Catad_tema Allergic diseases

Antihistamines: myths and reality

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

T.G. Fedoskova
State Research Center Institute of Immunology FMBA of Russia, Moscow

The main drugs that affect the symptoms of inflammation and control the course of diseases of allergic and non-allergic origin include antihistamines.
The article analyzes controversial points regarding the experience of using modern antihistamines, as well as some of their main characteristics. This will allow a differentiated approach to the selection of the optimal drug when carrying out complex therapy for 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 allergic and non-allergic diseases. In this paper debateable issues experience regarding 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-AGP), 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 symptomatic and basic therapy of allergic and pseudoallergic reactions, complex treatment of acute and chronic infectious diseases of various origins, as premedication during invasive and radiocontrast studies, surgical interventions, to prevent side effects of vaccination, etc. In other words, H 1 -AGP is advisable to use in conditions caused by the release of active inflammatory mediators of a specific and nonspecific nature, the main of which is histamine.

Histamine has a wide range of biological activities, realized through the activation of cell surface specific receptors. The main depot of histamine in tissues is mast cells, in the blood - basophils. It is also present in platelets, gastric mucosa, endothelial cells and neurons in the brain. Histamine has a pronounced hypotensive effect and is an important biochemical mediator for 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 - H1, H2, H3, H4, belonging to the superfamily of G-protein-coupled receptors (GPCRs). Stimulation of H1 receptors leads to the release of histamine and the implementation of symptoms of inflammation, mainly of allergic origin. Activation of H 2 receptors increases the secretion of gastric juice and its acidity. H3 receptors are present predominantly in the organs of the central nervous system (CNS). They function as histamine-sensitive presynaptic receptors in the brain and regulate the synthesis of histamine from presynaptic nerve endings. Recently, a new class of histamine receptors, expressed predominantly on monocytes and granulocytes, was identified - H4. These receptors are present in the bone marrow, thymus, spleen, lungs, liver, and intestines. The mechanism of action of H 1 -AGP is based on the 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 effector tissue structures.

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, it is quite difficult to choose between them for their most effective and rational use in specific clinical cases. In this regard, controversial points arise, and often myths arise about the use of H 1 -AGP, widely used in clinical practice. There are many works on this topic in the domestic literature, but there is no consensus on the clinical use of these drugs.

The myth about three generations of antihistamines
Many people 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 - newest - generation AGPs. They tried to include metabolites and stereoisomers of modern AGPs into the third generation. Currently, it is believed that these drugs are second-generation AGPs, 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 refer to antihistamines synthesized in the future, which will most likely differ from known compounds in a number of basic 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 antihypertensive drugs is subjectively noted by 40-80% of patients. Its absence in individual patients does not exclude an objective negative effect of these drugs on cognitive functions, of which patients may not complain (ability to drive, learn, etc.). Dysfunction of the central nervous system is observed even when using minimal doses of these drugs. The effect of first-generation antihypertensive drugs 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, and therefore do not reduce the mental and physical activity of patients. In addition, AGPs of the first and second generations differ in the presence or absence of side effects associated with stimulation of receptors of a different type, duration of action, and development of addiction.

The first AGPs - phenbenzamine (Antergan), pyrilamine maleate (Neo-Antergan) began to be used back in 1942. Subsequently, new antihypertensive drugs emerged for use in clinical practice. Until the 1970s Dozens of compounds belonging to this group of drugs were synthesized.

On the one hand, extensive clinical experience has been accumulated in the use of first-generation antihypertensive drugs; on the other hand, these drugs have not been tested in clinical studies that meet modern requirements of 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 cognitive function	Yes (in minimal doses)	No (in therapeutic doses)
Selectivity for H1 receptors	No	Yes
Pharmacokinetic studies	Few	A lot of
Pharmacodynamic studies	Few	A lot of
Scientific studies of different 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 has been detected. Category C - no studies have been conducted.

Since 1977, the pharmaceutical market has been replenished with new H 1 -AGPs, 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 antihypertensive drugs
Even regarding a number of side effects of first-generation antihypertensive drugs, there are misconceptions. Associated with the sedative effect of first-generation H 1 -AGPs is the myth that their use is preferable in the treatment of patients with concomitant insomnia, and if this effect is undesirable, it can be neutralized by using the drug at night. It should be remembered that first-generation antihypertensive drugs inhibit the REM sleep phase, which disrupts the physiological process of sleep and does not fully process information during sleep. When using them, breathing and heart rhythm may be disrupted, 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 arousal, which also negatively affects the quality of sleep. It is necessary to take into account the difference in the duration of the antiallergic effect (1.5-6 hours) and the sedative effect (24 hours), as well as the fact that long-term sedation is accompanied by impaired cognitive functions.

The presence of pronounced sedative properties debunks the myth about the advisability of using first-generation H 1 -AGP in elderly patients who use these drugs, guided by established stereotypes of habitual self-medication, as well as the recommendations of doctors who are not sufficiently informed about the pharmacological properties of 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 prescription of these drugs is the presence of diseases that are quite common among elderly patients - glaucoma, benign prostatic hyperplasia, bronchial asthma, chronic obstructive pulmonary disease, etc. . .

The myth that there is no place in clinical practice for first-generation antihypertensive drugs
Despite the fact that first-generation H 1 -AGPs (most of them were developed in the middle of the last century) can cause known side effects, they are still widely used in clinical practice today. Therefore, the myth that with the advent of a new generation of AGP there is no room left for the previous generation of AGP is invalid. The first generation H 1 -AGP has one undeniable advantage - the presence of injection forms, which are indispensable in providing emergency care, premedication before carrying out certain types of diagnostic examinations, surgical interventions, etc. In addition, some drugs have an antiemetic effect, reduce anxiety, and are effective against motion sickness. The additional anticholinergic effect of a number of drugs in this group is manifested in a significant reduction in itching and skin rashes with itchy dermatoses, acute allergic and toxic reactions to foods, medications, insect bites and stings. However, these drugs must be prescribed 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 first-generation H 1 -AGP contributed to the development of new second-generation antihistamines. The main directions for improving drugs were increasing selectivity and specificity, eliminating sedation and tolerance to the drug (tachyphylaxis).

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

Modern second-generation H 1 -AGPs have a significant antiallergic effect - they stabilize the mast cell membrane, suppress the eosinophil-induced release of interleukin-8, 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 first-generation H 1 -AGP in basic therapy of allergic diseases, in the genesis of which mediators of the late phase of allergic inflammation play a significant role.

In addition, an important characteristic of second-generation H1-AGPs is their ability to provide an additional anti-inflammatory effect by inhibiting the chemotaxis of eosinophils and neutrophil granulocytes, reducing the expression of adhesion molecules (ICAM-1) on endothelial cells, inhibiting IgE-dependent platelet activation and the release of 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 of an allergic nature, but also of an infectious origin.

The myth about the same safety of all second-generation AGPs
There is a myth among doctors that all second-generation H1-AGPs are similar in their safety. However, in this group of drugs there are differences associated with the peculiarities 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 use of a number of drugs (macrolide antibiotics, some antifungal, antiviral drugs, antidepressants, etc.), products (grapefruit) or alcohol that have an inhibitory effect on the oxygenase activity of the CYP3A4 cytochrome system P450.

Among the second generation N1-AGP there are:

“metabolized” drugs that have a 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 metabolism of H 1 -AGP of the second generation

The advantages of active metabolites, the intake of which is not accompanied by additional load on the liver, are obvious: the speed and predictability of the development of the effect, the possibility of joint administration 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 new N1-AGP agents that have appeared in recent years are obviously more effective than the previous ones has also not been confirmed. The works of foreign authors indicate that second-generation H 1 -AGPs, for example cetirizine, have more pronounced antihistamine activity than second-generation drugs, which appeared much later (Fig. 2).

Rice. 2. Antihistamine comparative 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 second-generation H 1 -AGPs, researchers assign a special place to cetirizine. Developed in 1987, it became the first original highly selective H1 receptor antagonist, obtained on the basis of a pharmacologically active metabolite of the previously known first-generation antihistamine - hydroxyzine. To this day, cetirizine remains a kind of standard of antihistamine and antiallergic action, used for comparison in the development of new antihistamines and antiallergic drugs. There is an opinion that cetirizine is one of the most effective antihistamine H1 drugs, it was more often used in clinical studies, 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 H1 receptors, which is higher than that of loratadine. It should also be noted that the drug has a significant specificity, since even in 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 AGPs and has a number of features. Among all known AGPs, the active metabolite cetirizine has the smallest volume of distribution (0.56 l/kg) and ensures full occupancy 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 higher than the concentration in the blood. Moreover, after a course of treatment, the therapeutic effect lasts up to 3 days. The pronounced antihistamine activity of cetirizine makes it stand out among modern antihistamines (Fig. 3).

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

The myth about the high cost of all modern AGPs
Any chronic disease does not immediately respond to even adequate therapy. As is known, 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 overall treatment costs due to an increased need for drug therapy. The selected drug must have the most effective therapeutic effect and be affordable. Doctors who remain committed to prescribing first-generation H 1 -AGPs explain their choice by referring to another myth that all second-generation AGPs are much more expensive than first-generation drugs. However, in addition to original drugs, there are generics on the pharmaceutical market, the cost of which is lower. For example, currently, in addition to the original (Zyrtec), 13 generics of cetirizine preparations are registered. The results of the pharmacoeconomic analysis are presented in table. 2 indicate 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 No. 20	Diazolin 100 mg No. 10	Tavegil 1 mg No. 20	Zyrtec 10 mg No. 7	Cetrin 10 mg No. 20
Average market value of 1 package	120 rub.	50 rub.	180 rub.	225 rub.	160 rub.
Frequency of reception	3 times/day	2 times/day	2 times/day	1 r/day	1 r/day
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 presented on the market of pharmacological drugs, a myth has arisen that all generics act approximately the same, so you can choose any one, focusing primarily on price.

Meanwhile, generics differ from each other, and not only in their 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, and the quality of active substances and excipients. The quality of active substances of drugs from different manufacturers may vary 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.). The generic must be safe to use and equivalent to the original drug. Two drugs are considered 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 drug should be determined in relation to the officially registered original drug. Studying bioequivalence is one of the stages of studying therapeutic equivalence. The FDA (Food and Drug Administration (USA)) annually issues and publishes the “Orange Book” with a list of drugs that are considered therapeutically equivalent to the original drugs. Thus, any doctor can make the optimal choice of a safe antihistamine, taking into account all possible characteristics of these drugs.

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

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

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

Rice. 5. Comparative assessment of the clinical effectiveness of cetirizine drugs in patients with chronic urticaria

Domestic and foreign experience in the use of Cetrin indicates its high therapeutic effectiveness in clinical situations when the use of second-generation H1-antihistamines is indicated.

Thus, when choosing the optimal H 1 -antihistamine drug from all drugs presented on the pharmaceutical market, one should be based not on myths, but on selection criteria, including maintaining a reasonable balance between effectiveness, safety and accessibility, the presence of a convincing evidence base, and high quality production .

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Currently, more than 85% of the total population of the entire planet is susceptible to various manifestations of allergies, and in the last few decades there has been a marked increase in the number of people with allergies. This is probably due to the development of an industry that produces chemical products that themselves are common allergens or create conditions for the formation of allergic reactions due to dysfunction of the endocrine and nervous systems.

It is also possible that the influence of hygiene (excessive use of antibacterial and other potent agents) deprives the human body of contact with many, which weakens the immune system (especially in childhood).

It should be remembered that allergy is a highly individual disease with inadequate reactions of the body to a variety of allergens, causing different painful symptoms at different times in different people. Allergic reactions underlie quite severe diseases, including, and, and can also accompany some infections (infectious allergies).

Causes of allergies

Allergy itself can be recognized by a sudden lacrimation , sneezing, redness of the skin and other unexpected painful manifestations. Most often, such allergic symptoms occur through direct contact with a specific allergen substance, recognized by the human body as the causative agent of the disease, as a result of which counteraction mechanisms are launched in it.

Modern doctors consider allergens to be both substances that exhibit a direct allergenic effect and agents that can increase the effect of other allergens.

A person’s response to exposure to various allergens largely depends on the genetic individual characteristics of his immune system . Reviews of numerous studies indicate the presence of a hereditary allergic predisposition. So, parents suffering from allergies are much more likely to give birth to a child with a similar pathology than a healthy married couple.

Main causes of allergies:

• waste products of domestic ticks;
• pollen of various flowering plants;
• foreign protein compounds contained in or;
• exposure to sunlight, cold;
• dust (book, household, street);
• disputes between different fungi or mold ;
• animal hair (mainly characteristic of cats, rabbits, dogs, chinchillas);
• chemical detergents and cleaners;
• medicinal drugs (,);
• food products, mainly eggs, fruits (oranges, persimmons, lemons), milk, nuts, wheat, seafood, soybeans, berries (viburnum, grapes, strawberries);
• insect/arthropod bites;
• latex;
• cosmetical tools;
• psychological/emotional;
• Unhealthy Lifestyle.

Types and symptoms of allergies

Respiratory allergies

A form of allergy characteristic of the influence of allergens entering the body from the outside during breathing. Such substances are collectively called - aeroallergens , which include pollen, fine dust, and various gases. This can also include respiratory tract allergies.

Symptoms of such painful conditions are: pulmonary wheezing, itching in the nose, severe, sometimes. The main negative symptoms manifest themselves in the form and bronchial asthma .

Dermatosis

A form of skin allergy, accompanied by various skin irritations and rashes. Occurs due to exposure to allergens such as: medications, aeroallergens, food, household chemicals, cosmetics.

It manifests itself as redness of the skin, severe swelling, itching, blistering, peeling, type rashes, and dry skin.

Allergic conjunctivitis

A form of allergy due to exposure to various allergens, in which the organs of vision are mainly affected and negative eye symptoms are noted.

The main symptoms manifest themselves in the form of: skin swelling in the periorbital area, burning sensation in the eyes, increased tearfulness.

Enteropathy

Anaphylactic shock

The most dangerous form of allergy, which can develop in a few seconds or up to five hours. The main causes of this condition are insect bites and the use of untested medications.

External forms (gel) are used mainly for skin itching ( itchy dermatoses ), caused by insect bites, as well as acquired due to itchy eczema, urticaria, contact allergies (to detergents, washing powder, synthetic or rough clothing fabric, etc.).

These external preparations are ineffective and are rarely used in the treatment of chronic skin allergic forms (for example, with). In combination with diet, these drugs can be recommended in the initial stages of treatment. exudative-catarrhal diathesis moderate in nature (when a baby develops a rash on the face associated with nutrition).

Local combination agents in the form of eye drops ( Ophthalmol , ), including first generation antihistamines, are used in the treatment allergic conjunctivitis , as well as those accompanied by conjunctivitis.

Such drops quite well relieve such negative symptoms as: redness and swelling of the eyelids, itching and watery eyes, while simultaneously providing an antimicrobial effect. In turn, nasal drops cope quite well with the manifestations of allergic rhinitis in all its forms (including hay fever ).

Side effects

Negative effects are mainly characteristic of systemic drugs, however, due to long-term use, they can also be observed when using external/local agents (especially in pediatrics).

Most often, first generation antihistamines accompany:

• strong sedatives /sleeping pills effects;
• decreased muscle tone;
• psychomotor agitation (especially in children and adults with long-term use);
• potentiation (increase) the effects of alcohol, sleeping pills And analgesic funds;
• /headache;
• local anesthetic effect;
• decreased blood pressure;
• anticholinergic effects (tremor of fingers, dry mouth, constipation, rapid heartbeat, visual disturbances);
• nausea/vomiting, abdominal pain;
• addictive .

Due to their hypnotic effect, drugs of this generation are not recommended for use by pupils, students, drivers and people engaged in potentially hazardous activities.

All such drugs cause a specific reaction tachyphylaxis (addiction), which is expressed by a noticeable decrease in effectiveness during long-term use and requires replacing the active ingredient of the drug with another substance every 20 days.

Advantages

In certain cases, doctors have learned to use some of the above-described disadvantages of 1st generation drugs to their advantage.

For example, sedative /hypnotic the effect of these medicinal products will be useful for allergic diseases with parallel unbearable skin itching ( atopic dermatitis during an exacerbation), bringing long-awaited sleep into the patient’s life.

Anticholinergic effects , including dry mucous membranes, is useful during therapy bronchitis (for allergic cough) and rhinitis (from a runny nose), accompanied by copious discharge of liquid secretion.

All first-generation drugs, even those produced abroad, are quite inexpensive, and domestic manufacturers produce even cheaper analogues.

Flaws

Due to pronounced negative systemic effects and the body’s addiction to the active ingredient of the drug, 1st generation drugs are not suitable for long-term therapy.

Drowsiness And sedative effect seriously limits the number of patients to whom these drugs can be prescribed.

List of 1st generation antihistamines, table

Active Ingredient	Trade names of drugs	Release form
	Allergin ; Grandim ; Diphenhydramine	pills; injection solution; rectal suppositories; oral granules	1 month (for suppositories and injections); 3 years (for tablets)
		external gel	0 months
	Ophthalmol ; Betadrine ; Dithadrine ; combined	eye drops	2 years; 0 months (for Ophthalmola )
Chloropyramine	Subrestin ; Supramin ;	pills; injection solution	1 month
Clemastine	Bravegil ; Rivtagil	pills; injection solution; syrup	6 years (for tablets); 1 year (for syrup)
	Pipolzin	pills; dragee; injection solution	2 months
Pheniramine	Avil	pills; syrup; injection solution	12 years (for tablets); 0 months (for syrup)
		capsules; oral drops; gel; emulsion (external)	1 month (for drops); 12 years (for capsules); 0 months (for external forms)
	(combined)	drops; spray; gel (nasal)	1 month (for drops); 6 years (for gel and spray)
Cyproheptadine		pills; syrup	2 years (for tablets); 6 months (for syrup)
Mebhydrolin		pills; dragee	1 year (for tablets); 3 years (for pills)
Hifenadine		pills	3 years

2nd generation drugs

As in the previous case, the list of second-generation antihistamines for allergies is mainly represented by oral dosage forms.

Pills ( , Gistalong , ), syrups ( , ) drops ( , Parlazin , Cetirizine ) capsules ( Semprex ) and suspensions ( , ) are used for almost all types of allergic manifestations, both for the treatment of adult patients and for the treatment of children.

Also on the pharmaceutical market there are eye drops of this generation of antihistamines, which are used for therapy allergic conjunctivitis in any form. These drops relieve the negative symptoms of rhinitis within 20 minutes, are not characterized by serious side effects, and help improve mucociliary clearance.

Second generation antihistamines have a number of advantages over their predecessors:

• prolonged action (high efficiency remains for 24 hours, which allows the patient to drink the recommended dose of the drug indicated for him only once a day);
• all therapeutic agents of this generation are not adsorbed by the gastrointestinal tract with food;
• minimal impact sedative /sleeping pills effect, due to the impossibility of the active ingredients of medicinal products passing through the blood-brain barrier;
• during the therapy, the patient’s physical activity and mental activity are practically not affected;
• anticholinergic effect (tremor of fingers, dry mouth, constipation, rapid heartbeat, visual disturbances) occurs very rarely;
• all second-generation drugs are not addictive and can be used for quite a long time (3-12 months) without changing the active substance (for example, throughout seasonal allergies as long as it takes until the allergen disappears);
• upon cessation of treatment, therapeutic effectiveness remains for another week.

Side effects

Among the negative effects of 2nd generation antihistamines, the most serious is considered cardiotoxic effect , manifesting itself in varying degrees of severity and requiring control over the patient’s cardiac activity during therapy.

Cardiotoxic effect becomes possible due to the ability of drugs of this generation to act on cardiac potassium channels, blocking them. The risk of this effect increases with impaired liver function, concurrent use of antifungal agents, antidepressants , macrolides , as well as drinking grapefruit juice. Naturally, such drugs are contraindicated for elderly patients and patients with disorders of the cardiovascular system.

Other most common negative side effects:

• impaired liver function;
• fast fatiguability;
• nausea;
• swelling ;
• asthenia;
• phenomena;
• nervous excitability and sedation (in children).

Advantages

Due to minimal negative systemic action and effect tachyphylaxis (addiction), 2nd generation drugs are ideally suited for long-term use and have proven themselves well in the treatment of allergies seasonal rhinoconjunctivitis And rhinitis , hay fever, atopic dermatitis (in complex therapy in the subacute stage) and bronchial asthma .

These medications can be prescribed to schoolchildren and students during the educational process, since they do not reduce their concentration.

Prolonged effectiveness, observed over 24 hours (which allows you to avoid unnecessary doses, but limit them to 1 time per day).

Flaws

Due to the relatively short practice of use, all possible positive/negative effects of second-generation drugs have not been studied as well as in the case of their predecessors. In particular, for this reason, most of them, according to the instructions for use, are contraindicated under 2 years of age, and the rest should not be given to children under six months.

List of 2nd generation antihistamines, table

Active Ingredient	Trade names of drugs	Release form	Age restrictions for use
Loratadine	Lovanik ; Clarisan ;	pills; syrup; oral suspension	3 years (for tablets); 1 year (for syrup and suspension)
Cetirizine	Alerza	pills	6 years
	Zyrtec ;	pills; oral drops	6 years (for tablets); 6 months (for drops)
		pills; syrup	6 years (for tablets); 2 years (for syrup)
		pills; syrup; oral drops	6 years (for tablets); 1 year (for syrup and drops)
Akrivastine	Semprex	capsules	12 years
Terfenadil	Trexyl ; Bronal	pills	3 years
	Terfenadine	pills; syrup; oral suspension	3 years
Ebastine	Elert	pills	6 years
		eye drops; nasal spray	4 years (for drops); 6 years (for spray)
Astemizole	Astemizole ; Gistalong	pills	2 years
	Gismanal	pills; oral suspension	2 years

3rd generation drugs

The entire list of allergy drugs of the new generation (third) can, in principle, be attributed to previous therapeutic agents, because the active ingredients of these drugs are pharmacologically active metabolites of some already known main ingredients of the latest generation (second) described above.

However, new generation antiallergic drugs were the last to enter the pharmaceutical market and many sources position them as 3rd and even 4th generation antihistamines.

The spectrum of positive effects of this generation of drugs covers almost all allergic manifestations known today. Tablets (,), syrups ( Eden , ), oral drops and solutions ( , ) can be used for therapy hay fever , allergic rhinitis , dermatological reactions and other allergic manifestations.

New generation antihistamines, in comparison with their predecessors, are characterized by the greatest selectivity (selectivity) of their action exclusively aimed at peripheral H1 receptors. It is thanks to this that their high antiallergic effectiveness can be traced, along with the absence of side effects inherent in 1st and 2nd generation drugs.

The distinctive characteristics of such medicines are:

• rapid absorption in the gastrointestinal tract along with high bioavailability, which help neutralize allergic reactions in the shortest possible time;
• drops, syrups and tablets do not cause and only when taken in excessive doses can lead to the development sedative actions;
• the patient’s performance and response remain at a high level;
• none cardiotoxic effects , which will make it possible to prescribe drugs of this generation to elderly patients;
• there is no addictive effect, which makes it possible to use these medications for a long period of time;
• there is practically no interaction with concurrently taken drugs from other pharmaceutical groups;
• the absorption of therapeutic agents does not depend on the time of food intake;
• active ingredients are excreted in unchanged form, relieving the load on the kidneys and liver.

Side effects

In rare cases, it is possible to develop:

• nausea;
• prolongation of the QT interval ;
• headaches/dizziness;
• increased appetite;
• skin hyperemia;
• dry mucous membranes.

Advantages

Long-lasting and rapid action, virtually no negative side effects (manifested as anticholinergic effects and suppression of the nervous system), once daily dosage.

Flaws

Like all relatively new drugs, the disadvantage of these drugs is incomplete clinical data regarding the safety of their use (especially in pediatrics). The price of drugs of this generation can be several times higher than the cost of their predecessors.

List of antihistamines 3-4 generations, table

Active Ingredient	Trade names of drugs	Release form	Age restrictions for use
Desloratadine	Trexyl Neo	pills	12 years
	Eden ; Lordes ; Fribris ;	pills; syrup	12 years (for tablets); 1 year (for syrup)
	Desal ; Alernova	pills; oral suspension	12 years (for tablets); 1 year (for suspension)
Levocetirizine		pills; oral drops	6 years (for tablets); 1 year (for drops)
	Zodak Express ; Caeser ;	pills	6 years
	Allegra ; Dinox ; Fexofast ; Allergo	pills	6 years

Modern pediatrics in its practice of treating allergies in children uses antihistamine antiallergic drugs for children of all three generations. In the younger age group, the most used oral dosage forms are children's drops and syrups; tablets are prescribed to children at a more conscious age, most often from 6 years of age.

Some nasal and eye allergy drops for children can be used from birth.

• In the countries of the post-Soviet space, especially in the acute period of allergies, pediatricians often prefer to use 1st generation of antihistamines for children up to one year old. Such drugs are characterized by rapid effectiveness and rapid elimination. They have been used in pediatrics for quite a long time, their positive and negative effects have been well studied, most of them are considered relatively safe (if taken as prescribed by a doctor, without exceeding the recommended doses), many drugs in this group can be used for newborns. If liquid dosage forms are unavailable, children under one year of age may take medications in the form of tablets, previously divided into parts recommended by the doctor and crushed. The most popular and effective drugs of systemic action of first generation antihistamines are: ,.
• Antihistamines 2nd generation are characterized by a longer duration of action, due to which they can be used once every 24 hours. Such drugs are more suitable for long-term therapy. They rarely lead to sleeping pills /sedative effect and other side effects inherent in 1st generation medications. Such medications are prescribed for children from 1 year of age (rarely from 6 months), since their effect on the body of infants has not been studied enough. In this generation, pediatricians most often use the following drugs: Zyrtec , .
• 3rd generation antihistamines It is characterized by very high efficiency and even fewer side effects. Liquid preparations of this generation (syrups, drops), due to their novelty, are used for the treatment of chronic allergic processes in children only when they reach the age of 12 months. Third generation children's medicines include: Eden , Desal .

Parents should remember that giving their child antiallergic drugs on their own is strictly prohibited. As Dr. Komarovsky wrote in his article: “ ... antihistamines can only be prescribed by a doctor and used strictly in accordance with his instructions«.

Antihistamines during pregnancy

Naturally, women with allergies who are planning to get pregnant or are already carrying a child are extremely interested in what kind of allergy pills can be taken during and after this, and is it possible to take such drugs during these periods in principle?

Let's start with the fact that when pregnancy It is better for a woman to avoid taking any medications, since their effects can be dangerous both for pregnant women and for their future offspring. Antihistamine tablets for allergies during pregnancy in the 1st trimester are strictly prohibited, except in extreme cases that threaten the life of the expectant mother. In the 2nd and 3rd trimester, the use of antihistamines is also allowed with great restrictions, since none of the existing therapeutic antiallergic drugs is 100% safe.

Women with allergies suffering from seasonal allergies , we can recommend planning your time in advance pregnancy when specific allergens are least active. For others, the best option would also be to avoid contact with substances that cause allergic reactions in them. If it is impossible to follow such recommendations, the severity of some allergic manifestations can be reduced by taking natural antihistamines (, and, zinc, pantothenic , And oleic acid) and then only after consulting a doctor.

Membrane stabilizers of mast cells

For the treatment of certain allergic reactions, mainly initial and

There are several groups of medications used for allergic diseases. This:

• antihistamines;
• membrane-stabilizing drugs - cromoglycic acid preparations () and ketotifen;
• topical and systemic glucocorticosteroids;
• intranasal decongestants.

In this article we will talk only about the first group - antihistamines. These are drugs that block H1-histamine receptors and, as a result, reduce the severity of allergic reactions. Today there are more than 60 antihistamines for systemic use. Depending on the chemical structure and the effects they have on the human body, these drugs are combined into groups, which we will discuss below.

What are histamine and histamine receptors, the principle of action of antihistamines

There are several types of histamine receptors in the human body.

Histamine is a biogenic compound formed as a result of a number of biochemical processes, and is one of the mediators that takes part in the regulation of vital functions of the body and plays a leading role in the development of many diseases.

Under normal conditions, this substance is in the body in an inactive, bound state, however, during various pathological processes (hay fever, hay fever, and so on), the amount of free histamine increases many times, which is manifested by a number of specific and nonspecific symptoms.

Free histamine has the following effects on the human body:

• causes spasm of smooth muscles (including bronchial muscles);
• dilates capillaries and reduces blood pressure;
• causes stagnation of blood in the capillaries and increased permeability of their walls, which entails thickening of the blood and swelling of the tissues surrounding the affected vessel;
• reflexively excites the cells of the adrenal medulla - as a result, adrenaline is released, which contributes to the narrowing of arterioles and an increase in heart rate;
• increases the secretion of gastric juice;
• plays the role of a neurotransmitter in the central nervous system.

Externally, these effects manifest themselves as follows:

• bronchospasm occurs;
• the nasal mucosa swells - nasal congestion and mucus discharge appear;
• itching, redness of the skin appears, all kinds of rash elements form on it - from spots to blisters;
• the digestive tract responds to an increase in the level of histamine in the blood with a spasm of the smooth muscles of the organs - there are pronounced cramping pains throughout the abdomen, as well as an increase in the secretion of digestive enzymes;
• on the part of the cardiovascular system, and may be observed.

There are special receptors in the body for which histamine has an affinity - H1, H2 and H3 histamine receptors. In the development of allergic reactions, the role played mainly by H1-histamine receptors located in the smooth muscles of internal organs, in particular the bronchi, in the inner lining - the endothelium - of blood vessels, in the skin, as well as in the central nervous system.

Antihistamines act specifically on this group of receptors, blocking the action of histamine through competitive inhibition. That is, the drug does not displace histamine already bound to the receptor, but occupies a free receptor, preventing histamine from attaching to it.

If all receptors are occupied, the body recognizes this and gives a signal to reduce histamine production. Thus, antihistamines prevent the release of new portions of histamine, and are also a means of preventing the occurrence of allergic reactions.

Classification of antihistamines

Several classifications of drugs in this group have been developed, but none of them is generally accepted.

Depending on the characteristics of the chemical structure, antihistamines are divided into the following groups:

• ethylenediamines;
• ethanolamines;
• alkylamines;
• quinuclidine derivatives;
• alphacarboline derivatives;
• phenothiazine derivatives;
• piperidine derivatives;
• piperazine derivatives.

In clinical practice, the classification of antihistamines by generation has become more widely used, of which today there are 3:

1. 1st generation antihistamines:

• diphenhydramine (diphenhydramine);
• doxylamine (donormil);
• clemastine (tavegil);
• chloropyramine (suprastin);
• mebhydrolin (diazolin);
• promethazine (pipolfen);
• quifenadine (fencarol);
• cyproheptadine (peritol) and others.

1. 2nd generation antihistamines:

• acrivastine (Semprex);
• dimethindene (fenistil);
• terfenadine (histadine);
• azelastine (allergodil);
• loratadine (lorano);
• cetirizine (cetrin);
• bamipin (Soventol).

1. 3rd generation antihistamines:

• fexofenadine (Telfast);
• desloratodine (erius);
• Levocetirizine.

1st generation antihistamines

First generation antihistamines have a pronounced sedative effect.

Based on the predominant side effect, drugs in this group are also called sedatives. They interact not only with histamine receptors, but also with a number of other receptors, which determines their individual effects. They act for a short time, which is why they require multiple doses throughout the day. The effect comes quickly. Available in different dosage forms - for oral administration (in the form of tablets, drops) and parenteral administration (in the form of an injection solution). Affordable.

With prolonged use of these drugs, their antihistamine effectiveness is significantly reduced, which necessitates the need for periodic - once every 2-3 weeks - drug changes.

Some 1st generation antihistamines are included in combination medications for the treatment of colds, as well as sleeping pills and sedatives.

The main effects of 1st generation antihistamines are:

• local anesthetic – associated with a decrease in membrane permeability to sodium; the most powerful local anesthetics from this group of drugs are promethazine and diphenhydramine;
• sedative – due to the high degree of penetration of drugs of this group through the blood-brain barrier (that is, into the brain); the degree of severity of this effect varies between drugs; it is most pronounced in doxylamine (it is often used as a hypnotic); the sedative effect increases with the simultaneous consumption of alcoholic beverages or taking psychotropic drugs; when taking extremely high doses of the drug, instead of the effect of sedation, pronounced agitation is observed;
• anti-anxiety, calming effect is also associated with the penetration of the active substance into the central nervous system; most expressed in hydroxyzine;
• anti-sickness and anti-emetic - some representatives of the drugs in this group inhibit the function of the labyrinth of the inner ear and reduce the stimulation of receptors of the vestibular apparatus - they are sometimes used for Meniere's disease and motion sickness in transport; This effect is most pronounced in drugs such as diphenhydramine and promethazine;
• atropine-like effect - causes dryness of the mucous membranes of the oral and nasal cavities, increased heart rate, visual impairment, urinary retention, constipation; may increase bronchial obstruction, lead to exacerbation of glaucoma and obstruction in cases of – not used for these diseases; These effects are most pronounced in ethylenediamines and ethanolamines;
• antitussive - drugs of this group, in particular diphenhydramine, act directly on the cough center located in the medulla oblongata;
• the antiparkinsonian effect occurs by inhibiting the effects of acetylcholine by the antihistamine;
• antiserotonin effect - the drug binds to serotonin receptors, alleviating the condition of patients suffering from migraine; especially pronounced in cyproheptadine;
• dilatation of peripheral vessels - leads to a decrease in blood pressure; is maximally expressed in phenothiazine preparations.

Since drugs in this group have a number of undesirable effects, they are not the drugs of choice for the treatment of allergies, but are still often used for it.

Below are some of the most commonly used representatives of the drugs in this group.

Diphenhydramine (diphenhydramine)

One of the first antihistamines. It has pronounced antihistamine activity, in addition, it has a local anesthetic effect, and also relaxes the smooth muscles of internal organs and is a weak antiemetic. Its sedative effect is similar in strength to the effects of neuroleptics. In high doses it also has a hypnotic effect.

It is quickly absorbed when taken orally and penetrates the blood-brain barrier. Its half-life is about 7 hours. It undergoes biotransformation in the liver and is excreted by the kidneys.

It is used for all kinds of allergic diseases, as a sedative and hypnotic, as well as in complex therapy for radiation sickness. Less commonly used for pregnancy vomiting and seasickness.

Orally prescribed in the form of tablets of 0.03-0.05 g 1-3 times a day for 10-14 days, or one tablet before bed (as a sleeping pill).

1-5 ml of 1% solution are administered intramuscularly, 0.02-0.05 g of the drug in 100 ml of 0.9% sodium chloride solution is administered intravenously.

Can be used in the form of eye drops, rectal suppositories, or creams and ointments.

Side effects of this drug are: short-term numbness of the mucous membranes, headache, dizziness, nausea, dry mouth, weakness, drowsiness. Side effects go away on their own, after reducing the dose or completely stopping the drug.

Contraindications are pregnancy, lactation, prostate hypertrophy, and angle-closure glaucoma.

Chloropyramine (suprastin)

It has antihistamine, anticholinergic, myotropic antispasmodic activity. It also has antipruritic and sedative effects.

It is quickly and completely absorbed when taken orally, the maximum concentration in the blood is observed 2 hours after administration. Penetrates the blood-brain barrier. Biotransformed in the liver, excreted by the kidneys and feces.

Prescribed for all kinds of allergic reactions.

It is used orally, intravenously and intramuscularly.

Orally, take 1 tablet (0.025 g) 2-3 times a day, with meals. The daily dose can be increased to a maximum of 6 tablets.

In severe cases, the drug is administered parenterally - intramuscularly or intravenously, 1-2 ml of a 2% solution.

When taking the drug, side effects such as general weakness, drowsiness, decreased reaction speed, impaired coordination of movements, nausea, and dry mouth are possible.

Strengthens the effect of sleeping pills and sedatives, as well as narcotic analgesics and alcohol.

Contraindications are similar to those of diphenhydramine.

Clemastine (tavegil)

In structure and pharmacological properties it is very close to diphenhydramine, but it acts longer (within 8-12 hours after administration) and is more active.

The sedative effect is moderate.

Take 1 tablet (0.001 g) orally before meals, with plenty of water, 2 times a day. In severe cases, the daily dose can be increased by 2, maximum 3 times. The course of treatment is 10-14 days.

Can be used intramuscularly or intravenously (within 2-3 minutes) - 2 ml of 0.1% solution per dose, 2 times a day.

Side effects are rare when taking this drug. Possible headache, drowsiness, nausea and vomiting, constipation.

Prescribed with caution to persons whose profession requires intense mental and physical activity.

Contraindications are standard.

Mebhydrolin (diazolin)

In addition to the antihistamine, it has anticholinergic and. Sedative and hypnotic effects are extremely weak.

When taken orally, it is slowly absorbed. The half-life is only 4 hours. Biotransformed in the liver and excreted in the urine.

Used orally, after meals, in a single dose of 0.05-0.2 g, 1-2 times a day for 10-14 days. The maximum single dose for an adult is 0.3 g, the daily dose is 0.6 g.

Generally well tolerated. Sometimes it can cause dizziness, irritation of the gastric mucosa, blurred vision, and urinary retention. In especially rare cases - when taking a large dose of the drug - a slowdown in the reaction rate and drowsiness.

Contraindications are inflammatory diseases of the gastrointestinal tract, angle-closure glaucoma and prostatic hypertrophy.

2nd generation antihistamines

Second generation antihistamines are characterized by high efficiency, rapid onset of action and a minimum of side effects, however, some of their representatives can cause life-threatening arrhythmias.

The goal of developing drugs in this group was to minimize sedation and other side effects while maintaining or even stronger antiallergic activity. And it was a success! Antihistamines of the 2nd generation have a high affinity specifically for H1-histamine receptors, with virtually no effect on choline and serotonin receptors. The advantages of these drugs are:

• rapid onset of action;
• long duration of action (the active substance binds to protein, which ensures longer circulation in the body; in addition, it accumulates in organs and tissues, and is also slowly excreted);
• additional mechanisms of antiallergic effects (suppress the accumulation of eosinophils in the respiratory tract associated with the entry of the allergen into the body, and also stabilize the membranes of mast cells), causing a wider range of indications for their use (,);
• with long-term use, the effectiveness of these drugs does not decrease, that is, there is no tachyphylaxis effect - there is no need to periodically change the drug;
• since these drugs do not penetrate or penetrate in extremely small quantities through the blood-brain barrier, their sedative effect is minimal and is observed only in patients who are particularly sensitive in this regard;
• do not interact with psychotropic drugs and ethyl alcohol.

One of the most adverse effects of 2nd generation antihistamines is their ability to cause fatal arrhythmias. The mechanism of their occurrence is associated with the blocking of potassium channels of the heart muscle by an antiallergic drug, which leads to a prolongation of the QT interval and the occurrence of arrhythmia (usually ventricular fibrillation or flutter). This effect is most pronounced in drugs such as terfenadine, astemizole and ebastine. The risk of its development increases significantly with an overdose of these drugs, as well as in the case of combining their use with antidepressants (paroxetine, fluoxetine), antifungals (intraconazole and ketoconazole) and some antibacterial agents (antibiotics from the macrolide group - clarithromycin, oleandomycin, erythromycin), some antiarrhythmics (disopyramide, quinidine), when the patient consumes grapefruit juice and severe.

The main form of release of 2nd generation antihistamines is tablets, but parenteral ones are not available. Some drugs (such as levocabastine, azelastine) are available in the form of creams and ointments and are intended for topical administration.

Let's take a closer look at the main drugs in this group.

Acrivastine (Semprex)

It is well absorbed when taken orally and begins to act within 20-30 minutes after administration. The half-life is 2-5.5 hours, it penetrates the blood-brain barrier in small quantities and is excreted unchanged in the urine.

It blocks H1-histamine receptors and has a slight sedative and anticholinergic effect.

It is used for all kinds of allergic diseases.

In some cases, while taking it, drowsiness and a decrease in reaction speed are possible.

The drug is contraindicated during pregnancy, lactation, severe, severe coronary heart disease, and children under 12 years of age.

Dimetindene (fenistil)

In addition to antihistamine, it has weak anticholinergic, antibradykinin and sedative effects.

It is quickly and completely absorbed when taken orally, the bioavailability (degree of digestibility) is about 70% (in comparison, when using cutaneous forms of the drug this figure is much lower - 10%). The maximum concentration of the substance in the blood is observed 2 hours after administration, the half-life is 6 hours for the regular form and 11 hours for the retard form. It penetrates the blood-brain barrier and is excreted in bile and urine in the form of metabolic products.

The drug is used orally and topically.

Adults take 1 capsule of retard orally at night or 20-40 drops 3 times a day. The course of treatment is 10-15 days.

The gel is applied to the affected areas of the skin 3-4 times a day.

Side effects are rare.

Contraindication is only the 1st trimester of pregnancy.

Strengthens the effects of alcohol, sleeping pills and tranquilizers on the central nervous system.

Terfenadine (histadine)

In addition to antiallergic, it has a weak anticholinergic effect. It does not have a pronounced sedative effect.

Well absorbed when taken orally (bioavailability is 70%). The maximum concentration of the active substance in the blood is observed after 60 minutes. Does not penetrate the blood-brain barrier. Biotransformed in the liver to form fexofenadine, excreted in feces and urine.

The antihistamine effect develops after 1-2 hours, reaches its maximum after 4-5 hours, and lasts for 12 hours.

The indications are the same as for other drugs in this group.

Prescribe 60 mg 2 times a day or 120 mg 1 time a day in the morning. The maximum daily dose is 480 mg.

In some cases, when taking this drug, the patient develops side effects such as erythema, fatigue, headache, drowsiness, dizziness, dry mucous membranes, galactorrhea (leakage of milk from the mammary glands), increased appetite, nausea, vomiting, in case of overdose - ventricular arrhythmias.

Contraindications include pregnancy and breastfeeding.

Azelastine (allergodil)

Blocks H1-histamine receptors and also prevents the release of histamine and other allergy mediators from mast cells.

It is quickly absorbed in the digestive tract and from the mucous membranes, the half-life is as much as 20 hours. Excreted in the form of metabolites in the urine.

Used, as a rule, for allergic rhinitis and.

When taking the drug, side effects are possible such as dryness and irritation of the nasal mucosa, bleeding from it and taste disorders when administered intranasally; irritation of the conjunctiva and a feeling of bitterness in the mouth - when using eye drops.

Contraindications: pregnancy, lactation, children under 6 years of age.

Loratadine (lorano, claritin, lorizal)

Long-acting H1-histamine receptor blocker. The effect after a single dose of the drug continues throughout the day.

There is no pronounced sedative effect.

When taken orally, it is absorbed quickly and completely, reaches maximum concentration in the blood after 1.3-2.5 hours, and is half eliminated from the body after 8 hours. Biotransformed in the liver.

Indications include any allergic diseases.

It is generally well tolerated. In some cases, dry mouth, increased appetite, nausea, vomiting, sweating, pain in joints and muscles, and hyperkinesis may occur.

Contraindications include hypersensitivity to loratadine and lactation.

Prescribed with caution to pregnant women.

Bamipin (Soventol)

H1-histamine receptor blocker for topical use. Prescribed for allergic skin lesions (urticaria), contact allergies, as well as frostbite and burns.

The gel is applied in a thin layer to the affected areas of the skin. After half an hour, the drug can be reapplied.

Cetirizine (Cetrin)

Metabolite of hydroxyzine.

It has the ability to easily penetrate the skin and quickly accumulate in it - this determines the rapid onset of action and high antihistamine activity of this drug. There is no arrhythmogenic effect.

It is rapidly absorbed when taken orally, its maximum concentration in the blood is observed 1 hour after administration. The half-life is 7-10 hours, but if renal function is impaired, it extends to 20 hours.

The range of indications for use is the same as for other antihistamines. However, due to the characteristics of cetirizine, it is the drug of choice in the treatment of diseases manifested by skin rashes - urticaria and allergic dermatitis.

Take 0.01 g in the evening or 0.005 g twice a day.

Side effects are rare. These are drowsiness, dizziness and headache, dry mouth, nausea.

3rd generation antihistamines

Third generation antihistamines have high antiallergic activity and are devoid of arrhythmogenic effect.

These drugs are active metabolites (metabolic products) of previous generation drugs. They are devoid of cardiotoxic (arrhythmogenic) effect, but retain the advantages of their predecessors. In addition, 3rd generation antihistamines have a number of effects that enhance their antiallergic activity, which is why their effectiveness in treating allergies is often higher than that of the substances from which they are produced.

Fexofenadine (Telfast, Allegra)

It is a metabolite of terfenadine.

Blocks H1-histamine receptors, prevents the release of allergy mediators from mast cells, does not interact with cholinergic receptors, and does not depress the central nervous system. It is excreted unchanged in feces.

The antihistamine effect develops within 60 minutes after a single dose of the drug, reaches its maximum after 2-3 hours, and lasts for 12 hours.

Side effects such as dizziness, headache, weakness are rare.

Desloratadine (erius, eden)

It is an active metabolite of loratadine.

Has anti-allergic, anti-edematous and antipruritic effects. When taken in therapeutic doses, it has virtually no sedative effect.

The maximum concentration of the drug in the blood is achieved 2-6 hours after oral administration. The half-life is 20-30 hours. Does not penetrate the blood-brain barrier. Metabolized in the liver, excreted in urine and feces.

In 2% of cases, while taking the drug, headaches, increased fatigue and dry mouth may occur.

In case of renal failure, prescribe with caution.

Contraindications include hypersensitivity to desloratadine. As well as periods of pregnancy and lactation.

Levocetirizine (aleron, L-cet)

Cetirizine derivative.

The affinity for H1-histamine receptors of this drug is 2 times higher than that of its predecessor.

Facilitates the course of allergic reactions, has a decongestant, anti-inflammatory, antipruritic effect. Practically does not interact with serotonin and cholinergic receptors, does not have a sedative effect.

When taken orally, it is quickly absorbed, its bioavailability tends to 100%. The effect of the drug develops 12 minutes after a single dose. The maximum concentration in blood plasma is observed after 50 minutes. It is excreted primarily by the kidneys. Excreted in breast milk.

Contraindicated in cases of hypersensitivity to levocetirizine, severe renal failure, severe galactose intolerance, deficiency of the lactase enzyme or impaired absorption of glucose and galactose, as well as during pregnancy and lactation.

Side effects are rare: headache, drowsiness, weakness, fatigue, nausea, dry mouth, muscle pain, palpitations.

Antihistamines and pregnancy, lactation

Therapy for allergic diseases in pregnant women is limited, since many drugs are dangerous to the fetus, especially in the first 12-16 weeks of pregnancy.

When prescribing antihistamines to pregnant women, the degree of their teratogenicity should be taken into account. All medicinal substances, in particular antiallergic ones, are divided into 5 groups depending on how dangerous they are to the fetus:

A – special studies have shown that there is no harmful effect of the drug on the fetus;

B – experiments on animals did not reveal any negative effects on the fetus; no special studies were conducted on humans;

C – experiments on animals have revealed a negative effect of the drug on the fetus, but this has not been proven in humans; drugs of this group are prescribed to a pregnant woman only when the expected effect outweighs the risk of its harmful effects;

D – the negative effect of this drug on the human fetus has been proven, but its use is justified in certain situations that threaten the life of the mother, when safer drugs were ineffective;

X – the drug is certainly dangerous for the fetus, and its harm exceeds any theoretically possible benefit for the mother’s body. These drugs are absolutely contraindicated in pregnant women.

Systemic antihistamines during pregnancy are used only when the expected benefit outweighs the possible risk to the fetus.

None of the drugs in this group are included in category A. Category B includes 1st generation drugs - tavegil, diphenhydramine, peritol; 2nd generation – loratadine, cetirizine. Category C includes Allergodil, Pipolfen.

The drug of choice for the treatment of allergic diseases during pregnancy is cetirizine. Loratadine and fexofenadine are also recommended.

The use of astemizole and terfenadine is unacceptable due to their pronounced arrhythmogenic and embryotoxic effects.

Desloratadine, suprastin, levocetirizine cross the placenta and are therefore strictly contraindicated for use by pregnant women.

Regarding the lactation period, we can say the following... Again, uncontrolled use of these drugs by a nursing mother is unacceptable, since no human studies have been conducted on the extent of their penetration into breast milk. If these medications are needed, the young mother is allowed to take the one that is approved for her child to take (depending on age).

In conclusion, I would like to note that even though this article describes in detail the drugs most commonly used in therapeutic practice and their dosages are indicated, the patient should start taking them only after consulting a doctor!

Which doctor should I contact?

If acute allergy symptoms appear, you can contact a therapist or pediatrician, and then an allergist. If necessary, a consultation with an ophthalmologist, dermatologist, ENT doctor, or pulmonologist is scheduled.

For allergic diseases, doctors prescribe antihistamines. What it is? Why are new generation drugs so much safer than classic antiallergic drugs?

Patients should know which medications help with mild and acute reactions, how to choose the appropriate remedy, taking into account the type and form of the disease, the patient’s age and contraindications. Parents will benefit from information about safe, effective antihistamines for children.

general information

Useful information about histamine receptor blockers:

• the main feature of antiallergic drugs is the suppression of reactions associated with exposure to irritants;
• upon contact with allergens, a special type of inflammatory process develops, against the background of which the body produces biologically active substances. Histamine, contained in mast cells, exhibits the greatest activity. Upon contact with an irritant, histamine receptors recognize the allergen, and a powerful release of histamine occurs. The result is negative symptoms of various kinds;
• Signs of allergic diseases are noticeable in various parts of the body. The main symptoms of an acute immune response: tissue swelling, skin, blisters, small blisters, red spots, erythema. Nasal congestion, sneezing, and bronchospasm often occur. Anaphylactic reactions are life-threatening; immediate use of antihistamines and urgent delivery of the patient to the hospital are required;
• Without antiallergic drugs, negative symptoms do not disappear, negative processes continue. The indolent form of allergies worsens health and causes discomfort;
• Acute signs of an immune response develop within 5-30 minutes. Delay in taking a tablet, syrup or drops for generalized symptoms can be fatal.

Properties

Antihistamines are suitable for eliminating or preventing signs of allergic reactions. Often, after relief of negative symptoms, it is necessary to take medication for several days/weeks to prevent relapses.

Active components eliminate symptoms and prevent the development of various types of allergies:

• medicinal;
• contact;
• respiratory;

In what cases should I take it?

Antihistamines:

• reduce the production of histamine in mast cells, preventing a new release of the active substance;
• neutralize histamine, which is active in the body.

Antiallergic drugs are suitable for eliminating negative symptoms and preventing exacerbations. It is important to know that antihistamines do not eliminate the cause of the immune response, and taking medications does not completely eliminate the body’s hypersensitivity.

Misbehavior: eat oranges if you are prone to food allergies and at the same time take Diazolin (Suprastin) in the hope that the active substance will quickly prevent the development of an acute reaction. The best option is to avoid contact with allergens; if this condition cannot be met, then you will have to take tablets or syrup during dangerous periods (seasonally).

Indications

Antiallergic compounds are prescribed for the following diseases:

• rhinitis, conjunctivitis (both seasonal and year-round);
• swelling, itching, redness when stung by a wasp, bee or bites of bedbugs, fleas;
• drug allergies;
• accompanied by itching;
• (negative reaction to pollen of certain plants);
• negative response to saliva, excrement, pet hair;
• intolerance to certain types of food or components (milk protein);
• anaphylactic reactions;
• , psoriasis;
• negative reaction to cold, heat, toxic substances, household chemicals, oils, paints and varnishes;
• allergic cough;

Contraindications

Restrictions depend on the name of the antiallergic drug. Classic formulations (1st generation) have more contraindications, new antihistamines have fewer.

One of the restrictions is the use of a certain form of release of antiallergic medicine: drops are prescribed for children under 2 years of age, syrups are allowed from the age of four, tablets are suitable for young patients aged 6-12 years.

Most antihistamines are not prescribed for the following conditions and diseases:

• hypersensitivity to the active substance, negative reactions to additional ingredients;
• pregnancy, breastfeeding time;
• the patient has not reached a certain age for safe use of a specific name;
• liver and kidney failure (severe stage).

On a note! Often, in case of pathologies of the urinary tract, liver, arterial hypertension, or elderly patient, the dosage and frequency of use are adjusted. A low concentration of the active substance has a more delicate effect on the body, side effects occur less frequently.

List and characteristics of antiallergic drugs

The first antiallergic drugs appeared in 1936. Classic formulations act quickly, but do not last long; side effects often develop while taking them; long-term therapy using outdated formulations is undesirable.

Scientists have developed effective, safe, long-acting medications for the treatment of chronic allergies. New generation drugs reduce the risk of negative reactions during therapy and contain a minimal concentration of histamine receptor blockers. The best option for an antiallergic drug for a particular patient is selected by the doctor.

First generation

Peculiarities:

• quickly stop acute reactions, reduce swelling, prevent the development of dangerous complications;
• the therapeutic effect occurs within 15-20 minutes, but lasts no more than 8 hours;
• reduce muscle tone;
• penetrate the blood-brain barrier and actively bind to brain receptors;
• sedative, anticholinergic effect, hypnotic effect;
• with prolonged use, the antiallergic effect decreases;
• drowsiness increases after taking psychotropic drugs and alcohol;
• To achieve an effect, a high dosage is needed, the drug is taken several times a day;
• many adverse reactions and contraindications;
• 1st generation antiallergic drugs are prescribed only for severe types of immune reactions. In some countries, this category is excluded from the list of approved medications.

List of drugs:

• Fenkarol.

Second

Characteristic:

• the sedative effect occurs infrequently;
• active components do not penetrate into the blood and do not interact with brain receptors;
• physical activity and speed of psychomotor reactions are maintained;
• prolonged effect: it is enough to take the daily dosage at a time;
• the list of side effects is shorter than that of classic formulations;
• There is no addictive effect, you can take it for two to three months;
• after discontinuation of the medication, the therapeutic effect lasts for about a week;
• drugs are not absorbed into the mucous membranes of the digestive tract;
• a moderate cardiotoxic effect remains. Problems with blood pressure, old age are contraindications for taking drugs in this category;
• the risk of side effects increases when combined with antidepressants, antimycotics, antibiotics, and in severe liver pathologies.

List of popular medications:

• Semprex.
• Trexil.

Third

Features of action and application:

• components of drugs after taking an antihistamine are converted into active metabolites;
• medications not only block histamine H1 receptors, but also eliminate the prerequisites for the further development of allergic reactions;
• there is no cardiotoxic and sedative effect, no negative effect on nervous regulation is observed;
• additional effects on cells involved in the immune response make it possible to use new agents in the treatment of most allergic diseases;
• the drugs are suitable for people whose activities involve operating complex mechanisms and vehicles;
• There are few restrictions for use; adverse reactions occur in a small percentage of patients.

List of 3rd generation antihistamines:

Go to the address and learn about the causes of urticaria in adults and methods of treating the disease.

Fourth

Characteristic:

• rapid relief of negative symptoms, the effect lasts a day or longer;
• active blocking of histamine receptors;
• elimination of all signs of allergies;
• no negative effects on the heart, central nervous system, gastrointestinal tract;
• the use of new generation antihistamines according to the instructions has a positive effect on the patient’s condition;
• fairly safe products suitable for adults and children;
• long-term use maintains the high efficiency of modern formulations;
• There are few restrictions - pregnancy, childhood (some formulations are not prescribed to the youngest patients), high sensitivity to the active components.

List of 4th generation antihistamines:

• Ebastine.
• Levocetirizine.
• Fexofenadine.
• Desloratadine.
• Bamipin.

Antihistamines for children

To eliminate signs of acute allergies, doctors prescribe 1st generation drugs:

• Suprastin (tablets).
• Diazolin (dragée).
• Tavegil (syrup).

In the chronic form of allergic diseases, the best effect with minimal impact on the growing organism is provided by new generation medications. The best option is syrup (from 2-4 years old) or drops (for the little ones).

Long-acting antiallergic agents:

• Zyrtec.
• Claritin.
• Zodak.
• Erius.
• Fenistil.
• Loratadine.

To eliminate swelling, severe itching, and rashes, a topical preparation - Fenistil-gel - is suitable. In case of severe reactions, doctors prescribe not only antihistamines, but also glucocorticosteroids - potent anti-inflammatory compounds.

Classic antihistamines often cause drowsiness and have a negative effect on the digestive system, heart, and central nervous system. For this reason, 1st generation drugs are prescribed to children only for acute reactions, swelling of the face, larynx, lips, neck, and threat of suffocation.

Antihistamines of all generations stop the signs of a negative response, but do not eliminate the cause of the body's increased sensitivity. The patient’s task is to minimize contact with the allergen and prevent the risk of relapse. If an allergic disease develops, the doctor will select the best antihistamine option.

The following video will tell you what antihistamines are. You will learn about what generations of antiallergic drugs exist, what are the side effects and features of their use, including for the treatment of:

People who experience allergies regularly buy antihistamines and know what they are.

When taken in a timely manner, tablets can help relieve a debilitating cough, swelling, rash, itching and redness of the skin. The pharmaceutical industry has been producing such drugs for many years, and each new batch is issued as a separate generation.

Today we will talk about the latest generation of antihistamines and look at the most effective of them.

General concept of antihistamines

To everyone who wants to understand in depth the question of what antihistamines are, doctors explain that these drugs are created to counteract histamine, an allergic mediator.

When the human body comes into contact with an irritant, specific substances are produced, among which histamine exhibits increased activity. In a healthy person, it is located in mast cells and remains inactive. When exposed to an allergen, histamine enters an active phase and provokes allergy symptoms.

To relieve negative reactions, medications were invented at different times that could reduce the amount of histamine and neutralize its harmful effects on humans. Thus, antihistamines are a general definition of all drugs that have the indicated effectiveness. To date, their classification includes 4 generations.

The advantages of the drugs in question are a gentle effect on the body, in particular on the cardiovascular system, rapid relief of symptoms and a prolonged effect.

Review of new generation antihistamines

Antihistamines are also called H1 receptor blockers. They are quite safe for the body, but still have some contraindications. For example, during pregnancy and childhood, a doctor has the right not to prescribe anti-allergy pills if their instructions list these conditions as contraindications.

All new generation antihistamines - list of new drugs:

• Erius.
• Xizal.
• Bamipin.
• Cetirizine.
• Ebastine.
• Fenspiride.
• Levocetirizine.
• Fexofenadine.
• Desloratadine.

It is difficult to single out the most effective 4th generation antihistamines from this list, since some of them appeared relatively recently and have not yet proven themselves 100%. Phenoxofenadine is considered a popular allergy treatment option. Taking tablets containing this substance does not have a hypnotic or cardiotoxic effect on the patient.

Medicines containing cetirizine are good at removing skin manifestations of allergosis. One tablet brings significant relief within 2 hours from the moment of use. The result lasts for a long time.

The drug Erius is an improved analogue of Loratadine. But its efficiency is approximately 2.5 times higher. Erius is suitable for children over 1 year of age who are prone to allergies. They are given the drug in liquid form at a dosage of 2.5 ml once a day. From 5 years of age, the dosage of Erius is increased to 5 ml. From the age of 12, the child is given 10 ml of medication per day.

The medicine Xyzal is also in high demand today. It prevents the release of inflammatory mediators. Effectiveness is determined by the reliable elimination of allergic reactions.

Feksadin (Allegra, Telfast)

The drug with fexofenadine reduces the production of histamine and completely blocks histamine receptors. Suitable for the treatment of seasonal allergies and chronic urticaria. The product is not addictive. The body is affected for 24 hours.

Fexadin should not be taken during pregnancy, breastfeeding or children under 12 years of age.

Zodak (Cetrin, Zyrtec, Cetirizine)

The effectiveness of the taken tablet is felt after 20 minutes, and after discontinuation of the drug it persists for another 72 hours. Zodak and its synonyms are used for the treatment and prevention of allergosis. Long-term use is allowed. The release form is not only tablets, but also syrup and drops.

In pediatrics, Zodak drops are used from 6 months. After 1 year, syrup is prescribed. Children can take tablets from 6 years of age. Dosages for each type of medication are selected individually.

Cetirizine should not be taken by pregnant women. If there is a need to treat allergies during lactation, the baby is temporarily weaned.

Xyzal (Suprastinex, Levocetirizine)

Xyzal drops and tablets work 40 minutes after administration.

The medication is indicated for the treatment of urticaria, allergies, and skin itching. For children, fourth-generation antihistamines for allergies called Xyzal are prescribed from 2 years and 6 years (drops and tablets, respectively). The pediatrician calculates the dosage based on the child’s age and weight.

Xyzal is prohibited during pregnancy. But it can be taken during breastfeeding.

Suprastinex helps well with seasonal allergies, when the body reacts to pollen from flowering plants. As the main medicine, it is used in the treatment of conjunctivitis and rhinitis of an allergic nature. Take Suprastinex with food.

Desloratadine (Erius, Lordestin, Dezal)

Desloratadine and its synonyms have antihistamine and anti-inflammatory properties.

They quickly treat seasonal allergies and recurrent hives, but sometimes cause side effects such as headaches and dry mouth. Desloratadine is sold in the form of tablets and syrup.

Doctors prescribe syrup for children 2–6 years old. Tablets are allowed to be used only from 6 years of age. Desloratadine is completely contraindicated for pregnant and lactating women. But for angioedema and bronchospasm, a specialist can choose a gentle option for using this medicine.

Antihistamines for babies

It is not recommended for newborns to take antihistamines. But sometimes situations arise when it is impossible to do without medication, for example, if the baby is stung by an insect. From 1 month of life, the child can be given Fenistil in drops.

Diphenhydramine, which was previously given to children on various occasions, is now prescribed by pediatricians only from the 7th month of life.

Suprastin is considered the most gentle option for the little ones. It quickly exhibits healing properties without causing the slightest harm to the body. Children are also prescribed Fenkarol and Tavegil. For urticaria, drug-induced dermatosis and food allergies, it is better to give Tavegil to the child. The tablets relieve swelling, restore skin color and work as an antipruritic agent.

Analogues of Tavegil are Donormil, Diphenhydramine, Bravegil and Clemastine. The child takes them if there are contraindications to the use of Tavegil.

From 2 to 5 years, the child’s body gradually strengthens and can normally tolerate stronger medications. For itchy skin, the names of antihistamines for this age group of patients, the specialist will consider the following:

Erius was mentioned above, now let’s focus on Tsetrin. These tablets can be used to prevent allergies in children prone to negative reactions. In case of individual intolerance to the constituent components, Cetrin is replaced with analogues - Letizen, Cetirinax, Zodak, Zetrinal. After 2 years, the child can take Astemizole.

From the age of 6, the list of antihistamines is expanded, since medications of different generations are suitable for such children - from 1 to 4. Younger schoolchildren can take Zyrtec, Terfenadine, Clemastine, Glencet, Suprastinex, Cesera tablets.

What Komarovsky says

Famous pediatrician E.O. Komarovsky does not advise parents to give antihistamines to young children unless absolutely necessary and without medical prescription. If a pediatrician or allergist considers it necessary to prescribe an antiallergic drug to a child, it can be taken for no more than 7 days.

Evgeniy Olegovich also prohibits combining antihistamines with antibiotics and says that it is not at all necessary to give a child an antihistamine tablet on the eve of vaccination or after vaccination.

Some parents, based on their own considerations, try to give their child Suprastin to drink before DPT, but Komarovsky does not see any point in this. The children's doctor explains that the body's reaction to the vaccine has nothing to do with allergies.

Women with allergies planning to have children are always interested in what antihistamines can be taken during pregnancy and preferably during lactation, or whether it is worth enduring the inconvenience associated with hay fever, rash and swelling. Doctors say that it is better for women not to take any medications during gestation, as they are potentially dangerous to the mother and fetus.