles capable of penetrating primarily into the peripheral bronchi. This process is carried out under the influence of compressed air through a compressor (compressor nebulizer) or under the influence of ultrasound (ultrasonic nebulizer).
Nebulizer therapy, creating high concentrations of the drug in the lungs, does not require coordination of inhalation with the act of inhalation, which has a significant advantage over MDI.
The effectiveness of inhalation depends on the aerosol dose and is determined by a number of factors:
the amount of aerosol produced,
ratio of inhalation and exhalation,
anatomy and geometry of the respiratory tract
Experimental data indicate that aerosols with a particle diameter of 2-5 microns are optimal for entry into the respiratory tract and, accordingly, recommended. Smaller particles (less than 0.8 microns) enter the alveoli, where they are quickly absorbed or exhaled, without remaining in the respiratory tract, without providing therapeutic effect. Larger particles (more than 10 microns) settle in the oropharynx. Thanks to nebulizer therapy, a higher therapeutic index of medicinal substances is achieved, which determines the effectiveness and safety of the treatment.
· the need to use high doses of drugs;
· targeted delivery of the drug to the respiratory tract;
· if complications occur with the use of usual doses of drugs and the frequency of use of inhaled corticosteroids and other anti-inflammatory drugs is high;
· in children, especially in the first years of life;
severity of the condition (lack of effective inspiration)
· no need to coordinate breathing with the intake of aerosol;
· the ability to use high doses of the drug and obtain a pharmacodynamic response in a short period of time;
· continuous supply of medicinal aerosol with fine particles;
· rapid and significant improvement in condition due to the effective entry of the drug into the bronchi;
· easy inhalation technique.
Preparations for nebulizer therapy are used in special containers, nebulas, as well as solutions produced in glass bottles. This makes it possible to easily, correctly and accurately dose the drug.
For inhalation through a nebulizer you need:
· pour liquid from the nebula or drip a solution from the bottle (single dose of the drug);
· add saline solution to the required volume of 2-3 ml (according to the instructions for the nebulizer;
· attach a mouthpiece or face mask;
· turn on the compressor, connect the nebulizer and compressor;
· perform inhalation until the solution is completely consumed;
· In children, preference is given to inhalation through the mouth using a mouthpiece;
· In children of the first years of life, a tight-fitting mask can be used.
Primary sanitization of the nebulizer is carried out at the substation. For this purpose, it is necessary to disassemble the nebulizer, rinse the nozzles with warm water and detergent, and dry (you cannot use a brush). Subsequently, the nebulizer and nozzles are sterilized in an autoclave at 120°C and 1.1 atmospheres (OST5).
Technical inspection of nebulizers is carried out once a year.
Table 3. Treatment of asthma exacerbation at the prehospital stage
ventolin 2.5 mg (1 nebula) or salgim 2.5 mg (1/2 bottle) through a nebulizer for 5-10 minutes;
berodual 1-2 ml (20-40 drops) through a nebulizer for 5-10 minutes;
.
ventolin 1.25-2.5 mg (1/2-1 nebula) via nebulizer for 5-10 minutes or salgim 1.25-2.5 mg (1/4-1/2 vial).
Berodual 0.5 ml - 10 drops. (children under 6 years old) and 1 ml - 20 drops (children over 6 years old) through a nebulizer for 5-10 minutes;
Evaluate therapy after 20 minutes
If the effect is achieved, repeat the same inhalation of the bronchodilator.
ventolin 2.5-5.0 mg (1-2 nebulas) or salgim 2.5-5.0 (1/2-1 vial) mg via nebulizer for 5-10 minutes
berodual 1-3 ml (20-60 drops) through a nebulizer for 5-10 minutes;
prednisolone oral mg, IV 60-90 mg or methylprednisolone IV; or pulmicort through a nebulizer mgk (1-2 nebulas) for 5-10 minutes
Evaluate therapy after 20 minutes
If the effect is unsatisfactory, repeat a similar inhalation of the bronchodilator
ventolin 2.5 mg (1 nebula) via nebulizer for 5-10 minutes or salgim (1/2 vial)
Berodual 0.5 ml - 10 drops. in children under 6 years of age and 1 ml - 20 drops (in children over 6 years of age) through a nebulizer for 5-10 minutes;
prednisolone - oral; IV 1 mg/kg
pulmicort (1/2-1 nebulamkg) through a nebulizer for 5-10 minutes;
Evaluate therapy after 20 minutes
If the effect is unsatisfactory, repeat a similar inhalation of the bronchodilator
Hospitalization for children in a hospital
ventolin, salgim or berodual in the same doses and prednisolone oral mg, intravenous mg (or methylprednisolone intravenous mg and pulmicort through a nebulizer mcg 1-2 nebulas for 5-10 minutes.
Ventolin or Salgim or Berodual in the same doses and prednisolone for children - intravenous mg or orally 1-2 mg/kg
pulmicort via nebulizer 000 mcg for 5-10 minutes.
Hospitalization
ventolin, salgim or berodual in the same doses and intravenous mg prednisolone (or intravenous mg methylprednisolone and pulmicort through a nebulizer mcg 1-2 nebulas for 5-10 minutes;
If ineffective, tracheal intubation, mechanical ventilation
ventolin or salgim or berodual in the same doses and prednisolone for children - at least mg IV or 1-2 mg/kg orally
pulmicort through a nebulizer for 5-10 minutes;
Tracheal intubation, mechanical ventilation
2. Hospitalization in the hospital
* If therapy for severe exacerbation is ineffective and there is a threat of respiratory arrest, it is possible to administer adrenaline to adults 0.1% - 0.5 ml subcutaneously. Children 0.01 ml/kg but not more than 0.3 ml
** In the absence of nebulizers or at the persistent request of the patient, it is possible to administer aminophylline 2.4% solution 10.0-20.0 ml intravenously for 10 minutes.
***Life-threatening signs: cyanosis, silent lung, weakened breathing, general weakness, in older children PEF is less than 33%. In this case, immediate hospitalization, use of beta-2 agonists in the required dose and frequency, oral prednisolone, oxygen therapy
Criteria for the effectiveness of the treatment:
1. A response to therapy is considered “good” if:
the condition is stable, shortness of breath and the amount of dry wheezing in the lungs have decreased; PSV
increased by 60 l/min, in children - by 12-15% from the original.
2. The response to therapy is considered “incomplete” if:
the condition is unstable, the symptoms are the same, areas with
poor respiratory conductivity, no increase in PSV.
3. A response to therapy is considered “poor” if:
symptoms remain the same or increase, PEF worsens.
Table 4. For the treatment of bronchial asthma
respiratory depression due to central muscle relaxant action
depression of the respiratory center
1st generation antihistamines
aggravate bronchial obstruction by increasing the viscosity of sputum, the affinity of diphenhydramine for H1-histamine receptors is much lower than that of histamine itself, histamine that has already bound to the receptors is not displaced, but only has a preventive effect, histamine does not play a leading role in the pathogenesis of an attack of bronchial asthma.
The effect has not been proven; only adequate rehydration is indicated to replenish fluid loss through sweat or due to increased diuresis after using aminophylline
Non-steroidal anti-inflammatory drugs (aspirin)
contraindicated in “aspirin” asthma, risk of aspirin intolerance
COMMON THERAPY ERRORS.
During exacerbation of asthma, the use of non-selective beta-agonists such as ipradol and asthmapent is undesirable due to high risk development of side effects. Traditionally used antihistamines (diphenhydramine, etc.) are ineffective for the treatment of bronchial obstruction, since their affinity for H1-histamine receptors is much lower than that of histamine itself and they do not displace histamine that has already bound to the receptors. In addition, histamine does not play a leading role in the pathogenesis of an asthma attack. The use of adrenaline, although effective, is fraught with serious side effects. Currently, when there is a wide choice of selective adrenergic agonists, the use of epinephrine is justified only for the treatment of anaphylaxis. The use of corglycon is unjustified due to its ineffectiveness in right ventricular failure. The combination of corglycone with aminophylline increases the risk of developing digitalis arrhythmias (including ventricular ones). In addition, there is no relationship between the dose and the effect of cardiac glycosides on sinus node activity, so their effect on heart rate during sinus rhythm is unpredictable.
According to modern concepts, hydration with the introduction of large amounts of liquid is ineffective (only rehydration is indicated to replenish fluid losses through sweat or due to increased diuresis after using aminophylline).
The use of narcotic analgesics is absolutely unacceptable due to the threat of depression of the respiratory center. The use of atropine is also not recommended due to possible disruption of the drainage function of the bronchi due to inhibition of the mucociliary system and increased viscosity of secretions in the bronchi.
Magnesium sulfate has certain bronchodilator properties, but its use as a means to relieve asthma attacks is not recommended.
An attack of suffocation is often accompanied by severe emotional disorders (fear of death, etc.), but the use of tranquilizers that depress breathing due to a central muscle relaxant effect is contraindicated.
Finally, an erroneous tactic is the use of aminophylline after adequate inhaled therapy with beta-2-agonists, as well as repeated intravenous injections (especially in patients receiving long-acting theophyllines) - the risk of side effects (tachycardia, arrhythmia) from such treatment outweighs the benefits of administration of aminophylline. Late administration of glucocorticoids (often in inadequate doses) in this situation is due to exaggerated fear of their use.
INDICATIONS FOR HOSPITALIZATION:
Hospitalization is indicated for patients with severe exacerbation of asthma and the threat of respiratory arrest; in the absence of a rapid response to bronchodilation therapy or in the event of further deterioration of the patient’s condition during the treatment started; with long-term use or recently discontinued use of systemic corticosteroids. Patients who have been admitted to the department several times should also be sent to the hospital. intensive care within the last year; patients not adhering to the asthma treatment plan and patients suffering from mental illness.
Clinical example of the effectiveness of nebulizer therapy .
Pneumonia (P) is an acute infectious disease of predominantly bacterial etiology, characterized by focal damage to the respiratory parts of the lungs with intra-alveolar exudation, detected by physical and/or x-ray examination and expressed in varying degrees by a febrile reaction and intoxication.
ETIOLOGY AND PATHOGENESIS .
P are caused by an infectious agent. Most often these are pneumococci, influenza bacillus, streptococci, staphylococci, mycoplasma and chlamydia. The widespread and not always justified use of antibiotics, especially broad-spectrum antibiotics, has led to the selection of resistant strains and the development of antibiotic resistance. Viruses are also capable of causing inflammatory changes in the lungs, affecting the tracheobronchial tree, creating conditions for the penetration of pneumotropic bacterial agents into the respiratory sections of the lungs.
The main route of infection is the airborne route of penetration of pathogens or aspiration of secretions containing microorganisms from the upper respiratory tract.
Less common is the hematogenous spread of pathogens (endocarditis of the tricuspid valve, septic thrombophlebitis of the pelvic veins) and the direct spread of infection from adjacent tissues (liver abscess) or infection from penetrating wounds chest.
CLINICAL PICTURE AND CLASSIFICATION.
Depending on the conditions of occurrence, clinical course, state of the patient’s immunological reactivity, the following types of P are distinguished:
Community-based (home, outpatient)
Hospital (nosocomial, in-hospital)
Against the background of immunodeficiency conditions
This classification is used to justify empirical therapy. Detailing P taking into account risk factors (chronic alcohol intoxication, against the background of COPD, viral infections, malignant and systemic diseases, chronic renal failure, previous antibiotic therapy, etc., allows you to take into account the entire range of possible pathogens and increases the targeting of initial antibiotic therapy
The clinical picture of P is determined both by the characteristics of the pathogen and the condition of the patient and consists of extrapulmonary symptoms and signs of damage to the lungs and bronchi.
1) Bronchopulmonary: cough, shortness of breath, chest pain, sputum production, sometimes hemoptysis, dullness of percussion sound, weakening of vesicular or bronchial breathing, crepitus, pleural friction noise;
2) Extrapulmonary: hypotension, weakness, tachycardia, sweating, chills, fever, confusion, acute psychosis, meningeal symptoms, decompensation of chronic diseases
In patients with chronic alcohol intoxication or severe concomitant diseases ( diabetes mellitus, congestive heart failure, cerebral infarction, etc.) or in the elderly, extrapulmonary symptoms may prevail over bronchopulmonary ones.
When P is localized in the lower parts of the lungs and when the diaphragmatic pleura is involved in the process (with lobar pneumonia- pleuropneumonia), pain can radiate into the abdominal cavity, simulating the picture of an acute abdomen.
In some cases, pleuropneumonia must be differentiated from pulmonary infarction, which is also characterized by the sudden onset of pain, often hemoptysis, and suffocation. However, at the onset of the disease, the presence of high temperature and intoxication are not pathognomonic. In these patients, it is possible to identify possible sources of thromboembolism (thrombophlebitis lower limbs, heart disease, post-infarction cardiosclerosis). When recording an ECG, symptoms of overload of the right heart are revealed (blockade of the right bundle branch, sign S I -Q III.).
For spontaneous pneumothorax acute development pain syndrome can be combined with increasing respiratory failure (tension spontaneous pneumothorax). Percussion reveals tympanitis, weakening of breathing, sometimes an increase in volume and limitation of respiratory excursions of the corresponding half of the chest.
Complications of P are pleurisy, abscess formation, pyopneumothorax and pleural empyema, adult respiratory distress syndrome, infectious toxic shock, broncho-obstructive syndrome, vascular insufficiency. In severe cases with severe intoxication, in weakened patients, the development of sepsis, infective endocarditis, myocardial and kidney damage is possible.
Lobar pneumonia, obligately associated with pneumococcal infection, is one of the most severe forms P. It is characterized by: acute onset of the disease with tremendous chills, cough, chest pain when breathing, rusty sputum, distinct percussion and auscultation changes in the lungs, a critical drop in body temperature; the development of hypotension, acute vascular insufficiency, respiratory distress syndrome in adults, infectious-toxic shock is possible.
With staphylococcal infections, which are more common during influenza epidemics, severe intoxication and purulent complications develop.
In the elderly and in people with alcohol dependence, they are often caused by gram-negative flora, in particular Klebsiella pneumoniae. With these Ps, extensive damage to the lung tissue with destruction, purulent complications, and intoxication is observed.
LIST OF QUESTIONS FOR A PATIENT WITH PNEUMONIA.
1) Time of onset of the disease.
2) Presence of risk factors aggravating the course of P
Chronic diseases, bad habits, etc.
3) Finding out the epidemiological history.
Identifying signs of a possible infectious disease.
4) Duration and nature of the temperature increase.
5) The presence of cough, sputum, its nature, hemoptysis.
6) The presence of pain in the chest, its connection with breathing, coughing
7) Is there shortness of breath, attacks of suffocation?
DIAGNOSTIC CRITERIA FOR PNEUMONIA.
1. The patient’s complaints of cough, sputum production, chest pain, shortness of breath
2. Acute onset of the disease
3. Changes during percussion (dullness of percussion sound) and auscultation (weakening of vesicular breathing, bronchial breathing, crepitus, pleural friction noise) of the lungs, manifestations of broncho-obstruction
4. Increase in temperature
5. Symptoms of intoxication
When examining a patient, it is necessary to measure temperature, respiratory rate, blood pressure, heart rate; palpate the abdomen to identify symptoms of decompensation of concomitant diseases.
If you suspect AMI, PE, in old age, with concomitant atherosclerosis, it is necessary to conduct an ECG study.
Detection of pneumonic infiltration during radiographic examination confirms the diagnosis of P.
Data from laboratory tests (peripheral blood analysis, biochemical studies), determination of blood gas composition are important for assessing the severity of the patient’s condition and choosing therapy.
Cytological examination of sputum makes it possible to clarify the nature of the inflammatory process and its severity.
Bacteriological examination of sputum, bronchial contents, and blood is important for the correction of antibacterial therapy, especially in severe cases of P.
Clinical example. Patient V., 44 years old, called the SS and NMP team due to the sudden onset of chills, an increase in temperature to 38.5, sharp pain in the right side, aggravated by breathing and movement. History of alcohol abuse.
He was hospitalized with a diagnosis of acute cholecystitis. During examination in the emergency department, surgical pathology was excluded, but dullness of percussion sound on the right in the lower parts of the lungs was revealed, as well as increased breathing and bronchophony there. The emergency department doctor suspected pneumonia. X-ray examination confirmed the diagnosis of lower lobe prolateral pleuropneumonia. Thus, in this case, in a patient with right-sided pleuropneumonia, pleural pain radiated to the right hypochondrium and imitated the picture of acute cholecystitis.
For a physician of SUI, the division of P according to severity is of great importance, which makes it possible to identify patients who require hospitalization and intensive care at the prehospital stage. The main clinical criteria for the severity of the disease are the degree of respiratory failure, the severity of intoxication, the presence of complications, and decompensation of concomitant diseases.
Criteria for severe pneumonia (Niederman et al., 1993).
1. Respiratory rate > 30 per minute.
2. Temperature above 38.5 C
3. Extrapulmonary foci of infection
4. Impaired consciousness
5. The need for artificial ventilation of the lungs
6. State of shock (SBP less than 90 mmHg or DBP less than 60 mmHg)
7. The need to use vasopressors for more than 4 hours.
8. Diuresis< 20 мл/ч или проявления острой почечной недостаточности.
Patients with risk factors for complications and death are also subject to hospitalization.
Risk factors that increase the likelihood of complications and mortality from pneumonia (Niederman et al., 1993).
1. Chronic obstructive pulmonary diseases
2. Diabetes mellitus
3. Chronic renal failure
4. Left ventricular heart failure
5. Chronic liver failure
6. Hospitalizations during the previous year.
7. Swallowing problems
8. Violation of higher nervous functions
12.Age over 65 years
Patients with P of moderate and severe course, with a complicated course, in the presence of risk factors, are subject to hospitalization. A number of patients at the prehospital stage may develop symptoms that require correction by a doctor of SUI.
ALGORITHM OF DOCTOR'S TACTICS SYNMP IN PNEUMONIA
Arterial hypotension in patients with lobar P (pleuropneumonia) occurs due to a generalized decrease in the tone of the smooth muscles of the walls of arterioles and small arteries and a decrease in total peripheral resistance. According to some authors, the reason for this is the immediate response of the vascular wall during an anaphylactic reaction of a sensitized organism to the breakdown products of pneumococcus, which in this case act not as toxins, but as antigens.. Patients with lobar P should be hospitalized in therapeutic departments in a lying position. Before hospitalization, you should not start antibacterial therapy or prescribe antipyretic or analgesic drugs, as this can lead to a drop in blood pressure, which is especially dangerous when transporting the patient.
To ensure maintenance of SBP at 100 mmHg. fluids are administered (iv drip isotonic solutions of sodium chloride, dextrose, dextran 40 in a total volume of 0 ml).
Acute respiratory failure - adult respiratory distress syndrome (ARDS). ARDS often develops in sepsis, bacterial shock, and in patients with immunodeficiency (chronic alcohol intoxication, neutropenia, drug addiction, HIV infection). In response to infection, a local inflammatory reaction develops, leading to vasodilation, increased permeability of the vascular wall, release of a number of cellular components (lysosomal enzymes, vasoactive amines, prostaglandins), and the complement system is activated, attracting neutrophils into the pulmonary microcirculation. Granulocytes and mononuclear cells accumulate at the site of injury and form a conglomerate with local fibroblasts and endothelial cells. Adhesion of neutrophils to the endothelium stimulates the release of toxic substances that damage it. As a result of damage to the endothelium of the pulmonary capillaries, pulmonary edema develops, clinically manifested by severe shortness of breath and severe hypoxemia, resistant to oxygen therapy, which causes an increased need for oxygen. Patients require mechanical ventilation. Diuretics are ineffective for pulmonary edema in patients with ARDS. IV administration of furosemide can improve gas exchange without reducing the degree of pulmonary edema, which may be explained by the redistribution of pulmonary blood flow (increasing it in well-ventilated areas of the lungs).
The main goal of therapy in the treatment of respiratory failure is to maintain tissue oxygenation. In ARDS, oxygen consumption in the periphery is directly proportional to its delivery. For arterial hypotension and decreased cardiac output, intravenous infusion of dobutamine in doses of kg/kg min is indicated.
Peripheral vasodilators worsen pulmonary hypoxemia by increasing intrapulmonary shunting. Arterial hemoglobin oxygen saturation is maintained above 90%, which is sufficient to maintain oxygen delivery to peripheral tissues. Currently, it is considered unproven that the use of glucocorticosteroids in high doses reduces the inflammatory process in the lungs. At the same time, high doses of glucocorticosteroids increase the risk of developing a secondary infection.
Infectious - toxic shock can complicate the course of lobar (pleuropneumonia), staphylococcal P., occurs in P. caused by gram-negative flora and in patients with risk factors. Treatment at the prehospital stage consists of infusion therapy and dobutamine administration. For more details, see the corresponding section.
Broncho-obstructive syndrome- see the corresponding section.
Pleural pain sometimes they are so severe that they require the administration of analgesics. The most rational use of drugs from the NSAID group (paracetamol 0.5 g per os, ibuprofen - 0.2 g per os; aspirin 0.5 - 1.0 g per os or parenterally in the form of lysine monoacetylsalicylate 2.0 g; diclofenac - 0.075 g per os or parenterally intramuscularly deep into the gluteal muscle 0.075 g). Analgin, which is still widely used as an analgesic, much more often causes serious undesirable effects (acute anaphylaxis, inhibition of hematopoiesis) and therefore cannot be recommended for use.
In patients with lobar P (pleuropneumonia), the administration of analgesics can provoke hypotension and it is better to refrain from their use at the prehospital stage.
PARACETAMOL. The maximum concentration in the blood is achieved 0.5-2 hours after administration, the duration of action is 3-4 hours.
Indications for use are mild to moderate pain, temperature above 38 C.
For liver and kidney diseases, chronic alcohol intoxication the drug should be used with caution.
Contraindications include a history of hypersensitivity reactions to the drug.
Undesirable effects (rarely develop): skin rash, cytopenias, liver damage (less commonly, kidney damage) in case of overdose, especially when drinking alcohol. With prolonged use, the development of acute pancreatitis is possible.
When combined with prokinetics and long-term combined use with indirect anticoagulants, the effect of prokinetics and anticoagulants may be enhanced.
Doses: adults are prescribed 0.5-1.0 g orally every hour, the maximum daily dose is 4 g.
ASPIRIN ( acetylsalicylic acid). The maximum concentration in the blood is achieved 2 hours after administration. Duration of action 4 hours.
Indications: mild to moderate pain, temperature above 38 C
In case of asthma, a history of allergic reactions, liver and kidney diseases, dehydration, during pregnancy and in elderly patients, the drug should be used with caution.
In children under 12 years of age, nursing mothers, with peptic ulcers, hemophilia, hypersensitivity to aspirin and other NSAIDs, severe renal and liver failure, and in the 3rd trimester of pregnancy, the use of aspirin is contraindicated.
Undesirable effects include gastrointestinal dyspepsia, bronchospasm, and skin reactions. With long-term use, ulcerogenic effects, increased bleeding time, thrombocytopenia, and hypersensitivity reactions are possible.
When combined with other NSAIDs and glucocorticosteroids, the risk of developing undesirable effects increases; with anticoagulants, the risk of bleeding increases. Combined use with cytostatics and antiepileptic drugs increases the toxicity of these drugs.
Doses: adults - 0.25 - 1.0 g every hour, maximum dose 4 g / day.
Lysine monoacetylsalicylate is an aspirin derivative for parenteral administration. Surpasses it in the speed of development and strength of the analgesic effect. Single dose 2 g, maximum - up to 10 g per day. Adverse reactions are similar to the effects of aspirin.
IBUPROFEN The maximum concentration in the blood develops 1-2 hours after oral administration, the analgesic and antipyretic effects last up to 8 hours. Ibuprofen is prescribed for mild to moderate pain, temperature above 38 C
Contraindications are hypersensitivity to NSAIDs, severe renal and liver failure, peptic ulcer, third trimester of pregnancy.
Undesirable effects: gastrointestinal dyspepsia, hypersensitivity reactions, bronchospasm; cytopenias, autoimmune syndromes, with a course of treatment, ulcerogenic effects, worsening renal and hepatic failure, headache, dizziness, hearing loss, orientation, photosensitivity, rarely papillary necrosis, aseptic meningitis.
Combined use with other NSAIDs and glucocorticosteroids increases the risk of developing undesirable effects. When combined with fluoroquinolones, it is possible to develop a convulsive syndrome. When combined with diuretics, ACE inhibitors, beta blockers, there is a decrease in the therapeutic effect of these drugs and an increase in the risk of side effects. When combined with cytostatics, antiepileptic drugs, lithium drugs, their effects increase; when combined with anticoagulants, the risk of hemorrhagic complications increases; when combined with cardiac glycosides, NSAIDs can increase their plasma concentration.
DICLOFENAC. The maximum concentration in the blood develops after 0.5 - 2 hours. after oral administration and after min. after intramuscular injection.
Indications - see above
Contraindications: see above, as well as exacerbation of chronic intestinal diseases, porphyria.
Interactions: typical for drugs of the NSAID group (see above).
Doses: mg/day in two to three doses orally, 75 mg intramuscularly deep into the gluteal muscle.
Timely initiation of antibiotic therapy has a decisive influence on the course of P and its outcome. When a patient is admitted to a hospital, the choice of antibiotic is made taking into account the above clinical features.
ANTIBIOTIC THERAPY FOR PNEUMONIA.
Most common pathogens
First line antibiotics
P non-severe course in patients under 60 years of age with a clear medical history
P in patients 60 years of age and older and/or with concomitant pathology
II generation cephalosporins
P severe course
III generation cephalosporins
P in immunocompromised patients
III generation antipseudomonas cephalosporins
(antipseudomonas penicillins) + aminoglycosides,
III generation cephalosporins
amoxicillin - clavulanate + aminoglycoside,
5.3 PULMONARY ARTERY THROMBOEMBOLISM
Pulmonary embolism (PE) is a syndrome caused by embolism of the pulmonary artery or its branches by a thrombus and is characterized by severe cardiorespiratory disorders, and when small branches are blocked, by symptoms of the formation of hemorrhagic pulmonary infarctions.
ETIOLOGY AND PATHOGENESIS.
Most common cause and the source of embolization of the branches of the pulmonary artery are thrombi from the deep veins of the lower extremities in phlebothrombosis (about 90% of cases), much less often - from the right parts of the heart in heart failure and hyperextension of the right ventricle. Predisposing factors are prolonged immobility, surgery on the pelvic organs or lower parts abdominal cavity, trauma, obesity, intake oral contraceptives, pregnancy, malignant neoplasms, myocardial infarction, dilated cardiomyopathy, congestive heart failure, atrial fibrillation, sepsis, stroke, spinal cord injury, erythremia, nephrotic syndrome.
CLINICAL PICTURE, CLASSIFICATION AND DIAGNOSTIC CRITERIA.
There are no clinical signs pathognomonic for PE; the diagnosis at the prehospital stage can be suspected based on a combination of anamnestic data, the results of an objective examination and electrocardiographic symptoms.
CLINICAL-ELECTROCARDIOGRAPHIC PICTURE OF THE BODY.
Sudden onset with the appearance of shortness of breath (72% of cases) and acute chest pain (86%), often acute vascular insufficiency with the appearance of pallor, cyanosis, tachycardia (87%), a drop in blood pressure until the development of collapse and loss of consciousness (12%) . With the development of a pulmonary infarction, in 10-50% of cases, hemoptysis appears in the form of streaks of blood in the sputum. On examination, signs may be detected pulmonary hypertension and acute pulmonary heart disease - swelling and pulsation of the neck veins, expansion of the borders of the heart to the right, pulsation in the epigastrium, increasing with inspiration, emphasis and bifurcation of the second tone on the pulmonary artery, enlargement of the liver. Dry wheezing may occur over the lungs.
ECG signs (appear in 25% of cases).
Signs of overload of the right atrium (P-pulmonale - a high pointed P wave in leads II, III, aVF) and the right ventricle (McGean-White syndrome - a deep S wave in lead I, a deep Q wave and negative wave T in lead III with possible elevation of the ST segment; incomplete blockade of the right bundle branch),
Thus, despite the lack of clear diagnostic criteria, PE can be diagnosed at the prehospital stage based on a thorough comprehensive assessment of the medical history, examination data and ECG. The final verification of the diagnosis is carried out in the hospital. Sometimes an X-ray examination reveals a high dome of the diaphragm, disc-shaped atelectasis, congestion of one of the roots of the lungs or a “cut off” root, depletion of the pulmonary pattern over the ischemic area of the lung, a peripheral triangular shadow of inflammation or pleural effusion, but in most patients there are no radiographic changes. The diagnosis is confirmed by pulmonary perfusion scintigraphy, which allows one to detect characteristic triangular areas of decreased pulmonary perfusion (method of choice), as well as X-ray contrast pulmonary angiography (pulmonary angiography), which reveals areas of reduced blood flow.
Clinically, acute, subacute and recurrent course of pulmonary embolism is distinguished (Table 13).
OPTIONS FOR BODY FLOW.
Characteristic clinical features
Sudden onset, chest pain, shortness of breath, drop in blood pressure, signs of acute cor pulmonale
Progressive respiratory and right ventricular failure, signs of infarction pneumonia, hemoptysis
Repeated episodes of shortness of breath, fainting, signs of pneumonia
When analyzing the clinical picture, the SUI physician should receive answers to the following questions.
1) Is there shortness of breath, and if so, how did it arise (acutely or gradually).
With PE, shortness of breath occurs acutely, orthopnea is not typical.
2) Is there pain in the chest?
May resemble angina pectoris, localized behind the sternum, and may intensify with breathing and coughing.
3) Was there any unmotivated fainting?
PE is accompanied or manifested by syncope in approximately 13% of cases.
4) Is there hemoptysis?
Appears with the development of pulmonary infarction.
5) Is there swelling of the legs (paying attention to their asymmetry).
Deep vein thrombosis of the legs is a common source of pulmonary embolism.
6) Have there been any recent surgeries, injuries, heart disease with congestive heart failure, arrhythmias, is he taking oral contraceptives, is he pregnant, is he being seen by an oncologist.
The presence of predisposing factors for pulmonary embolism (for example, paroxysmal atrial fibrillation) should be taken into account by the physician when acute cardiorespiratory disorders occur in the patient.
TREATMENT ALGORITHM
The main directions of treatment for PE at the prehospital stage include pain relief, prevention of continued thrombosis in the pulmonary arteries and repeated episodes of PE, improvement of microcirculation (anticoagulant therapy), correction of right ventricular failure, arterial hypotension, hypoxia (oxygen therapy), relief of bronchospasm.
In cases of severe pain and to relieve the pulmonary circulation and reduce shortness of breath, narcotic analgesics are used (for example, 1 ml of a 1% morphine solution IV in fractions). This allows not only to effectively relieve pain, but also to reduce the shortness of breath characteristic of pulmonary embolism. For side effects and contraindications to the use of morphine, see the “Myocardial infarction” section.
With the development of infarction pneumonia, when chest pain is associated with breathing, coughing, and body position, it is more appropriate to use non-narcotic analgesics (for example, intravenous administration of 2 ml of a 50% analgin solution).
The survival of patients with pulmonary infarction directly depends on the possibility of early use of anticoagulants. It is advisable to use direct anticoagulants - heparin intravenously in a dose of 00 IU. Heparin does not lyse the thrombus, but stops the thrombotic process and prevents the growth of the thrombus distal and proximal to the embolus. By weakening the vasoconstrictor and bronchospastic effect of thorombocyte serotonin and histamine, heparin reduces spasm of the pulmonary arterioles and bronchioles, favorably influencing the course of phlebothrombosis, heparin serves to prevent relapses of pulmonary embolism. For side effects and contraindications to the use of heparin, see the “Myocardial infarction” section.
If the course of the disease is complicated by right ventricular failure, hypotension or shock, therapy with dopamine or dobutamine is indicated (see section "Shock"). To improve microcirculation, rheopolyglucin ml is additionally administered intravenously at a rate of up to 1 ml per minute. Reopolyglucin not only increases blood volume and increases blood pressure, but also has an antiaggregation effect. If shock persists during the above treatment, they switch to pressor therapy with amino acids and dopamine diluted in 400 ml of rheopolyglucin, while 1 ml of the resulting solution contains 500 mcg of dopamine, one drop contains 25 mcg. The initial rate of administration is 5 mcg/kg min under blood pressure control with a gradual increase in dose to 15 mcg/kg min. 2 ml of 0.2% norepinephrine solution is diluted in 250 ml of isotonic sodium chloride solution and administered at an initial rate of drops per minute (when hemodynamics stabilize, the rate is reduced to drops per minute).
For pulmonary embolism, long-term oxygen therapy is indicated. With the development of bronchospasm and stable blood pressure (SBP not lower than 100 mm Hg), a slow (stream or drip) intravenous administration of 10 ml of a 2.4% solution of aminophylline is indicated. Eufillin reduces pressure in the pulmonary artery, has antiplatelet properties, and has a bronchodilator effect.
COMMON THERAPY ERRORS.
In case of pulmonary infarction in patients with pulmonary embolism, the use of hemostatic agents is inappropriate, since hemoptysis occurs against the background of thrombosis or thromboembolism.
It is also inappropriate to prescribe cardiac glycosides for acute right ventricular failure, since these drugs do not affect the right side of the heart alone and do not reduce afterload on the right ventricle. Digitalization, however, is fully justified in patients with a tachysystolic form of atrial fibrillation, which is often the cause of thromboembolism.
INDICATIONS FOR HOSPITALIZATION.
If PE is suspected, hospitalization is mandatory.
5.4 PURPENT DISEASES OF THE LUNG AND PLEURUM.
Acute abscess, gangrene of the lung is a purulent-necrotic melting of the pulmonary parenchyma (with gangrene, the necrosis is more extensive, without clear boundaries, tending to spread; clinically the disease is very severe general condition patient).
ETIOLOGY AND PATHOGENESIS.
The main causes of destructive changes in the lungs are: complication of acute P (often post-influenza) - in 63-95% of cases; aspiration (infection entering the lung from the oral cavity - carious teeth, periodontal disease, chronic tonsillitis). In recent years, it has been established that in 50-60% of observations, exclusively anaerobic microflora is aspirated (Fusobact. nucleatum, Fusobact. necrophorum, Bacter. fragilis, Bacter. melaninogenus, etc.).
In addition, the most common pathogens are: hemolytic staphylococcus and gram-negative microflora.
Among other reasons for the development of acute abscess and gangrene of the lung, it is necessary to point out the hematogenous-embolic route (in 0.8-9.0% of cases), post-traumatic factor, obstruction of the bronchi (tumor, foreign body).
It should be emphasized that acute abscesses and gangrene of the lung most often develop in patients weakened by chronic diseases, in persons with alcohol dependence; for severe systemic diseases, against the background of CNLD.
acute abscesses and gangrene of the lung is varied and depends on the size of necrotic areas of lung tissue, complicated or uncomplicated course, patient’s age, concomitant pathology, individual characteristics of the body, etc. With a lung abscess in the initial (first) period of the disease (before opening the abscess into the bronchus), the severity of the patient’s condition is determined by purulent intoxication due to the impossible evacuation of pus and necrotic masses from the destruction cavities naturally through the draining bronchi. Patients complain of high fever, chills, pain in the corresponding half of the chest, cough with scanty sputum. On physical examination, breathing on the “sick” side is weakened and the percussion sound is shortened. With severe damage to the lung tissue, crepitating rales may be heard. X-ray data indicate inflammatory infiltration of the lung without clear boundaries.
The first period of illness lasts on average 7-10 days.
In the second period of the disease (after opening the abscess into the bronchus), the pathognomonic symptom will be copious discharge of purulent sputum, often with an unpleasant odor, “a mouthful.” If arrosion of the bronchial vessels occurs, pulmonary hemorrhage will occur. At the same time, the temperature decreases, intoxication decreases, and health improves. A physical examination may reveal a cavity in the lung upon percussion, and upon auscultation, bronchial breathing with an amphoric tint. X-ray semiotics are characteristic - a rounded cavity surrounded by an infiltrative shaft, with a horizontal level of liquid in its lumen.
Sputum (macroscopically) has three layers: pus, cloudy liquid, and a foamy layer.
Lung gangrene is characterized by more extensive necrosis of the pulmonary parenchyma (than with an abscess), without clear boundaries, occupying several segments, a lobe or the entire lung. The disease progresses rapidly, with hectic fever, severe intoxication, chest pain on the affected side, shortness of breath. Sputum is produced that is dirty gray or brown (more often) in color with a fetid odor, detectable at a distance, often with sequestration of lung tissue. Sometimes the disease is complicated by pulmonary hemorrhage (hemoptysis), which can be fatal. Over the affected area, a shortening of the percussion sound and sharply weakened (or bronchial) breathing are determined. Blood and sputum tests show changes characteristic of an acute abscess, but more pronounced. X-rays of the lungs reveal massive infiltration without clear boundaries, occupying a lobe or the entire lung. If a decay cavity has appeared and it communicates with the lumen of the bronchus, then radiologically this is determined in the form of irregularly shaped clearing (single or multiple), possibly with the presence of free or parietal sequesters.
It should be emphasized that acute abscess and gangrene of the lung are fraught with the development of a number of severe, sometimes fatal complications: arrosive bleeding (especially when the process is localized in the hilar zones), pyopneumothorax (with subpleural abscesses), sepsis, pericarditis, damage to the opposite lung.
Acute purulent pleurisy
Acute purulent pleurisy is inflammation of the pleura, characterized by the formation of purulent exudate.
Acute purulent pleurisy (pleural empyema) can be primary (after penetrating chest injury, lung surgery, diagnostic thoracoscopy, when applying an artificial pneumothorax) or secondary (with complications of purulent-inflammatory diseases of the lungs and opening of subpleural abscesses). In the latter case, along with pus, air also enters the pleural cavity (pyopneumothorax). The bacterial spectrum of the contents of the pleural cavity in 62.5% of patients indicates an association of pathogens from 2-5 different species (staphylococcus, Proteus, Escherichia coli and Pseudomonas aeruginosa). Bacteriological studies in 28% of cases revealed various types of non-clostridial anaerobes (bacteroides, fusobacteria, putrid streptococcus, etc.).
Acute secondary pleural empyema is characterized by the fact that the inflammatory process from the lung (pneumonia, abscess, cavity, festering cyst) passes to the pleura, usually on the same side. There are sharp pains in the corresponding half of the chest, a rise in temperature to 38.5-39 C, signs of respiratory failure (due to compression of the lung by pus and purulent-destructive changes in the lung tissue itself), cough with the release of purulent sputum. An objective examination reveals symptoms of intoxication, limitation of respiratory movements of one half of the chest, dullness of percussion sound and a sharp weakening of breathing (or it is not carried out at all, which happens more often). X-ray examination indicates darkening on the side of the empyema, displacement of the mediastinum to the opposite side. In case of pyopneumothorax, the horizontal level and the gas above it are determined. Depending on the amount of purulent fluid in the pleural cavity, and accordingly the degree of collapse of the lung, limited, subtotal and total pyopneumothorax are distinguished.
Spontaneous nonspecific pneumothorax
Spontaneous pneumothorax (SP) is an accumulation of air in the pleural cavity. It develops, as a rule, without previous symptoms (in conditions of complete health). Air entry occurs from the defect(s) of subpleurally located air bullae. Most researchers believe that the formation of bullae is associated with congenital inferiority of the lung parenchyma. IN Lately There have been reports of cases of a familial form of the disease - hereditary spontaneous pneumothorax (hereditary emphysema). It is believed to be caused by alpha-1 antitrypsin deficiency, which is inherited in an autosomal recessive manner. The right lung is most often affected; bilateral (usually alternating) pneumothorax is observed in 17.7% of cases.
spontaneous pneumothorax is quite typical: the appearance of sharp pain in the corresponding half of the chest (often without apparent reason), shortness of breath (its severity depends on the degree of lung collapse). The pain radiates to the shoulder, neck, epigastric region, behind the sternum (especially with left-sided pneumothorax), often simulating angina pectoris or myocardial infarction. A physical examination reveals shortness of breath, tympanitis on percussion on the affected side, weakening (or absence) of breathing on auscultation. The diagnosis is confirmed by X-ray data: pneumothorax of varying severity is observed on the affected side and the lung is collapsed. With a large pneumothorax, there may be a shift of the mediastinum to the opposite side. A thorough examination of the lungs is necessary to determine the possible cause of pneumothorax - bullous emphysema, tuberculous cavity, abscess (with these diseases, pneumothorax is a complication). Sometimes large subpleurally located bullae of the first segment can be identified on radiographs.
PRINCIPLES OF TREATMENT MEASURES.
Intervention at the prehospital stage is limited to symptomatic therapy.
1) Pain syndrome - before transporting the patient to the hospital, in case of severe pleural pain, non-narcotic analgesics - ketarolac, tramadol - can be administered. With pneumothorax, the intensity of the pain syndrome may require the administration of narcotic analgesics. The drug of choice in this case should be considered a 2% solution of promedol. It must be taken into account that more powerful drugs, morphine and fentanyl, have a depressant effect on the respiratory center and can worsen hypoxia.
2) Arterial hypotension - transportation of patients to the hospital in order to avoid the development of orthostatic collapse should be carried out in a supine position. With low blood pressure (SBP< 100) целесообразно во время транспортировки проводить в/в инфузию раствора полиглюкина.
3) Respiratory failure - develops with massive damage to the lung tissue. To reduce the degree of hypoxia during transportation, humidified oxygen is inhaled through nasal cannulas or a mask.
4) The increase in respiratory failure during pneumothorax may be associated with the valve mechanism of its development. In this case, tension pneumothorax requires emergency decompression, which is performed by inserting one or more large-diameter injection needles into the pleural cavity. This manipulation requires preliminary anesthesia by administering 1 ml of a 2% promedol solution.
INDICATIONS FOR HOSPITALIZATION.
Suppurative lung diseases, as well as cases of pneumothorax, require emergency hospitalization of patients in the thoracic surgery department.
Bronchial asthma (BA) is a chronic inflammatory disease of the airways (AD), in which many cells and cellular elements play a role. Chronic inflammation causes the development of bronchial hyperreactivity, leading to repeated episodes of generalized bronchial obstruction of varying severity, reversible spontaneously or with treatment. According to WHO, about 300 million people worldwide suffer from asthma.
Therapy of asthma involves the predominant use of inhaled forms of medications, which are divided into drugs for stopping an attack and drugs for long-term control. β-adrenergic receptor agonists, available on the pharmaceutical market in various dosage forms, have properties to stop an asthma attack and control the course of the disease.
All processes occurring in the body, starting from the cellular level, are strictly coordinated with each other in time, speed and place of occurrence. This consistency is achieved due to the presence of complex regulatory mechanisms, which is carried out through the secretion of certain substances by some cells and their reception by others. The vast majority of such substances (neurotransmitters, hormones, prostaglandins) act on the cell without penetrating into it, but by interacting with special protein macromolecules - receptors built into the outer surface of the cell (surface membrane).
Cell membrane is a bimolecular layer of phospholipids sandwiched between two layers of adsorbed proteins. The non-polar hydrophobic ends of the phospholipid molecules are directed towards the middle of the membrane, and the polar hydrophilic ends are directed towards the edges separating it from the aqueous phase. Large protein molecules are included in the lipid bilayer matrix. Some proteins penetrate the entire thickness of the membrane, while others are embedded in only one of the layers (neurotransmitter receptors, adenylate cyclase). The membrane has some fluidity, and proteins and lipid molecules can move along its plane. The fluidity of a membrane is determined by its molecular composition and electrical properties: with an increase in cholesterol content, fluidity decreases, and with an increase in the content of unsaturated or branching hydrophobic tails of phospholipid molecules, it increases.
The influence of circulating catecholamines occurs through interaction with adrenergic receptors (AR). According to the definition of B.N. Manukhin, adrenergic receptors are functional cell formations that perceive the influence of a neurotransmitter and hormone of the adrenergic system and transform it into a specific quantitatively and qualitatively adequate reaction of the effector cell. The number of such receptors is small—a few per square micron of surface. This determines another feature of regulation - the effective quantities of regulators are negligibly small. In order to change the metabolism and functional activity of the entire cell, which includes hundreds of millions of different molecules, binding of 2-5 regulator molecules to the cell membrane is apparently sufficient. In the entire chain from the receptor to the cellular reaction in question, the signal is amplified 10-100 million times.
Adrenergic receptors were initially characterized according to their functional response to stimulation when inhibited by various pharmacological agents. They were subsequently qualified according to their affinity similarity when bound by labeled ligands. α-adrenergic receptors are defined as oligomeric proteins localized on the surface of cell membranes; β-adrenergic receptors have been identified as proteolipids and nucleoproteins. In 1948, R. Ahlquist established that adrenergic receptors are divided into two types - α and β. A. Lands in 1967 determined that there are subtypes of β-AR. The use of molecular biology methods has confirmed the heterogeneity of adrenergic receptor subtypes as products of different genes. This made it possible to further identify at least nine subtypes of adrenergic receptors: α 1A, α 1B, α 1C, α 2A, α 2B, α 2C, β 1, β 2, β 3.
β-adrenergic receptors , identified as proteolipids and nucleoproteins, are located on the sarcolemma of cells, which makes them easily accessible to the neurotransmitter and hormone of the sympathoadrenal system. β-adrenergic receptors are not stable formations, but rather a dynamic structure, the properties of which can vary in response to physiological stress, diseases, and medications. The role of receptor modulators capable of transforming α- and β-adrenergic receptors can be played by endorphins, adenyl nucleotides, prostaglandins and other substances of endogenous and exogenous origin, including cations. The entire complex of receptors must be considered as a single system that ensures the interaction of cells with the environment, since almost all studied receptor populations are functionally interconnected through systems of second messengers and the cytoskeleton.
Hormone-sensitive adenylate cyclase signaling system (ACS) plays a key role in the regulation of the most important growth and metabolic processes of the cell. The molecular mechanisms of functional coupling of proteins—components of the ACS, despite the large number of works devoted to this problem, have not been sufficiently studied; however, individual determinants responsible for the process of transmitting a hormonal signal from the receptor to the effector systems of the cell have now already been identified. In this aspect, the adrenoreactive complex has been most fully studied. According to modern views, he is complex system, localized in the plasma membrane and consisting of at least three molecular components: receptor, regulatory and catalytic. The latter is adenylate cyclase, an enzyme that catalyzes the synthesis of cyclic adenosine monophosphate (cAMP). The regulatory component by its nature is a protein that is involved in the implementation of regulatory influences on the catalytic function of adenylate cyclase by agents of non-hormonal nature - nucleotides, anions, etc.
Along with this, guanyl nucleotides are credited with the function of hormone-induced coupling of the receptor and catalytic components. There is evidence indicating the participation of membrane lipids in this process. The heterogeneity of the participants in the interface indicates its complexity. These and a number of other facts served as the basis for the assumption of the existence of an independent (fourth) component in the hormone-sensitive system, which has a coupling function. In the absence of a hormonal signal, these components exist independently of each other; in its presence, they interact, forming a temporary short-lived complex.
Activation of adenylate cyclase requires binding of the agonist to the receptor and subsequent formation of the hormone-receptor-Ns-protein complex. During the activation process, the ACS proteins move in the membrane, the efficiency of which depends on the proportion of liquid crystalline lipids. Changes in the macrostructure of the cell membrane significantly alter the effectiveness of the effects of hormonal substances. Disturbances in the cyclic nucleotide system cause changes in the sensitivity of cells to nervous and humoral influences, which, in turn, can underlie or aggravate the course of many pathological processes.
β-adrenergic receptors form complexes with a heterotrimetric guanosine triphosphate (GTP) cluster consisting of α-, β- and γ-protein subunits. The formation of this complex changes the properties of both the receptor and the G protein. Subsequently, the Gs α -GTP subunit can activate adenylate cyclase. This stimulation is carried out with the participation of guanosine triphosphatase, GTP hydrolysis and the formation of guanosine diphosphate (GDP). Gs α-GDP binds to the βγ subunits, allowing the complex to cycle again. During stress and physical activity, the production of catecholamines, which stimulate β-adrenergic receptors, increases significantly. This causes the formation of cAMP, which activates phosphorylase, which causes the breakdown of intramuscular glycogen and the formation of glucose and is involved in the activation of calcium ions. In addition, catecholamines increase membrane permeability for calcium ions and mobilize Ca 2+ from intracellular stores.
A Brief History of β-Agonists. The history of the use of β-agonists is the consistent development and introduction into clinical practice of drugs with increasingly increasing β 2 -adrenergic selectivity and increasing duration of action.
The sympathomimetic adrenaline (epinephrine) was first used in the treatment of patients with bronchial asthma in 1900. The short duration of action and a large number of side effects stimulated the search for more attractive drugs.
In 1940, isoproterenol appeared. It was destroyed in the liver as quickly as adrenaline (with the participation of catecholomethyltransferase), and therefore was characterized by a short duration of action, and the resulting metabolites (methoxyprenaline) had a β-blocking effect.
The first selective β 2 -agonist was salbutamol in 1970. Then terbutaline and fenoterol appeared. The new drugs retained their speed of action (onset after 35 minutes) with a noticeable increase in duration (46 hours). This improved the ability to control asthma symptoms during the day, but did not prevent night attacks.
The new possibility of taking individual β2-agonists orally (salbutamol, terbutaline, formoterol, bambuterol) to some extent solved the problem of nocturnal asthma attacks. However, the need to take higher doses (> 20 times) contributed to the emergence of adverse events associated with stimulation of α- and β 1 -adrenergic receptors. In addition, lower therapeutic efficacy of these drugs was also revealed.
The advent of long-acting inhaled β2-agonists salmeterol and formoterol significantly changed the possibilities of asthma therapy. The first to appear on the market was salmeterol, which lasted for 12 hours but had a slow onset. Soon it was joined by formoterol, with a rate of onset of effect similar to salbutamol. Already in the first years of use of long-acting β2-agonists, it was noted that they help reduce exacerbations of asthma, reduce the number of hospitalizations, and also reduce the need for inhaled corticosteroids.
The most effective route of administering drugs for asthma, including β 2 -agonists, is inhalation. The important advantages of this path are:
— the possibility of direct delivery of drugs to the target organ;
— minimization of undesirable effects.
Of the currently known delivery vehicles, metered-dose aerosol inhalers are the most commonly used, and metered-dose inhalers and nebulizers are less commonly used. Oral β2-agonists in the form of tablets or syrups are used extremely rarely, mainly as an additional treatment for frequent nocturnal asthma symptoms or a high need for inhaled short-acting β2-agonists in patients receiving high doses of inhaled glucocorticosteroids (ICS) (> 1000 mcg beclomethasone /day) .
The bronchi contain non-innervated β 2 -adrenergic receptors, stimulation of which causes bronchodilation at all levels of the bronchial hierarchy. β 2 receptors are widely present in the respiratory tract. Their density increases as the diameter of the bronchi decreases, and in patients with asthma, the density of β 2 receptors in the airway is higher than in healthy people. This is due to an increase in the level of cAMP and a decrease in the content of intracellular Ca 2+ in the smooth muscles of the respiratory tract. ARs are transmembrane receptors whose structure is based on a polypeptide chain of several hundred amino acids. β 2 -AR forms a hydrophobic region in the cell membrane, consisting of 7 transmembrane domains; The N-terminal region is located outside the cell, the C-terminal region is in the cytoplasm. The structure responsible for interaction with the β 2 agonist is located on the outer surface of the cell. Inside the cell, β 2 -ARs are associated with various types of regulatory G proteins. G proteins interact with adenylate cyclase, which is responsible for the synthesis of cAMP. This substance activates a number of enzymes designated as cAMP-dependent protein kinases, one of which (protein kinase A) inhibits the phosphorylation of myosin light chains, hydrolysis of phosphoinositide, activates the redistribution of calcium from intra- to extracellular space, and the opening of large calcium-activated potassium channels. In addition, β2-agonists can bind to potassium channels and directly cause relaxation of smooth muscle cells, independent of an increase in intracellular cAMP concentration.
Numerous β 2 receptors are found on the surface of mast cells, neutrophils, eosinophils, and lymphocytes.
Effects of respiratory β 2 -adrenergic agonists.β 2 -agonists are considered as functional antagonists that cause the reverse development of bronchoconstriction, regardless of the constrictor effect that has taken place. This circumstance seems extremely important, since many inflammatory mediators and neurotransmitters have a bronchoconstrictor effect.
As a result of the effect on β-adrenergic receptors localized in various parts of the DP, additional effects of β 2 -agonists are revealed, which explain the possibility of their preventive use.
Stimulation of β 2 -adrenergic receptors of epithelial cells, glandular cells, vascular smooth muscles, macrophages, eosinophils, mast cells reduces the release of inflammatory mediators and endogenous spasmogens, helps restore mucociliary clearance and microvascular permeability. Blockade of the synthesis of leukotrienes, interleukins and tumor necrosis factor-alpha by mast cells and eosinophils prevents the degranulation of mast cells and eosinophils, inhibiting the release of histamine, mucus secretion, and improves mucociliary clearance, suppresses the cough reflex, reduces permeability blood vessels. Stimulation of β 2 -adrenergic receptors of cholinergic fibers reduces bronchoconstriction caused by hyperparasympathicotonia.
Microkinetic diffusion theory G. Andersen. The duration of action and the time of onset of the bronchodilator effect are determined by the different lipophilicity of β 2 -agonists. Formoterol occupies an intermediate position in terms of lipophilicity (420 ± 40 units) between salbutamol (11 ± 5 units) and salmeterol (12,450 ± 200 units). Salmeterol penetrates the lipophilic layer of the membrane and then slowly diffuses through the membrane to the receptor, leading to its prolonged activation (with a later onset of action). Salbutamol, entering the aqueous environment of the interstitial space, quickly interacts with the receptor and activates it without forming a depot. Formoterol forms a depot in the plasma membrane, from where it diffuses into the extracellular environment and then binds to β 2 -AR.
Racemates. Selective β 2 -agonist preparations are racemic mixtures of two optical isomers R and S in a 50:50 ratio. It has been established that the pharmacological activity of R-isomers is 20-100 times higher than that of S-isomers. The R-isomer of salbutamol has been shown to exhibit bronchodilator properties. At the same time, the S-isomer has exactly the opposite properties: it has a pro-inflammatory effect, increases hyperreactivity, and enhances bronchospasm; in addition, it is metabolized much more slowly. Recently, a new nebulizer preparation was created containing only the R-isomer, effective at a dose of 25% of the racemic mixture.
Full and partial β 2 -AR agonists. The completeness of β-agonism is determined in comparison with isoprenaline, which is able to activate the receptor in the same way as natural catecholamines. Salmeterol is called “salbutamol on a stalk”: its molecule consists of an active part (which directly interacts with the receptor and is actually salbutamol) and a long lipophilic part, which provides a prolonged effect by binding to the inactive part of the receptor. In this case, partial β 2 -agonists increase the concentration of cAMP by 2-2.5 times. The “hinge” mechanism of β 2 -AR activation by salmeterol and the need to occupy 1 of its 30 possible spatial positions determine partial agonism. Formoterol is a full β 2 -AR agonist: after its use, the intracellular concentration of cAMP increases 4 times. This circumstance is clinically most pronounced in patients who do not respond to salmeterol therapy (EFORA, 2003).
Development of tolerance. Intense stimulation of β 2 -agonists of β 2 -AR leads to inhibition of signal transmission (desensitization of receptors), internalization of receptors (reduction in the number of receptors on the membrane surface), and subsequently to the cessation of the synthesis of new receptors (down-regulation). Desensitization of β 2 -AR is based on phosphorylation of the cytoplasmic regions of the receptor by cAMP-dependent protein kinases. It should be noted that β-receptors of smooth muscles of the respiratory tract have a fairly significant reserve, and therefore they are more resistant to desensitization than receptors of non-respiratory zones. Desensitization of β 2 -AR causes a decrease in response by 40% after 2 weeks of formoterol use and by 54% after a similar use of salmeterol. It has been established that healthy individuals quickly develop tolerance to high doses of salbutamol, but not to fenoterol and terbutaline. At the same time, in patients with asthma, tolerance to the bronchodilator effect of β 2 -agonists rarely appears; tolerance to their bronchoprotective effect develops much more often. H.J. van der Woude et al. (2001) found that against the background of regular use of formoterol and salmeterol by patients with asthma, their bronchodilator effect does not decrease; the bronchoprotective effect is higher for formoterol, but the bronchodilator effect of salbutamol is significantly less pronounced. Recovery of β 2 -AR during desensitization occurs within several hours, and during down-regulation - within several days. ICS provide rapid (within 1 hour) recovery and high density of β 2 -AR on the membranes of target cells, preventing the development of the down-regulation phenomenon.
Pharmacogenetics. Many researchers associate individual variability in the response to β 2 -agonists and the development of tolerance to their bronchodilator effect with gene polymorphism. Nine variants of β 2 -adrenergic receptor gene polymorphism have been identified, of which 2 are particularly common. They are associated with the replacement of amino acids in the extracellular N-fragment of the gene: β 2 -adrenergic receptors-16 with the replacement of arginine (Arg-16) with glycine (Gly-16) and β 2 -adrenergic receptors-27 with the replacement of glutamine (Gln-27) with glutamic acid(Glu-27). The Gly-16 variant is associated with the development of severe asthma with frequent nocturnal attacks and decreased effectiveness of salbutamol. The second option determines the high activity of methacholine in relation to bronchoconstriction. The β 2 -AP polymorphism (replacement of threonine with isoleucine at position 164 in the IV transmembrane domain) alters the binding of salmeterol to the exosite, reducing the duration of action of salmeterol (but not formoterol) by 50%.
Safety and potential risk. Salmeterol and formoterol exhibit long-acting β 2 -agonist properties only in the form of inhaled drugs, which explains the low incidence of undesirable effects (the absorbed fraction is quickly inactivated). The higher bronchodilator activity of formoterol is not accompanied by an increase in the frequency of adverse effects. A feature of formoterol is the proven dose-dependent nature of the bronchodilator effect: with increasing dose, additional bronchodilation occurs.
The selectivity of β 2 -adrenergic agonists is relative and dose-dependent. Minor activation of α- and β1-adrenergic receptors, unnoticeable at usual average therapeutic doses, becomes clinically significant when the dose of the drug or the frequency of its administration during the day is increased. The dose-dependent effect of β2-agonists must be taken into account in the treatment of exacerbations of asthma, especially life-threatening conditions, when repeated inhalations for a short time are 5-10 times higher than the permissible level daily dose.
β 2 -adrenergic receptors are found in a variety of tissues and organs, especially in the left ventricle, where they make up 14% of all β-adrenergic receptors, and in the right atrium (26% of all β-adrenergic receptors). Stimulation of these receptors can lead to the development of adverse effects (> 100 mcg salbutamol):
- tachycardia;
- myocardial ischemia;
- arrhythmia;
- decrease in diastolic blood pressure upon stimulation of vascular ∆ receptors;
- hypokalemia, prolongation of the QT interval and fatal arrhythmias (with activation of large potassium channels);
— hypoxemia and worsening respiratory failure as a result of dilatation of the vessels of the pulmonary circulation system in the hyperinflation zone in patients with chronic obstructive pulmonary diseases;
- skeletal muscle tremor (with stimulation of skeletal muscle β-receptors).
With systemic administration of large doses, an increase in the levels of free fatty acids, insulin, glucose, pyruvate and lactate is possible. Therefore, additional glycemic control is recommended in patients with diabetes. Undesirable cardiac effects are especially pronounced in conditions of severe hypoxia during exacerbations of asthma: an increase in venous return (especially in the orthopneic position) can cause the development of Bezold-Jarisch syndrome with subsequent cardiac arrest.
The anti-inflammatory effect of β 2 -agonists, which helps modify acute bronchial inflammation, can be considered to be inhibition of the release of inflammatory mediators from mast cells and a decrease in capillary permeability. At the same time, during a biopsy of the bronchial mucosa of BA patients regularly taking β2-agonists, it was found that the number of inflammatory cells, including activated ones (macrophages, eosinophils, lymphocytes), does not decrease. Regular use of β 2 -agonists can mask the development of exacerbations of asthma, including fatal ones.
For the first time, serious doubts about the safety of inhaled β-agonists arose in the 1960s, when an “epidemic of deaths” among patients with asthma broke out in a number of countries (England, Australia, New Zealand). Ages from 5 to 34 years for the period 1961-1967. 3,500 people died (at a rate of 2 per 1,000,000). Then publications began to appear in the press about how asthma patients were found dead with an empty (or almost empty) aerosol inhaler in their hands. Mortality was hypothesized to be related to the development of fatal arrhythmias and β-receptor blockade by isoproterenol metabolites, although a causal relationship between β-agonist use and increased mortality has never been established.
A connection has been identified between fenoterol intake and an increase in mortality from asthma in New Zealand in the 80s of the last century. As a result epidemiological research conducted in Canada (W.O. Spitzer et al., 1992), it was shown that an increase in the frequency deaths associated with high-dose inhaled β2-agonist therapy. At the same time, patients with uncontrolled and severe asthma are less adherent to taking anti-inflammatory drugs - inhaled corticosteroids. Misconceptions about the ability of salmeterol to relieve acute asthma attacks led to at least 20 deaths from asthma being reported in the first 8 months after the drug was introduced on the pharmaceutical market in the United States. Based on the results of the SMART study, it was decided to use long-acting β 2 -agonists (LABA) only in combination with ICS. Moreover, the addition of LABA is equivalent to doubling the dose of ICS.
Dosage regimen for inhaled short-acting β 2 -agonists (SABA). They are the drugs of choice for situational symptomatic control of asthma, as well as for preventing the development of symptoms of exercise asthma (PAE). Their regular use can lead to loss of adequate control over the course of the disease. M.R. Sears et al. (1990) found in a group of asthma patients who consumed fenoterol regularly (4 times a day) poor control over asthma symptoms, more frequent and severe exacerbations. Patients who used fenoterol on demand showed an improvement in respiratory function, morning peak expiratory flow, and a decrease in response to a bronchoprovocation test with methacholine. There is evidence that regular use of salbutamol is accompanied by an increase in the frequency of episodes of AFU and an increase in the severity of inflammation in the DP.
Short-acting β-agonists should be used only when required. Patients receiving high (more than 1.4 aerosol cans per month) doses require effective anti-inflammatory therapy. The bronchoprotective effect of β-agonists is limited to 3-4 inhalations per day. Oral β-agonists help improve performance by increasing muscle mass, protein and lipid anabolism, and psychostimulation. Thus, 41 of the 67 athletes with AFU who regularly used SABA at the 1984 Olympic Games received medals of varying denominations.
Dosage regimen for long-acting inhaled β2-agonists. The differences between salmeterol and formoterol are that bronchodilation occurs quickly after using the latter, and there are significantly fewer adverse events than with salbutamol. These drugs can be prescribed as monotherapy in patients with mild asthma and as bronchoprotectors in AFU. When using formoterol more than 2 times a week, it is necessary to add ICS to the treatment.
To date, no studies have been conducted that comply with the principles of good clinical practice (GCP) in which the disease-modifying effect of LABA monotherapy has been proven.
Studies conducted to date indicate the possibility of earlier administration of long-acting inhaled β 2 -agonists. The addition of formoterol to 400-800 mcg/day of ICS (budesonide) provides more complete and adequate control compared to increasing the dose of ICS.
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Beta agonists
Beta-agonists(syn. beta-agonists, beta-agonists, beta-adrenergic stimulants, beta-agonists). Biological or synthetic substances that cause stimulation of β-adrenergic receptors and have a significant effect on the main functions of the body. Depending on the ability to bind to different subtypes of β-receptors, β1- and β2-adrenergic agonists are distinguished.
Physiological role of β-adrenergic receptors
Cardioselective β1-blockers include talinolol (Cordanum), acebutolol (Sectral) and celiprolol.
Use of beta-agonists in medicine
Non-selective β1-, β2-adrenergic agonists isoprenaline and orciprenaline are used short-term to improve atrioventricular conduction and increase the rhythm during bradycardia
β1-adrenergic agonists: Dopamine and dobutamine are used to stimulate the force of heart contraction in acute heart failure caused by myocardial infarction, myocarditis, or other causes.
Short-acting β2-agonists, such as fenoterol, salbutamol and terbutaline are used in the form of metered aerosols to relieve asthma attacks in bronchial asthma, chronic obstructive pulmonary disease (COPD) and other broncho-obstructive syndromes. Intravenous fenoterol and terbutaline are used to reduce labor and when there is a threat of miscarriage.
Long-acting β2-agonists salmeterol is used for prevention, and formoterol is used for both prevention and relief of bronchospasm in bronchial asthma and COPD in the form of metered aerosols. They are often combined in one aerosol with inhaled corticosteroids to treat asthma and COPD.
Side effects of beta-agonists
When using inhaled beta-agonists, tachycardia and tremor are most common. Sometimes - hyperglycemia, central nervous system stimulation, decreased blood pressure. When administered parenterally, all these phenomena are more pronounced.
Overdose
Characterized by a drop in blood pressure, arrhythmias, decreased ejection fraction, confusion, etc.
Treatment is the use of beta blockers, antiarrhythmic drugs, etc.
The use of β2-adrenergic agonists in healthy people temporarily increases resistance to physical activity, since they “keep” the bronchi in an expanded state and promote the rapid opening of a second wind. This was often used by professional athletes, in particular cyclists. It should be noted that in the short term, β2-agonists do increase exercise tolerance. But their uncontrolled use, like any doping, can cause irreparable harm to health. Addiction develops to β2-adrenergic agonists (in order to “keep the bronchi open” you have to constantly increase the dose). Increasing the dose leads to arrhythmias and the risk of cardiac arrest.
In some cases, anticholinergics are used in combination with beta-2 agonists. However, combination drugs are rarely used in the treatment of asthma, because Treatment with standard drugs, such as beta-2 agonists or ipratropium bromide, is more effective and allows for selective dosing of each drug. The advantage is that this combination has synergism and reduces the risk of side effects of the constituent components. Combination therapy also leads to a greater bronchodilator effect compared to monotherapy and can significantly increase its duration. The main combination drugs of ipratropium with beta-2 agonists are ipratropium/fenoterol (Berodual®) and ipratropium/salbutamol (Combivent®). These drugs are mainly used as part of complex therapy for severe attacks of suffocation - inhalation through a nebulizer.
From methylxanthines The drugs theophylline and aminophylline are used in the treatment of bronchial asthma.
Due to a number of adverse side effects that can occur with overdose of these drugs, monitoring of theophylline blood concentrations is required. Aminophylline (a mixture of theophylline and ethylenediamine, which is 20 times more soluble than theophylline itself) is administered intravenously very slowly (at least 20 minutes). Intravenous aminophylline plays an important role in the relief of severe asthma attacks that are tolerant to nebulized forms of beta-2 agonists. Aminophylline is also used in patients with heart failure when it is combined with asthma or bronchitis, and with hypertension of the pulmonary circulation. In the body, aminophylline releases free theophylline.
