Medications for bronchial asthma

The main goals of treatment of patients with bronchial asthma:

• establishment and maintenance of control over manifestations of bronchial asthma;
• prevention of exacerbations of the disease;
• maintenance of respiratory function at a level as close as possible to normal;
• maintenance of normal vital activity;
• prevention of side effects in treatment;
• preventing the development of an irreversible component of bronchial obstruction;
• prevention of death.

Criteria for the control (controlled course) of bronchial asthma:

• minimal (ideally absent) symptoms, including nocturnal asthma;
• minimal (extremely rare) exacerbations;
• absence of emergency visits to the doctor;
• minimal need for inhalation of beta2-agonists;
• lack of activity limitations, including physical activity;
• daily fluctuations PSV <20%; minimal (or absent) side effects of drugs;
• normal or close to normal PSV.

The main groups of drugs used to treat bronchial asthma

Anti-inflammatory drugs:

1. Sodium cromoglycate (intal)
2. Sodium nedokromil (tayled)
3. Ditk
4. Gyukokortikoidy (mainly local - e form of inhalation and also inside and parenteral)

Bronchodilators:

1. Stimulants adrenergic receptors:
   1. stimulants of alpha and beta-2-adrenoceptors (adrenaline, ephedrine);
   2. stimulants of beta2- and beta1-adrenergic receptors (isadrine, novrinin, euspyran);
   3. selective beta2-adrenostimulants.
      • short-acting - salbutamol, terbutaline, salmefamol, ipradol;
      • long-acting - salmeterol, formoterol).
2. Anticholinergic agents:
   1. ipratropium bromide (atrogen);
   2. beardwool;
   3. trooventol;
3. Methylxanthines:
   1. aminophylline;
   2. teofillin

Treatment of patients with bronchial asthma should be individualized, take into account etiological, clinico-pathogenetic options and include:

• elimination activities (elimination of contact with significant for the patient and potential allergens, as well as nonspecific irritants);
• drug therapy (pathogenetic and symptomatic);
• non-drug treatment methods (naturotherapy).

The main significance in the phase of exacerbation of bronchial asthma is drug therapy. It provides suppression of inflammatory beatings of the bronchial mucosa and restoration of their normal patency. For this purpose, two main groups of drugs are used: anti-inflammatory drugs and bronchodilators.

Effects on the pathophysiological stage

In the pathophysiological stage, bronchospasm develops, swelling, inflammation of the bronchial mucosa and as a result, an attack of suffocation. Many activities in this phase contribute to the immediate arrest of an attack of suffocation.

[1], [2], [3], [4], [5], [6], [7], [8]

Bronchodilators

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

1. Stimulants adrenergic receptors.
2. Methylxanthines.
3. M-holinoblokatory (holinolitiki).
4. Alpha-adrenoblockers.
5. Calcium antagonists.
6. Spasmolytics

[9], [10], [11], [12], [13], [14], [15], [16]

Stimulants of adrenergic receptors

In the smooth muscles of the bronchi, there are alpha and beta2-adrenergic receptors, through which the sympathetic nervous system has a regulating effect on the bronchial tone. Excitation of beta2 receptors leads to bronchial dilatation, excitation of alpha (postsynaptic) adrenorenoreceptors causes bronchospasm and a narrowing of the bronchial vessels (this leads to a decrease in the edema of bronchial mucosa).

The mechanism of bronchial dilatation with stimulation of beta2-adrenergic receptors 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 facilitates the transport of Ca ++ ions from myofibrils to the sarcoplasmic reticulum, which delays the interaction of actin and myosin in the muscles of the bronchus, which as a result relaxes.

Stimulants of beta-adrenergic receptors do not have an anti-inflammatory effect and are not the basic means for the treatment of asthma. Most often they are used to exacerbate the disease to stop the attack of suffocation.

Stimulants adrenergic receptors are divided into the following subgroups:

• beta1,2- and alpha-adrenostimulators (epinephrine, ephedrine, theofedrine, solutane, efatin);
• beta1 and beta2-adrenoceptors (isadrine, novrinin, euspyran);
• selective beta2-adrenostimulants.

Beta1,2- and alpha-adrenergic stimulants

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

The drug is released in ampoules of 1 ml of 0.1% solution and is used to stop the attack of bronchial asthma. Subcutaneously injected 0.3-0.5 ml, in the absence of effect after 10 minutes, the administration is repeated in the same dose. The drug acts for 1-2 hours, it is rapidly destroyed by catechol-O-methyltransferase.

Possible side effects of adrenaline (they develop with frequent use of it and especially in elderly people suffering from coronary artery disease simultaneously): tachycardia, extrasystole, the appearance of pain in the heart (due to increased myocardial oxygen demand), sweating, tremor, agitation, increased blood pressure, hyperglycemia.

With frequent use of adrenaline, the effect of aftereffect is possible: from adrenaline is formed metanephrine, blocking β-receptors in the bronchi, which contributes to the enhancement of bronchospasm.

Contraindications to the use of adrenaline:

• hypertonic disease;
• exacerbation of IHD;
• diabetes;
• toxic goiter.

Ephedrine is an indirect stimulant of alpha and beta-adrenergic receptors. The drug displaces norepinephrine from the presynaptic endings of the sympathetic nerves, slows its re-uptake, increases the sensitivity of adrenoreceptors to noradrenaline and adrenaline, releases epinephrine from the adrenal cortex. In addition, it has a slight direct alpha-stimulating effect, it is used for relief of attacks of bronchial asthma, as well as for chronic bronchial obstruction. To stop the attack, 1 ml of a 5% solution is injected subcutaneously. The action begins in 15-30 minutes and lasts about 4-6 hours, i.e. In comparison with adrenaline acts later, but more longly. When chronic bronchial obstruction is used in tablets of 0.25 g (1 tablet 2-3 times a day), in inhalations (0.5-1 ml of 5% solution in dilution isotonic sodium chloride solution 1: 3, 1: 5).

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

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

Theophedrine is a combined preparation of the following composition: theophylline, theobromine, caffeine - 0.5 g, amidopyrine, phenacitin - 0.2 g, ephedrine, phenobarbital, extract of belladonna - 0.2 g, labelin - 0.0002.

Bronchodilating effect is caused by ephedrine, theophylline, theobromine. It is usually prescribed for chronic bronchial obstruction of 1 / 2-1 tablet in the morning and evening. Possible relief of light attacks of suffocation.

Solutan is a combined preparation, it has a bronchodilator (holino-spasmolytic) and expectorant effect. It is used for chronic bronchial obstruction of 10-30 drops 3 times a day. Consider the possibility of intolerance to primrose and other components of the drug.

Efatin - comes in the form of an aerosol. Contains ephedrine, atropine, novocaine. It is prescribed for 2-3 breaths 3 times a day.

The drug stops the attacks of bronchial asthma, however, before using the drug, you should find out the tolerability of novocaine.

[17], [18], [19], [20], [21], [22], [23], [24]

β2- and β1-adrenostimulators

β2- and β1-adrenostimulants stimulate beta2-adrenergic receptors in the bronchi and expand them, but at the same time stimulate myocardial beta 1-adrenoreceptors and cause tachycardia, an increase in myocardial oxygen demand. Stimulation of beta2 receptors also causes an expansion of the bronchial artery and branches of the pulmonary artery (possibly the development of the "bronchial closure" syndrome).

Shadrin (isopropylnoradrenaline) - is produced in tablets of 0.005 g, in vials of 25 ml of 0.5% solution and 100 ml of 1% solution, and also in the form of a dosed aerosol.

To relieve a mild attack of bronchial asthma take one tablet under the tongue (or keep in the mouth until completely dissolved). With sublingual administration, the effect begins 5-10 minutes and lasts about 2-4 hours.

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

Frequent use of Shadrin can cause an increase and a weighting of asthma attacks due to the fact that the decay product of 3-methoxyisoprenaline has a blocking effect on beta2 receptors.

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

Shadrin's Analogues:

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

Selective beta2-adrenostimulyagory

Selective beta2-adrenostimulants selectively stimulate beta2-adrenergic receptors of the bronchi, causing their dilatation, almost do not have a stimulating effect on myocardial beta 1-adrenoreceptors.

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

The mechanism of action of selective beta2-adrenostimulants:

• excitation of beta2-adrenoreceptors and bronchial dilatation;
• improvement of mucociliary clearance;
• depression of degranulation of mast cells and basophils;
• prevention of the release of lysosomal enzymes from neutrophils;
• a decrease in the permeability of membranlosolomes.

Selective beta2-adrenostimulants are proposed to be classified as follows:

• selective:
  • short-acting: salbutamol (ventolin), terbutaline (bricanil), salmefamol, ipradol;
  • long-acting: salmeterol, formoterol, sulfuric acid, volmax, clenbuterol;
• having partial selectivity: fenoterol (berotek), orciprenaline sulfate (alupent, astomopent).

Prolonged selective beta2-adrenostimulants

Prolonged selective beta2-adrenostimulants were synthesized in the late 1980s, the duration of action of these drugs was about 12 hours, the prolonged effect was due to their accumulation in the lung tissue.

Salmeterol (sulfur) is used in the form of a dosed aerosol 50 μg 2 times a day. This dose is sufficient for patients with bronchial asthma of the lung and moderate course. With a more severe course of the disease, a dose of 100 mcg is administered twice a day.

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

Volmax (salbutamol SR) is an oral form of prolonged action of salbutamol. Each tablet contains 4 or 8 mg of salbutamol, consisting of an outer impermeable shell and an inner core. In the outer shell there is an opening permitting osmotically controlled release of the preparation. The controlled release mechanism of salbutamol provides a gradual intake of the active substance for a long time, which allows you to prescribe the drug only 2 times a day and use it for the prevention of bronchial asthma.

Clenbuterol hydrochloride (spiro pent) - used in tablets of 0.02 mg 2 times a day, in severe cases, you can increase the dose to 0.04 mg 2 times a day.

In contrast to salbutamol and other short-acting beta2-stimulants, the effect of prolonged drugs does not occur quickly, so they are used mainly not for relief, but for the prevention of attacks of suffocation, including nocturnal. These drugs also have an anti-inflammatory effect, as they reduce vascular permeability, prevent the activation of neutrophils, lymphocytes, macrophages, inhibit the release of histamine, leukotrienes and prostaglandins from mast cells. Extended selective beta2-stimulants less often cause a decrease in the sensitivity of beta receptors to them.

According to some researchers, long-acting beta2-adrenostimulants should be more often combined with glucocorticoids in inhalations. In Russia, a beta-agonist of extended action of 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 nighttime asthma.

Short-acting selective beta2-adrenostimulators

Salbutamol (ventolin) is available in the following forms:

• dosed aerosol, prescribe 1-2 breaths 4 times a day, 1 breath = 100 mcg. It is used to stop an attack of bronchial asthma. With inhalation, only 10-20% of the administered dose reaches the distal parts of the bronchi and alveoli. This drug, unlike adrenaline and Shadrin, is not subjected to methylation with the participation of catechol-O-methyltransferase, i.e. It does not transform into the lungs into metabolites with a beta-blocking effect. Most of the inhaled salbutamol used is deposited in the upper respiratory tract, swallowed, absorbed in the gastrointestinal tract, can cause side effects (palpitation, hand tremor), but they are poorly expressed and are observed only in 30% of patients. Salbutamol is considered one of the safest β-sympathomimetics - bronchodilators. The drug can also be used in the form of inhalations with a nebulizer (5 mg in an isotonic solution of sodium chloride for 5-15 minutes, not more than 4 times a day), using a spinhaler in powder form 400 mg not more than 4 times a day. The use of the sphaler allows increasing the intake of salbutamol into the small bronchi;
• tablets of 0.002 g and 0.004 g for oral administration, are applied 1-4 times a day for chronic bronchial obstruction in a daily dose of 8-16
  mg.

Ventodisk - a new form of ventolin, consists of 8 bubbles sealed in a double layer of foil. Each vial contains the smallest powder of salbutamol (200-400 μg) and lactose particles. Inhalation of the drug from the ventodisk after piercing it with a needle is performed with the help of a special inhaler - diskhayler. The use of the ventodisk allows the introduction of salbutamol even with shallow breathing. It is inhaled 4 times a day for relief of attacks of bronchial asthma.

Salmefamol is available in the form of metered aerosols, it is used to stop the attack of asthma - 1-2 inhalations 3-4 times a day, one breath = 200 mcg.

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

• dosed aerosol for cupping an attack of bronchial asthma, appoint 1 breath 3-4 times a day, 1 inspiration = 250 mcg;
• ampoules of 1 ml of 0.05% solution is injected intramuscularly by 0.5 ml to 4 times a day for arresting the attack;
• tablets of 2.5 mg, administered orally 1 tablet 3-4 times a day for chronic bronchial obstruction;
• tablets of extended action on 5 and 7.5 mG (on 1 tablet 2 times a day).

Iprradol is available in the following forms:

• Dosed aerosol for cupping an attack of bronchial asthma, 1-2 inhalations 3-4 times a day, 1 inspiration = 200 mcg;
• ampoules of 2 ml of a 1% solution are prescribed intravenously for relief of an attack of bronchial asthma;
• tablets of 0.5 mg, apply 1 tablet 2-3 times a day inward for the treatment of chronic bronchial obstruction.

Short-acting selective beta2-adrenostimulants start their action with inhalation after 5-10 minutes (in some cases before), the maximum of action is manifested after 15-20 minutes, the duration of action is 4-6 hours.

Partially selective beta2-adrenostimulants

These drugs stimulate significantly and predominantly beta2-adrenergic receptors of the bronchi and cause bronchodilation, but still to a certain extent (especially with excessive use) stimulate beta 1-adrenoreceptors of the myocardium and can cause tachycardia.

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

• a metered aerosol for cupping an attack of a bronchial asthma, appoint or nominate on 1-2 inspirations 4 times a day, one inspiration is equaled to 0.75 mg;
• ampoules for cupping an attack of bronchial asthma on 1 ml of 0.05% solution, injected subcutaneously, intramuscularly (1ml); intravenously drip (1-2 ml in 300 ml of 5% glucose);
• tablets of 0.02 g for the treatment of chronic bronchial obstruction, take 1 tablet 4 times a day inside.

Fenoterol (berotek) is available in the form of a dosed aerosol. It is used to stop an attack of bronchial asthma. It is prescribed for 1 inhalation 3-4 times a day, 1 inhalation = 200 mcg.

In recent years, the combined preparation of a dytec-dosed aerosol is produced, one dose contains 0.05 mg of phenoterolhydrobromide (beroteka) and 1 mg of disodium salt of chromoglycino acid (intala).

Ditek has the property of preventing degranulation of mast cells and expanding bronchi (through the excitation of beta2-adrenergic receptors of the bronchi). Therefore, it can be used both for the prevention of asthma attacks and for their arrest. It is prescribed 2 doses 4 times a day every day, in case of an attack, 1-2 more doses can be inhaled.

Side effects in the treatment of beta-adrenostimulators:

• Excessive use of drugs causes tachycardia, extrasystole, frequent attacks of angina pectoris, these phenomena are most pronounced in nonselective and in partially selective beta2-adrenostimulants;
• with long-term admission of beta-blockers or their overdose develops resistance to them, worsening bronchial patency (the effect of tachyphylaxis).

Side effects are associated, on the one hand, with the appearance of beta-adrenergic blockade with metabolic products and in a number of cases the decrease in the number of beta receptors, and on the other hand, with the violation of the drainage function of the bronchi due to the development of the "closure" syndrome (enlargement of bronchial vessels and increased edema of the bronchial mucosa). In order to reduce the syndrome of "lung closure" it is recommended to combine the intake of 0-adrenostimulants with the use of euphyllin or ephedrine (the latter stimulates α-receptors, narrows the vessels and reduces bronchial edema).

Side effects are less frequent and less pronounced with selective beta2-adrenergic stimulants.

When treating inhaled sympathomimetics, the following rules should be observed (success of treatment for 80-90% depends on the correct inspiration):

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

Some patients can not synchronize the inspiration with the moment the drug is delivered. It is recommended to use such spacers, individual ultrasonic inhalers (nebulizers), to switch to inhalation of drugs in powder form with the help of spinhalers, discalysers, turbochargers or ingestion of tableted forms.

Spacers are containers with which patients receive a metered aerosol without having to coordinate pressure on the cylinder valve and inhale. Using a spacer reduces the side effects of inhaled drugs, including glucocorticoids, and increases their intake into the lungs.

Methylxanthines

Of the methylxatine group, theophylline, theobromine, and euphyllin are used.

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

The mechanism of action of theophylline:

• inhibits phosphodiesterase, thereby decreasing the destruction and accumulating cAMP in the smooth muscles of the bronchi. This facilitates the transport of Ca ++ ions from myofibrils to the sarcoplasmic reticulum, and, consequently, the interaction of actin and myosin is delayed and the bronchus relaxes;
• inhibits the transport of calcium ions through the slow channels of cell membranes;
• inhibits the degranulation of mast cells and the release of mediators of inflammation;
• blocks adenosine purine receptors of the bronchi, while eliminating the bronchospastic 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 a small circle of 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.

Eufillin is produced in ampoules of 10 ml of 2.4% solution. Intravenous introduction of 10-20 ml of isotonic sodium chloride solution should be carried out very slowly (within 5 minutes). With rapid administration, a drop in blood pressure, dizziness, nausea, tinnitus, palpitation, reddening of the face, a feeling of heat are possible.

Introduced intravenously, euphyllin acts for about 4 hours, in smokers the effect of the drug is weaker and less prolonged (about 3 hours). Intravenous drip introduction of the drug prolongs its effect up to 6-8 hours and significantly less causes the above-described adverse reactions. Intravenously, 10 ml of a 2.4% solution in 300 ml of isotonic sodium chloride solution is drip-fed.

Significantly less often for relief of an attack of bronchial asthma, intramuscular injection of 1 ml of a 24% solution of euphyllin is used, its stopping effect is much weaker.

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

Inside take eufillin, produced in tablets of 0.15 g, it is prescribed after meals. However, when taking tablets, there may be gastric irritation, the appearance of nausea, pain in the epigastric region.

To reduce these phenomena, you can recommend the use of euphyllin in capsules, the eco-fayl use of euphyllin and ephedrine enhances the bronchodilator effect of both drugs.

You can make powder and apply in capsules 3 times a day:

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

Eufillin when ingested is better absorbed in the form of alcohol solutions.

You can recommend the following prescriptions:

• eufillina - 5 g
• Ethyl alcohol 70% - 60 ml
• distilled water up to - 300 ml

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

• eufillina - 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.

For treatment of chronic bronchial obstruction and prevention of nocturnal asthma attacks, euphyllinum in candles is widely used:

• eufillina - 0.36 g
• cocoa butter - 2 g

Euphyllinum in suppositories is valid for about 8-10 hours. Introduce 1 suppository into the anus at night (preferably after spontaneous emptying of the intestine or after a preliminary cleansing enema). Possible repeated administration in the morning.

You can use the suppository diprofilina to 0.5 g. This is 7-beta, 3-dihydroxypropyl) - theophylline, which by pharmacological properties is close to euphyllin.

Theophylline - is used to treat chronic bronchial obstruction. Produced in the form of powders (taken 0.1-0.2 g 3 times a day), in suppositories of 0.2 g (introduced into the rectum at night to prevent nighttime asthma attacks). We can recommend a copy of B. Ye. Votchal:

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

Take 1-2 tablespoons 3 times a day.

Long-acting theophylline preparations

The main shortcomings of conventional theophylline include a small breadth of therapeutic effect (10-20 μg / ml), fluctuations in the level of the drug in the blood between the doses, rapid elimination from the body, the need for oral administration 4 times a day.

In the 1970s, long-acting theophylline preparations appeared. Advantages of prolonged drugs are as follows:

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

Prolonged theophylline preparations are divided into 2 groups: preparations of the first generation (effective 12 hours and appointed twice a day) and preparations of the second generation (valid 24 hours and are prescribed once a day).

Treatment with theophylline prolonged action is advisable to conduct under the control of the concentration of the drug in the blood. Theophylline has a small breadth of therapeutic effect.

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

Most theophylline therapies have a half-life of 11-12 hours, the therapeutic concentration in the blood is reached after 3-5 half-lives, i.e. After 36-50 hours or 3 days from the start of treatment. Evaluate the effect and correct the dose of theophylline no earlier than 3 days after the start of treatment.

In mild cases, intoxication with theophylline is manifested by nausea, vomiting, tachycardia, in more severe - ventricular arrhythmias, arterial hypotension, hypoglycemia. The most formidable complication of theophylline overdose is seizures (due to blockade of the central adenosine receptors).

In intoxication with theophylline, the stomach is washed, activated charcoal, symptomatic agents (antiarrhythmic, anticonvulsant, potassium preparations), in more severe cases, hemosorption.

Smoking promotes the removal of theophylline from the body. At smokers the maximum concentration of prolonged theophyllines is almost 2 times lower than that of non-smokers.

The pharmacokinetics of theophyllines are characterized by circadian rhythms. When administered in the morning dose of theophylline, the rate of absorption is higher than the evening dose. With a two-time intake of prolonged drugs, the peak daily concentration falls at 10 am, the night time at 2 am.

In our country, from the extended theophylline preparations, theopec, teobsolong is most often used.

Teopek - pills of the theophylline of prolonged action, contain 0.3 g of theophylline in combination with a composite polymer carrier, which provides a dosed release of theophylline in the gastrointestinal tract. After receiving theopeke, the maximum concentration of theophylline in the blood is observed after 6 hours.

The release of theophylline from tablets teopeka occurs only when washed 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 can not be crushed.

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

In 1990, VG Kukes published the following data on the clinical pharmacology of theopeca:

• one-time dose reception 0.3 g does not cause changes in the patients' condition, with the course treatment by the theopec the effect was noted on 3-5 days;
• in the absence of effect, increasing the dose to 400, 450, maximum up to 500 mg of the theopeca per reception leads to a significant bronchodilator effect. The optimal concentration of theophylline in the blood is created by taking 2 times a day;
• the drug reliably reduces the pressure in the pulmonary artery. Yu.B. Belousov (1993) gives the following recommendations for the treatment of theopecks:
• it is advisable to start treatment with a single minimal dose;
• a single minimal dose is increased gradually after 3-7 days by 50-150 mg, depending on the clinical effect and concentration of theophylline in the blood;
• the drug is used 2 times a day;
• at frequent nocturnal attacks of a dyspnea 2/3 of a daily dose appoint or nominate in the evening, 1/3 - in the morning;
• application of the drug at night in a double dose leads to an increase in the concentration of theophylline in the serum above the norm;
• in patients with nocturnal attacks of asthma, the most rational one-time use of the drug at night in a dose of 300-450 mg;
• in the absence of a strict dependence of the onset of asthma attacks on the time of day, 300 mg are prescribed in the morning and in the evening.

Theotard-retard-capsule contains 200, 350 or 500 mg of anhydrous theophylline. After ingestion 100% is absorbed. During the first 3 days, the drug is taken 1 capsule 2 times a day (200 mg for children, 350 mg for adults, and 500 mg if necessary).

Teobiolong tablets prolonged action, containing 0.1 theophylline in combination with a biosoluble polymer. Assign inside after eating (without crushing and not dissolving in water). Treatment begins with a dose of 0.1 g twice daily with an interval of 12 hours. After 2-3 days, in the absence of side effects, the dose is increased: 0.2-0.3 g is prescribed 2-3 times a day depending on therapeutic effectiveness and tolerability.

Single dose should not exceed 0.3 g, daily - 0.6 g.

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

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

Abroad, different prolonged theophylline preparations are available in the form of tablets or capsules with granules called Teodur, Teotard, Durofillin Retard, Retafil, and others.

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

Retafil - is released in tablets of 0.2 and 0.3 g. In 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 - in the morning and in the evening.

The side effects of theophylline

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 on the part of the digestive organs are possible (nausea, anorexia, vomiting, diarrhea). When theophylline concentration is 20-30 μg / ml, the cardiovascular system is affected, which is manifested by tachycardia, cardiac arrhythmias. In the most severe cases, development of flutter and ventricular fibrillation is possible. The risk of unfavorable effects on the cardiovascular system increases in persons over 40 years old, as well as in patients with IHD.

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

To avoid the development of side effects when treating theophylline with prolonged action, it is necessary to consider the following factors:

• age of the patient;
• severity of the course of bronchial asthma;
• accompanying illnesses;
• possible interactions with other drugs;
• the feasibility of monitoring the concentration of theophylline in the blood with prolonged use.

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

M-holinoblokatory (holinolitiki)

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

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

The maximum density of cholinergic receptors is characteristic for large and less pronounced bronchi of medium caliber. In small bronchi, cholinergic receptors are much smaller and they play a small role in the development of their spasm. This explains the lower effectiveness of anticholinergics in the treatment of bronchial asthma in comparison with stimulants of beta-adrenergic receptors. Unlike cholinergic, adrenergic receptors are located evenly throughout the bronchial tree, with a slight predominance of α-receptors in the middle bronchi and beta receptors in the smaller ones. That is why beta-adrenostimulants are highly effective in diseases that occur with obstruction of small bronchi - bronchial asthma and distal bronchitis.

M-cholinolytics block M-cholinergic structures and thereby reduce the bronchoconstrictor effect of the vagus nerve.

This means are shown primarily in the development of the vagotonic (cholinergic) variant of bronchial asthma. In these cases, systemic phenomena of vagotonia are often found: combination with duodenal ulcer, inclination to arterial hypotension, bradycardia, palmar hyperhidrosis, etc.

Quite often anticholinergics can also be effective in atonic bronchial asthma, chronic obstructive bronchitis.

The most commonly used anticholinergics.

Atropine - can be used to stop the attack of asthma, for this purpose, inject 0.5-1 ml of 0.1% solution subcutaneously. In a number of cases, it is possible to obtain a stopping effect by inhalation of a finely dispersed aerosol (0.2-0.3 mg atropine in a dilution of 1: 5, 1:10) for 3-5 minutes. The therapeutic effect lasts about 4-6 hours. Atropine is effective in bronchial obstruction of moderate severity. In case of an overdose of atropine dryness in the mouth, dilated pupils, disruption of accommodation, tachycardia, hypotension of the intestine, difficulty urinating occur. Atropine is contraindicated in cases of glaucoma.

Platifillin - 1 ml 0.2% solution is administered subcutaneously 1-3 times a day, powders - inside 0.002-0.003 g 3 times a day. Apply in injections for cupping an attack of bronchial asthma, in powders - for the treatment of chronic bronchial obstruction.

Metacin - 1 ml of 0.1% solution is injected subcutaneously to stop an asthma attack. As antispasmodic action surpasses atropine, has less pronounced side effects. In tablets, 0.002 g 3 times a day is used to treat chronic bronchial obstruction.

Extract of belladonna - used in powders with chronic bronchial obstruction of 0.015 g 3 times a day.

Here are some of the prescriptions that contain cholinolytics, for the relief of mild asthma attacks and for the treatment of chronic bronchial obstruction:

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

Take 1 powder 3 times a day.

• Eufillina 0.15
• Ephedrine 0.025
• diphenhydramine 0,025
• Papaverina 0.03
• Platifillin 0.003

Take 1 powder 3 times a day.

• Euphypia 0 15 g
• Platifillin 0.003 g
• Ephedrine 0.015 g
• Phenobarbital 0.01 g

Take 1 powder 3 times a day.

Ipratropium bromide (atrovent), a quaternary derivative of atropine, is an anticholinergic drug that acts predominantly 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 for cholinergic receptors, which is expressed in a higher bronchodilator activity than atropine and less mucosal suppression when inhaled.

With inhalation administration of the drug, its absorption is minimal. We can assume 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 of 90 minutes on average, the duration of action is 5-6 hours. Increasing the dose increases the duration of the action. In comparison with atropine, the effect of the drug on the bronchi is stronger and prolonged with less pronounced effect on the cholinergic receptors of other organs (heart, intestine, salivary glands). In this regard, atroventa significantly fewer side effects and better tolerability compared with atropine.

Atrovent is used for relief of mild attacks of suffocation (mainly with vagotonic forms), as well as in tonic obstructive bronchitis with hyperactivity of the cholinergic system. In addition, atrovent is indicated in tracheobronchial dyskinesia, with asthma physical effort and in the case of emphysematous type of chronic bronchial obstruction. Produced in the form of a dosed aerosol. Assign 2 breaths (1 breath = 20 μg) 3-4 times a day.

Atvent is also produced in other forms:

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

Oxytropium bromide - close to the atrovent.

Trventol - a domestic drug, by action is close to atroventu. It is prescribed for 2 inhalations (1 inspiration = 40 mcg) 3-4 times a day for prophylactic intake and 2 inhalations for arresting an attack of suffocation. After a single inhalation of 80 mcg, the bronchodilating effect begins in 20-30 minutes, reaches a maximum after 1 h and lasts up to 5 h.

Atrovent and troventol combine well with stimulants of beta2-adrenergic receptors.

Berodual is a combined aerosol preparation containing cholinoligic atrovent and beta-beta-adrenostimulator berotek (fenoterol). This combination allows you to get a bronchodilator effect with a smaller dose of fenoterol (beroteka). Each dose of berodual contains 0.5 mg of fenoterol and 0.02 mg of atrovent. The drug is indicated for relief of acute attacks of suffocation, 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, if necessary 4 times a day. The beginning of the drug - after 30 seconds, the maximum effect develops after 2 hours, the duration of the action does not exceed 6 hours.

General indications for the use of anticholinergics in bronchial asthma:

• bronchoobstructive syndrome on the background of inflammatory diseases of the bronchi (M-holinoblokatory - a means of choice);
• bronchial obstruction, provoked by physical exertion, cold, inhalation of dust, gases;
• bronchoobstructive syndrome with severe bronchorrhea;
• arresting the attack of suffocation in patients with contraindications to the appointment of beta2-adrenostimulyatorov.

Alpha-blockers

Block α-receptors of bronchi and thus can cause a bronchodilator effect. However, this action is weak and widespread use of these drugs in the treatment of bronchial asthma is not received.

Droperidol - 1 ml of 0.025% solution is administered intramuscularly or intravenously, sometimes it is used in complex therapy of the first stage of asthmatic status. The drug has a calming effect, can relieve the excitement of 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), because these processes, as well as the chemotaxis of eosinophils, the release of mast cells from biologically active substances (histamine, a slowly acting substance) depend on the penetration of ions calcium 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 was found that calcium antagonists can prevent the development of hypoxemic pulmonary hypertension in patients with bronchial asthma. For this, you can use nifedipine (Corinfar, foridone, kordafen) 10-20 mg 3-4 times a day inside (with asthma physical effort - under the tongue).

Calcium antagonists are also useful in the combination of bronchial asthma with arterial hypertension.

GB Fedoseev (1990) studied the influence of coronfar on bronchial patency and received the following results:

• One-time administration of 20 mg does not cause significant changes in bronchial patency, i.e. Does not have a bronchodilator effect;
• nifedipine reduces the sensitivity and hyperreactivity of bronchi to acetalcholine is most effective daily dose of 60 mg, total dose of 840 mg;
• calcium antagonists should treat patients with bronchial asthma, with improved reactivity and bronchial sensitivity under the influence of a single exposure to the drug.

[31]

Spasmolytics

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

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

But-shpa - applying in tablets to 0.04 g 3 times a day inside - in injections - 2 ml solution intramuscularly, intravenously.

G. B. Fedoseev proposes to carry out chronotherapy and chronoprophylaxis of bronchial asthma. The greatest worsening of bronchial patency occurs during the period from 0 to 8 hours (in many patients at 4 am). Taking medications, in particular inhalation: bronchodilators, should be timed to the moment of the expected attack. Inhalation of beta-adrenomimetics is prescribed for 30-45 minutes before the expected attack of bronchial patency, intala - for 15-30 minutes, beclometha - for 30 minutes, the use of euphyllinum - for 45-60 minutes.

Expectorants and phytotherapy

With bronchial asthma, the use of expectorants is justified, since by facilitating the departure of sputum, they improve bronchial patency and allow faster relief of exacerbation of bronchial asthma.

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

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

Likorin - an alkaloid, contained in plants of the family Amarylla and lily. Strengthens the secretion of bronchial glands, dilutes sputum, reduces the tone of bronchial muscles. Assigned inside by 0.1-0.2 mg 3-4 times a day.

Glitsiram - applied to 0.05 g 3 times a day in tablets inside, the drug is obtained from licorice root, has expectorant, anti-inflammatory and stimulating the adrenal glands.

Infusion of herbs of thermopsis - is prepared from 0.8 g per 200 ml of water, taken 1 tablespoon 6 times a day.

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

The anti-asthma medicine Traskov in 1 liter of medicine contains sodium iodide and potassium iodide in 100 grams, infusion of a set of medicinal herbs (nettle leaves, horsetail grass, mint leaves - 32 grams, herb, anise fruit, pine needles - 12.5 grams, hips - 6 g), in addition, glycerin - 100 g, silver nitrate - 0.003 g, soda - 19 g. Take 1 teaspoon 3 times a day for warm milk 30 minutes after eating. The course of treatment is 4-5 weeks.

Medicinal fees containing medicinal plants with expectorant action (mother-and-stepmother, plantain, linden, thyme).

Ε. Shmerko and I. Mazan (1993), together with the intake of doses, recommend phytoapplication to the posterior half of the thorax. They help to sputum and relax the muscles of the bronchi.

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

The method of treatment of bronchial asthma with the introduction of novocain to the points of Zakharyin-Ged

With bronchial asthma, skin reactions in the Zakharyin-Ged zones change, while in a number of cases there is a positive effect of acupuncture, including when exposed to these points. LI Gurskaya (1987) proposed the method of treating patients with bronchial asthma by introducing a 1% solution of novocaine into the Zakharyin-Ged zones, taking into account its double action: the needle itself (the effect of acupuncture) and the effect of novocain solution on the nerve endings of the Zakharyin-Ged zones.

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

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

To achieve a therapeutic effect, it is often sufficient to conduct only one or two treatment cycles with various interruptions between them, depending on the patient's condition; subsequent cycles (up to the fifth) are conducted according to the scheme of the first cycle of treatment 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. From these zones, Novocaine treatment is started in all cycles.