Classification of antihistamines by generation table. Antihistamines

"EFFICIENT PHARMACOTHERAPY"; No. 5; 2014; pp. 50-56.

T.G. Fedoskova
SSC Institute of Immunology, FMBA of Russia, Moscow

To the main drugs that affect the symptoms of inflammation and control the course of allergic and non-allergic diseases. allergic genesis include antihistamines.
The article analyzes the discussion points regarding the experience of using modern antihistamines, as well as some of their main characteristics. This will allow a differentiated approach to the choice of the optimal drug in the complex therapy of various diseases.
Keywords: antihistamines, allergic diseases, cetirizine, Cetrin

ANTIHISTAMINES: MYTHS AND REALITY

T.G. Fedoskova
State Science Center Institute of Immunology, Federal Medical and Biological Agency, Moscow

Antihistamines belong to main drugs influencing symptoms of inflammation and controlling course of both of allergic and non-allergic diseases. In this paper debatable issues regarding experience of using current antihistamines as well as some of their characteristics are analyzed. It may let to make a differential choice to administer appropriate drugs for a combination therapy of different diseases.
key words: antihistamines, allergic diseases, cetirizine, Cetrine

Type 1 antihistamines (H1-AHP), or type 1 histamine receptor antagonists, have been widely and successfully used in clinical practice for more than 70 years. They are used as part of the symptomatic and basic therapy of allergic and pseudo-allergic reactions, complex treatment acute and chronic infectious diseases of various genesis, as a premedication during invasive and radiopaque examinations, surgical interventions, for prevention side effects vaccinations, etc. In other words, H 1 -AHP is advisable to use in conditions caused by the release of active mediators of inflammation of a specific and non-specific nature, the main of which is histamine.

Histamine has a wide spectrum of biological activity, realized through the activation of cell surface specific receptors. The main depot of histamine in the tissues are mast cells, in the blood - basophils. It is also present in platelets, gastric mucosa, endothelial cells, and brain neurons. Histamine has a pronounced hypotensive action and is an important biochemical mediator in all clinical symptoms of inflammation of various origins. That is why antagonists of this mediator remain the most popular pharmacological agents.

In 1966, the heterogeneity of histamine receptors was proven. Currently, 4 types of histamine receptors are known - H 1 , H 2 , H 3 , H 4 belonging to the superfamily of receptors associated with G-proteins (G-protein-coupled receptors -GPCRs). Stimulation of H 1 receptors leads to the release of histamine and the realization of inflammation symptoms, mainly of allergic origin. Activation of H 2 receptors increases secretion gastric juice and its acidity. H3 receptors are predominantly present in the organs of the central nervous system (CNS). They perform the function of histamine-sensitive presynaptic receptors in the brain, regulate the synthesis of histamine from presynaptic nerve endings. Recently identified new class histamine receptors, expressed mainly on monocytes and granulocytes, - H 4 . These receptors are present in bone marrow, thymus, spleen, lungs, liver, intestines. The mechanism of action of H 1 -AHP is based on reversible competitive inhibition of histamine H 1 receptors: they prevent or minimize inflammatory reactions, preventing the development of histamine-induced effects, and their effectiveness is due to the ability to competitively inhibit the effect of histamine on the loci of specific H 1 receptor zones in the effector structures of tissues.

Currently, over 150 types of antihistamines are registered in Russia. These are not only H 1 -AGP, but also drugs that increase the ability of blood serum to bind histamine, as well as drugs that inhibit the release of histamine from mast cells. Due to the variety of antihistamines, make a choice between them for their most effective and rational use in specific clinical cases It's hard enough. In this regard, there are debatable points, and often myths are born about the use of H 1 -AHP, which are widely used in clinical practice. In the domestic literature, there are many works on this topic, however, there is no consensus on the clinical use of these drugs (PM).

The myth of three generations of antihistamines
Many are mistaken in thinking that there are three generations of antihistamines. Some pharmaceutical companies present new drugs that have appeared on the pharmaceutical market as third-generation AGPs. Attempts were made to classify metabolites and stereoisomers of modern AGPs to the third generation. Currently, these drugs are considered to be second-generation antihistamines, since there is no significant difference between them and previous second-generation drugs. According to the Consensus on Antihistamines, it was decided to reserve the name "third generation" to denote future synthesized antihistamines, which are likely to differ from known compounds in a number of key characteristics.

There are many differences between first and second generation AGPs. This is primarily the presence or absence of a sedative effect. A sedative effect when taking first-generation antihistamines is subjectively noted by 40-80% of patients. Its absence in individual patients does not exclude the objective negative effect of these drugs on cognitive functions, which patients may not complain about (the ability to drive a car, learn, etc.). Dysfunction of the central nervous system is observed even with the use of minimal doses of these drugs. The effect of first-generation antihistamines on the central nervous system is the same as when using alcohol and sedatives (benzodiazepines, etc.).

Second-generation drugs practically do not penetrate the blood-brain barrier, so they do not reduce mental and physical activity patients. In addition, antihistamines of the first and second generations differ in the presence or absence of side effects associated with stimulation of other types of receptors, duration of action, development of addiction.

The first AGPs - phenbenzamine (Antergan), pyrilamine maleate (Neo-Antergan) began to be used as early as 1942. Subsequently, new antihistamines have appeared for use in clinical practice. Until the 1970s Dozens of compounds belonging to this group of drugs have been synthesized.

On the one hand, a large clinical experience has been accumulated in the use of first-generation antihistamines, on the other hand, these drugs have not undergone examination in clinical trials corresponding to modern requirements evidence-based medicine.

Comparative characteristics of AGP of the first and second generations are presented in Table. 1 .

Table 1.

Comparative characteristics of AGP of the first and second generations

Properties	First generation	Second generation
Sedation and effects on cognition	Yes (in minimal doses)	No (in therapeutic doses)
Selectivity for H 1 receptors	No	Yes
Pharmacokinetic studies	Few	A lot of
Pharmacodynamic studies	Few	A lot of
Scientific studies of various doses	No	Yes
Studies in newborns, children, elderly patients	No	Yes
Use in pregnant women	FDA Category B (diphenhydramine, chlorpheniramine), Category C (hydroxyzine, ketotifen)	FDA Category B (loratadine, cetirizine, levocetirizine), Category C (desloratadine, azelastine, fexofenadine, olopatadine)

Note. FDA (US Food and Drug Administration) - Food and Drug Administration (USA). Category B - no teratogenic effect of the drug was detected. Category C - studies have not been conducted.

Since 1977, the pharmaceutical market has been replenished with new H 1 -AHPs, which have clear advantages over first-generation drugs and meet modern requirements for AGPs set out in the EAACI (European Academy of Allergology and Clinical Immunology) consensus documents.

The myth about the benefits of the sedative effect of first-generation antihistamines
Even with regard to some of the side effects of first-generation antihistamines, there are misconceptions. The sedative effect of first-generation H1-HPA is associated with the myth that their use is preferable in the treatment of patients with concomitant insomnia, and if this effect is undesirable, it can be leveled by using the drug at night. At the same time, it should be remembered that first-generation antihistamines inhibit the phase of REM sleep, due to which the physiological process of sleep is disturbed, and there is no complete processing of information in sleep. Their use may cause respiratory failure, heart rate which increases the risk of developing sleep apnea. In addition, in some cases, the use of high doses of these drugs contributes to the development of paradoxical excitation, which also negatively affects the quality of sleep. It is necessary to take into account the difference in the duration of the preservation of the antiallergic effect (1.5-6 hours) and the sedative effect (24 hours), as well as the fact that prolonged sedation is accompanied by impaired cognitive functions.

The presence of pronounced sedative properties debunks the myth of the advisability of using first-generation H1-AHP in elderly patients who use these drugs, guided by the prevailing stereotypes of habitual self-treatment, as well as the recommendations of doctors who are not sufficiently informed about pharmacological properties drugs and contraindications to their use. Due to the lack of selectivity of effects on alpha-adrenergic receptors, muscarinic, serotonin, bradykinin and other receptors, a contraindication to the appointment of these drugs is the presence of diseases that are quite common among the elderly patients - glaucoma, benign hyperplasia prostate, bronchial asthma, chronic obstructive pulmonary disease, etc. .

The myth about the absence of a place in clinical practice for first-generation antihistamines
Despite the fact that first-generation H1-AHPs (most of them developed in the middle of the last century) are capable of causing known side effects, they are still widely used in clinical practice today. Therefore, the myth that with the advent of the new generation of AHD there is no place left for the previous generation of AHD is invalid. The H 1 -AGP of the first generation has one indisputable advantage - the presence of injectable forms that are indispensable in the provision of emergency care, premedication before carrying out certain types of diagnostic examination, surgical interventions etc. In addition, some drugs have an antiemetic effect, reduce the state of increased anxiety, and are effective in motion sickness. An additional anticholinergic effect of a number of drugs of this group is manifested in a significant reduction in itching and skin rashes with itching dermatoses, acute allergic and toxic reactions to food, drugs, insect bites and stings. However, it is necessary to prescribe these drugs with strict consideration of indications, contraindications, severity of clinical symptoms, age, therapeutic dosages, and side effects. The presence of pronounced side effects and the imperfection of the first generation H 1 -AGP contributed to the development of new second generation antihistamine drugs. The main directions of improvement of drugs were the increase in selectivity and specificity, the elimination of sedation and tolerance to the drug (tachyphylaxis).

Modern H 1 -AGP of the second generation have the ability to selectively affect H 1 receptors, do not block them, but, being antagonists, they transfer them to an “inactive” state without violating their physiological properties, have a pronounced anti-allergic effect, a rapid clinical effect, act long (24 hours), do not cause tachyphylaxis. These drugs practically do not penetrate the blood-brain barrier, therefore, do not cause a sedative effect, cognitive impairment.

Modern H 1 -AGP of the second generation have a significant anti-allergic effect - they stabilize the membrane of mast cells, suppress the release of interleukin-8 induced by eosinophils, granulocyte-macrophage colony-stimulating factor (Granulocyte Macrophage Colony-Stimulating Factor. GM-CSF) and soluble intercellular adhesion molecule 1 (Soluble Intercellular Adhesion Molecule-1, sICAM-1) from epithelial cells, which contributes to greater efficiency compared to the first generation H 1 -AHP in the basic therapy of allergic diseases, in the genesis of which mediators play a significant role late phase allergic inflammation.

Besides, important characteristic The second generation H1-AHP is their ability to provide an additional anti-inflammatory effect by inhibiting the chemotaxis of eosinophils and neutrophilic granulocytes, reducing the expression of adhesion molecules (ICAM-1) on endothelial cells, inhibiting IgE-dependent platelet activation and releasing cytotoxic mediators. Many doctors do not pay due attention to this, however, the listed properties make it possible to use such drugs for inflammation, not only allergic nature but also of infectious origin.

The myth of the same safety of all second-generation AHDs
There is a myth among physicians that all second-generation H1-HPAs are similar in their safety. However, in this group of drugs there are differences associated with the peculiarity of their metabolism. They may depend on the variability in the expression of the CYP3A4 enzyme of the liver cytochrome P 450 system. Such variability may be due to genetic factors, diseases of the hepatobiliary system, simultaneous administration of a number of drugs (macrolide antibiotics, some antimycotic, antiviral drugs, antidepressants, etc.), products (grapefruit) or alcohol that have an inhibitory effect on the oxygenase activity of the CYP3A4 cytochrome P450 system.

Among the H1-AGP of the second generation, there are:

"metabolizable" drugs therapeutic effect only after undergoing metabolism in the liver with the participation of the CYP 3A4 isoenzyme of the cytochrome P450 system with the formation of active compounds (loratadine, ebastine, rupatadine);

active metabolites - drugs that enter the body immediately in the form of an active substance (cetirizine, levocetirizine, desloratadine, fexofenadine) (Fig. 1).

Rice. 1. Features of the metabolism of H 1 -AGP of the second generation

The advantages of active metabolites, the intake of which is not accompanied by an additional burden on the liver, are obvious: the speed and predictability of the development of the effect, the possibility joint reception with various drugs and foods that are metabolized with the participation of cytochrome P450.

The myth about the higher efficiency of each new AGP
The myth that appeared in last years new H1-AGP means are obviously more effective than the previous ones, also did not find confirmation. The works of foreign authors indicate that second-generation H1-AHP, for example, cetirizine, have a more pronounced antihistamine activity than second-generation drugs that appeared much later (Fig. 2).

Rice. 2. Comparative antihistamine activity of cetirizine and desloratadine on the effect on the skin reaction caused by the administration of histamine within 24 hours

It should be noted that among the H 1 -AGP of the second generation, researchers assign a special place to cetirizine. Developed in 1987, it was the first original highly selective H1 receptor antagonist based on the pharmacologically active metabolite of the previously known first-generation antihistamine, hydroxyzine. Until now, cetirizine remains a kind of standard of antihistamine and antiallergic action, used for comparison in the development of the latest antihistamine and antiallergic drugs. There is an opinion that cetirizine is one of the most effective antihistamine H 1 drugs, it has been used more often in clinical trials, the drug is preferable for patients who respond poorly to therapy with other antihistamines.

The high antihistamine activity of cetirizine is due to the degree of its affinity for H 1 receptors, which is higher than that of loratadine. It should also be noted the significant specificity of the drug, since even at high concentrations it does not have a blocking effect on serotonin (5-HT 2), dopamine (D 2), M-cholinergic receptors and alpha-1-adrenergic receptors.

Cetirizine meets all the requirements for modern second generation antihistamines and has a number of features. Among all known antihistamines, the active metabolite cetirizine has the smallest volume of distribution (0.56 l/kg) and provides full employment of H1 receptors and the highest antihistamine effect. The drug is characterized by a high ability to penetrate the skin. 24 hours after taking a single dose, the concentration of cetirizine in the skin is equal to or exceeds the concentration of its content in the blood. At the same time, after a course of treatment, the therapeutic effect persists for up to 3 days. The pronounced antihistamine activity of cetirizine favorably distinguishes it among modern antihistamines (Fig. 3).

Rice. 3. Efficacy of a single dose of second-generation H 1 -AHP in suppressing histamine-induced whealing over 24 hours in healthy men

The myth about the high cost of all modern AGPs
Any chronic disease is not immediately amenable to even adequate therapy. It is known that insufficient control over the symptoms of any chronic inflammation leads not only to a deterioration in the patient's well-being, but also to an increase in the total cost of treatment due to an increase in the need for drug therapy. The selected drug should have the most effective therapeutic effect and be affordable. Physicians who remain committed to prescribing first-generation H1-AHP explain their choice by referring to another myth that all second-generation antihistamines are significantly more expensive than drugs first generation. However, in addition to the original drugs on the pharmaceutical market, there are generics, the cost of which is lower. For example, at present, 13 generics are registered from cetirizine drugs in addition to the original one (Zyrtec). The results of pharmacoeconomic analysis presented in Table. 2, testify to the economic feasibility of using Cetrin, a modern second-generation AGP.

Table 2.

Results of comparative pharmacoeconomic characteristics of H1-AGP of the first and second generations

A drug	Suprastin 25 mg № 20	Diazolin 100 mg №10	Tavegil 1 mg № 20	Zyrtec 10 mg No. 7	Cetrin 10 mg № 20
Average market value of 1 pack	120 rub.	50 rub.	180 rub.	225 rub.	160 rub.
Multiplicity of reception	3 r/day	2 r / day	2 r / day	1 r / day	1 r / day
The cost of 1 day of therapy	18 rub.	10 rub.	18 rub.	32 rub.	8 rub.
Cost of 10 days of therapy	180 rub.	100 rub.	180 rub.	320 rub.	80 rub.

The myth that all generics are equally effective
The question of the interchangeability of generics is relevant when choosing the optimal modern antihistamine drug. Due to the variety of generics on the market pharmacological agents, a myth arose that all generics act approximately the same, so you can choose any, focusing primarily on the price.

Meanwhile, generics differ from each other, and not only pharmacoeconomic characteristics. The stability of the therapeutic effect and the therapeutic activity of the reproduced drug are determined by the features of the technology, packaging, the quality of active substances and excipients. The quality of the active substances of the preparations different manufacturers may differ significantly. Any change in the composition of excipients can contribute to a decrease in bioavailability and the occurrence of side effects, including hyperergic reactions of various nature (toxic, etc.). Generic must be safe to use and equivalent original drug. Two medicinal products are considered to be bioequivalent if they are pharmaceutically equivalent, have the same bioavailability and, when administered at the same dose, are similar, providing adequate efficacy and safety. According to the recommendations of the World Health Organization, the bioequivalence of a generic should be determined in relation to the officially registered original drug. The study of bioequivalence is one of the stages in the study of therapeutic equivalence. The FDA (Food and Drug Administration - Food and Drug Administration (USA)) annually publishes and publishes the "Orange Book" with a list of drugs that are considered therapeutically equivalent to the original. So any doctor can do optimal choice safe antihistamine drug, taking into account all the possible characteristics of these drugs.

One of the highly effective generics of cetirizine is Cetrin. The drug acts quickly, for a long time, has a good safety profile. Cetrin is practically not metabolized in the body, the maximum serum concentration is reached one hour after ingestion, with prolonged use it does not accumulate in the body. Cetrin is available in 10 mg tablets, indicated for adults and children from 6 years of age. Cetrin is completely bioequivalent to the original drug (Fig. 4).

Rice. 4. The average dynamics of the concentration of cetirizine after taking the compared drugs

Cetrin is successfully used as part of the basic therapy of patients with allergic rhinitis with sensitization to pollen and household allergens, allergic rhinitis associated with atopic bronchial asthma, allergic conjunctivitis, urticaria, including chronic idiopathic urticaria, pruritic allergic dermatoses, angioedema, and also as symptomatic therapy for acute viral infections in patients with atopy. When comparing the performance indicators of cetirizine generics in patients with chronic urticaria, the best results were noted with the use of Cetrin (Fig. 5).

Rice. 5. Comparative evaluation of the clinical efficacy of cetirizine preparations in patients with chronic urticaria

Domestic and foreign experience in the use of Cetrin indicates its high therapeutic efficacy in clinical situations where the use of second-generation H 1 antihistamines is indicated.

Thus, when choosing the optimal H 1 -antihistamine drug from all drugs on the pharmaceutical market, one should not be based on myths, but on selection criteria that include maintaining a reasonable balance between efficacy, safety and availability, the presence of a convincing evidence base, High Quality production.

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Histamine pathophysiology andH 1-histamine receptors

Histamine and its effects mediated through H 1 receptors

Stimulation of H 1 receptors in humans leads to an increase in smooth muscle tone, vascular permeability, itching, slowing of atrioventricular conduction, tachycardia, activation of the branches of the vagus nerve that innervates the respiratory tract, an increase in cGMP levels, an increase in the formation of prostaglandins, etc. In table. 19-1 shows localization H 1 receptors and the effects of histamine mediated through them.

Table 19-1. Localization H 1 receptors and the effects of histamine mediated through them

The role of histamine in the pathogenesis of allergy

Histamine plays a leading role in the development of atopic syndrome. In IgE-mediated allergic reactions, a large amount of histamine enters the tissues from mast cells, causing the occurrence of the following effects by acting on H 1 receptors.

In the smooth muscles of large vessels, bronchi and intestines, activation of H1 receptors causes a change in the conformation of the Gp protein, which, in turn, leads to the activation of phospholipase C, which catalyzes the hydrolysis of inositol diphosphate to inositol triphosphate and diacylglycerols. An increase in the concentration of inositol triphosphate leads to the opening of calcium channels in the ER (“calcium depot”), which causes the release of calcium into the cytoplasm and an increase in its concentration inside the cell. This leads to the activation of calcium/calmodulin-dependent kinase of myosin light chains and, accordingly, to the contraction of smooth muscle cells. In the experiment, histamine causes a biphasic contraction of the smooth muscles of the trachea, consisting of a fast phase contraction and a slow tonic component. Experiments have shown that the fast phase of contraction of these smooth muscles depends on intracellular calcium, while the slow phase depends on the entry of extracellular calcium through slow calcium channels unblocked by calcium antagonists. Acting through H 1 receptors, histamine causes contraction of the smooth muscles of the respiratory tract, including the bronchi. In the upper sections of the respiratory tract, there are more histamine H 1 receptors than in the lower ones, which is essential in the degree of severity of bronchospasm in the bronchioles during the interaction of histamine with these receptors. Histamine induces bronchial obstruction as a result of a direct effect on the smooth muscles of the respiratory tract, reacting with histamine H 1 receptors. In addition, through H 1 receptors, histamine increases the secretion of fluid and electrolytes in the airways and causes increased mucus production and airway edema. Patients with bronchial asthma are 100 times more sensitive to histamine than healthy individuals when conducting a histamine provocation test.

In the endothelium of small vessels (postcapillary venules), the vasodilating effect of histamine is mediated through H 1 receptors in reagin-type allergic reactions (through H 2 receptors of smooth muscle cells of venules, along the adenylate cyclase pathway). Activation of H 1 receptors leads (via the phospholipase pathway) to an increase in the intracellular level of calcium, which, together with diacylglycerol, activates phospholipase A 2, causing the following effects.

Local release of endothelium-relaxing factor. It enters neighboring smooth muscle cells and activates guanylate cyclase. As a result, the concentration of cGMP, which activates cGMP-dependent protein kinase, increases, which leads to a decrease in intracellular calcium. With a simultaneous decrease in the level of calcium and an increase in the level of cGMP, smooth muscle cells of postcapillary venules relax, which leads to the development of edema and erythema.

When phospholipase A2 is activated, the synthesis of prostaglandins, mainly the prostacyclin vasodilator, increases, which also contributes to the formation of edema and erythema.

Classification of antihistamine drugs

There are several classifications of antihistamines (histamine H1 receptor blockers), although none of them is considered generally accepted. According to one of the most popular classifications, antihistamines are divided into I and II generation drugs according to the time of creation. First-generation drugs are also commonly called sedatives (according to the dominant side effect), in contrast to second-generation non-sedative drugs. Antihistamines of the first generation include: diphenhydramine (diphenhydramine*), promethazine (diprazine*, pipolfen*), clemastine, chloropyramine (suprastin*), hifenadine (fenkarol*), sequifenadine (bicarfen*). Second generation antihistamines: terfenadine*, astemizole*, cetirizine, loratadine, ebastine, cyproheptadine, oxatomide* 9, azelastine, acrivastine, mebhydroline, dimethindene.

Currently, it is customary to isolate the third generation of antihistamines. It includes fundamentally new drugs - active metabolites, which, in addition to high antihistamine activity, are characterized by the absence of a sedative effect and the cardiotoxic effect characteristic of second-generation drugs. The III generation of antihistamines include fexofenadine (telfast *), desloratadine.

In addition, according to the chemical structure, antihistamines are divided into several groups (ethanolamines, ethylenediamines, alkylamines, derivatives of alphacarboline, quinuclidine, phenothiazine *, piperazine * and piperidine *).

Mechanism of action and main pharmacodynamic effects of antihistamine drugs

Most of the antihistamines used have specific pharmacological properties, which characterizes them as a separate group. These include the following effects: antipruritic, decongestant, antispastic, anticholinergic, antiserotonin, sedative and local anesthetic, as well as the prevention of histamine-induced bronchospasm.

Antihistamines are histamine H 1 receptor antagonists, and their affinity for these receptors is much lower than that of histamine (Table 19-2). That is why these drugs are not able to displace the histamine associated with the receptor, they only block unoccupied or released receptors.

Table 19-2. Comparative effectiveness of antihistamine drugs by the degree of blockade H 1-histamine receptors

Accordingly, blockers H 1 Histamine receptors are most effective in preventing immediate allergic reactions, and in the case of a developed reaction, they prevent the release of new portions of histamine. The binding of antihistamines to receptors is reversible, and the number of blocked receptors is directly proportional to the concentration of the drug at the location of the receptor.

The molecular mechanism of action of antihistamines can be represented as a scheme: blockade of the H 1 receptor - blockade of the phosphoinositide pathway in the cell - blockade of the effects of histamine. The binding of drugs to the histamine H 1 receptor leads to a “blockade” of the receptor, i.e. prevents the binding of histamine to the receptor and the launch of a cascade in the cell along the phosphoinositide pathway. Thus, the binding of an antihistamine drug to the receptor causes a slowdown in the activation of phospholipase C, which leads to a decrease in the formation of inositol triphosphate and diacylglycerol from phosphatidylinositol, as a result, the release of calcium from intracellular depots slows down. A decrease in the release of calcium from intracellular organelles into the cytoplasm in various cell types leads to a decrease in the proportion of activated enzymes that mediate the effects of histamine in these cells. In the smooth muscles of the bronchi (as well as the gastrointestinal tract and large vessels), the activation of calcium-calmodulin-dependent kinase of myosin light chains slows down. This prevents the contraction of smooth muscles caused by histamine, especially in patients with bronchial asthma. However, in bronchial asthma, the concentration of histamine in the lung tissue is so high that modern H1-blockers are not able to block the effects of histamine on the bronchi through this mechanism. In the endothelial cells of all postcapillary venules, antihistamine drugs prevent the vasodilating effect of histamine (directly and through prostaglandins) in local and generalized allergic reactions (histamine also acts through the histamine H 2 receptors of smooth muscle cells

venule through the adenylate cyclase pathway). Blockade of histamine H 1 receptors in these cells prevents an increase in intracellular calcium levels, ultimately slowing down the activation of phospholipase A2, which leads to the development of the following effects:

Slowing down the local release of the endothelium-relaxing factor, which penetrates into neighboring smooth muscle cells and activates guanylate cyclase. Inhibition of guanylate cyclase activation reduces the concentration of cGMP, then the fraction of activated cGMP-dependent protein kinase decreases, which prevents a decrease in calcium levels. At the same time, the normalization of the level of calcium and cGMP prevents the relaxation of smooth muscle cells of postcapillary venules, that is, it prevents the development of edema and erythema caused by histamine;

A decrease in the activated fraction of phospholipase A2 and a decrease in the synthesis of prostaglandins (mainly prostacyclin), vasodilation is blocked, which prevents the occurrence of edema and erythema caused by histamine by its second mechanism of action on these cells.

Based on the mechanism of action of antihistamine drugs, these drugs should be prescribed to prevent allergic reactions of the reagin type. The appointment of these drugs in the developed allergic reaction is less effective, since they do not eliminate the symptoms of developed allergies, but prevent their occurrence. Histamine H1-receptor blockers prevent the reaction of bronchial smooth muscles to histamine, reduce itching, and prevent histamine-mediated expansion of small vessels and their permeability.

Pharmacokinetics of antihistamine drugs

The pharmacokinetics of first-generation H 1 -receptor blockers of histamine is fundamentally different from the pharmacokinetics of second-generation drugs (Table 19-3).

Penetration of the first generation antihistamines through the BBB leads to a pronounced sedative effect, which is considered a significant drawback of this group of drugs and significantly limits their use.

Antihistamines of the second generation are relatively hydrophilic and therefore do not penetrate the BBB and, therefore, do not cause a sedative effect. It is known that 80% of astemizole* is excreted 14 days after the last dose, and terfenadine* - 12 days later.

Pronounced ionization of diphenhydramine at physiological values pH and active non-specific interaction with serum

Oral albumin determines its effect on H 1 - histamine receptors located in various tissues, which leads to quite pronounced side effects of this drug. In the blood plasma, the maximum concentration of the drug is determined 4 hours after its administration and is equal to 75-90 ng / l (at a dose of 50 mg). The half-life is 7 hours.

The peak concentration of clemastine is reached 3-5 hours after a single oral dose of 2 mg. The half-life is 4-6 hours.

Terfenadine* is rapidly absorbed when taken orally. Metabolized in the liver. The maximum concentration in tissues is determined 0.5-1-2 hours after taking the drug, the half-life is

The maximum level of unchanged astemizole * is noted within 1-4 hours after taking the drug. Food reduces the absorption of astemizole * by 60%. The peak concentration of drugs in the blood with a single oral administration occurs after 1 hour. The half-life of the drug is 104 hours. Hydroxyastemizole and norastemizole are its active metabolites. Astemizol * penetrates the placenta, in a small amount - into breast milk.

The maximum concentration of oxatomide * in the blood is determined 2-4 hours after ingestion. The half-life is 32-48 hours. The main metabolic pathway is aromatic hydroxylation and oxidative dealkylation on nitrogen. 76% of the absorbed drug is attached to plasma albumin, from 5 to 15% is excreted in breast milk.

Table 19-3. Pharmacokinetic parameters of some antihistamine drugs

The maximum level of cetirizine in the blood (0.3 μg / ml) is determined 30-60 minutes after taking this drug at a dose of 10 mg. Renal

the clearance of cetirizine is 30 mg / min, the half-life is about 9 hours. The drug is stably associated with blood proteins.

The peak plasma concentration of acrivastin is reached 1.4-2 hours after administration. The half-life is 1.5-1.7 hours. Two-thirds of the drug is excreted unchanged by the kidneys.

Loratadine is well absorbed in the gastrointestinal tract and after 15 minutes it is determined in the blood plasma. Food does not affect the degree of absorption of drugs. The half-life of the drug is 24 hours.

Antihistamines of the 1st generation

For blockers of H 1 -receptors of histamine of the first generation, some features are characteristic.

sedative action. Most antihistamines of the first generation, easily soluble in lipids, penetrate well through the BBB and bind to the H1 receptors of the brain. Apparently, the sedative effect develops with the blockade of central serotonin and m-cholinergic receptors. The degree of development of the sedative effect varies from moderate to severe and increases when combined with alcohol and psychotropic drugs. Some drugs in this group are used as sleeping pills (doxylamine). Rarely, instead of sedation occurs psychomotor agitation(more often in medium therapeutic doses in children and in high toxic doses in adults). Due to the sedative effect of the drugs, they cannot be used during the period of work requiring attention. All H 1 -receptor blockers of histamine I generation potentiate the action of sedative and hypnotic drugs, narcotic and non-narcotic analgesics, monoamine oxidase inhibitors and alcohol.

anxiolytic action, characteristic of hydroxyzine. This effect, possibly, occurs due to the suppression of the activity of some parts of the subcortical formations of the brain by hydroxyzine.

atropine-like action. This effect is associated with the blockade of m-cholinergic receptors, most characteristic of ethanolamines and ethylenediamines. Characterized by dry mouth, urinary retention, constipation, tachycardia and blurred vision. In non-allergic rhinitis, the effectiveness of these drugs increases due to the blockade of m-cholinergic receptors. However, it is possible to increase bronchial obstruction due to an increase in the viscosity of sputum, which is dangerous in bronchial asthma. Blockers of H 1 -receptors of histamine I generation can exacerbate glaucoma and cause acute urinary retention in prostate adenoma.

Antiemetic and antihypertensive action. These effects may also be associated with the central m-anticholinergic action of these drugs. Diphenhydramine, promethazine, cyclizine*, mecli-

zine * reduce the stimulation of vestibular receptors and inhibit the function of the labyrinth, and therefore can be used for motion sickness.

Some blockers of H 1 -receptors of histamine reduce the symptoms of parkinsonism, which is due to the blockade of the central m-cholinergic receptors.

Antitussive action. Most characteristic of diphenhydramine, is realized due to the direct action on cough center in the medulla oblongata.

Antiserotonin action. Cyproheptadine possesses it to the greatest extent, therefore it is used for migraine.

The effect of blockade of a 1 adrenaline receptors with peripheral vasodilation is especially characteristic of drugs of the phenothiazine series. This can lead to a transient decrease in blood pressure.

Local anesthetic action is typical for most drugs in this group. The local anesthetic effect of diphenhydramine and promethazine is stronger than that of novocaine*.

Tachyphylaxis- a decrease in the antihistamine effect with long-term use, confirming the need for alternating drugs every 2-3 weeks.

Pharmacodynamics of H1-receptor blockers of histamine I generation

All blockers of H 1 histamine receptors of the first generation are lipophilic and, in addition to H 1 histamine receptors, also block m-cholinergic receptors and serotonin receptors.

When prescribing histamine receptor blockers, it is necessary to take into account the phase course of the allergic process. Histamine H1-receptor blockers should be used mainly for the prevention of pathogenetic changes in the event of a patient's alleged encounter with an allergen.

Blockers of H 1 -receptors of histamine I generation do not affect the synthesis of histamine. In high concentrations, these drugs are able to cause degranulation of mast cells and the release of histamine from them. H1-receptor blockers of histamine are more effective in preventing the action of histamine than in eliminating the consequences of its influence. These drugs inhibit the response of bronchial smooth muscles to histamine, reduce itching, prevent histamine from increasing vasodilation and increase their permeability, and reduce the secretion of endocrine glands. It has been proven that H 1 -receptor blockers of histamine of the 1st generation have a direct bronchodilatory effect, and most importantly, they prevent the release of histamine from mast cells and blood basophils, which is considered the basis for the use of these drugs.

as a preventive measure. At therapeutic doses, they do not significantly affect cardiovascular system. With forced intravenous administration, they can cause a decrease in blood pressure.

Blockers of H 1 -receptors of histamine of the 1st generation are effective in the prevention and treatment of allergic rhinitis (effectiveness is about 80%), conjunctivitis, itching, dermatitis and urticaria, angioedema, some types of eczema, anaphylactic shock, with edema caused by hypothermia. Blockers of H 1 -receptors of histamine of the first generation are used in conjunction with sympathomimetics for allergic rhinorrhea. Piperazine* and phenothiazine* derivatives are used to prevent nausea, vomiting and dizziness caused by sudden movements in Meniere's disease, vomiting after anesthesia, radiation sickness and morning vomiting in pregnant women.

Local application of these drugs takes into account their antipruritic, anesthetic and analgesic effect. It is not recommended to use them for a long time, since many of them can cause hypersensitivity and have a photosensitizing effect.

Pharmacokinetics of histamine H-receptor blockers of the 1st generation

Blockers of H 1 -receptors of histamine of the first generation differ from second-generation drugs in the short duration of action with a relatively rapid onset of the clinical effect. The effect of these drugs occurs, on average, 30 minutes after taking the drug, reaching a peak within 1-2 hours. The duration of action of first-generation antihistamines is 4-12 hours. metabolism and excretion by the kidneys.

Most of the first-generation H1-receptor blockers of histamine are well absorbed from the gastrointestinal tract. These drugs pass through the BBB, the placenta, and also enter breast milk. The highest concentrations of these drugs are found in the lungs, liver, brain, kidneys, spleen, and muscles.

Most blockers of H 1 -receptors of histamine I generation are metabolized in the liver by 70-90%. They induce microsomal enzymes, which, with prolonged use, can reduce their therapeutic effect, as well as the effect of other drugs. Metabolites of many antihistamines are excreted within 24 hours in the urine and only small amounts are excreted unchanged.

Side effects and contraindications to the appointment

Side effects caused by H 1 blockers of histamine receptors of the first generation are presented in Table. 19-4.

Table 19-4. Adverse drug reactions of 1st generation antihistamines

Large doses of histamine H1 receptor blockers can cause agitation and convulsions, especially in children. With these symptoms, barbiturates should not be used, as this will cause an additive effect and significant depression of the respiratory center. Cyclizine* and chlorcyclizine* are teratogenic and should not be used for vomiting in pregnant women.

Drug Interactions

Blockers of H 1 -receptors of histamine I generation potentiate the effects of narcotic analgesics, ethanol, hypnotics, tranquilizers. May enhance the effect of CNS stimulants in children. With prolonged use, these drugs reduce the effectiveness of steroids, anticoagulants, phenylbutazone (butadione *) and other drugs that are metabolized in the liver. Their combined use with anticholinergics can lead to an excessive increase in their effects. MAO inhibitors enhance the effect of antihistamine drugs. Some first-generation drugs potentiate the effect of adrenaline and norepinephrine on the cardiovascular system. Blockers of H 1 -receptors of histamine of the first generation are prescribed for the prevention of clinical symptoms of allergy, in particular, rhinitis, which often accompanies atopic bronchial asthma, for the relief of anaphylactic shock.

Antihistamines II and III generations

The second generation drugs include terfenadine *, astemizole *, cetirizine, mekvipazine *, fexofenadine, loratadine, ebastine, to the third generation of histamine H1 receptor blockers - fexofenadine (telfast *).

The following features of H 1 -receptor blockers of histamine II and III generations can be distinguished:

High specificity and high affinity for H 1 histamine receptors with no effect on serotonin and m-cholinergic receptors;

The rapid onset of the clinical effect and the duration of action, which is usually achieved by a high degree of protein binding, accumulation of the drug or its metabolite in the body and delayed excretion;

Minimal sedative effect when using drugs in therapeutic doses; some patients may experience moderate drowsiness, which is rarely the reason for discontinuation of the drug;

Lack of tachyphylaxis with prolonged use;

The ability to block potassium channels in the cells of the conduction system of the heart, which is associated with prolongation of the interval Q-T and a violation of the heart rhythm (ventricular tachycardia of the "pirouette" type).

In table. 19-5 presents a comparative description of some H 1 -receptor blockers of histamine II generation.

Table 19-5. Comparative characteristics of H1-receptor blockers of histamine II generation

The end of the table. 19-5

Pharmacodynamics of histamine H-receptor blockers of the II generation

Astemizole * and terfenadine * do not have choline and β-adrenergic blocking activity. Astemizol * blocks α-adrenergic and serotonin receptors only in high doses. Blockers of H 1 -receptors of histamine II generation have a weak therapeutic effect in bronchial asthma, since the smooth muscles of the bronchi and bronchial glands are affected not only by histamine, but also by leukotrienes, platelet activating factor, cytokines and other mediators that cause the development of the disease. The use of only blockers of H 1 -receptors of histamine does not guarantee complete relief of allergic bronchospasm.

Features of the pharmacokinetics of H 1 -receptor blockers of histamine II generation All blockers of H 1 -receptors of histamine II generation act for a long time (24-48 hours), and the time for the development of the effect is short - 30-60 minutes. About 80% of astemizole * is excreted 14 days after the last dose, and terfenadine * - after 12 days. The cumulative effect of these drugs, which occurs without changing the functions of the central nervous system, allows them to be widely used in outpatient practice in patients with hay fever, urticaria, rhinitis, neurodermatitis, etc. Blockers of H 1 -receptors of histamine of the II generation are used in the treatment of patients with bronchial asthma with individual selection of doses.

For H 1 -receptor blockers of histamine II generation in varying degrees characterized by a cardiotoxic effect due to blocking

each potassium channel of cardiomyocytes and expressed by prolongation of the interval Q-T and arrhythmia on the electrocardiogram.

The risk of this side effect increases when antihistamines are combined with inhibitors of the cytochrome P-450 3A4 isoenzyme (Appendix 1.3): antifungal drugs (ketoconazole and itraconazole *), macrolides (erythromycin, oleandomycin and clarithromycin), antidepressants (fluoxetine, sertraline and paroxetine) , when drinking grapefruit juice, as well as in patients with severe liver dysfunction. The combined use of the above macrolides with astemizole * and terfenadine * in 10% of cases leads to a cardiotoxic effect associated with prolongation of the interval QT. Azithromycin and dirithromycin * are macrolides that do not inhibit the 3A4 isoenzyme, and therefore do not cause interval prolongation Q-T when taken simultaneously with blockers of H 1 -receptors of histamine of the second generation.

Spring. Nature is awakening… Primroses are blooming… Birch, alder, poplar, hazel let out coquettish earrings; buzzing bees, bumblebees, collecting pollen ... The season begins (from lat. pollinis pollen) or hay fever - allergic reactions to plant pollen. Summer is coming. Cereals bloom, tart wormwood, fragrant lavender ... Then autumn comes and ragweed becomes the “mistress”, the pollen of which is the most dangerous allergen. During the flowering of the weed, up to 20% of the population suffers from lacrimation, cough, allergic. And here is the long-awaited winter for allergy sufferers. But here many are waiting for a cold allergy. Spring again ... And so all year round.

And also off-season allergies to animal hair, cosmetics, house dust and more. Plus drug allergies, food. In addition, in recent years, the diagnosis of "allergy" is made more often, and the manifestations of the disease are more pronounced.

Alleviate the condition of patients with drugs that relieve the symptoms of allergic reactions, and above all - antihistamines (AHP). Histamine, which stimulates H1 receptors, can be called the main culprit of the disease. It is involved in the mechanism of occurrence of the main manifestations of allergies. Therefore, antihistamines are always prescribed as antiallergic drugs.

Antihistamines - blockers of H1 histamine receptors: properties, mechanism of action

The mediator (biologically active mediator) histamine affects:

• Skin, causing itching, hyperemia.
• Respiratory tract, causing edema, bronchospasm.
• Cardiovascular system, causing increased vascular permeability, cardiac arrhythmia, hypotension.
• Gastrointestinal tract, stimulating gastric secretion.

Antihistamines relieve symptoms caused by endogenous histamine release. They prevent the development of hyperreactivity, but do not affect either the sensitizing effect (hypersensitivity) of allergens, or the infiltration of the mucosa by eosinophils (a type of leukocyte: their content in the blood increases with allergies).

Antihistamines:

It should be borne in mind that the mediators involved in the pathogenesis (mechanism of occurrence) of allergic reactions include not only histamine. In addition to it, acetylcholine, serotonin and other substances are “guilty” of inflammatory and allergic processes. Therefore, drugs that have only antihistamine activity stop only acute manifestations allergies. Systematic treatment requires complex desensitizing therapy.

Generations of antihistamines

We recommend reading:

By modern classification There are three groups (generations) of antihistamines:
H1 histamine blockers of the first generation (tavegil, diphenhydramine, suprastin) - penetrate through a special filter - the blood-brain barrier (BBB), act on the central nervous system, exerting a sedative effect;
H1 histamine blockers II generation (fencarol, loratadine, ebastine) - do not cause sedation (in therapeutic doses);
H1 histamine blockers of the III generation (Telfast, Erius, Zyrtec) are pharmacologically active metabolites. They do not pass through the BBB, they have a minimal effect on the central nervous system, therefore they do not cause sedation.

The characteristics of the most popular antihistamines are shown in the Table:

	loratadine CLARITINE	cetirizine
comparative efficiency
Efficiency
Duration actions
Time effect
Frequency dosing
unwanted phenomena
Elongation QT interval
Sedative action
Gain the effects of alcohol
Side effects erythromycin
Increase weight
application
Opportunity use in children
Application in pregnant women	Maybe		contraindicated
Application during lactation	contraindicated	contraindicated	contraindicated
Necessity
Necessity
Necessity			contraindicated
price treatment
Price 1 day of treatment, c.u.
Price

	astemizole HISMANAL	terfenadine	fexofenadine
comparative efficiency
Efficiency
Duration actions		18 - 24 hours
Time effect
Frequency dosing
comparative efficiency
Elongation QT interval
Sedative action
Gain the effects of alcohol
Side effects when used together with ketoconazole and erythromycin
Increase weight
application in specific patient populations
Opportunity use in children	> 1 of the year
Application in pregnant women	Maybe	contraindicated	Maybe
Application during lactation	contraindicated	contraindicated	contraindicated
Necessity dose reduction in the elderly
Necessity dose reduction in renal failure
Necessity dose reduction in hepatic impairment	contraindicated	contraindicated
price treatment
Price 1 day of treatment, c.u.
Price monthly course of treatment, c.u.

Benefits of 3rd generation antihistamines

This group includes pharmacologically active metabolites of some drugs of previous generations:

• fexofenadine (telfast, fexofast) - an active metabolite of terfenadine;
• levocetirizine (ksizal) - a derivative of cetirizine;
• desloratadine (erius, desal) is the active metabolite of loratadine.

For drugs latest generation significant selectivity (selectivity) is characteristic, they act exclusively on peripheral H1 receptors. Hence the benefits:

1. Efficiency: rapid absorption plus high bioavailability determine the rate of removal of allergic reactions.
2. Practicality: do not affect performance; the absence of sedation plus cardiotoxicity eliminates the need for dose adjustments in elderly patients.
3. Safety: not addictive - this allows you to prescribe long courses of therapy. There is practically no interaction with concomitantly taken drugs; absorption does not depend on food intake; the active substance is excreted “as is” (unchanged), i.e., target organs (kidneys, liver) do not suffer.

Prescribe medications for seasonal and chronic rhinitis, dermatitis, allergic bronchospasm.

3rd generation antihistamines: names and dosages

note: dosages are for adults.

Feksadin, telfast, fexofast take 120-180 mg x 1 time per day. Indications: symptoms of hay fever (sneezing, itching, rhinitis), idiopathic (redness, pruritus).

Levocetirizine-teva, xyzal are taken 5 mg x 1 time per day. Indications: chronic allergic rhinitis, idiopathic urticaria.

Desloratadin-teva, Erius, Desal are taken 5 mg x 1 time per day. Indications: seasonal hay fever, chronic idiopathic urticaria.

Third generation antihistamines: side effects

With their relative safety, third-generation H1 histamine receptor blockers can cause: agitation, convulsions, dyspepsia, abdominal pain, myalgia, dry mouth, insomnia, headache, asthenic syndrome, nausea, drowsiness, dyspnea, tachycardia, blurred vision, weight gain, paronyria (unusual dreams).

Antihistamines for children

Ksizal drops are prescribed for children: older than 6 years in daily dose 5 mg (= 20 drops); from 2 to 6 years in a daily dose of 2.5 mg (= 10 drops), more often 1.25 mg (= 5 drops) x 2 times a day.
Levocetirizine-teva - dose for children over 6 years old: 5 mg x 1 time per day.

Erius syrup is allowed for children aged 1 to 6 years: 1.25 mg (= 2.5 ml of syrup) x 1 time per day; from 6 to 11 years: 2.5 mg (= 5 ml of syrup) x 1 time per day;
adolescents from 12 years old: 5 mg (= 10 ml of syrup) x 1 time per day.

Erius is able to inhibit the development of the first phase of an allergic reaction and inflammation. When chronic course urticaria is the reverse development of the disease. The therapeutic efficacy of Erius in the treatment of chronic urticaria was confirmed in a placebo-controlled (blinded) multicenter study. Therefore, Erius is recommended for use in children from one year old.

Important: A study of the effectiveness of Erius lozenges in the pediatric group has not been conducted. But the pharmacokinetic data revealed in the study of the determination of drug doses with the participation of pediatric patients indicate the possibility of using lozenges of 2.5 mg in the age group of 6-11 years.

Fexofenadine 10 mg is prescribed for adolescents from 12 years of age.

The doctor tells about allergy drugs and their use in pediatrics:

Prescribing antihistamines during pregnancy

During pregnancy, third-generation antihistamines are not prescribed. In exceptional cases, the use of telfast or fexofast is allowed.

Important: Information on the use of drugs of the fexofenadine (Telfast) group by pregnant women is not enough. Since studies conducted on experimental animals did not reveal signs of an adverse effect of Telfast on general course pregnancy and intrauterine development, the medicine is considered conditionally safe for pregnant women.

Antihistamines: from diphenhydramine to erius

Many allergy sufferers owe the first generation of antihistamines an improvement in well-being. "Side" drowsiness was taken for granted: but the nose does not flow and the eyes do not itch. Yes, the quality of life suffered, but what to do - the disease. The latest generation of antihistamines has made it possible for a large cohort of allergy sufferers not only to get rid of allergy symptoms, but also to live a normal life: drive a car, play sports, without the risk of falling asleep on the go.

4th generation antihistamines: myths and reality

Often in the advertising of drugs for the treatment of allergies, the term “new generation antihistamine”, “fourth generation antihistamine” slips. Moreover, this non-existent group often ranks not only anti-allergic drugs of the latest generation, but also drugs under new trademarks belonging to the second generation. This is nothing more than a marketing gimmick. In the official classification, only two groups of antihistamines are indicated: the first generation and the second. The third group is pharmacologically active metabolites, for which the term "H1 histamine blockers of the III generation" has been assigned.

Dear friends, I greet you!

Acrivastine (Semprex) and terfenadine also belonged here, but they caused severe cardiac arrhythmias, even death, so they disappeared from the shelves.

pros:

1. High selectivity for H1 receptors.
2. They do not have a sedative effect.
3. They operate for a long time.
4. Side effects when taking them are noted much less frequently.
5. They are not addictive, so they can be used for a long time.

Minuses:

Safe at recommended dosages. Passing through the liver, they are metabolized by it. But if the functions are impaired, non-metabolized forms of the active substance accumulate in the blood, which can cause heart rhythm disturbances. You have probably seen that some of the annotations mention the QT interval. This is a special section of the electrocardiogram, the lengthening of which indicates the likelihood of ventricular fibrillation and sudden death.

In this regard, patients with impaired liver and kidney function need to change the dose.

3rd generation antihistamines

This group of drugs includes desloratadine ( Erius, Lordestin, Desal, etc.), levocetirizine ( Xizal, Suprastinex and others), fexofenadine ( Allegra, Feksadin, Fexofast, etc.).

These are active metabolites of second-generation drugs, so their metabolic products do not accumulate in the blood, causing heart problems, and do not interact with other drugs. medicines causing side effects.

Pros:

• Outperforms their predecessors in performance.
• They act quickly and for a long time.
• They do not have a sedative effect.
• Do not slow down the reaction rate.
• Do not enhance the effect of alcohol.
• They are not addictive, so they can be used for a long time.
• They do not have a toxic effect on the heart muscle.
• There is no need to change the dose in patients with impaired liver and kidney function.
• The safest.

I didn't find any cons in general.

Here you go. The preparatory work is done, you can move on to the preparations.

First of all, let's sketch out what might be of interest to an allergy sufferer who asks you for an antiallergic drug.

He wants the drug:

• Was efficient.
• Started to act quickly.
• Taken once a day.
• Didn't cause drowsiness.
• Did not reduce the reaction rate (for drivers of vehicles).
• Was compatible with alcohol.

And you and I, as always, are still interested in nursing, children and the elderly.

This is how we will analyze the active substances using the example of the most popular over-the-counter drugs.

1 generation.

Suprastin pills

• Begins to act in 15-30 minutes, the action lasts 3-6 hours.
• shown with any allergic reactions, except for bronchial asthma. In general, antihistamines are not the main drugs for asthma. They are weak for asthmatics. If they are used, then only in combination with bronchodilators. And the first generation does cause dryness of the mucous membranes, making it difficult to expectorate.
• Causes drowsiness.
• Pregnant, lactating is contraindicated.
• Children - from 3 years (for this form).
• A lot of side effects.
• It is better not to recommend for the elderly.
• Drivers can't.
• The effect of alcohol enhances.

Tavegilpills

Everything is the same as suprastin, only it lasts longer (10-12 hours), so it is taken less often.

Other differences:

• The sedative effect is less compared to Suprastin, but the therapeutic effect is also weaker.
• Children - from 6 years old (for this form).

Diazolintablets, dragees

• It begins to act in 15-30 minutes, the action can last for an incomprehensible amount. They write that even up to 2 days. Then the question is the frequency of reception.
• Children from 3 years old. Up to 12 years - a single dose of 50 mg, then - 100 mg.
• May cause irritability in children.
• Pregnant, lactating women are not allowed.
• Not recommended for the elderly.
• Drivers can't.

Fenkarolpills

• It penetrates poorly through the BBB, so the sedative effect is negligible.
• Starts working in an hour.
• From 3 to 12 years old - 10 mg tablets, from 12 years old - 25 mg, from 18 years old - 50 mg.
• In pregnancy - weigh the risk / benefit, contraindicated in the 1st trimester.
• Nursing is not allowed.
• Side effects are much less than those discussed above.
• Drivers of vehicles beware.

2 generation

Claritin (loratadine) tablets, syrup

• Begins to act 30 minutes after ingestion.
• The action lasts 24 hours.
• Does not cause drowsiness.
• Does not cause arrhythmias.
• Indications: hay fever, urticaria, allergic dermatitis.
• Lactation is not allowed.
• Pregnancy - with caution.
• Children - syrup from 2 years old, tablets from 3 years old.
• Does not enhance the effect of alcohol.
• Drivers can.

I noticed that the instructions for generics indicate that it is contraindicated during pregnancy. Why, then, is there a “loophole” for Claritin in the form of a vague “with caution”?

Zyrtec (cetirizine ) - tablets, drops for oral administration

• Begins to act within an hour, the effect lasts 24 hours.
• Does not have a sedative effect (in therapeutic doses).
• Indications: urticaria, dermatitis, Quincke's edema.
• Effective for cold allergies.
• The greatest effect was shown in the treatment skin allergies.
• Children - drops from 6 months, tablets - from 6 years.
• Refrain from alcohol.
• Drivers, be careful.

Kestin (ebastine)- coated tablets 10 mg, 20 mg and lyophilized 20 mg

• The effect of the film-coated tablets begins after 1 hour and lasts 48 hours ( record holder!).
• After 5 days of admission, the effect persists for 72 hours.
• Indications: hay fever, urticaria, other allergic reactions.
• Pregnancy, lactation - contraindicated.
• Children: from 12 years old.
• Drivers can.
• Hearts - with caution.
• 20 mg film-coated tablets - recommend if lower dosage fails.
• 20 mg lyophilized tablets dissolve instantly in the mouth: for those who find it difficult to swallow.

Fenistil (dimetindene) drops, gel

• Drops - the maximum concentration in the blood after 2 hours.
• Indications: hay fever, allergic dermatoses.
• Drops for children - from 1 month. Caution up to 1 year to avoid apnea (stop breathing) against the background of a sedative effect.
• Pregnancy - except for the 1st trimester.
• Nursing is not allowed.
• Contraindicated - bronchial asthma, prostate adenoma, glaucoma.
• The effect of alcohol enhances.
• Drivers better not.
• Gel - for skin dermatosis, insect bites.
• Emulsion - easy to take on the road, ideal for a bite: thanks to the roll-on applicator, it can be applied pointwise.

3rd generation

Aerius (desloratadine) - tablets, syrup

• Begins to act in 30 minutes and lasts 24 hours.
• Indications: hay fever, urticaria.
• Especially effective in allergic rhinitis - eliminates nasal congestion. It has not only anti-allergic, but also anti-inflammatory effect.
• Pregnancy and lactation - contraindicated.
• Children - tablets from 12 years old, syrup from 6 months.
• Side effects are very rare.
• Drivers can.
• The effect of alcohol does not enhance.

Allegra (fexofenadine) - tab. 120, 180 mg

• Begins to act in an hour, and the action lasts 24 hours.
• Indications: allergic (tablet 120 mg), urticaria (tablet 180 mg).
• Pregnancy and lactation - contraindicated.
• Children - from 12 years old.
• Drivers, be careful.
• Seniors, be careful.
• The effect of alcohol - no indication.

Nasal and ophthalmic antihistamines

Allergodil- nasal spray.

It is used for allergic rhinitis in children from 6 years old and adults 2 times a day.

Suitable for long term use.

Allergodil eye drops - children from 4 years old and adults 2 times a day for allergic.

Sanorin-analergin

It is used from the age of 16 for allergic rhinitis. It is good because it contains vasoconstrictor and antihistamine components, i.e. acts both on the cause of allergic rhinitis and on the symptom (congestion). Begins to act in 10 minutes, and the action lasts 2-6 hours.

Pregnant and lactating is contraindicated.

Vizin Alergi- eye drops.

Contains only an antihistamine component. It is applied from 12 years, not on lenses. Not recommended for pregnant and lactating women.

That's all.

Finally, I have questions for you:

1. What other popular antihistamines have I not mentioned here? Their features, chips?
2. What questions should you ask a customer asking for an allergy remedy?
3. Have something to add? Write.

With love to you, Marina Kuznetsova

To suppress the development of an allergic reaction, it is necessary to take an antihistamine. Currently, there are a huge number of medicines from this group. All of them are divided by generations. The list of new generation antihistamines is quite wide and allows you to choose the best medicine for treatment. In the article we will take a closer look at the most effective medicines in this category.

General concept

Most people have heard of antihistamines, but not everyone knows what they are and how they work. This is the name of a group of drugs that can act on histamine receptors, a mediator of allergic reactions. Upon contact with an irritant, the human body begins to produce specific substances, among which histamine is the most active. When this substance “meets” with certain receptors, symptoms such as tearing, reddening of the skin, itching, and a rash develop.

Antiallergic drugs are able to block these receptors and, as a result, resist the appearance of unpleasant symptoms. Without them, negative processes in the body will continue.

Currently, there is a significant increase in the number of people suffering from this or that type of allergy. Inappropriate reaction immune system It can develop against the background of disorders of the endocrine or nervous system, but most often the cause is external irritants: plant pollen, wool, dust, chemicals, some foods.

Treatment with antihistamines

In most cases, allergies cannot be completely cured. Get rid of unpleasant symptoms or drugs that affect histamine receptors will help prevent their occurrence.

To date, there are several generations of these medicines. And if the first antiallergic drugs brought not only long-awaited relief, but also many side effects, then the new generation antihistamines, the list of which we will consider below, are practically devoid of drawbacks and have practically no contraindications for use.

Medicines of this category are prescribed in the following cases:

• with year-round or seasonal rhinitis;
• with a negative reaction to flowering plants;
• when symptoms of food and drug allergies occur;
• with atopic dermatitis;
• with urticaria and itching of the skin;
• with bronchial asthma;
• with angioedema;
• with allergic conjunctivitis.

New generation antihistamines: an overview

Among all antiallergic medicines, the latest generation of drugs are considered the safest. They are prodrugs, which means that when they enter the body, the substances contained in the composition are converted into active metabolites. Such drugs act only on histamine H-1 receptors and do not negative impact to the central nervous system.

The list of new generation antihistamines is small, however, compared with their predecessor drugs, they can be prescribed to almost all patients suffering from various types allergic reactions. Such funds allow you to quickly stop the already manifested symptoms and do not have a toxic effect on the heart. The following drugs are popular:

• "Cetirizine".
• "Fexofenadine".
• "Erius".
• "Fexofast".
• "Ksizal".
• "Levocetirizine".
• "Desal".
• "Caesera".
• "Desloratadine".
• "Kestin".

Features of drugs

The most common antiallergic drugs of the latest generation are those that contain fexofenadine in their composition. The substance belongs to selective inhibitors of H-1 histamine receptors and is able to stabilize mast cell membranes. The component inhibits the process of migration of leukocytes to the focus of the inflammatory process.

4th generation antihistamines based on cetirizine are considered one of the most effective. They are able to quickly stop the development of skin allergic reactions. They have a pronounced antipruritic and antiexudative effect.

Each of the modern anti-allergy drugs is prescribed only after the examination. The dosage regimen and duration of use is determined strictly individually.

"Erius": a description of the medication

An antihistamine based on desloratadine is produced by a branch of the pharmaceutical company Schering-Plough Corporation / USA in Belgium. You can buy medicines in tablet form and in the form of syrup. In addition to the main active ingredient, the tablets contain titanium dioxide, talc, calcium hydrogen phosphate dihydrate, lactose monohydrate, white wax, corn starch, microcrystalline cellulose.

The syrup contains such auxiliary components as lemon acid, sorbitol, sodium benzoate, propylene glycol, sodium citrate dihydrate, sucrose. Tablets are packaged in packs of 7 and 10 pieces per blister. The syrup is liquid yellow color and is in vials of 60 and 120 ml.

Indications for appointment

Tablets "Erius" instructions for use recommend taking with seasonal rhinitis, lacrimation, itching of the nasal mucosa, seasonal pollinosis, chronic idiopathic urticaria. As prescribed by a specialist, the medication can also be used for other allergic conditions. For example, many patients say that "Erius" copes well with signs of neurodermatitis, food allergies, atopic dermatitis.

As part of complex therapy, an antihistamine can be taken for chicken pox, pink lichen, scabies and pseudo-scabies. Erius will effectively eliminate severe itching and help you sleep.

In pediatric practice, an antiallergic drug is used in the form of a syrup. The manufacturer claims that it can be given to babies older than 1 year. The dosage will depend on the age category. Erius tablets are suitable for adult patients and children from 12 years of age. Instructions for use recommends taking 1 tablet (5 mg) per day.

"Cetirizine": reviews

Modern antiallergic drugs are able to stop the development of the disease at the earliest stages. This is extremely important in severe allergic reactions. That is why many experts in the list of new generation antihistamines in the first place is "Cetirizine". An agent based on the active ingredient of the same name quickly relieves bronchospasm, attacks of bronchial asthma, and prevents the development of Quincke's edema. In addition, the medication will be effective for hives, pollinosis, hay fever, eczema, allergic dermatitis.

The antihistamine drug "Cetirizine" is available in the form of drops for oral administration, syrup and tablets. In 1 ml liquid solution contains 10 mg of cetirizine. One tablet contains the same amount of active substance. A noticeable effect from the use of a histamine H-1 receptor blocker can be seen an hour after administration. The duration of action is 24 hours. In bronchial asthma, it is used in combination with the bronchodilator drug Fenspiride.

Contraindications and side effects

Treatment with cetirizine should be discontinued if hypersensitivity to the main component and hydroxyzine. It is forbidden to prescribe an antihistamine to people who are on hemodialysis or have kidney failure, during breastfeeding and pregnancy. Contraindications are also conditions associated with lactase deficiency, glucose-galactose malabsorption and lactose intolerance. With caution take "Cetirizine" simultaneously with barbiturates, ethanol-containing drugs and opioid analgesics.

Excellent tolerance is a huge advantage of the drug. Side effects while taking tablets, drops or syrup are extremely rare. This is mainly due to an overdose of the active substance. In such cases, the following symptoms may develop:

• dizziness;
• migraine;
• nervous excitement;
• tachycardia;
• insomnia;
• urinary retention;
• myalgia;
• skin rashes, eczema.

What is Kestin?

Another effective histamine receptor blocker is Kestin. It produces pharmaceutical company Nycomed Danmark ApS (Denmark). Modern antiallergic agent is quite expensive. The average price of tablets (10 pieces per pack) is 380-400 rubles.

What is the composition of this medicine? Ebastine is the main component that blocks histamine H-1 receptors. The substance quickly eliminates spasms of the smooth muscles of the bronchi, reduces exudation, stops the manifestation of skin allergic reactions. "Kestin" is available in the form of tablets, which may contain various amounts of ebastine (10 or 20 mg) and syrup. The manufacturer also offers lozenges containing 20 mg of the active substance.

Who suits?

Any 4th generation antihistamines, including Kestin, can be taken only after consultation with an allergist. Most often, the drug is prescribed to adult patients. The instruction allows the use of tablets in pediatric practice, but only if the child is over 12 years old. Lozenges are prescribed only from the age of 15. The syrup can be used to treat children from 6 years of age.

"Kestin" effectively eliminates the symptoms of year-round and seasonal rhinitis of various origins, conjunctivitis, urticaria, Quincke's edema. The drug relieves symptoms caused by drug, food, insect allergies.

It is worth refraining from using "Kestin" during pregnancy, lactation, with intolerance to ebastine or other components of the drug. Lozenges are not prescribed for patients suffering from phenylketonuria. Under the supervision of a physician, an antihistamine is used for coronary disease, hypokalemia, renal and hepatic failure.

Description of the drug "Ksizal"

If necessary, symptomatic treatment of allergic skin reactions, urticaria, rhinorrhea, Quincke's edema, hay fever, many prefer modern means"Ksizal". The cost of one package is 420-460 rubles. The drug is produced at pharmaceutical factories in Belgium, Switzerland and Italy.

The main active component of Xyzal is levocetirizine. The substance has pronounced anti-allergic properties. The active metabolite is able to prevent the development of allergies or significantly alleviate the course of the pathological condition. Substance reduces permeability vascular walls, blocks the activity of cytokines and inflammatory mediators, inhibits the movement of eosinophils. The clinical effect of the drug persists for 24 hours.

When are they assigned?

In the list of new allergy drugs, Xyzal occupies the first position due to its quick effect and safety. A modern drug has practically no contraindications to the appointment and rarely provokes the development of side effects. It is recommended to use it for a variety of allergic reactions: Quincke's edema, hay fever, allergic dermatitis, itching, sneezing, nasal congestion against the background of seasonal or year-round rhinitis.

In the form of drops, "Ksizal" can be prescribed to babies from 2 years old. The tablets are suitable for use in children from 6 years of age and adults. The drug received many positive recommendations related to ease of use. One tablet of "Ksizal" can relieve allergy symptoms for a whole day.

"Levocetirizine" for allergies

The drug "Levocetirizine" is a cheaper analogue of "Ksizal". The cost of one package (10 tablets) ranges from 230-250 rubles. Also, the medicine can be purchased in the form of syrup and drops.

The active substance of the drug is able to block the endings of H-1 histamine receptors, thereby preventing the development of an inadequate response of the immune system. Allergy tablets "Levocetirizine" will be effective for hay fever, allergic dermatitis, seasonal and chronic rhinitis, lacrimation, sneezing, angioedema, urticaria.

The drug is not used to treat children under 6 years of age, during pregnancy and breastfeeding, with hypersensitivity to the components in the composition and severe renal failure.

The drug "Bamipin"

The list of new generation antihistamines includes agents intended for systemic use. However, in some cases, local medication is also required. To cope with skin manifestations of allergies, you should use special gels. One of these external medicines is Bamipin. It can be used already with the appearance of the first symptoms of urticaria, an allergic reaction to insect bites, itching of the skin, thermal burns. The drug is also available in the form of tablets.