Drugs for seasonal allergies in spring: pharmacological features. Table of drugs

Seasonal allergies: systemic effects

The allergy season in Russia begins in mid-April (plus or minus adjustments depending on the climate zone). Hay fever is associated with plant allergens that appear in the air when plants begin to flower (pollination). An immunological reaction when pollen enters the body with inhaled air, as a rule, is expressed in the form of symptoms of rhinnorea, sneezing, itching and swelling of the eyelids and nasal mucosa, lacrimation, and redness of the eyes.

Allergic manifestations of hay fever can be affected by local and systemic means. Local include nasal and eye drops and sprays, systemic include antiallergic or antihistamines for oral administration and injection. Most antiallergic drugs are over-the-counter, and there are a lot of people suffering from seasonal allergies, so from year to year, starting in spring, pharmacists are faced with the need to offer, advise, and sell customers a product that will help them get rid of an unpleasant condition. Most often (and this corresponds to clinical recommendations), the choice falls on systemic drugs, by taking which you can immediately get rid of all the symptoms that cause discomfort. In our article we will review the antihistamines for internal use currently available in Russia, and recall the features of the use of some of them. In this case, we are not interested in injectable forms, since they are used for quick help in emergency conditions.

Quite a lot of antiallergic drugs for oral administration have been synthesized, however, they are all divided into two generations. Drugs based on active metabolites and stereoisomers do not belong to the third generation. According to the scientific views enshrined in the Antihistamine Consensus, the as-yet-undeveloped third-generation antihistamine would have to be fundamentally different from existing compounds.

The basic principle of the drugs is to block the well-known H1-histamine receptors.

Oldies

1st generation antihistamines (diphenhydramine, chloropyramine, clemastine, dimethindene, mebhydrolin, promethazine) are also called sedatives due to the most important and common side effect. However, in the desire to help, it is wrong to recommend such drugs to people with concomitant insomnia, since sleep will not be physiological, and its quality will suffer. As a result, a person will still feel sleep-deprived and feel drowsy during the day. In addition to sedation, their use is accompanied by depression of cognitive functions and a decrease in reaction speed. Representatives of the group are non-selective and can block alpha-adrenergic receptors, muscarinic, serotonin, M-cholinergic receptors and others. This causes their side effects and contraindications. For example, “old” generation medications cannot be prescribed for angle-closure glaucoma, prostate adenoma, gastric and duodenal ulcers, intestinal and bladder atony, cardiovascular diseases, and bronchial asthma. When counseling older people, this point is important, since they often have such pathologies.

Medicines in this group are not used for more than 7-10 days, since the body gets used to it and the effect of the medicine is weakened. 1st generation drugs bind to histamine receptors competitively, so their complex is quickly destroyed. You need to take these medications 3-4 times a day, which is inconvenient.

On the other hand, their use is justified in a number of cases, precisely due to their non-selectivity (antiemetic, anti-anxiety effect, etc.) and the presence of injectable forms, which is important in emergency situations.

As for allergic rhinitis (seasonal and year-round) and for hay fever, the use of 1st generation antihistamines is undesirable, since they, having an M-cholinergic effect, can cause dry mucous membranes, increase the viscosity of secretions and contribute to the development of sinusitis and sinusitis.

Representatives

Diphenhydramine is a prescription drug in all dosage forms with a pronounced sedative effect. One of its uses is seasickness and air sickness. Cannot be used with ethanol and UV radiation should be avoided when taking.

Chloropyramine is a classic antagonist of H1 - 1st generation histamine receptors.

Dimetindene is the only antihistamine approved for children from the first month. In children under one year of age, it is used under the strict supervision of a doctor. It has all the characteristic properties of representatives of the 1st generation. It is also available in the form of extended-release capsules for once daily dosing.

Mebhydrolin - unlike other representatives, penetrates slightly into the central nervous system, so the sedative effect is rather weakly expressed.

Clemastine - similar in pharmacological properties to diphenhydramine, has a strong antihistamine and antipruritic effect, duration of action is 12 hours, therefore, unlike other drugs in the group, it is taken twice a day.

Beginners

2nd generation antihistamines (cetirizine, levocetirizine, loratadine, desloratadine, rupatadine) have significant advantages compared to the first group. These are the lack of sedation in most patients, highly specific long-term binding of histamine H1 receptors and lack of affinity for other receptors. The medication does not depend on food intake, tachyphylaxis does not occur, which means it can be taken for a long time. Another advantageous feature of these drugs is their anti-inflammatory effect.

“New” generation drugs are taken once a day.

Nota Bene! Although the new generation does not cause sedation, in some individual cases such side effects are possible. Buyers should be warned about this.

Representatives

Cetirizine is an active metabolite of hydroxyzine, developed in 1987 and became the first highly selective H1 blocker. It still remains the “gold standard” in allergy therapy and a standard for comparison. Effective for 24 hours, the effect after the end of administration lasts up to three days. Children's forms are allowed from 6 months. Use in children 6-12 months. under the strict supervision of a doctor.

Levocetirizine, the active enantiomer of cetirizine, has twice the affinity for H1 receptors as cetirizine. Has fast action. Does not require hepatic metabolism, its bioavailability is almost 100%. It has a minimum of side effects, minimal possibility of interaction with other medications, and can be prescribed for liver diseases.

Loratadine is a metabolized drug. When passing through the liver, it is transformed into the active metabolite desloratadine. Therefore, its effect may vary depending on the condition of the liver. This factor must be taken into account if the patient is taking additional medications or has liver disease.

When taken together with inducers of liver enzymes of the cytochrome P450 system (ethanol, St. John's wort, barbiturates, etc.), the therapeutic effect will decrease, and when taken with inhibitors (erythromycin, ketoconazole, cimetidine, etc.), side effects may appear/intensify.

Rupatadine is a relatively new drug and is found in pharmacies and prescriptions quite rarely. It is also metabolized in the liver to desloratadine, 3-hydroxydesloratadine, 5-hydroxydesloratadine and 6-hydroxydesloratadine. The drug can cause fatal arrhythmia, so it is prescribed with caution to patients with a prolonged QT interval, hypokalemia, persistent proarrhythmic conditions, such as clinically significant bradycardia, acute myocardial ischemia. It is not recommended to take rupatadine with grapefruit juice, macrolides, antifungal drugs (imidazole derivatives), or simultaneous use with statins. Age 65 and older is a reason to choose an alternative.

Desloratadine is an active metabolite of loratadine. It is superior in potency to loratadine. Its effect is more predictable and does not depend on the activity of enzymes of the cytochrome P450 system. When taking other medications, the problem of drug interactions is eliminated. Liver diseases do not affect its effectiveness.

The following medications should be highlighted separately:

Intermediate position

Hifenadine and Sehifenadine have a similar structure and stand apart because they have both the properties of the first and second generation. They do not penetrate the BBB, do not depress the central nervous system and are devoid of sedative and hypnotic effects. They do not affect adrenergic and M-cholinergic receptors. But, like 1st generation drugs, they have a short effect and are prescribed 2-3 times a day.

Mast cell stabilizers

Ketotifen is a special drug among antiallergic drugs. Sometimes it is referred to as the 1st generation. Stabilizes mast cells and prevents histamine and other mediators from being released. It also has a weak H1-blocking effect. Prescribed for a period of at least 3 months, 2 times a day. Cancel gradually, over 2-4 weeks. Since the effect develops over 1-2 months, people suffering from hay fever should start taking it in advance. The main indication of ketotifen is bronchial asthma.

Cromoglicic acid - although it has an oral form, is taken orally only for food allergies; for hay fever, it is used in the form of nasal and eye drops, sprays and aerosols. The effect occurs after a few days or weeks, so you need to start using the drug well in advance, before the onset of the flowering season. In this case, its use will be most effective. Therapy is carried out throughout the season.

The choice of systemic antihistamine for hay fever depends on many factors. Data on effectiveness, convenience and safety of use clearly indicate in favor of drugs from the 2nd generation. Having information on all the drugs available in the arsenal, it will be easy to suggest the right drug and argue your professional point of view.

Table of drugs:

TABLE FOR DOWNLOAD

Interested in the article? You can find out even more in the section Working in a pharmacy

Stopping or reducing contact with the allergen are so-called elimination measures.

The basis of any method of successful treatment of allergies is, first of all, the elimination of contact with the allergen.
In most cases, this is enough to completely get rid of allergy symptoms or significantly reduce its manifestations. If the cause is not eliminated, then, unfortunately, even the best anti-allergy medications will only provide a temporary effect. If you know the allergen for sure, try to eliminate it, which will help get rid of the allergy. In some cases, this is easy to do: you can always refuse an exotic fruit or a certain type of cosmetics. Sometimes this is difficult: for example, to completely get rid of dust or not to come into contact with pollen from flowering plants. And in some cases, especially if a person has several irritants at once, it is simply impossible to completely eliminate everything. In this case, it is important to minimize contact with the allergen.

The most common causes of allergies are household allergens and food, which is why during treatment, first of all, attention should be paid to a hypoallergenic lifestyle and a special diet.

The most common household allergen is house dust. This is a whole complex of allergens, which includes the epidermis of humans and animals, microscopic spores of mold and yeast, insect waste products, etc.

What helps against household allergies and creating a hypoallergenic lifestyle is written in detail here. Adhering to a hypoallergenic lifestyle is important not only for those who are allergic to dust, but also for all people suffering from any allergies, as well as those with a hereditary predisposition to allergic diseases.

A hypoallergenic diet is one of the allergy treatment methods that plays a special role in the treatment of allergic diseases, especially if there is a food allergy without clear indications of any type of product. In this case, it is recommended to exclude all highly allergenic foods from the diet: chocolate, strawberries, strawberries, citrus fruits, tomatoes, red apples, fish, chicken, eggs, etc. It is also necessary to avoid foods with dyes and preservatives, hot and spicy dishes, alcohol and carbonated drinks, and limit salt intake. The nonspecific hypoallergenic diet is described in detail here. Adhering to such a diet is recommended for all allergy sufferers and persons predisposed to allergic reactions.

If you are allergic to pollen, then a special diet is prepared that takes into account the risk of cross-reactions with pollen allergens. The dusting/blooming calendar and cross-allergy table can be found at the links above.

Choice of therapy for allergic rhinosinusitis

Allergic rhinosinusitis (AR) remains one of the most common diseases in otorhinolaryngology, despite the constantly growing arsenal of methods for its treatment. Many of them are not adequate to the etiopathogenesis of AR and therefore are ineffective. This especially applies to traditional surgical treatment of polypous rhinosinusitis.

.
Nasal polypotomy is only a symptomatic palliative measure that does not eliminate the disease itself and does not prevent subsequent relapses. It should be especially emphasized that AR, as a rule, is not an independent disease, but is associated with pathology of other parts of the respiratory tract, which must be taken into account when prescribing therapy. According to many authors, pathological changes in the nasal cavity and paranasal sinuses occur in 80–100% of patients with chronic nonspecific lung diseases.
Since AR and bronchial asthma (BA) are related in etiology and pathogenesis, quite often these diseases accompany or precede each other, being the result of general sensitization of the body, and represent a manifestation of a single allergic reaction of the entire respiratory tract - respiratory allergy.

Otorhinolaryngologists have a fairly large selection of methods to influence the course of AR. If the causative allergen is known, then first of all it is necessary to exclude or at least minimize the patient’s contact with this allergen.

Allergic inflammation of the nasal mucosa can be caused by components of house and library dust, plant and tree pollen, animal hair, bird feathers, food products, various chemicals (including cosmetics) used in everyday life and at work, and infectious agents. To reduce the frequency of contacts with the listed allergens, it is necessary to remove carpets and upholstered furniture from the home, regularly wet clean the room and change bed linen, remove animals from the house or at least from the patient’s bedroom. Recently, hypoallergenic cosmetics and bedding have appeared, but it is often not possible to completely eliminate patient contact with allergens.

Conservative therapy

It is possible to influence the course of seasonal and year-round AR (including in the case of combination with BA) using the most effective and pathogenetically substantiated method of treating allergies - specific immunotherapy (SIT).

In the process of regular introduction into the patient's body of a gradually increasing dose of the allergen, the concentration of blocking antibodies increases, which have a greater affinity for the allergen than immunoglobulins E (reagins), and therefore successfully compete with them.
In addition, initially suppressed specific suppressor T-lymphocytes are activated, inhibiting the process of formation of reagins to this antigen. Timely started and systematically carried out (SIT) can significantly alleviate the course of the disease
, reduce the likelihood of expanding the spectrum of allergens, prevent the transition of mild forms of allergy (for example, AR) to more severe ones (BA) and reduce the amount, dose and frequency of use of antiallergic drugs.
SIT is indicated for patients sensitized to those allergens for which the clinical effectiveness and safety of this treatment method have been established. It is used in cases where it is not possible to take measures to prevent the patient from contacting the allergen. Therefore, this type of treatment is indicated to a greater extent for year-round AR. Children and young people, as well as patients with AR without asthma, respond better to treatment. A significant negative aspect of SIT is the possibility of developing anaphylactic shock and acute angioedema
of vital organs, sometimes leading to death. Such severe side effects most often occur due to non-compliance with instructions for carrying out SIT, unreasonable excess of doses of the administered allergen and untimely initiation of anti-anaphylactic measures. The choice of SIT is advisable if the patient has been receiving various antiallergic drugs for a long time. Studies have shown that of all anaphylactic reactions that occur during drug treatment, SIT accounts for only 20%. If all the rules for carrying out this type of hyposensitization are followed, the risk of a systemic anaphylactic reaction is extremely low. Only an allergist with experience in performing such procedures has the right to perform SIT.

Glucocorticosteroids

Today, glucocorticosteroids (GCS) can be called the most effective antiallergic drugs that are widely used in the treatment of all forms of AR.

As a result of the use of GCS, swelling of the nasal mucosa, mucous-watery discharge, the volume of polyps are reduced, and the patency of the nasal passages and natural anastomoses of the paranasal sinuses is improved. These properties of GCS are traditionally used by otorhinolaryngologists to treat allergic diseases of the nasal cavity and paranasal sinuses.

Currently, it is extremely rare to resort to systemic administration of corticosteroids for AR.

(prednisolone, dexamethasone, etc.).
When using them, there is a high risk of developing side effects, such as osteoporosis, arterial hypertension, immunosuppression, diabetes mellitus, etc. Relatively recently, intranasal topical corticosteroids
, which have pronounced advantages - low systemic bioavailability, exclusively local action, high efficiency, low number of side effects , possibility of inhalation use.
This group included flunisolide, budesonide, betamethasone, triamcinolone, beclomethasone, fluticasone, mometasone
. The absence of systemic effects as a result of the use of these drugs is explained by the peculiarities of their pharmacokinetics. A minimal amount of the administered drug enters the systemic circulation, which does not affect the functions of the hypothalamic-pituitary-adrenal system and does not cause the development of severe side effects even in the case of a fairly long-term use of a topical corticosteroid. Locally acting corticosteroids have extremely low bioavailability.

The use of local corticosteroids after surgical treatment helps prevent the development of early relapse. A stable remission is often achieved: patients do not complain of difficulty in nasal breathing or mucous-watery discharge from the nasal cavity. Objectively, there is an absence of polypous tissue in the lumen of the nasal passages and swelling of the mucous membrane. Thus, the quality of life of patients improves for a fairly long period and the likelihood of repeated surgery decreases. The latter circumstance is especially important for patients suffering from both asthma and AR, since any operation in the nasal cavity in such patients is fraught with the development of an asthmatic attack or worsening the course of asthma.

For year-round AR, GCS therapy is carried out in courses.

The effect occurs faster in the case of the edematous form. In case of seasonal AR, endonasal inhalations of corticosteroids should begin 1.5–2 weeks before the start of flowering of those plants to whose pollen allergens the patient is sensitized, and continue throughout the entire period of pollination.

For the treatment of the polypous form of AR, the method of “medical polypotomy”

, which consists of conducting a short course of general GCS therapy (
prednisolone
in tablet form is most often used for this purpose). It is used only in the 3rd stage (severe course) of polypous rhinosinusitis, when monotherapy with topical steroids carried out in the treatment of stages 1 and 2 is ineffective. This course is a preparatory stage for therapy with intranasal corticosteroids.

H1-histamine receptor antagonists

Since histamine plays a major role in the pathogenesis of AR, the use of drugs that block H1-histamine receptors in the complex treatment of this disease is quite justified. They have a greater effect on the severity of itching, rhinorrhea and sneezing than on the degree of nasal obstruction. H1-antagonists can be considered the drug of choice if these symptoms predominate in the clinical picture of AR.

Today, antihistamines with a pronounced sedative effect, such as diphenhydramine, promethazine, chloropyramine (1st generation drugs), are used less and less often. They were replaced by new generation drugs: loratadine (clarotadine), levocabastine, terfenadine

and many others. These highly effective and fast-acting drugs do not have a sedative effect. Many of them have a dosage regimen that is convenient for the patient - once a day. Levocabastine is formulated as an intranasal spray. This dosage form allows you to quickly create the required concentration of the drug directly at the site of inflammation.

Antihistamines for the conservative treatment of polyposis AR are used only in combination with intranasal corticosteroids. During surgical treatment, they are used as preoperative preparation and in the postoperative period. By reducing the permeability of the vascular wall, these drugs potentiate the effect of GCS, and also contribute to a more rapid disappearance of postoperative edema and improve the results of surgical treatment.

Mast cell membrane stabilizers

Relatively recently, mast cell membrane stabilizers, traditionally used to treat patients with asthma, began to be used in the treatment of AR. The active substance in these preparations is sodium cromoglycate

, which has a pronounced antiallergic effect. The mechanism of action is due to inhibition of mast cell degranulation and the secretion of histamine and other biologically active substances. In addition, sodium cromoglycate inhibits the activation of monocytes, neutrophils and eosinophils. It is used in the treatment of all forms of AR. In the case of the seasonal form, treatment should begin 2 weeks before contact with the allergen and continue throughout the entire period of pollination, as in the case of treatment with topical steroids.

Ascorbic acid, rutoside and calcium gluconate

have long been used to treat patients with AR.
They compact the vascular wall, reduce the degree of vascular permeability, thereby reducing the severity of edema. Physiotherapeutic methods of treatment
(electric and phonophoresis, hydroaeroionization, endonasal inhalations) are also widely used These drugs and methods do not play a major role in the treatment of AR and are used only as concomitant therapy to enhance the effect of intranasal corticosteroids and antihistamines.

Leukotriene receptor antagonists

There are significant features in treatment when AR is combined with BA. Any surgical intervention in the nasal cavity and paranasal sinuses with this combination is fraught with the occurrence of an asthmatic attack or a worsening of the course of asthma. On the other hand, polyps and swollen turbinates greatly complicate nasal breathing and irritate the so-called asthmagenic zones of the nasal cavity, thereby contributing to the progression of asthma. Therefore, in such patients, the indications for surgical treatment should be narrowed and preference should be given to conservative methods. This problem is especially acute in the case of the aspirin triad.

, since in this disease the percentage of recurrence of polyposis after surgical interventions is especially high and BA often has a severe course. In such conditions, leukotriene receptor antagonists are increasingly used.

The share of leukotrienes (LT) in the development of allergic inflammation is very high. They increase the degree of vascular permeability, promote the mobilization and activation of pro-inflammatory cells in the airways, participate in the release of other pro-inflammatory agents, and increase the secretory activity of the mucous glands. The effect of LT is mediated by specific receptors. Currently, two types of these receptors are known: CysLT1 and CysLT2. Of the LT receptor antagonists, only CysLT1 blockers are used in clinical practice. These drugs include the following: zafirlukast, pranlukast, montelukast

. LT receptor antagonists allow treatment to be carried out on an outpatient basis, which reduces the cost of treatment by saving medications required to prepare the patient for surgery and manage the postoperative period.

Surgery

Surgical methods are still widely used in the treatment of AR. The main problem that a rhinosurgeon most often has to deal with is the recurrence of polyposis and swelling of the nasal turbinates. In some cases, the growth of polypous tissue is so intense that the patient is forced to resort to surgical treatment 2-3 times a year or more often.

Comparing surgical and therapeutic methods, we can say that the use of even the latest advances in rhinosurgery allows us to influence only the final result of the pathological process, without in any way affecting the pathogenesis of AR. In this sense, surgical treatment is symptomatic, relieving the patient of the manifestations of the disease. It does not interrupt the chain of its development and therefore has virtually no effect on the duration of remission. Modern pharmacotherapeutic treatment of year-round AR, unlike surgical treatment, is pathogenetic in nature, since it is aimed at blocking the effects of biologically active substances and cells directly involved in the development of the pathological process. Therefore, the problem of treating the polypous form of AR should be considered more from a therapeutic than from a surgical point of view. Further progress in this area, according to many foreign scientists, should be associated not with the development of surgical technologies, but with the introduction of new therapeutic methods.

Loratadine –

Clarotadine (trade name)

(Akrikhin)

Pharmacotherapy

Another of the most important methods of treating allergies is pharmacotherapy, or the use of medications to eliminate the symptoms of the disease and prevent relapses.

There are the following groups of anti-allergy drugs:

• antihistamines;
• mast cell membrane stabilizers;
• glucocorticosteroid drugs;
• symptomatic anti-allergy medications.

Antihistamines (H1-histamine receptor blockers) are widely used for various allergic diseases. They quickly and effectively eliminate clinical manifestations or prevent their development. Their mechanism of action is associated with the blockade of histamine receptors, which helps get rid of allergies due to the cessation of the action of histamine, a substance that is released in large quantities and determines the development of the main symptoms of the disease: runny nose, sneezing, nasal congestion, itching, redness, etc.

H1-histamine receptor blockers reduce the body's response to histamine, relieve the spasm of smooth muscles caused by it, reduce capillary permeability and tissue swelling, and have an antipruritic effect.

Offers from suppliers and manufacturers, descriptions from the “Encyclopedia of Medicines” can be found by following the links in the Classification section.”
Antiallergic drugs - drugs for the prevention and treatment of allergic diseases, occupy one of the most important segments of the pharmaceutical market. The incidence of allergoses is steadily increasing. The frequency of acutely developing severe allergic reactions is high, where the patient’s life depends on timely pharmacotherapy. The number of chronic patients is also increasing, the quality and duration of life of which are determined by the level and adequacy of the therapy provided. The results of a survey of doctors and pharmacists show that specialists have a high need for information about the clinical pharmacology of antiallergic drugs. In a narrow sense, antiallergic drugs include antagonists of allergy mediators and stabilizers of mast cell membranes, the pharmacological characteristics of which are the subject of this article. Antagonists of allergy mediators are more often called antihistamines. The term is generally accepted, but is becoming outdated because it does not reflect the pharmacodynamics of most drugs, especially representatives of the latest generations, which are antagonists not only of histamine, but also of other mediators, in particular serotonin, bradykinins, and leukotrienes. The mechanism of action of drugs in this group is based on reversible competitive inhibition of H1-histamine receptors. In tissues, histamine is synthesized by mast cells, and in the blood by basophils. It serves as a mediator of various physiological and pathological reactions in various tissues and cells. Histamine is not only associated with mast cells and basophils: it has also been found in platelets, gastric mucosa, endothelial cells and neurons in the brain. Histamine has a direct effect on the heart, disrupting both its contractility and electrophysiological parameters. It also has a pronounced hypotensive effect and is an important biochemical mediator of inflammation in allergic diseases. The action of histamine is mediated by three types of receptors, designated H1, H2 and H3. Acting through the H1 and H2 receptors, histamine causes arterial hypotension (due to vasodilation), tachycardia, hyperemia and headache, while activation of only the H2 receptors leads to increased secretion and acidity of gastric juice. Stimulation of H3 receptors located in the brain may have a negative modulatory effect. Blockade of H1 receptors leads primarily to suppression of the allergic reaction, while blockade of H2 receptors primarily inhibits the secretion of gastric juice. Antihistamine drugs that compete with histamine at the level of H1 receptors in target organs are designated as H1 blockers or H1 receptor blockers. They have a weak effect on H3 receptors (the effects associated with them have not been studied enough) and have virtually no effect on H2 receptors. Thanks to the blockade of H1 receptors, antihistamines have a bronchodilator effect in bronchospasm caused by histamine, an antispasmodic effect on intestinal smooth muscles, prevent vasodilation (except coronary ones, the tone of which is regulated by H2 receptors) and “blood loss into the own vessels” caused by histamine. They normalize the increased permeability of the vascular wall, especially in the capillary bed. Thus, H1 receptor blockers prevent or minimize allergic reactions by blocking histamine-induced effects, and the effectiveness of antihistamines is ensured by their ability to competitively inhibit the effect of histamine on the loci of specific H1 receptor zones in effector tissue structures. There are several classifications of antihistamines. Based on their chemical structure, they are divided into the following groups:

Note: * the drugs are not registered in the Russian Federation.
Structural features determine some of the properties of the drugs. Most ethanolamine derivatives are characterized by pronounced m-cholinergic and sedative effects. Among the alkylamines, there are the most active H1 receptor antagonists; they are characterized by weak sedative properties (although some patients sometimes exhibit a pronounced sedative effect), but quite often an increase in the excitability of the nervous system is observed. Most piperazine derivatives also exhibit a mild sedative effect (except hydroxyzine). Phenothiazines have anticholinergic properties similar to those of ethanolamine derivatives. Drugs in this group are often used as antiemetics. Piperidine derivatives have the most pronounced selectivity towards H1 receptors in the absence or weak expression of anticholinergic properties and effects on the nervous system. But the increasingly used division of drugs into generations is more justified:

Comparative characteristics of the main antagonists of allergy mediators of 1-4 generations
(Lesiovskaya E.E. et al, 2001)
The on-line version of the article does not provide
first generation antihistamines

- ethanolamines, ethylenediamines, alkylamines, piperazines and phenothiazines - in the treatment of allergic rhinoconjunctivitis, urticaria and other allergic diseases has been established for a long time. However, although all of these drugs quickly (usually within 15-30 minutes) alleviate allergy symptoms, most of them (for example, diphenhydramine and chloropyramine) have a pronounced sedative effect and can cause unwanted reactions at recommended doses, interact with other drugs and alcohol. The sedative effect is due to the ability of first-generation antihistamines to penetrate the blood-brain barrier. The use of these remedies is effective for severe runny nose of allergic origin, sneezing and eye allergy symptoms. They are less effective for nasal congestion, a symptom not associated with endogenous histamine release.

Antihistamines are the first choice for maintenance treatment of chronic urticaria, and second-generation drugs are as effective in reducing urticaria and itching as first-generation drugs. Under the influence of antihistamines for chronic urticaria, allergic inflammation of the skin decreases after a few hours. It has been established that second-generation drugs (clemastine, cyproheptadine) reduce the number, size and duration of urticarial lesions. Topical use of antihistamines may cause sensitization, so it is better to prescribe them orally. Second-generation antihistamines selectively act on peripheral H1 receptors and have less neurotoxicity and sedative effect.

Third generation antihistamines include: astemizole, levocabastine, hydroxyzine, acrivastine, dimethindene. Antihistamines are one of the most commonly used treatments for allergic rhinoconjunctivitis. They provide very fast and effective relief of the following symptoms: rhinorrhea, itching, sneezing, eye symptoms. Antihistamines are also the first choice in the treatment of chronic urticaria. Identification of the allergen that provokes the development of symptoms in a particular patient makes it possible to use tactics to limit exposure to this allergen. Although complete cessation of contact with the allergen can eliminate the symptoms of allergic rhinoconjunctivitis, in practice it is extremely difficult and almost impossible to maintain the elimination effect for a long time. Eliminating contact with the allergen is feasible only for those patients in whom allergic rhinoconjunctivitis is caused by a specific environmental factor, for example, a favorite animal. However, even if the allergen is removed from the patient's environment, the positive effect may last only a few weeks or months. In anyone with chronic urticaria, it is important to obtain a thorough medical history to rule out any type of physical, drug, food, or supplement-related urticaria. However, the cause of urticaria, despite all the care with which the patient and the doctor try to determine it, often remains unclear. This type of urticaria is called idiopathic. Fourth generation drugs - ebastine (kestin), bamipin, loratidine, cytirizine, fensperide. They have a long duration of action, low stimulating activity of central H3 receptors, and are safe for the cardiovascular system. One of these drugs is Ebastine. The structure of diphenylpyraline was adapted to produce ebastine; a long aliphatic side chain was introduced into the nitrogen atom of the piperidine ring. This chain was carefully selected to give the molecule a long duration of action, low stimulatory activity at central H3 receptors, and cardiovascular safety. In addition, the aliphatic side chain was chosen so that the ebastine molecule does not form stereoisomers. This distinguishes ebastine from its main competitors, which have a racemic composition. Thus, ebastine, unlike its main optically active competitors, enters the body in the form of a simple compound and not a mixture of racemates

The drug in a single dose has a rapid antihistamine effect; the maximum antihistamine effect of ebastine coincides with the peak concentration in plasma and is achieved 2 hours after administration.
One study found that ebastine and astemizole, used for a week at a daily dose of 10 mg, equally suppressed the histamine-induced reaction (blister formation and skin flushing) for 24 hours. In contrast, loratadine, cytirizine and terfenadine, recommended for once daily use at a dose of 120 mg, showed marked fluctuations in antihistamine potential in the same studies. Drug interaction studies
According to a study examining the interaction between ebastine 20 mg and alcohol, blood alcohol levels did not change after administration of ebastine, and the usual plasma pharmacokinetics of carebastine were maintained. In addition, ebastine did not change the level of diazepam in the blood plasma and did not enhance the effect of this sedative drug; adiazepam, in turn, did not affect the pharmacokinetics of carebastine. Ebastine in a single dose of 20 mg in 12 healthy individuals did not interact with cimetidine, a known inhibitor of cytochrome P-450 activity in the liver, when the latter was administered repeatedly. Cimetidine did not affect the conversion of ebastine to carebastine and its subsequent elimination.

Taking ebastine at a dose of 20 mg per day for 10 days, accompanied on the 5th day by a single dose of warfarin at a dose of 25 mg, had no effect on prothrombin time and did not cause clinically significant manifestations. The pharmacokinetic parameters of carebastine and mirror isomers of warfarin also did not change. There were no significant changes in the pharmacokinetics of theophylline and carebastine with the combined use of ebastine and theophylline.

The same study, conducted with chronic ketoconazole administration, determined measurable plasma ebastine concentrations (ranging from 20.3 to 55.7 ng/mL) after a single dose of 20 mg ebastine. It turned out that chronic use of ketoconazole changes the metabolism of ebastine in a single dose, leading to its accumulation in the form of an unmetabolized compound. 12 hours after taking ebastine, in 50% of cases its concentration in plasma was close to the lower limit of measurable, and after 24 hours it was not possible to determine ebastine in plasma. The study showed that multiple doses of erythromycin alter the metabolism of a single dose (20 mg) of ebastine, leading to its accumulation as an unmetabolized substance. The interaction of ebastine with ketoconazole and erythromycin (which can prolong the OT interval) has been studied. In both cases of combination therapy, there were pharmacokinetic and pharmacodynamic interactions; there was an increase in the OT interval by 18-19 ms. (4.7%-5%).

There was no interaction between ebastine and theophylline, warfarin, cimetidine, diazepam and alcohol.

In the case of taking ebastine with food, an increase in the concentration of carebastine in plasma and the area under the curve by 1.5-2 times was observed. At the same time, the time to reach maximum concentration did not increase. The use of ebastine with food does not affect the clinical effect of the drug.

So, indications for the use of ebastine and other antihistamines:

• · Year-round and seasonal allergic rhinitis, hay fever;
• · Histamine-mediated dermatoses (atopic dermatitis, urticaria, Quincke's edema, eczema);
• Serum sickness, hemorrhagic vasculitis;
• · Nausea, vomiting, dizziness (including in diseases of “movement”, labyrinthine and vestibular disorders);
• · Diseases of the central nervous system accompanied by increased vascular permeability, including Meniere's syndrome, chorea, encephalitis;
• · Iatrogenic extrapyramidal disorders (for example, while taking antipsychotics);
• · Colds (in combination therapy);
• · Hyperthermia in case of poisoning, infections;
• · Neuroses and neurosis-like conditions, psychoses, accompanied by sleep disturbances, restlessness, and anxiety.

The use of 1st and 2nd generation drugs is gradually being reduced; they are increasingly prescribed for indications not related to allergic reactions.
3rd generation drugs provide a sufficient duration of action; the most effective are 4th generation drugs, which, along with antagonism towards allergy mediators, have a stabilizing effect on mast cell membranes. However, the high cost of treatment makes them inaccessible to most patients. The main disadvantages of mediator antagonists are:

• - lack of a normalizing effect on disorders in the immune system underlying allergic reactions;
• - relatively late intervention in the pathogenesis of an allergic reaction;
• - the need for long-term prophylactic use and cessation of the protective effect immediately after the end of administration;
• - own allergenicity with an increased likelihood of developing allergic reactions with long-term use;
• - various side effects
• — impossibility of use during pregnancy and lactation;
• — restrictions for use in pediatric practice.

Typical side effects are typical for drugs in this group:

• - from the central nervous system - drowsiness, dizziness, headache, feeling of fatigue, decreased attention span;
• - from the gastrointestinal tract - dry mouth, dyspepsia, vomiting, epigastric pain, constipation (typical of drugs with m-anticholinergic action);
• - from the urinary system - urinary retention (typical of drugs with m-anticholinergic action);
• - on the part of the respiratory system - thickening of bronchial secretions, difficulty in sputum separation, a feeling of constriction in the chest (characteristic of drugs with m-anticholinergic action);
• - allergic reactions;
• - increased intraocular pressure, disturbances of accommodation (typical of drugs with m-anticholinergic action).

In addition to these side effects, each drug has its own unique drug complications.
Antagonists of allergy mediators are contraindicated in pregnancy, lactation, risk professions (in the presence of sedation), hypersensitivity to the drug or its structural analogues. Drugs with anticholinergic properties should not be used for glaucoma, prostate adenoma, tachyarrhythmias, stenotic ulcers of the stomach and duodenum, and stenosis of the bladder neck. Some drugs also have other contraindications. In recent years, the search for new antagonists of allergy mediators has been successful - selective leukotriene antagonists zafirlukast (Acolate) and montelukast (Singulair) have been created, zileuton, an inhibitor of 5-lipoxygenase, an enzyme involved in the formation of leukotrienes, is in clinical trials from arachidonic acid in neutrophils, macrophages and mast cells. The drugs eliminate swelling of the mucous membrane and spasm of bronchial smooth muscles caused by a mixture of leukotrienes (LTS4, LTD4, LTE4) called a slow-reacting substance of anaphylaxis. The drugs are indicated for the prevention of attacks in mild to moderate bronchial asthma. The effect develops after a week of use. When prescribing drugs, side effects were noted: dyspepsia, headaches, increased levels of transaminases in the blood plasma

The first stabilizer of mast cell membranes was the sodium salt of cromoglycic acid (intal, cromosol). The drug was developed on the basis of furanochromone kellin from the fruits of Ammi visnaga (L.) Lam. The mechanism of action of sodium cromoglycate is complex:

• - blockade of the secretion of primary and secondary mediators and cytokines from mast cells caused by allergens and nonspecific irritants (physical activity, cold, pollen, etc.);
• - decreased activity of macrophages, neutrophils, eosinophils and platelets involved in the development of allergic reactions;
• - suppression of reflex bronchoconstrictor reactions that occur when vagus nerve receptors and efferent nerves are mediated by C-fibers.

At the molecular level, the membrane-stabilizing effect is associated with inhibition of phosphodiesterase, leading to a decrease in intracellular calcium, and blockade of membrane chloride channels, which reduces the tone of the vagus nerve and the secretion of neuropeptides by C-fibers.
Allergic rhinitis is characterized by copious liquid mucous discharge from the nose. The nasal mucosa swells, swells, and becomes pale gray in color. Itching in the nose, sneezing, and headache are often noted. With allergic inflammation of the nose and its accessory cavities, swelling of the mucous membrane is sometimes so pronounced that so-called allergic polyps are formed. Under the influence of cromosol, polypous changes in the mucous membrane disappear. The drug reduces mucous discharge from the nose, itching in the nose, sneezing, and nasal congestion.

Some patients have increased sensitivity not only to plant pollen, but also to their fruits and seeds. If a person reacts violently, for example, to sunflower pollen, it is possible that seeds and sunflower halva will also be an allergen for him. If the allergen is hazel or birch pollen, then hazelnuts, hazelnuts and even birch sap can also become an allergen. If you are allergic to cereal pollen, you may develop an allergy to products made from rye, wheat flour, rice, oatmeal, and semolina. Those who are allergic to alder or oak pollen may experience severe painful effects when consuming decoctions and infusions of alder cones or oak bark. Patients with hay fever should use medicinal herbs extremely carefully, since many of them have the same allergenic properties as pollen. Honey in any form and quantity, both internally and in cosmetics, is also not recommended. Bees collect pollen from plants; honey contains a lot of plant pollen. Cosmetic creams that contain plant pollen can also provoke hay fever. Factors predisposing to damage to the ENT organs are the predominance of plant-carbohydrate foods in the diet, hereditary seasonality (mainly in the spring), injuries and chronic gastrointestinal diseases. Factors predisposing to damage to the ENT organs are the predominance of plant-carbohydrate foods in the diet, hereditary seasonality (mainly in the spring), injuries and chronic gastrointestinal diseases. The cause of an allergic runny nose can also be house dust, epidermal substances (animal hair, fluff, etc.). The occurrence of a runny nose is influenced by infection, especially chronic infection. Bacteria in the mucous membrane of the nose and its paranasal sinuses not only cause increased sensitivity, but also increase the permeability of the mucous membrane to other allergens, contributing to the development and maintenance of allergic inflammation. Traditional drugs for the treatment of allergic rhinitis - sympathomimetics - reduce the protective properties of the nasal mucosa and thereby contribute to the chronicization of the pathological process. In addition, the use of sympathomimetics can lead to sleep disturbances, nervousness, and anxiety. Their use should be avoided in diabetes mellitus, in patients with hypertension or Graves' disease. In addition, due to regular use of nasal sprays for 3-4 days, rebound hyperemia and increased runny nose are possible. And such a sympathomimetic as phenylpropanolamine, included in many antiallergic drugs, is abused by teenagers, and it is even sold on the US black market as a substitute for cocaine or amphetamine. Even at two or three times the therapeutic dose, this drug can cause severe hypertension, seizures, and intracranial bleeding.

Cromosol is not only a reliable remedy for the prevention and treatment of allergic rhinitis, but is also well tolerated by patients. The drug is poorly absorbed, so its side effects are minimal. Very rarely, at the beginning of treatment, a feeling of irritation of the nasal mucosa may occur, and even less often - coughing, a feeling of tightness in the chest. Cromosol can be administered immediately before imminent contact with the antigen. For chronic allergic rhinitis, Cromosol effectively reduces the severity of symptoms and the need for antihistamines, thereby reducing their unwanted side effects. It is believed that Cromosol not only eliminates the signs of allergic rhinitis, but also effectively prevents seasonal attacks in patients with allergic rhinitis. Unfortunately, the drug is not always effective. Currently, the only way to determine this is through a four-week trial of therapy.

The main advantages and disadvantages of cromoglycic acid:

The structural analogue of sodium cromoglycic acid, nedocromil, is 4-10 times superior to it in membrane stabilizing activity, without differing in the mechanism of action.
The ability to reduce the secretion of mediators by mast cells is also expressed to a certain extent in 4th generation allergy mediator antagonists. An intermediate place between the two groups of antiallergic drugs is occupied by ketotifen (zaditen, ketof). It blocks H1 receptors, restores the sensitivity of b2 adrenergic receptors to agonists, reduces the secretion of mediators by mast cells and basophils, and has an inhibitory effect on the activity of leukotrienes and platelet activating factor. The similarity of ketotifen to cromoglycic acid is manifested in its gradual development. It blocks H1 receptors, restores the sensitivity of b2 adrenergic receptors to agonists, reduces the secretion of mediators by mast cells. The effect of the drug does not develop immediately, but against the background of continuous use for 3-6 months. The side effects of ketotifen are close to those of antagonists of allergy mediators. In 10-20% of patients it causes drowsiness and decreased attention. With long-term use, increased appetite, weight gain, and thrombocytopenia are observed. Antiallergic drugs are one of the most widely used groups of drugs.
Research conducted by SPHFA specialists has established that this group is not evenly represented in pharmacies in the northwestern region. Mast cell membrane stabilizers are available in almost all pharmacies, but a variety of dosage forms is provided in only 68% of institutions. The number of allergy mediator antagonists ranges from 48% to 71% of the drugs registered in Russia, with drugs of the 3rd and 4th generations being the least represented, which contradicts the clinical significance of these drugs and does not contribute to providing quality care for patients with allergies. The list of over-the-counter drugs included 9 antiallergic drugs: acrivastine, bamipine, clemastine, sodium cromoglycate, loratadine, mebhydrolin, fexofenadine, chloropyramine, cetirizine, and the list of vital and essential drugs included 4 drugs quifenadine, ketotifen, sodium cromoglycate, nedocromil. It is important that these lists include the most effective and safe drugs. In conditions of constantly growing demand for antiallergic drugs, it is also necessary to expand their domestic production. Literature
1. Lesiovskaya E.E., Sakaeva I.V., Safaryan V.V. Antiallergic drugs on the pharmaceutical market of North-West Russia: pharmacological characteristics. Remedium North-West, 2001, No. 1 2. Chuchalin AG, Kolganova NA Chemaev AL, Grobova OM, Kalinina EP, Tcherbakov IT Associated bronchial and intestinal mucous dysfunction in patients with atopic disease // Abstract form XV Congres Mondial D'asthmologie/XV WORLD Congress of asthmology, 24-27 anpe/ifl 1996. -1996. 3. Gregg Y. Epidemiological aspects in Ashma // Edited ny T3.H. dark, S. Godfrey S 2nd Ed. London, Chapman and Hall (Medical) Ltd. - 1983. ~ P. 242-284. 4. Jackson R., Sears MR, Beagiehole R., Rea MN International Frends in Asthma Chest // 1988. - V. 94.-P. 914-919. 5. Somorin AO, Hunponu Musu 0.0., Mumcuoglu Y. Meiner DC Mite allergy in Nigerians studies of house dust mites in house of allergic patients in Lagos, ir. // J. Med. Sci. -1978. - V- 147. - P. 26. 6. Stjernberg N., Ekiund A., Nystrom L. Rosenhall, Emmelen A., Stromovist LH Prevalence of bronchial asthma and chronic bronchitis in a communit... in Worthern Swedch, relation to environmental, and occupational exposure to sulfur dioxide // Eur. Y. Respira. Dis. -1985. - V. 65. - P. 41-49. 7. Viegi G., Paoletti P., Carrozzi L., et al. Prevalence rates of respiratory symptoms in Italian general population samples; exposed to different levels of airpollution // Environ. Health Perspective. - 1991. - V. 94.-P. 95-99.

Classification of antihistamines

According to the classification adopted by EAACI (European Academy of Allergy and Clinical Immunology), there are 2 generations of antihistamines*.

Antihistamines (AGDs) 1st generation

1st generation drugs were developed in the middle of the last century, but some are still used today. They have many side effects: they cause drowsiness, can have a negative effect on the gastrointestinal tract, cardiovascular system, vision, and cause dryness of the mucous membranes of the respiratory tract. Such drugs must be taken several times a day, which is very inconvenient. And with prolonged use they become addictive*.

Antihistamines of the 2nd or latest generation

2nd generation drugs are more modern drugs. In terms of safety and ease of use, they are superior to drugs of the previous generation. They do not cause drowsiness, a person maintains concentration and attention. The absence of sedation is especially important for people who spend a lot of time driving a car or working with equipment.

These drugs have a precisely selective effect only on H1-histamine receptors, do not block other types of receptors, and therefore are devoid of most of the side effects of 1st generation AGPs. They can be used for most concomitant diseases, which is very important, since allergies as the only problem are very rare. The effect of the latest generation of allergy medications lasts more than 24 hours, which is very convenient and allows you to take a tablet only once a day. In this case, there is no need to adjust to meals, because the absorption of modern drugs usually does not depend on the presence of contents in the stomach. In addition, drugs in this group are not addictive.

2nd generation AGPs are also a heterogeneous group. There are two subgroups:

• metabolized drugs that have a therapeutic effect only after transformation in the liver (loratadine, ebastine, rupatadine);
• active metabolites - the latest generation of allergy medications that enter the body in the form of an active substance (cetirizine, levocetirizine, desloratadine, fexofenadine).

The main advantages of active metabolites are a faster and more predictable effect, no additional burden on the liver, and the ability to be taken together with other medications that also pass through the liver.

In some classifications, active metabolites are even classified as 3rd generation antihistamines, which, however, contradicts the generally accepted classification.*

The 2nd generation AGP, active metabolites, includes Cetrin®.

Mast cell membrane stabilizers are used in the treatment of upper and lower respiratory tract allergies. They inhibit the release of histamine and other active substances from mast cells, preventing the exacerbation of allergic diseases, such as bronchial asthma.

Glucocorticosteroids (GCS) are used for various allergic diseases. They have a pronounced antiallergic effect, simultaneously affecting the majority of cells involved in the allergic process. This group of drugs can be prescribed for allergic rhinitis in the form of a spray, for bronchial asthma in the form of inhalers, for atopic dermatitis in the form of ointments or creams. In especially severe cases, tablets and injectable corticosteroids are added to these forms.

Symptomatic therapy is also widely used in the treatment of allergies. For example, with bronchial asthma you cannot do without bronchodilators, and with allergic rhinitis - without vasoconstrictor drugs against allergies, etc. It is important to remember that each person is individual, has his own severity of symptoms and severity of the disease, so only a specialist can select those drugs and that treatment regimen that is suitable in each specific case.

Antihistamines in the treatment of chronic urticaria: a literature review

Information on the treatment of urticaria and angioedema (AO) presented in this review is based on the principles of evidence-based medicine, i.e., on the results of randomized and other scientific studies. The letters “A–D” are used to indicate levels of evidence, with A being the highest level (good evidence of effectiveness) and D representing recommendations based on weak evidence.

Antihistamines (H1-histamine receptor blockers, H1-HBs) of the second generation are the first choice drugs for all patients with chronic urticaria (CU) (A) [1–3]. Their administration leads to a reduction in itching, the duration of the rash and an improvement in the quality of life of patients. However, the use of drugs does not always result in the complete disappearance of rashes and itching, since the appearance of symptoms can be caused by the action of other mediators, as well as histamine, not only through H1-, but also through H2-receptors.

The place of antihistamines in the treatment of chronic urticaria and evidence of effectiveness

Second generation antihistamines, such as cetirizine [4], desloratadine [3, 5], ebastine [6], fexofenadine [7, 8], levocetirizine [9], loratadine [2], mizolastine [10] and rupatadine [11], have been well studied in randomized clinical trials (RCTs) for the treatment of CU. Despite the fact that some of these drugs are positioned as “III generation antihistamines,” this term should only be used to designate drugs with new properties [12]. Unfortunately, to date there are no drugs with such properties.

Drug treatment should begin with the standard dose of non-sedating H1-BG recommended in the manufacturer's instructions (A) [1]. For daily or frequent symptoms, the drug is prescribed on a regular basis rather than on demand to prevent rashes and itching. It is necessary to offer patients a choice of at least two systemic antihistamines of the second generation, since the effect and tolerability may differ in each individual patient (A) [13].

Sometimes, to control severe urticaria/angioedema, doses of second-generation H1-BG may be required above the therapeutic doses described in the instructions (B). In this case, in patients with no or poor response to therapy with standard doses of H1-BG, the potential effectiveness of an increased dose of the drug usually outweighs the possible risk [14, 15]. One study showed an increase in the effectiveness of therapy in the majority of patients with CU when taking levocetirizine at a daily dose 4 times higher than the manufacturer's recommended dose [16]. Many experts agree that in all cases, if there is a need for second- and third-line drugs, it is better to increase the dose of non-sedating H1-BG to 2-4 times a day, taking into account possible side effects and the patient’s body weight. In this case, it is necessary to weigh the benefits and risks of using the drug and warn the patient about the increased likelihood of side effects. It is important to emphasize here that from a legal point of view, the doctor does not have the right to deviate from the instructions for the use of a particular drug. To date, in all instructions for second generation antihistamines approved in Russia, there are no recommendations for increasing the dose. Prescribing an increased dose of the drug is possible only “off-label” and must be accompanied by the informed consent of the patient and the conclusion of a consultation with an entry in the primary medical documentation.

Some doctors recommend using two different second-generation antihistamines on the same day (eg, morning and evening) (D) because some patients may benefit from one drug better than the other. However, this recommendation is based only on empirical evidence and results from RCTs are needed to confirm it. According to current evidence (B) [1], increasing the daily dose of the same drug should be preferred to using a combination of different drugs.

The addition of H2-GD to CU therapy may result in greater control of urticaria than H1-GD monotherapy (C) [17, 18]. If there is no effect within 3–4 weeks, N2-BG should be discontinued.

RCTs were conducted to compare the effectiveness of treatment of patients with chronic hyperplasia with antihistamine drugs of the first and second generations. In one study, cetirizine 10 mg once daily for control of itching and rash resulted in a faster onset of action than hydroxyzine 25 mg three times daily, although they had similar efficacy (B) [19]. Comparative studies between different second-generation H1-GDs did not demonstrate pronounced statistically and clinically significant differences (B) [7, 20, 21].

Adding sedative H1-BG at night may help with sleep disturbance associated with severe nocturnal itching. Despite the fact that sedatives need to be taken 3–4 times a day, they can be prescribed for urticaria, for example, in the absence of effect from second generation H1-GD (C) [22]. Some doctors recommend regular use of these drugs, believing that tolerance develops to the sedative effect within 1 week. However, objective testing usually does not confirm tolerance. This is because H1 receptors in the central nervous system (CNS) are no different from H1 receptors in peripheral tissues such as the skin.

The evidence base for the use of H1-BG for the treatment of physical urticaria, including dermographic, cold, pressure, cholinergic, and solar urticaria, is still limited, although some studies have shown some effectiveness (C) [23].

Antihistamines are less effective for the treatment of other forms of urticaria, such as pigmentary and cutaneous mastocytosis, as well as urticarial vasculitis and urticaria associated with cryopyrin-mediated autoinflammatory diseases (C) [24].

On the other hand, H1-BG are highly effective in allergic and AO combined with urticaria and itching. The drugs are ineffective for non-allergic isolated AO, including hereditary types I, II, III and acquired, associated with cancer or the use of angiotensin-converting enzyme inhibitors [25].

International generic and trade names, as well as doses and frequency of use in children and adults are given in table. 1.

Side effects

Fexofenadine, loratadine, desloratadine, cetirizine sometimes have a mild anticholinergic effect. Cetirizine and fexofenadine cause sedation in approximately 10% of cases [26]. This may be due to genetic polymorphism of the MDR1 gene, which encodes the P glycoprotein (a transporter involved in the elimination of many drugs, including antihistamines), which mediates changes in the pharmacokinetics of these drugs in some patients.

Sedative H1-BGs have a pronounced effect on the central nervous system (they can cause drowsiness, lethargy, weakness, decreased concentration, etc.) (Table 2).

H2 receptor antagonists are characterized by a significant number of side effects; Cimetidine should be used with caution due to its interaction with many drugs, as well as due to a possible decrease in potency, headache, arthralgia, myalgia, central nervous system damage and the cardiotoxic effect of the drug.

Duration of therapy

For most patients with CC, 3–6 months of regular therapy (D) is recommended [1, 27], with periodic discontinuation or dose reduction of the drug in the absence of symptoms of the disease. In patients with a long history of urticaria and AO, treatment is possible for 6–12 months with gradual withdrawal of drugs for several weeks. In patients with intermittent, episodic symptoms, therapy may be prescribed “on demand” or prophylactically before important life events.

Cromones and ketotifen

Cromones administered orally are not absorbed from the gastrointestinal tract and are usually ineffective for urticaria. However, some authors have noted the effectiveness of the mast cell membrane stabilizer ketotifen in patients with cold [28], cholinergic [29], dermographic [29] and delayed pressure urticaria [30]. Trial therapy with ketotifen is possible in the absence of effect from antihistamines [31, 32].

Features of antihistamine therapy for urticaria in children, pregnant women and the elderly

All antihistamines can be used in children over 12 years of age. Some recommendations from countries in Europe and the USA indicate the possibility of safely prescribing the following drugs in young children: I generation - hydroxyzine and alimemazine (from 6 years), diphenhydramine, clemastine, promethazine, cyproheptadine and ketotifen (from 2 years); II generation - only cetirizine, loratadine and desloratadine can be used for chronic urticaria in children from 2 years of age, ebastine, fexofenadine and levocetirizine - only from 6 years of age [33]. Cetirizine (after processing the results of the ETAC study) became the first antihistamine approved by the Food and Drugs Administration of the United States (FDA) for use in children from 6 months for the treatment of perennial allergic rhinitis and HC. The safety of long-term use (up to 18 months) of non-sedating second-generation H1-GDs in young children, in contrast to first-generation antihistamines, has been proven in RCTs [34–36].

The decision to prescribe these or other drugs in young children is made individually in each specific case after assessing the benefit/risk ratio.

When choosing drugs for a pregnant patient with urticaria, it is necessary to take into account the risk categories of prescribing drugs to pregnant women in the FDA classification (Tables 3 and 4) [37, 38].

It is necessary to avoid the use of systemic drugs in pregnant patients, especially in the first trimester [39]. However, if necessary, it is necessary to begin (or continue) treatment with antihistamines as the drug of choice in patients with urticaria. I generation H1-BG were previously recommended as the most studied and safe drugs during pregnancy. But at present, sufficient information has been accumulated confirming the safety of second-generation antihistamines, which, together with the absence of sedatives and other side effects compared to their predecessors, gives the right to prefer their use during pregnancy (C) [40]. As needed, the smallest doses of loratadine or desloratadine, as the most studied drugs, should be used, and if they are ineffective, diphenhydramine (C) should be used [27, 39]. The use of astemizole and terfenadine is unacceptable due to its arrhythmogenic effect, as well as the embryotoxic effect detected in animal tests.

The potential benefit to the mother should be weighed against the risk to the fetus when prescribing any drugs during pregnancy; explain to the patient the need to take antihistamines during pregnancy in case of acute or recurrent urticaria, inform about the presence of minimal risk and maintaining the health of the mother in the interests of the fetus.

All antihistamines pass into breast milk. Breastfed children receive approximately 0.1% of the drug dose when administered orally by the mother. First generation H1-GD may cause sedation and other side effects in such children [41, 42]. During lactation, it is possible to use (if necessary) the smallest doses of loratadine or cetirizine (C) [39, 43].

Like all drugs during pregnancy and lactation, N1-BG should be used in the minimum effective dose.

Elderly individuals are predisposed to the development of side effects from the central nervous system when using drugs that penetrate the blood-brain barrier. When prescribed to this group of patients, first generation N1-GD, even at the doses recommended by the manufacturer, there is a high risk of sedation, cognitive dysfunction, impairment of attention, speech and other side effects [41, 42].

In addition, polypharmacy often occurs in elderly patients, so the likelihood of interaction between sedating antihistamines and other drugs increases.

I generation H1-GDs are contraindicated in patients with glaucoma and prostate hypertrophy [41, 42].

Conclusion

Urticaria/AO is a heterogeneous group of diseases characterized by a variety of clinical manifestations and different mechanisms of development. Therefore, it is logical that a stepwise approach should be used to treat it, based on the form of urticaria, severity, pathogenesis and course characteristics. The algorithm for this approach is given in other publications [1, 15], where recommendations for the use of individual drugs are also discussed and evidence of their effectiveness is provided.

It must be remembered that antihistamines are indicated for almost all patients with urticaria, with the exception of some patients with isolated AO, in particular with hereditary ones. In addition, unless specifically indicated, it is advisable to avoid prescribing antihistamines and other systemic drugs in the first trimester of pregnancy, despite the fact that studies have not shown a teratogenic effect. The addition of a leukotriene receptor blocker to antihistamine therapy in adult patients may have an additional effect when exacerbation of urticaria is associated with food pseudoallergens, aspirin, or the presence of functional autoantibodies.

Currently, additional research is required on existing drugs for the treatment of urticaria, especially chronic, and the search for new highly effective drugs. It should be taken into account that, unlike antihistamines, the use of most second- and third-line drugs, in particular cyclosporine and omalizumab, is associated with high costs and/or a significant risk of severe side effects.

Literature

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P. V. Kolkhir1, Candidate of Medical Sciences N. G. Kochergin, Doctor of Medical Sciences, Professor O. A. Kosoukhova

GBOU VPO First Moscow State Medical University named after. I. M. Sechenova Ministry of Health of the Russian Federation, Moscow

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