Medications for bronchial asthma

The main goals of treatment for patients with bronchial asthma:

• establishing and maintaining control over the manifestations of bronchial asthma;
• prevention of exacerbations of the disease;
• maintaining respiratory function at a level as close to normal as possible;
• maintaining normal life activity;
• prevention of side effects during treatment;
• prevention of the development of the irreversible component of bronchial obstruction;
• prevention of fatal outcome of the disease.

Criteria for control (controlled course) of bronchial asthma:

• minimal (ideally absent) symptoms, including nocturnal asthma;
• minimal (extremely rare) exacerbations;
• no emergency visits to the doctor;
• minimal need for beta2-agonist inhalations;
• no restrictions on activity, including physical activity;
• daily fluctuations in PEF < 20%; minimal (or absent) side effects of drugs;
• normal or close to normal PSV values.

The main groups of drugs used to treat bronchial asthma

Anti-inflammatory drugs:

1. Sodium cromoglycate (Intal)
2. Sodium nedocromil (tayled)
3. Ditek
4. Glucocorticoids (mainly locally - in the form of inhalations, as well as orally and parenterally)

Bronchodilators:

1. Adrenergic receptor stimulants:
   1. alpha- and beta1-2-adrenergic receptor stimulants (adrenaline, ephedrine);
   2. beta2- and beta1-adrenergic receptor stimulants (isadrin, novodrin, euspiran);
   3. selective beta2-adrenergic agonists.
      • short-acting - salbutamol, terbutaline, salmefamol, ipradol;
      • long-acting - salmeterol, formoterol).
2. Anticholinergics:
   1. ipratropium bromide (Atrovent);
   2. berodual;
   3. troventol;
3. Methylxanthines:
   1. euphyllin;
   2. theophylline

Treatment of patients with bronchial asthma should be individualized, taking into account the etiological, clinical and pathogenetic variants and include:

• elimination measures (elimination of contact with allergens that are significant for the patient and potential allergens, as well as non-specific irritants);
• drug therapy (pathogenetic and symptomatic);
• non-drug treatments (naturotherapy).

The main role in the exacerbation phase of bronchial asthma is played by drug therapy. It involves suppressing inflammatory lesions of the bronchial mucosa and restoring their normal patency. For this purpose, two main groups of drugs are used: anti-inflammatory drugs and bronchodilators.

Impact on the pathophysiological stage

In the pathophysiological stage, bronchospasm, edema, inflammation of the bronchial mucosa and, as a result, an attack of suffocation develop. Many measures in this phase contribute to the immediate relief of an attack of suffocation.

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Bronchodilators

Bronchodilators are a large group of drugs that dilate the bronchi. Bronchodilators (bronchodilators) are divided as follows:

1. Adrenergic receptor stimulants.
2. Methylxanthines.
3. M-anticholinergics (anticholinergics).
4. Alpha adrenergic blockers.
5. Calcium antagonists.
6. Antispasmodics.

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Adrenergic receptor stimulants

The smooth muscles of the bronchi contain alpha- and beta2-adrenoreceptors, through which the sympathetic nervous system has a regulating effect on bronchial tone. Excitation of beta2-receptors leads to dilation of the bronchi, excitation of alpha- (postsynaptic) adrenoreceptors causes a bronchoconstrictive effect and narrowing of the bronchial vessels (this leads to a decrease in edema of the bronchial mucosa).

The mechanism of bronchial dilation during stimulation of beta2-adrenoreceptors is as follows: beta2-adrenoreceptor stimulants increase the activity of adenyl cyclase, this leads to an increase in the content of cyclic 3,5-AMP, which, in turn, promotes the transport of Ca++ ions from myofibrils to the sarcoplasmic reticulum, which delays the interaction of actin and myosin in the bronchial muscles, which relaxes as a result.

Beta-adrenergic receptor stimulants do not have an anti-inflammatory effect and are not basic means for the treatment of asthma. They are most often used during an exacerbation of the disease to relieve an attack of suffocation.

Adrenergic receptor stimulants are divided into the following subgroups:

• beta1,2- and alpha-adrenergic stimulants (adrenaline, ephedrine, theophedrine, solutan, efatin);
• beta1 and beta2-adrenergic agonists (isadrin, novodrin, euspiran);
• selective beta2-adrenergic agonists.

Beta1,2- and alpha-adrenergic agonists

Adrenaline stimulates beta2-adrenoreceptors of the bronchi, which leads to bronchodilation; stimulates α-receptors, which causes spasm of the bronchial vessels and reduces bronchial edema. Stimulation of a-adrenoreceptors also leads to an increase in blood pressure, excitation of beta2-receptors of the myocardium leads to tachycardia and an increase in the myocardial oxygen demand.

The drug is available in ampoules of 1 ml of 0.1% solution and is used to stop an attack of bronchial asthma. 0.3-0.5 ml is administered subcutaneously; if there is no effect after 10 minutes, the administration is repeated at the same dose. The drug acts for 1-2 hours, it is quickly destroyed by catechol-O-methyltransferase.

Adrenaline may have side effects (they develop with frequent use and especially in elderly people who also suffer from coronary heart disease): tachycardia, extrasystole, pain in the heart (due to increased myocardial oxygen demand), sweating, tremor, agitation, dilated pupils, increased blood pressure, hyperglycemia.

With frequent use of adrenaline, an aftereffect may develop: adrenaline forms metanephrine, which blocks β-receptors in the bronchi, which contributes to increased bronchospasm.

Contraindications to the use of adrenaline:

• hypertension;
• exacerbation of coronary heart disease;
• diabetes mellitus;
• toxic goiter.

Ephedrine is an indirect stimulant of alpha- and beta-adrenoreceptors. The drug displaces norepinephrine from the presynaptic endings of sympathetic nerves, inhibits its reuptake, increases the sensitivity of adrenoreceptors to norepinephrine and adrenaline, and releases adrenaline from the adrenal cortex. In addition, it has a slight direct alpha-stimulating effect and is used to relieve attacks of bronchial asthma and chronic bronchial obstruction. To relieve an attack, 1 ml of a 5% solution is administered subcutaneously. The effect begins in 15-30 minutes and lasts for about 4-6 hours, i.e., compared to adrenaline, it acts later but lasts longer. For chronic bronchial obstruction, it is used in tablets of 0.25 g (1 tablet 2-3 times a day), in inhalations (0.5-1 ml of 5% solution diluted with isotonic sodium chloride solution 1:3, 1:5).

Side effects are similar to those of adrenaline, but are less pronounced and are reduced with the simultaneous use of diphenhydramine.

Broncholitin contains ephedrine, glaucine, sage, take 1 tablespoon 4 times a day.

Theophedrine is a combination drug with the following composition: theophylline, theobromine, caffeine - 0.5 g each, amidopyrine, phenacetin - 0.2 g each, ephedrine, phenobarbital, belladonna extract - 0.2 g, labelin - 0.0002 g.

The bronchodilator effect is due to ephedrine, theophylline, theobromine. It is usually prescribed for chronic bronchial obstruction, 1/2-1 tablet in the morning and evening. It is possible to relieve mild asthma attacks.

Solutan is a combination drug that has a bronchodilator (cholinergic and antispasmodic) and expectorant effect. It is used for chronic bronchial obstruction, 10-30 drops 3 times a day. The possibility of intolerance to primrose and other components of the drug should be taken into account.

Efatin - is produced in the form of an aerosol. Contains ephedrine, atropine, novocaine. Prescribed 2-3 inhalations 3 times a day.

The drug relieves attacks of bronchial asthma, however, before using the drug, you should find out how tolerable novocaine is.

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Β2- and β1-adrenergic stimulants

Β2- and β1-adrenergic stimulants stimulate beta2-adrenergic receptors in the bronchi and dilate them, but simultaneously stimulate beta1-adrenergic receptors of the myocardium and cause tachycardia, an increase in the myocardium's need for oxygen. Stimulation of beta2-receptors also causes dilation of the bronchial arteries and branches of the pulmonary artery (development of "bronchial closure" syndrome is possible).

Shadrin (isopropylnorepinephrine) is available in tablets of 0.005 g, in inhalation bottles of 25 ml of 0.5% solution and 100 ml of 1% solution, and also in the form of a metered-dose aerosol.

To relieve a mild attack of bronchial asthma, take one tablet under the tongue (or keep it in the mouth until it dissolves completely). When taken sublingually, the effect begins in 5-10 minutes and lasts for about 2-4 hours.

You can use inhalation of 0.1-0.2 ml of 0.5% or 1% solution or with a metered dose inhaler Medihaler - 0.04 mg per 1 breath, the bronchodilator effect begins after 40-60 seconds and lasts 2-4 hours. The drug is used in any form 2-3 times a day.

Frequent use of Shadrin may cause more frequent and severe attacks of bronchial asthma due to the fact that the breakdown product 3-methoxyisoprenaline has a blocking effect on beta2 receptors.

Side effects of the drug: tachycardia, agitation, insomnia, extrasystole.

Analogues of Shadrin:

• Novodrin (Germany) - inhalation bottles (100 ml of 1% solution), 0.02 g tablets for sublingual administration;
• Euspiran in tablets of 0.005 g and inhalation bottles of 25 ml of 1% solution (20 drops per inhalation). Dosed aerosols of Euspiran are also available.

Selective beta2-adrenergic agonists

Selective beta2-adrenergic stimulants selectively stimulate beta2-adrenergic receptors of the bronchi, causing their dilation, and have almost no stimulating effect on beta1-adrenergic receptors of the myocardium.

They are resistant to the action of catechol-O-methyltransferase and monoamine oxidase.

Mechanism of action of selective beta2-adrenergic agonists:

• excitation of beta2-adrenergic receptors and dilation of the bronchi;
• improving mucociliary clearance;
• inhibition of mast cell and basophil degranulation;
• prevention of the release of lysosomal enzymes from neutrophils;
• decreased permeability of membrane lysosomes.

Selective beta2-adrenergic agonists are proposed to be classified as follows:

• selective:
  • short-acting: salbutamol (Ventolin), terbutaline (Bricanil), salmefamol, ipradol;
  • long-acting: salmeterol, formoterol, serevent, volmax, clenbuterol;
• possessing partial selectivity: fenoterol (berotek), orciprenaline sulfate (alupent, astmopent).

Prolonged-release selective beta2-adrenergic agonists

Prolonged selective beta2-adrenergic stimulants were synthesized in the late 80s; the duration of action of these drugs is about 12 hours; the prolonged effect is due to their accumulation in the lung tissue.

Salmeterol (Sereven) is used as a metered aerosol of 50 mcg 2 times a day. This dose is sufficient for patients with mild to moderate bronchial asthma. For more severe cases of the disease, a dose of 100 mcg 2 times a day is prescribed.

Formoterol is used in the form of a metered-dose aerosol of 12-24 mcg 2 times a day or in tablets of 20, 40, 80 mcg.

Volmax (salbutamol SR) is an oral form of prolonged-release salbutamol. Each tablet contains 4 or 8 mg of salbutamol, consists of an outer impermeable shell and an inner core. The outer shell has an opening that allows for osmotically controlled release of the drug. The controlled release mechanism of salbutamol ensures gradual delivery of the active substance over a long period of time, which allows the drug to be prescribed only 2 times a day and used for the prevention of bronchial asthma.

Clenbuterol hydrochloride (spiropent) - is used in tablets of 0.02 mg 2 times a day, in severe cases the dose can be increased to 0.04 mg 2 times a day.

Unlike salbutamol and other short-acting beta2-stimulants, prolonged-release preparations do not have a rapid effect, so they are used primarily not to relieve but to prevent asthma attacks, including nocturnal ones. These preparations also have an anti-inflammatory effect, as they reduce vascular permeability, prevent the activation of neutrophils, lymphocytes, macrophages, and inhibit the release of histamine, leukotrienes, and prostaglandins from mast cells. Prolonged selective beta2-stimulants are less likely to cause a decrease in the sensitivity of beta receptors to them.

According to some researchers, long-acting beta2-adrenergic stimulants should be more often combined with glucocorticoids in inhalations. In Russia, the prolonged-action beta-agonist Soltos is produced in the form of 6 mg tablets, the duration of action is more than 12 hours, taken 1-2 times a day. It is especially effective for nocturnal asthma.

Short-acting selective beta2-adrenergic agonists

Salbutamol (Ventolin) is available in the following forms:

• metered aerosol, prescribed 1-2 inhalations 4 times a day, 1 inhalation = 100 mcg. It is used to relieve an attack of bronchial asthma. When used by inhalation, only 10-20% of the administered dose reaches the distal bronchi and alveoli. At the same time, the drug, unlike adrenaline and Shadrin, is not subject to methylation with the participation of catechol-O-methyltransferase, i.e. it is not transformed in the lungs into metabolites with a beta-blocking effect. Most of the salbutamol used by inhalation settles in the upper respiratory tract, is swallowed, absorbed in the gastrointestinal tract, can cause side effects (palpitations, hand tremors), but they are weakly expressed and are observed in only 30% of patients. Salbutamol is considered one of the safest β-sympathomimetics - bronchodilators. The drug can also be used in the form of inhalations using a nebulizer (5 mg in isotonic sodium chloride solution for 5-15 minutes no more than 4 times a day), using a spinhaler in powder form at 400 mg no more than 4 times a day. The use of a spinhaler allows for increased delivery of salbutamol to the small bronchi;
• tablets of 0.002 g and 0.004 g for oral administration, used 1-4 times a day for chronic bronchial obstruction in a daily dose of 8-16
  mg.

Ventodisc is a new form of Ventolin, consisting of 8 vials sealed in a double layer of foil. Each vial contains the finest powder of salbutamol (200-400 mcg) and lactose particles. Inhalation of the drug from Ventodisc after piercing it with a needle is performed using a special inhaler - a diskhaler. Using Ventodisc allows you to administer Salbutamol even with shallow breathing. Inhaled 4 times a day to relieve attacks of bronchial asthma.

Salmefamol is available in the form of metered-dose aerosols and is used to relieve asthma attacks - 1-2 inhalations 3-4 times a day, one inhalation = 200 mcg.

Terbutaline (6ricanil) is available in the following forms:

• metered-dose aerosol for stopping an attack of bronchial asthma, prescribed 1 inhalation 3-4 times a day, 1 inhalation = 250 mcg;
• ampoules of 1 ml of 0.05% solution, administered intramuscularly at 0.5 ml up to 4 times a day to relieve an attack;
• tablets of 2.5 mg, taken orally, 1 tablet 3-4 times a day for chronic bronchial obstruction;
• Extended-release tablets of 5 and 7.5 mg (1 tablet 2 times a day).

Ipradol is available in the following forms:

• metered-dose aerosol for relieving an attack of bronchial asthma, 1-2 inhalations 3-4 times a day, 1 inhalation = 200 mcg;
• ampoules of 2 ml of 1% solution, administered intravenously to relieve an attack of bronchial asthma;
• 0.5 mg tablets, taken 1 tablet 2-3 times a day orally for the treatment of chronic bronchial obstruction.

Short-acting selective beta2-adrenergic agonists begin to act after inhalation in 5-10 minutes (in some cases earlier), the maximum effect appears after 15-20 minutes, the duration of action is 4-6 hours.

Partially selective beta2-adrenergic agonists

These drugs significantly and predominantly stimulate beta2-adrenergic receptors of the bronchi and cause bronchodilation, but still to a certain extent (especially with excessive use) stimulate beta1-adrenergic receptors of the myocardium and can cause tachycardia.

Alupent (astmopent, orciprenaline) is used in the following forms:

• metered aerosol for stopping an attack of bronchial asthma, prescribed 1-2 inhalations 4 times a day, one inhalation equals 0.75 mg;
• ampoules for stopping an attack of bronchial asthma, 1 ml of 0.05% solution, administered subcutaneously, intramuscularly (1 ml); intravenously by drip (1-2 ml in 300 ml of 5% glucose);
• 0.02 g tablets for the treatment of chronic bronchial obstruction, take 1 tablet 4 times a day orally.

Fenoterol (berotek) is available as a metered-dose aerosol. It is used to relieve an asthma attack. It is prescribed as 1 inhalation 3-4 times a day, 1 inhalation = 200 mcg.

In recent years, a combined drug called ditec has been produced - a metered-dose aerosol, one dose containing 0.05 mg of fenoterol hydrobromide (berotek) and 1 mg of disodium salt of cromoglycic acid (intala).

Ditek has the property of preventing mast cell degranulation and expanding the bronchi (through stimulation of beta2-adrenoreceptors of the bronchi). Therefore, it can be used both for the prevention of asthma attacks and for their relief. It is prescribed 2 doses 4 times a day daily, in case of an attack, another 1-2 doses can be inhaled.

Side effects of beta-adrenergic agonists:

• excessive use of drugs causes tachycardia, extrasystole, and increases the frequency of angina attacks; these phenomena are most pronounced in non-selective and partially selective beta2-adrenergic agonists;
• With prolonged use of beta-blockers or their overdose, resistance to them develops, bronchial patency worsens (tachyphylaxis effect).

Side effects are associated, on the one hand, with the occurrence of beta-adrenergic receptor blockade by metabolic products and a decrease in the number of beta receptors in some cases, and, on the other hand, with a disruption of the drainage function of the bronchi due to the development of the "locking" syndrome (dilation of the bronchial vessels and an increase in the swelling of the bronchial mucosa). In order to reduce the "lung locking" syndrome, it is recommended to combine the intake of 0-adrenergic stimulants with the intake of euphyllin or ephedrine (the latter stimulates α-receptors, constricts blood vessels and reduces bronchial swelling).

Side effects are less frequent and less pronounced when using selective long-acting beta2-adrenergic agonists.

When treating with inhaled sympathomimetics, the following rules must be observed (the success of treatment is 80-90% dependent on correct inhalation):

• Before administering the drug, take a deep breath;
• inhale slowly 1-2 seconds before pressing the inhaler valve (pressing it should occur at the moment of maximum inhalation speed);
• After inhaling the drug, hold your breath for 5-10 seconds.

Some patients cannot synchronize their inhalation with the moment the drug is administered. Such patients are recommended to use spacers, individual ultrasonic inhalers (nebulizers), switch to inhalation of drugs in powder form using spinhalers, diskhalers, turbohalers or to oral administration of tablet forms.

Spacers are containers that allow patients to receive a metered aerosol without having to coordinate pressing the cylinder valve and inhaling. Using a spacer reduces the side effects of inhaled drugs, including glucocorticoids, and increases their delivery to the lungs.

Methylxanthines

From the group of methylxatins theophylline, theobromine, and euphylline are used.

Euphyllin is a compound of theophylline (80%) and ethylenediamine (20%), used for better dissolution of theophylline. The main component of euphyllin is theophylline.

Mechanism of action of theophylline:

• inhibits phosphodiesterase, as a result of which destruction is reduced and accumulation of cAMP in the smooth muscles of the bronchi occurs. This promotes the transport of Ca++ ions from myofibrils to the sarcoplasmic reticulum, and, consequently, the reaction of actin and myosin interaction is delayed and the bronchus relaxes;
• inhibits the transport of calcium ions through slow channels of cell membranes;
• inhibits mast cell degranulation and the release of inflammatory mediators;
• blocks adenosine purine receptors of the bronchi, thereby eliminating the bronchoconstrictive effect of adenosine and the inhibitory effect on the release of norepinephrine from the presynaptic endings of the sympathetic nerves;
• improves renal blood flow and increases diuresis, increases the strength and frequency of heart contractions, lowers pressure in the pulmonary circulation, improves the function of the respiratory muscles and diaphragm.

Theophylline is considered as a drug for the relief of bronchial asthma (euphyllin) and as a means of basic therapy.

Euphyllin is available in 10 ml ampoules of 2.4% solution. Intravenous administration of 10-20 ml of isotonic sodium chloride solution should be done very slowly (over 5 minutes). Rapid administration may cause a drop in blood pressure, dizziness, nausea, tinnitus, palpitations, facial flushing, and a feeling of heat.

Euphyllin administered intravenously acts for about 4 hours; in smokers, the effect of the drug is weaker and shorter (about 3 hours). Intravenous drip administration of the drug extends its effect to 6-8 hours and significantly less often causes the side effects described above. 10 ml of a 2.4% solution in 300 ml of isotonic sodium chloride solution is administered intravenously by drip.

Much less frequently, intramuscular injection of 1 ml of a 24% solution of euphyllin is used to relieve an attack of bronchial asthma; its relieving effect is much weaker.

In chronic bronchial obstruction, plural forms of euphyllin are used.

Euphyllin is taken internally, released in tablets of 0.15 g, it is prescribed after meals. However, when taking tablets, irritation of the stomach, nausea, pain in the epigastric region are possible.

To reduce these phenomena, it is recommended to take aminophylline in capsules; the combined use of aminophylline and ephedrine enhances the bronchodilatory effect of both drugs.

You can prepare a powder and use it in capsules 3 times a day:

• euphyllin - 0.15 g
• ephedrine - 0.025 g papaverine - 0.02 g

When taken orally, Euphyllin is better absorbed in the form of alcohol solutions.

The following prescriptions can be recommended:

• euphyllin - 5 g
• ethyl alcohol 70% - 60 ml
• distilled water up to - 300 ml

Take 1-2 tablespoons 3-4 times a day.

• euphyllin - 3 g
• ephedrine - 0.4 g
• potassium iodide - 4 g
• ethyl alcohol 50% - 60 ml
• distilled water up to 300 ml

Take 1-2 tablespoons 3-4 times a day after meals.

Euphyllin in suppositories is widely used to treat chronic bronchial obstruction and prevent nocturnal asthma attacks:

• euphyllin - 0.36 g
• cocoa butter - 2 g

Euphyllin in suppositories acts for about 8-10 hours. 1 suppository is inserted into the anus at night (preferably after spontaneous bowel movement or after a preliminary cleansing enema). Repeated administration in the morning is possible.

You can use 0.5 g diphylline suppositories. This is 7-beta, 3-dioxypropyl) - theophylline, which is similar in pharmacological properties to euphylline.

Theophylline - is used to treat chronic bronchial obstruction. It is available in powder form (taken 0.1-0.2 g 3 times a day), in suppositories of 0.2 g (inserted into the rectum at night to prevent night asthma attacks). We can recommend the prescription of B. E. Votchal:

• theophylline - 1.6 g
• ephedrine - 0.4 g
• sodium barbital - 3 g
• ethyl alcohol 50% - 60 ml
• distilled water - up to 300 ml

Take 1-2 tablespoons 3 times a day.

Extended-release theophylline preparations

The main disadvantages of conventional theophylline include a narrow range of therapeutic action (10-20 mcg/ml), fluctuations in the level of the drug in the blood between doses, rapid elimination from the body, and the need to take it orally 4 times a day.

In the 1970s, prolonged-release theophylline preparations appeared. The advantages of prolonged-release preparations are as follows:

• reduction in the frequency of receptions;
• increasing dosing accuracy;
• more stable therapeutic effect;
• prevention of asthma attacks in response to physical activity;
• prevention of night and morning attacks of suffocation.

Prolonged-release theophylline preparations are divided into 2 groups: first-generation preparations (active for 12 hours and prescribed twice a day) and second-generation preparations (active for 24 hours and prescribed once a day).

Treatment with prolonged-release theophyllines should be carried out under control of the drug concentration in the blood. Theophylline has a small breadth of therapeutic action.

The minimum therapeutic concentration of theophylline in the blood is 8-10 mcg/ml, a concentration above 22 mcg/ml is considered toxic.

Most extended-release theophylline preparations have a half-life of 11-12 hours, the therapeutic concentration in the blood is achieved after 3-5 half-lives, i.e. after 36-50 hours or on the 3rd day from the start of treatment. The effect should be assessed and the dose of theophylline should be adjusted no earlier than on the 3rd day from the start of treatment.

In mild cases, theophylline intoxication manifests itself as nausea, vomiting, tachycardia, in more severe cases - ventricular arrhythmia, arterial hypotension, hypoglycemia. The most serious complication of theophylline overdose is convulsions (due to blockade of central adenosine receptors).

In case of theophylline intoxication, the stomach is washed, activated charcoal and symptomatic drugs (antiarrhythmic, anticonvulsant, potassium preparations) are prescribed, and in more severe cases, hemosorption is performed.

Smoking promotes the elimination of theophylline from the body. In smokers, the maximum concentration of prolonged theophyllines is almost 2 times lower than in non-smokers.

The pharmacokinetics of theophyllines is characterized by circadian rhythms. When taking the morning dose of theophylline orally, the absorption rate is higher than in the evening. When taking prolonged-release preparations twice a day, the peak of daytime concentration occurs at 10 a.m., and at night - at 2 a.m.

In our country, the most commonly used extended-release theophylline preparations are theopec and theobtsolong.

Teopec - prolonged-release theophylline tablets, containing 0.3 g of theophylline in combination with a composite polymer carrier, which provides a metered release of theophylline in the gastrointestinal tract. After taking Teopec, the maximum concentration of theophylline in the blood is observed after 6 hours.

The release of theophylline from theopec tablets occurs only when they are washed down with water in an amount of at least 250 ml. This creates a higher concentration of theophylline in the blood.

The tablet can be divided in half, but must not be crushed.

According to the instructions, in the first 1-2 days the drug is prescribed at 0.15 g (1/2 tablet) 2 times a day, subsequently the single dose is increased to 0.3 g 2 times a day (morning and evening).

In 1990, V. G. Kukes published the following data on the clinical pharmacology of Teopec:

• a single dose of 0.3 g does not cause changes in the condition of patients; with a course of treatment with Teopec, the effect was noted on the 3-5th day;
• if there is no effect, increasing the dose to 400, 450, maximum 500 mg of theopec per dose leads to a reliable bronchodilator effect. The optimal concentration of theophylline in the blood is achieved when taken twice a day;
• The drug reliably reduces pressure in the pulmonary artery. Yu. B. Belousov (1993) gives the following recommendations for treatment with Teopec:
• It is advisable to start treatment with a single minimum dose;
• a single minimum dose is gradually increased over 3-7 days by 50-150 mg, depending on the clinical effect and the concentration of theophylline in the blood;
• the drug is used 2 times a day;
• for frequent nocturnal attacks of suffocation, 2/3 of the daily dose is prescribed in the evening, 1/3 in the morning;
• use of the drug at night in a double dose leads to an increase in the concentration of theophylline in the blood serum above the norm;
• in patients with nocturnal attacks of suffocation, the most rational method is a single use of the drug at night in a dose of 300-450 mg;
• if there is no strict dependence of the occurrence of asthma attacks on the time of day, 300 mg is prescribed in the morning and evening.

Theotard - retard capsule contains 200, 350 or 500 mg of anhydrous theophylline. After oral administration, 100% is absorbed. During the first 3 days, the drug is taken 1 capsule 2 times a day (children are prescribed 200 mg, adults - 350 mg, if necessary, the dose can be increased to 500 mg).

Teobiolong prolonged-release tablets containing 0.1 theophylline in combination with a biosoluble polymer. Prescribed orally after meals (without crushing or dissolving in water). Treatment begins with a dose of 0.1 g twice a day at 12-hour intervals. After 2-3 days, if there are no side effects, the dose is increased: 0.2-0.3 g is prescribed 2-3 times a day, depending on therapeutic efficacy and tolerability.

A single dose should not exceed 0.3 g, daily dose - 0.6 g.

Increasing the single dose above 0.3, and the daily dose above 0.6 g is permissible only in rare cases, under strict medical supervision and under control of the concentration of theophylline in the blood, which should not exceed 20 mcg/ml.

Compared to Teopec, the drug acts somewhat longer and more often causes palpitations and headaches.

Abroad, various prolonged-release theophylline preparations are produced in the form of tablets or capsules with granules under the names "Theodur", "Theotard", "Durophylline-retard", "Retafil", etc.

The content of theophylline in tablets and capsules ranges from 0.1 to 0.5 g.

Retafil - is available in tablets of 0.2 and 0.3 g. During the first week of treatment, the daily dose of the drug is 300 mg. Then the dose is increased to 600 mg. The drug is taken 2 times a day - morning and evening.

Theophylline side effects

The severity and nature of the side effects of theophylline depend on the concentration of the drug in the blood. At a theophylline concentration of 15-20 mcg/ml, side effects from the digestive organs (nausea, anorexia, vomiting, diarrhea) are possible. At a theophylline concentration of 20-30 mcg/ml, the cardiovascular system is affected, which is manifested by tachycardia, cardiac arrhythmias. In the most severe cases, ventricular flutter and fibrillation may develop. The risk of developing adverse effects on the cardiovascular system increases in people over 40 years of age, as well as in patients suffering from coronary heart disease.

At higher concentrations of theophylline in the blood, pronounced changes in the central nervous system are observed (insomnia, hand tremor, psychomotor agitation, convulsions). In some cases, metabolic disorders may occur - hyperglycemia, hypokalemia, hypophosphatemia, metabolic acidosis, respiratory alkalosis. Sometimes polyuria develops.

To avoid the development of side effects during treatment with extended-release theophylline, the following factors must be taken into account:

• age of the patient;
• severity of bronchial asthma;
• concomitant diseases;
• possible interactions with other drugs;
• the advisability of monitoring the concentration of theophylline in the blood during long-term use.

Contraindications to prolonged theophyllines: increased individual sensitivity to theophylline, pregnancy, breastfeeding, epilepsy, thyrotoxicosis, myocardial infarction.

M-anticholinergics (anticholinergics)

The parasympathetic system and cholinergic receptors play a major role in the formation of bronchial hyperreactivity and the development of bronchial asthma. Hyperstimulation of cholinergic receptors leads to increased degranulation of mast cells with the release of a large number of inflammation mediators, which contributes to the development of inflammatory and bronchospastic reactions and their equivalents in the bronchi.

Therefore, a decrease in the activity of cholinergic receptors may have a beneficial effect on the course of bronchial asthma.

The maximum density of cholinergic receptors is characteristic of large bronchi and is less pronounced in medium-sized bronchi. In small bronchi, there are significantly fewer cholinergic receptors and they play a minor role in the development of their spasm. This explains the lower effectiveness of anticholinergics in the treatment of bronchial asthma compared to beta-adrenergic receptor stimulants. Unlike cholinergic receptors, adrenergic receptors are located evenly throughout the bronchial tree, with a slight predominance of α-receptors in medium bronchi and beta-receptors in small bronchi. That is why beta-adrenergic stimulants are highly effective in diseases that occur with obstruction of small bronchi - bronchial asthma and distal bronchitis.

M-anticholinergics block M-cholinergic reactive structures and thereby reduce the bronchoconstrictive effect of the vagus nerve.

These drugs are indicated primarily in the development of the vagotonic (cholinergic) variant of bronchial asthma. In these cases, systemic phenomena of vagotonia are often detected: combination with ulcerative disease of the duodenum, tendency to arterial hypotension, bradycardia, hyperhidrosis of the palms, etc.

Quite often, anticholinergics are also effective in atonic bronchial asthma and chronic obstructive bronchitis.

The most commonly used anticholinergics are the following:

Atropine - can be used to stop an asthma attack, for this purpose 0.5-1 ml of 0.1% solution is administered subcutaneously. In some cases, a stopping effect can be achieved by inhaling a fine aerosol (0.2-0.3 mg of atropine in a dilution of 1:5, 1:10) for 3-5 minutes. The therapeutic effect lasts for about 4-6 hours. Atropine is effective for moderate bronchial obstruction. An overdose of atropine causes dry mouth, dilated pupils, accommodation disorder, tachycardia, intestinal hypotension, and difficulty urinating. Atropine is contraindicated in glaucoma.

Platyphylline - 1 ml of 0.2% solution is prescribed subcutaneously 1-3 times a day, powders - orally 0.002-0.003 g 3 times a day. Used in injections to relieve an attack of bronchial asthma, in powders - to treat chronic bronchial obstruction.

Metacin - 1 ml of 0.1% solution is administered subcutaneously to relieve an asthma attack. It has a superior antispasmodic effect to atropine and has less pronounced side effects. In tablets, 0.002 g is used 3 times a day to treat chronic bronchial obstruction.

Belladonna extract - used in powder form for chronic bronchial obstruction, 0.015 g 3 times a day.

Here are some prescriptions containing anticholinergics for the relief of mild asthma attacks and for the treatment of chronic bronchial obstruction:

• Metacin 0.004 g
• Belladonna extract 0.01 g
• Ephedrine 0.015 g
• Theophylline 0.1 g

Take 1 powder 3 times a day.

• Euphyllin 0.15
• Ephedrine 0.025
• Diphenhydramine 0.025
• Papaverine 0.03
• Platyphylline 0.003

Take 1 powder 3 times a day.

• Euphiplia 0 15 g
• Platyphylline 0.003 g
• Ephedrine 0.015 g
• Phenobarbital 0.01 g

Take 1 powder 3 times a day.

Ipratropium bromide (Atrovent) is a quaternary derivative of atropine, an anticholinergic drug that acts primarily on bronchial cholinergic receptors. It is characterized by high activity as a competitive antagonist of the neurotransmitter acetylcholine, binds to cholinergic receptors in the smooth muscles of the bronchi and suppresses vagus-mediated bronchoconstriction. Ipratropium bromide is more selective in relation to cholinergic receptors, which is expressed in higher bronchodilator activity compared to atropine and less suppression of mucus formation when used by inhalation.

When the drug is administered by inhalation, its absorption is minimal. It can be considered that its action is local in nature without accompanying systemic effects. The action of ipratropium bromide begins 5-25 minutes after inhalation, reaches a maximum on average after 90 minutes, the duration of action is 5-6 hours. Increasing the dose increases the duration of action. Compared with atropine, the effect of the drug on the bronchi is stronger and longer lasting with a less pronounced effect on the cholinergic receptors of other organs (heart, intestines, salivary glands). In this regard, atrovent has significantly fewer side effects and is better tolerated compared to atropine.

Atrovent is used to relieve mild asthma attacks (mainly in vagotonic forms), as well as in tonic obstructive bronchitis with hyperactivity of the cholinergic system. In addition, Atrovent is indicated for tracheobronchial dyskinesia, exercise-induced asthma, and in the case of emphysematous chronic bronchial obstruction. It is available as a metered-dose aerosol. Prescribed 2 inhalations (1 inhalation = 20 mcg) 3-4 times a day.

Atrovent is also available in other forms:

• capsules for inhalation (0.2 mg per capsule) - inhale 1 capsule 3 times a day;
• solution for inhalation - a 0.025% solution of the drug is used (1 ml contains 0.25 mg) 4-8 drops using a spray device 3-5 times a day.

Oxytropium bromide is close to atrovent.

Troventol is a domestic drug, similar in action to Atrovent. It is prescribed 2 inhalations (1 inhalation = 40 mcg) 3-4 times a day for prophylactic use and 2 inhalations to relieve an asthma attack. After a single inhalation of 80 mcg, the bronchodilator effect begins after 20-30 minutes, reaches a maximum after 1 hour and lasts up to 5 hours.

Atrovent and troventol combine well with beta2-adrenergic receptor stimulants.

Berodual is a combined aerosol preparation containing the anticholinergic atrovent and the beta2-adrenergic agonist berotek (fenoterol). This combination allows for a bronchodilator effect to be achieved with a lower dose of fenoterol (berotek). Each dose of berodual contains 0.5 mg of fenoterol and 0.02 mg of atrovent. The preparation is indicated for the relief of acute asthma attacks, as well as for the treatment of chronic bronchial obstruction. The usual dose for adults is 1-2 doses of aerosol 3 times a day, 4 times a day if necessary. The onset of action of the preparation is after 30 seconds, the maximum effect develops after 2 hours, the duration of action does not exceed 6 hours.

General indications for the use of anticholinergics in bronchial asthma:

• broncho-obstructive syndrome against the background of inflammatory diseases of the bronchi (M-anticholinergics are the drug of choice);
• bronchial obstruction caused by physical exertion, cold, inhalation of dust, gases;
• broncho-obstructive syndrome with severe bronchorrhea;
• relief of asthma attacks in patients with contraindications to the administration of beta2-adrenergic stimulants.

Alpha blockers

They block α-receptors of the bronchi and thus can cause a bronchodilating effect. However, this effect is weakly expressed and these drugs have not received wide application in the treatment of bronchial asthma.

Droperidol - is prescribed at 1 ml of 0.025% solution intramuscularly or intravenously, sometimes used in complex therapy of stage I asthmatic status. The drug has a calming effect, can relieve agitation in patients in a state of asthmatic status.

[ 25 ], [ 26 ], [ 27 ], [ 28 ], [ 29 ], [ 30 ]

Calcium antagonists

Calcium antagonists are substances that inhibit the entry of calcium ions into cells through potential-dependent calcium channels.

Calcium antagonists can prevent and reduce the pathogenetic mechanisms of bronchial asthma (bronchospasm, hypersecretion of mucus, inflammatory edema of the bronchial mucosa), since these processes, as well as chemotaxis of eosinophils, the release of biologically active substances (histamine, slow-acting substance) from mast cells depend on the penetration of calcium ions into the corresponding cells through slow calcium channels.

However, clinical studies have not shown a significant effect of calcium antagonists in the treatment of atopic bronchial asthma.

At the same time, it has been found that calcium antagonists can prevent the development of hypoxemic pulmonary hypertension in patients with bronchial asthma. For this purpose, nifedipine (corinfar, foridon, cordafen) can be used at 10-20 mg 3-4 times a day orally (in case of asthma of physical effort - under the tongue).

Calcium antagonists are also advisable in the combination of bronchial asthma and arterial hypertension.

G. B. Fedoseyev (1990) studied the effect of corinfar on bronchial patency and obtained the following results:

• a single dose of 20 mg does not cause significant changes in bronchial patency, i.e. does not have a bronchodilatory effect;
• nifedipine reduces the sensitivity and hyperreactivity of the bronchi to acetylcholine; the most effective daily dose is 60 mg, the total dose is 840 mg;
• Calcium antagonists should be used to treat patients with bronchial asthma, with improvement in bronchial reactivity and sensitivity indicators following a single dose of the drug.

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Antispasmodics

Of the antispasmodics, isoquinoline derivatives are mainly used - papaverine and no-shpa. The mechanism of the antispasmodic action of these drugs is not completely clear. In recent years, it has been established that they are phosphodiesterase inhibitors and cause intracellular accumulation of cAMP, which ultimately leads to relaxation of smooth muscles, including in the bronchi. These drugs can be used to improve bronchial patency, but usually in combination with other bronchodilators.

Papaverine - is used in tablets of 0.04 g 3 times a day orally; in injections - 2 ml of 1% solution intramuscularly.

No-shpa - taken in tablets of 0.04 g 3 times a day orally - in injections - 2 ml of solution intramuscularly, intravenously.

G. B. Fedoseyev suggests chronotherapy and chronoprophylaxis of bronchial asthma. The greatest deterioration of bronchial patency is observed in the period from 0 to 8 am (in many patients at 4 am). Taking medications, in particular inhalation: bronchodilators, should be timed to coincide with the expected attack. Inhalations of beta-adrenergic agonists are prescribed 30-45 minutes before the expected attack of bronchial patency, intal - 15-30 minutes, beclomet - 30 minutes, taking euphyllin - 45-60 minutes.

Expectorants and herbal medicine

In case of bronchial asthma, the use of expectorants is justified, since by facilitating the discharge of sputum, they improve bronchial patency and allow for a quicker relief of exacerbation of bronchial asthma.

Here we will present those medicinal and herbal remedies that are most suitable for the treatment of bronchial asthma due to their good tolerability.

Bromhexine (bisolvon) - is prescribed in a dose of 8 mg, in tablets, 3 times a day. It can be used in the form of inhalations: 2 ml of the drug is diluted with distilled water in a ratio of 1:1, the effect is noted after 20 minutes and lasts 4-8 hours, 2-3 inhalations are done per day. In very severe cases, bromhexine is administered 2 ml of 0.2% subcutaneously, intramuscularly, intravenously 2-3 times a day. The course of treatment is 7-10 days. The drug is well tolerated.

Lycorine is an alkaloid found in plants of the Amaryllis and Liliaceae families. It increases the secretion of bronchial glands, liquefies sputum, and reduces the tone of the bronchial muscles. It is prescribed orally at 0.1-0.2 mg 3-4 times a day.

Glycyram - is used 0.05 g 3 times a day in tablets orally, the drug is obtained from licorice root, has an expectorant, anti-inflammatory and adrenal stimulating effect.

Thermopsis herb infusion - prepared from 0.8 g per 200 ml of water, taken 1 tablespoon 6 times a day.

Potassium iodide - a 3% solution of 1 tablespoon is used 5-6 times a day. It should be noted that not all patients tolerate iodides well.

Traskov's anti-asthmatic mixture: 1 liter of the mixture contains sodium iodide and potassium iodide 100 g each, an infusion of a set of medicinal herbs (nettle leaves, horsetail grass, mint leaves - 32 g each, adonis grass, anise fruits, pine needles - 12.5 g each, rose hips - 6 g), in addition, glycerin - 100 g, silver nitrate - 0.003 g, soda - 19 g. Take 1 teaspoon 3 times a day with warm milk 30 minutes after meals. The course of treatment is 4-5 weeks.

Herbal teas containing medicinal plants with expectorant properties (coltsfoot, plantain, linden, thyme).

E. Shmerko and I. Mazan (1993) recommend herbal applications to the back of the chest along with the intake of herbal mixtures. They promote the discharge of phlegm and relaxation of the bronchial muscles.

[ 32 ], [ 33 ], [ 34 ], [ 35 ], [ 36 ], [ 37 ], [ 38 ], [ 39 ]

Method of treating bronchial asthma by introducing novocaine into the Zakharyin-Ged points

In bronchial asthma, skin reactions in the Zakharyin-Ged zones change, while in some cases a positive effect of acupuncture is noted, including when acting on these points. L. I. Gurskaya (1987) proposed a method of treating patients with bronchial asthma by introducing a 1% solution of novocaine into the Zakharyin-Ged zones, taking into account its dual action: the needle prick itself (the effect of acupuncture) and the effect of the novocaine solution on the nerve endings of the Zakharyin-Ged zones.

Patients are injected with a 1% solution of novocaine into the Zakharyin-Ged zone at one time (without removing the needle) first intradermally, then the needle is advanced and the drug is injected subcutaneously. This method cannot be used to treat patients with novocaine intolerance.

Novocaine is injected into the Zakharyin-Ged zones in cycles: the first cycle is 12 days, the second is 10 days, the third is 8 days, the fourth is 6 days, the fifth is 4 days.

To achieve a therapeutic effect, it is often sufficient to carry out only one or two treatment cycles with different intervals between them depending on the patient's condition; subsequent cycles (up to the fifth) are carried out according to the scheme of the first treatment cycle, taking into account the number of days of each cycle.

If necessary, the dose of novocaine for administration to each zone can be increased to 1-2 ml. The most sensitive zones are 1, 2, 3, 4. Novocaine treatment begins with these zones in all cycles.