Fenistil is a drug of which generation. Generations of antihistamines

Many home first-aid kits contain medicines, the purpose and mechanism of action of which people do not understand. Antihistamines are also such drugs. Most allergy sufferers choose their own medicines, calculate the dosage and course of therapy, without consulting a specialist.

Antihistamines - what are they in simple terms?

The term is often misinterpreted. Many people think that these are just drugs for allergies, but they are intended to treat other diseases as well. Antihistamines are a group of medicines that block the immune response to external stimuli. These include not only allergens, but also viruses, fungi and bacteria (infectious agents), toxins. The medications in question prevent the occurrence of:

• swelling of the mucous membranes of the nose and throat;
• redness, blisters on the skin;
• itching;
• excessive secretion of gastric juice;
• narrowing of blood vessels;
• muscle spasms;
• swelling.

How do antihistamines work?

The main protective role in the human body is played by leukocytes or white blood cells. There are several types of them, one of the most important is mast cells. After maturation, they circulate through the bloodstream and integrate into connective tissues, becoming part of the immune system. When hazardous substances enter the body, mast cells release histamine. It is a chemical essential for the regulation of digestive processes, oxygen metabolism, and blood circulation. Its excess leads to allergic reactions.

In order for histamine to provoke negative symptoms, it must be absorbed by the body. For this, there are special H1 receptors located in the inner lining of blood vessels, smooth muscle cells and the nervous system. How antihistamines work: The active ingredients in these medicines trick the H1 receptors. Their structure and structure is very similar to the substance in question. Medicines compete with histamine and are absorbed by receptors instead of it, without causing allergic reactions.

As a result, the chemical that triggers the unwanted symptoms remains inactive in the blood and is later excreted naturally. The antihistamine effect depends on how many H1 receptors the drug has been able to block. For this reason, it is important to start treatment as soon as the first allergy symptoms appear.

The duration of therapy depends on the generation of the drug and the severity of pathological signs. How long to take antihistamines is up to the doctor to decide. Some drugs can be used no more than 6-7 days, modern pharmacological agents of the latest generation are less toxic, therefore, they can be used for 1 year. It is important to consult a specialist before taking it. Antihistamines can build up in the body and cause poisoning. Some people subsequently become allergic to these medicines.

How often can antihistamines be taken?

Most of the manufacturers of the described products release them in a convenient dosage, which involves the use of only 1 time per day. The question of how to take antihistamines, depending on the frequency of occurrence of negative clinical manifestations, is decided with the doctor. The presented group of medicines refers to symptomatic methods of therapy. They must be used whenever signs of illness appear.

New antihistamines can also be used as prophylaxis. If contact with an allergen cannot be definitely avoided (poplar fluff, ragweed flowering, etc.), you should use the medicine in advance. Taking antihistamines first will not only alleviate negative symptoms, but eliminate their appearance. The H1 receptors will already be blocked when the immune system tries to initiate a defense response.

Antihistamines - list

The very first drug of this group was synthesized in 1942 (Fenbenzamine). From that moment on, a massive study of substances capable of blocking H1 receptors began. To date, there are 4 generations of antihistamines. Early drug options are rarely used due to unwanted side effects and toxic effects on the body. Modern medicines are characterized by maximum safety and quick results.

Antihistamines of the 1st generation - list

This type of pharmacological agent has a short-term effect (up to 8 hours), can be addictive, sometimes it provokes poisoning. Antihistamines of the 1st generation remain popular only because of their low cost and pronounced sedative (sedative) effect. Names:

• Daedalon;
• Bicarfen;
• Suprastin;
• Tavegil;
• Diazolin;
• Clemastine;
• Diprazine;
• Loredix;
• Pipolfen;
• Setastin;
• Dimebon;
• Cyproheptadine;
• Fenkarol;
• Peritol;
• Quifenadine;
• Dimetindene;
• other.

Antihistamines 2nd generation - list

35 years later, the first H1 receptor blocker without sedation and toxic effects on the body was released. Unlike their predecessors, 2nd generation antihistamines work much longer (12-24 hours), do not cause addiction and do not depend on food and alcohol intake. They provoke fewer dangerous side effects and do not block other receptors in tissues and blood vessels. New generation antihistamines - list:

• Taldan;
• Astemizole;
• Terfenadine;
• Bronal;
• Allergodil;
• Fexofenadine;
• Rupafin;
• Trexil;
• Loratadine;
• Histadil;
• Zyrtec;
• Ebastine;
• Astemisan;
• Clarisens;
• Histalong;
• Cetrin;
• Semprex;
• Kestin;
• Acrivastine;
• Gismanal;
• Cetirizine;
• Levocabastine;
• Azelastine;
• Histimet;
• Lorahexal;
• Claridol;
• Rupatadine;
• Lomilan and analogues.

Antihistamines 3rd generation

Based on previous drugs, scientists have obtained stereoisomers and metabolites (derivatives). At first, these antihistamines were marketed as a new subgroup of medicines, or 3rd generation:

• Glenzet;
• Ksizal;
• Ceser;
• Suprastinex;
• Fexofast;
• Zodak Express;
• L-Cet;
• Loratek;
• Feksadin;
• Erius;
• Desal;
• NeoClaritin;
• Lordestine;
• Telfast;
• Fexofen;
• Allegra.

Later, this classification caused controversy and controversy in the scientific community. To make a final decision on the listed funds, a group of experts was assembled for independent clinical trials. According to the evaluation criteria, third-generation allergy drugs should not affect the functioning of the central nervous system, produce a toxic effect on the heart, liver and blood vessels, and interact with other medications. According to the research results, none of the indicated drugs meets these requirements.

Antihistamines 4 generations - list

In some sources, Telfast, Suprastinex and Erius are referred to this type of pharmacological agent, but this is an erroneous statement. Antihistamines of the 4th generation have not yet been developed, as well as the third. There are only improved forms and derivatives of the previous drug options. The most modern drugs are still 2 generations.

The selection of funds from the described group should be carried out by a specialist. Some people are better off with 1st generation allergy medications due to the need for sedation; others do not. Similarly, the doctor recommends the form of release of the medication, depending on the symptoms. Systemic drugs are prescribed with pronounced signs of the disease, in other cases, local remedies can be dispensed with.

Antihistamine tablets

Oral medications are necessary for the rapid removal of clinical manifestations of pathology that affect several body systems. Internal antihistamines begin to act within an hour and effectively relieve swelling of the throat and other mucous membranes, relieve a runny nose, lacrimation and skin symptoms of the disease.

Effective and safe allergy pills:

• Fexofen;
• Alersis;
• Tsetrilev;
• Altiva;
• Rolinoz;
• Telfast;
• Amertil;
• Eden;
• Fexofast;
• Cetrin;
• Allergomax;
• Zodak;
• Tigofast;
• Allertek;
• Cetrinal;
• Eridez;
• Trexil Neo;
• Zilola;
• L-Cet;
• Alerzin;
• Glenzet;
• Ksizal;
• Aleron Neo;
• Lordes;
• Erius;
• Allergostop;
• Fribris and others.

Antihistamine drops

In this dosage form, both local and systemic drugs are produced. Allergy drops for oral administration;

• Zyrtec;
• Desal;
• Fenistil;
• Zodak;
• Ksizal;
• Parlazin;
• Backorder;
• Allergonix and analogues.

Topical antihistamines for the nose:

• Tizine Allergy;
• Allergodil;
• Lekrolin;
• Cromohexal;
• Sanorin Anallergin;
• Vibrocil and others.

There are several groups of medicines used for allergic diseases. It:

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

In this article, we will only talk 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 on the human body, these drugs are combined into groups, which we will talk about 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 involved in the regulation of vital body functions and playing a leading role in the development of many diseases.

Under normal conditions, this substance is in the body in an inactive, bound state, however, with various pathological processes (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 a spasm of smooth muscles (including the muscles of the bronchi);
• expands capillaries and lowers blood pressure;
• causes stagnation of blood in the capillaries and an increase in the permeability of their walls, which entails thickening of the blood and edema of the tissues surrounding the affected vessel;
• reflexively stimulates the cells of the adrenal medulla - as a result, adrenaline is released, which contributes to the narrowing of the arterioles and an increase in the heart rate;
• enhances the secretion of gastric juice;
• plays the role of a neurotransmitter in the central nervous system.

Outwardly, these effects are manifested as follows:

• bronchospasm occurs;
• the nasal mucosa swells - nasal congestion appears and mucus is released from it;
• itching, redness of the skin appears, all sorts of elements of the rash 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 can be noted.

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

Antihistamines affect precisely this group of receptors, blocking the action of histamine in the form of competitive inhibition. That is, the drug does not displace the histamine already bound to the receptor, but occupies the free receptor, preventing histamine from attaching to it.

If all receptors are occupied, the body recognizes this and gives a signal to reduce the production of histamine. 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;
• derivatives of alphacarboline;
• derivatives of phenothiazine;
• piperidine derivatives;
• derivatives of piperazine.

In clinical practice, the classification of antihistamines by generation has become more widely used, which today are distinguished by 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);
• dimetindene (fenistil);
• terfenadine (histadine);
• azelastine (allergodil);
• loratadine (lorano);
• cetirizine (cetrin);
• bamipin (soventol).

1. 3rd generation antihistamines:

• fexofenadine (telfast);
• desloratodine (erius);
• levocetirizine.

1st generation antihistamines

Antihistamines of the 1st generation have a pronounced sedative effect.

For 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 repeated admission during 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 a solution for injection). Affordable.

With prolonged use of these drugs, their antihistamine effectiveness is significantly reduced, which necessitates a periodic - 1 time in 2-3 weeks - change of the drug.

Some 1st generation antihistamines are included in combination medicines for colds, as well as sleeping and anxiety medications.

The main effects of 1st generation antihistamines are:

• local anesthetic - associated with a decrease in membrane permeability to sodium; the most powerful local anesthetic agents in this group 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 severity of this effect is different for different drugs, it is most pronounced in doxylamine (it is often used as a hypnotic); the sedative effect increases with the simultaneous use of alcoholic beverages or the use of psychotropic drugs; when taking extremely high doses of the drug, instead of the effect of sedation, pronounced agitation is noted;
• anti-anxiety, sedative effect is also associated with the penetration of the active substance into the central nervous system; the most pronounced in hydroxyzine;
• anti-pumping and antiemetic - some representatives of this group of drugs inhibit the function of the labyrinth of the inner ear and reduce the stimulation of the 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, promethazine;
• atropine-like action - cause dryness of the mucous membranes of the oral and nasal cavities, increased heart rate, visual impairment, urinary retention, constipation; can aggravate bronchial obstruction, lead to exacerbation of glaucoma and obstruction when - with these diseases are not used; these effects are most pronounced in ethylenediamines and ethanolamines;
• antitussive - drugs in this group, in particular, diphenhydramine, have an effect directly on the cough center located in the medulla oblongata;
• the antiparkinsonian effect is obtained by inhibiting the effects of acetylcholine with an antihistamine;
• antiserotonin effect - the drug binds to serotonin receptors, alleviating the condition of patients suffering from migraines; especially pronounced in cyproheptadine;
• expansion of peripheral vessels - leads to a decrease in blood pressure; the most pronounced in phenothiazine preparations.

Since drugs in this group have a number of undesirable effects, they are not the drugs of choice for treating allergies, but they 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 a 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 agent. Its sedative effect is similar in strength to the effects of antipsychotics. In high doses, it also has a hypnotic effect.

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

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

Inside it is prescribed in the form of tablets of 0.03-0.05 g 1-3 times a day for 10-14 days, or one tablet at bedtime (as a sleeping pill).

Intramuscularly inject 1-5 ml of a 1% solution, intravenously drip - 0.02-0.05 g of the drug in 100 ml of 0.9% sodium chloride solution.

It 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 pass on their own, after dose reduction or complete withdrawal of the drug.

Contraindications are pregnancy, lactation, prostatic hypertrophy, angle-closure glaucoma.

Chloropyramine (Suprastin)

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

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

It is prescribed for all kinds of allergic reactions.

It is used orally, intravenously and intramuscularly.

Inside, you should 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 are possible such as general weakness, drowsiness, a decrease in the speed of reactions, impaired coordination of movements, nausea, dry mouth.

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

Contraindications are similar to those of diphenhydramine.

Clemastine (tavegil)

In terms of structure and pharmacological properties, it is very close to diphenhydramine, but it acts for a longer period (within 8-12 hours after ingestion) and is more active.

The sedative effect is moderate.

It is applied orally 1 tablet (0.001 g) 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.

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

Side effects are rare with this drug. Headache, drowsiness, nausea and vomiting, constipation are possible.

It is 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 an anticholinergic and. The sedative and hypnotic effects are extremely weak.

Ingestion is slowly absorbed. The half-life is only 4 hours. Biotransformed in the liver, excreted in the urine.

It is applied 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, urinary retention. In especially rare cases - when taking a large dose of the drug - a slowdown in the speed of reactions and drowsiness.

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

2nd generation antihistamines

Antihistamines of the second generation are characterized by high efficacy, rapid onset of action and a minimum of side effects, but some of their representatives can cause life-threatening arrhythmias.

The purpose of the development of drugs in this group was to minimize sedative and other side effects while maintaining or even stronger antiallergic activity. And it succeeded! Antihistamines of the 2nd generation have a high affinity specifically for H1-histamine receptors, practically without affecting choline and serotonin receptors. The advantages of these drugs are:

• rapid onset of action;
• long duration of action (the active substance binds to the protein, which ensures its 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, which is associated with the intake of an allergen, and also stabilize the membranes of mast cells), which determine a wider range of indications for their use (,);
• with prolonged use, the effectiveness of these drugs does not decrease, that is, the effect of tachyphylaxis is absent - 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 especially 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 the potassium channels of the heart muscle by the antiallergic agent, which leads to an extension of the QT interval and the occurrence of arrhythmias (as a rule, fibrillation or flutter of the ventricles). 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 a combination of their intake with antidepressants (paroxetine, fluoxetine), antifungal (intraconazole and ketoconazole) and some antibacterial agents (antibiotics from the macrolide group - clarithromycin, oleandomycin), erythromycin (disopyramide, quinidine), when the patient consumes grapefruit juice and expressed.

The main form of release of 2nd generation antihistamines is tableted, while parenteral drugs are absent. Some drugs (such as levocabastine, azelastine) are available in the form of creams and ointments and are intended for topical administration.

Let's consider the main drugs in this group in more detail.

Acrivastin (Semprex)

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

Blocks H1-histamine receptors, to a small extent has a sedative and anticholinergic effect.

It is used for all kinds of allergic diseases.

On the background of admission, in some cases, drowsiness and a decrease in the reaction rate are possible.

The drug is contraindicated during pregnancy, lactation, with severe, severe coronary and, as well as children under 12 years of age.

Dimetindene (fenistil)

In addition to the antihistamine, it has weak anticholinergic, anti-bradykinin and sedative effects.

It is quickly and completely absorbed when taken orally, the bioavailability (degree of assimilation) is about 70% (in comparison, when using the 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 ingestion, the half-life is 6 hours for the usual and 11 hours for the retard form. It penetrates through the blood-brain barrier, is excreted in bile and urine in the form of metabolic products.

Apply the drug internally and topically.

Inside, adults take 1 retard capsule 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 skin 3-4 times a day.

Side effects are rare.

Only the 1st trimester of pregnancy is a contraindication.

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

Terfenadine (histadine)

In addition to antiallergic, it has a weak anticholinergic effect. It has no pronounced sedative effect.

It is well absorbed when taken orally (bioavailability is 70%). The maximum concentration of the active substance in the blood is noted after 60 minutes. It does not penetrate the blood-brain barrier. Biotransformed in the liver with the formation of fexofenadine, excreted in feces and urine.

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

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

Assign 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 such side effects as erythema, fatigue, headache, drowsiness, dizziness, dry mucous membranes, galactorrhea (milk flow from the mammary glands), increased appetite, nausea, vomiting, in case of an overdose - ventricular arrhythmias.

Contraindications are pregnancy and lactation.

Azelastine (allergodil)

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

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

They are 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 disturbances with intranasal use; 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.

Loratadin (lorano, claritin, lorizal)

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

There is no pronounced sedative effect.

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

The indications are any allergic diseases.

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

Contraindication is hypersensitivity to loratadine and lactation.

Prescribe with caution to pregnant women.

Bamipin (soventol)

Topical H1-histamine receptor blocker. It is prescribed for allergic skin lesions (urticaria), contact allergies, as well as for frostbite and burns.

The gel is applied in a thin layer to the affected skin. After half an hour, reapplication of the drug is possible.

Cetirizine (cetrin)

Metabolite of hydroxyzine.

It has the ability to freely 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 noted 1 hour after ingestion. The half-life is 7-10 hours, but in case of impaired renal function, it lengthens to 20 hours.

The range of indications for use is the same as for other antihistamines. However, due to the peculiarities 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

Antihistamines of the third generation have high antiallergic activity and are devoid of arrhythmogenic effect.

These drugs are active metabolites (metabolic products) of the previous generation. They lack the cardiotoxic (arrhythmogenic) effect, but retained 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, does not inhibit the central nervous system. It is excreted unchanged with feces.

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

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

Desloratadine (Erius, Eden)

It is an active metabolite of loratadine.

It has anti-allergic, anti-edematous and antipruritic effects. When taken in therapeutic doses, it practically does not have a sedative effect.

The maximum concentration of the drug in the blood is reached 2-6 hours after ingestion. The half-life is 20-30 hours. Does not penetrate the blood-brain barrier. It is metabolized in the liver, excreted in the urine and feces.

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

With renal failure, appoint with caution.

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

Levocetirizine (Aleron, L-cet)

Derivative of cetirizine.

The affinity for H1-histamine receptors in 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 rapidly absorbed, its bioavailability tends to 100%. The drug develops in 12 minutes after a single dose. The maximum concentration in blood plasma is observed after 50 minutes. It is excreted mainly by the kidneys. Excreted in breast milk.

Contraindicated in case of hypersensitivity to levocetirizine, severe renal failure, severe galactose intolerance, lactase enzyme deficiency 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 for the fetus, especially in the first 12-16 weeks of pregnancy.

When prescribing antihistamines for 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 - during experiments on animals, no negative effects on the fetus were found, special studies on humans were not carried out;

C - experiments on animals revealed a negative effect of the drug on the fetus, however, in relation to humans, it has not been proven; drugs in this group are prescribed to a pregnant woman only when the expected effect exceeds the risk of its harmful effects;

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

X - the drug is certainly dangerous to the fetus, and its harm exceeds any theoretically possible benefit to 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 potential risk to the fetus.

Of the drugs in this group, none are included in category A. Category B includes drugs of the 1st generation - 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, therefore it is categorically contraindicated for use by pregnant women.

With regard to the lactation period, we can say the following ... Again, uncontrolled intake of these drugs by a nursing mother is unacceptable, since no studies have been conducted on the degree of their penetration into breast milk. If it is necessary for these drugs, a young mother is allowed to take one that is allowed for her child (depending on age).

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

For citation: E. N. Kareva The choice of an antihistamine: a pharmacologist's view // BC. Medical Review. 2016. No. 12. S. 811-816

The article is devoted to the problem of choosing an antihistamine drug from the point of view of a pharmacologist

For citation. E. N. Kareva The choice of an antihistamine: a pharmacologist's view // BC. 2016. No 12.P. 811–816.

Antihistamines (AGPs) are the first line of treatment for most allergic diseases. They relate mainly to non-prescription drugs, have long and firmly entered our practice and have been used for more than half a century. Often the choice of these drugs is carried out empirically or even at the mercy of patients, however there are many nuances that determine how effective a particular drug will be for a particular patient, which means that the choice of these drugs must be approached no less responsibly than, for example, the choice antibiotics.
Each specialist in his clinical practice has probably come across situations when a particular drug did not have the desired clinical effect or caused hyperergic reactions. What does it depend on and how can the risks be minimized? The variability of the response to a drug is most often associated with the activity of metabolic enzymes in the patient's liver; the situation is aggravated in the case of polypharmacy (5 or more prescribed drugs at the same time). Therefore, one of the real ways to reduce the risk of an inadequate reaction of the body to a drug is to choose a drug that is not metabolized in the liver. In addition, when choosing AGP, it is important to evaluate the following parameters: the strength and speed of the onset of the effect, the possibility of long-term use, the benefit / risk ratio (efficacy / safety), ease of use, the possibility of using it in case of concomitant pathology in combination with other drugs in a given patient, the route of elimination , the need for dose titration, price.
To solve this problem, consider the current information on histamine and antihistamines.
Histamine and its role in the body
Histamine in the human body performs a number of physiological functions, plays the role of a neurotransmitter and participates in many pathobiological processes (Fig. 1).

The main histamine depot in the body is mast cells and basophils, where it is in the form of granules in a bound state. The largest number of mast cells is localized in the skin, mucous membranes of the bronchi and intestines.
Histamine realizes its activity exclusively through its own receptors. Modern concepts of the functional load of histamine receptors, their localization and mechanisms of intracellular signaling are shown in Table 1.

In addition to physiological functions, histamine is involved in the development of an inflammatory process of any nature. Histamine causes itching, sneezing and stimulates the secretion of the nasal mucosa (rhinorrhea), contraction of the smooth muscles of the bronchi and intestines, tissue hyperemia, dilation of small blood vessels, increased vascular permeability to water, proteins, neutrophils, the formation of inflammatory edema (nasal congestion).
Not only for allergic diseases, but also for any pathological processes with a pronounced inflammatory component, the level of histamine in the body is always increased. This is shown in chronic infectious and inflammatory diseases of the respiratory and urogenital tract, acute respiratory viral infections, influenza. At the same time, the daily amount of histamine in urine with influenza is about the same as with exacerbation of allergic diseases. Therefore, a pathogenetically grounded and clinically useful step is to reduce the activity of the histamine system in conditions of its increased activity. In principle, the histaminergic activity of the body can be suppressed either through a decrease in the amount of free histamine (inhibition of synthesis, activation of metabolism, inhibition of release from the depot), or through blockade of signals of histamine receptors. In clinical practice, drugs have been used that stabilize the membranes of mast cells, thereby preventing the release of histamine. However, the onset of the desired action when using them has to wait a long time, and the therapeutic efficacy of this group of drugs is very moderate, so they are used exclusively for prophylactic purposes. A quick and pronounced effect is achieved when using antihistamines.

Classification of antihistamines
According to the classification adopted by the European Academy of Allergists and Clinical Immunologists, all antihistamines are divided into 2 generations, depending on their effect on the central nervous system.
Antihistamines of the 1st generation
First-generation H1 antagonists cross the blood-brain barrier (BBB) ​​and can both stimulate and suppress the central nervous system (Fig. 2). As a rule, the latter occurs in most patients. The sedative effect when taking AGP of the 1st generation is subjectively noted by 40–80% of patients. The absence of a sedative effect in individual patients does not exclude an objective negative effect of these drugs on cognitive functions, which patients may not pay attention to (ability to drive, learn, etc.). Dysfunction of the central nervous system is observed even with the use of minimal doses of these funds. The effect of the 1st generation AGP on the central nervous system is the same as with the use of alcohol and sedatives. Stimulation has been reported in some patients treated with conventional doses of antihistamines and manifests itself as anxiety, nervousness, and insomnia. Usually, central excitement is characteristic of an overdose of 1st generation antihistamines; it can lead to seizures, especially in children.

When taking AGP I generation, in addition to the sedative effect and the effect on cognitive functions, the following are observed:
short-term effect (forced intake 3-4 times a day);
rapid development of tachyphylaxis (it is necessary to change the drug every 7-10 days);
low selectivity of action: in addition to histamine H1 receptors, they block receptors for acetylcholine, adrenaline, serotonin, dopamine and ion channels, causing many side effects: tachycardia, dry mucous membranes, increased viscosity of sputum. They can increase intraocular pressure, interfere with urination, cause stomach pain, constipation, nausea, vomiting, and increase body weight. That is why these drugs have a number of serious restrictions for use among patients with glaucoma, benign prostatic hyperplasia, cardiovascular pathology, etc.
In acute poisoning with AGPs of the 1st generation, their central effects pose the greatest danger: the patient experiences excitement, hallucinations, ataxia, impaired coordination, convulsions, etc. Fixed, dilated pupils on a flushed face, together with sinus tachycardia, urinary retention, dry mouth and fever. are similar to signs of atropine poisoning.
In children with an overdose of AHP of the 1st generation, excitement and convulsions may occur, therefore, experts in many countries urge to abandon the treatment of children from this group of drugs or to use them under strict control. In addition, sedation can impair the learning and performance of children in school.

New AGPs (II generation) do not penetrate the BBB, do not have a sedative effect (Fig. 2).
Note: drugs of the third generation have not yet been developed. Some pharmaceutical companies are introducing new drugs that have appeared on the pharmaceutical market as AGP III - the newest - generation. Attempts have been made to classify metabolites and stereoisomers of modern AGPs as generation III. However, it is currently believed that these drugs belong to the II generation AGP, since there is no significant difference between them. According to the Consensus on Antihistamines, it was decided to reserve the name “third generation” to denote AGPs synthesized in the future, which will differ from the known compounds in a number of basic characteristics.
Unlike old drugs, second generation AGPs practically do not penetrate the BBB and do not cause a sedative effect, therefore they can be recommended to drivers, people whose work requires concentration of attention, schoolchildren and students. The term "practically" is used here, because in very rare cases and when taking drugs of the second generation, cases of sedation are possible, but this is rather an exception to the rule and depends on the individual characteristics of the patient.
AGPs of the second generation are capable of selectively blocking H1-receptors, rapidly exerting a clinical effect with a long-term effect (over 24 hours), as a rule, they are not addictive (no tachyphylaxis). Due to their higher safety profile, they are preferred for elderly patients (over 65 years of age).

II generation antihistamines
Features of pharmacokinetics
II generation AGP metabolism
All II generation AGPs are divided into 2 large groups, depending on the need for metabolic activation in the liver (Fig. 3).

The need for metabolic activation in the liver is associated with a number of problems, the main of which are the danger of drug interactions and the late onset of the maximum therapeutic effect of the drug. The simultaneous use of two or more drugs that are metabolized in the liver can lead to a change in the concentration of each drug. In the case of parallel use of an inducer of enzymes of drug metabolism (barbiturates, ethanol, St. John's wort, etc.), the metabolic rate of antihistamine increases, the concentration decreases and the effect is not achieved or is weakly expressed. With the simultaneous use of liver enzyme inhibitors (antifungal azoles, grapefruit juice, etc.), the rate of AGP metabolism slows down, which causes an increase in the concentration of "prodrug" in the blood and an increase in the frequency and severity of side effects.
The most successful variant of antihistamines is drugs that are not metabolized in the liver, the effectiveness of which does not depend on concomitant therapy, and the maximum concentration is achieved in the shortest possible time, which provides a quick onset of action. An example of such a second generation AGP is the drug cetirizine.

The speed of the onset of the effect of AGP II generation
One of the most important aspects of the drug's action is the speed of the onset of the effect.
Among AGPs of the second generation, the shortest period of reaching C max was noted for cetirizine and levocetirizine. It should be noted that the antihistaminic effect begins to develop much earlier and is minimal in drugs that do not require preliminary activation in the liver, for example, in cetirizine - after 20 minutes (Table 2).

Distribution of AGP II generation
The next most important characteristic of a drug is the volume of distribution. This indicator indicates the predominant localization of the drug: in plasma, intercellular space or inside cells. The higher this indicator, the more the drug enters the tissues and into the cells. The small volume of distribution indicates that the drug is predominantly in the vascular bed (Fig. 4). For AGP, localization in the bloodstream is optimal because its main target cells (immunocompetent blood cells and vascular endothelium) are represented here.

The values ​​of the volume of distribution (liter / kg) in the II generation AGP are ascending as follows: cetirizine (0.5)< фексофенадин (5,4–5,8) < дезлоратадин (49) < эбастин (100) < лоратадин (119) (рис. 5). Малый объем распределения обеспечивает: а) высокие концентрации данного АГП на поверхности клеток-мишеней, следовательно, точно направленное действие и высокую терапевтическую эффективность; б) отсутствие накопления в паренхиматозных органах и безопасность применения.

Features of pharmacodynamics
The pharmacological effects of antihistamines are mediated by histamine receptors, selectivity for different subtypes, the strength and duration of binding to which vary from drug to drug. A distinctive characteristic of II generation AGPs of cetirizine is its high affinity - the ability to bind histamine H1 receptors for a long time: their occupancy 4 hours after taking the drug is 90%, after 24 hours - 57%, which exceeds similar indicators of other AGPs. The most important property of antihistamines is their ability to reduce the expression of histamine H1 receptors, thereby reducing the sensitivity of tissues to histamine.
According to the strength of the antihistamine action, AGPs of the second generation can be arranged in the following order: cetirizine >> ebastine> fexofenadine >> loratadine (Fig. 6).

The antiallergic effect of individual antihistamines (cetirizine) includes the so-called additional, extra-H1-receptor action, together with which the anti-inflammatory action of the drug is realized.
Side effects of antihistamines
Side effects of AGP include anticholinergic effects (dry mouth, sinus tachycardia, constipation, urinary retention, blurred vision), adrenolytic (hypotension, reflex tachycardia, anxiety), antiserotonin (increased appetite), central antihistamine effect (sedation, increased appetite), blockade potassium channels in the heart (ventricular arrhythmia, QT prolongation). The selectivity of the action of drugs on target receptors and the ability to penetrate or not to penetrate the BBB determine their effectiveness and safety.
Among AGPs of the second generation, the drugs cetirizine and levocetirizine have the lowest affinity for M-cholinergic receptors, which means almost complete absence of anticholinergic action (Table 3).

Some antihistamines can cause arrhythmias. "Potentially cardiotoxic" are terfenadine and astemizole. Due to the ability to cause potentially fatal arrhythmias - flutter-blinking (metabolic disturbance in liver disease or against the background of CYP3A4 inhibitors), terfenadine and astemizole have been banned for use since 1998 and 1999. respectively. Among the currently existing antihistamines, ebastine and rupatadine have cardiotoxicity, and they are not recommended for use in persons with prolonged QT interval, as well as with hypokalemia. Cardiotoxicity increases when taken simultaneously with drugs that lengthen the QT interval - macrolides, antifungal agents, calcium channel blockers, antidepressants, fluoroquinolones.

Cetirizine
Cetirizine occupies a special place among the drugs of the second generation. Along with all the advantages of non-sedating antihistamines, cetirizine demonstrates properties that distinguish it from a number of new generation drugs and ensure its high clinical efficacy and safety. In particular, it has additional antiallergic activity, a fast onset of the effect, it has no danger of interacting with other medicinal substances and food, which opens up the possibility of safely prescribing the drug to patients in the presence of concomitant diseases.
The effect of cetirizine consists of the effect on both phases of allergic inflammation. The antiallergic effect includes the so-called extra-H1-receptor action: inhibition of the release of leukotrienes, prostaglandins in the nasal mucosa, skin, bronchi, stabilization of mast cell membranes, inhibition of eosinophil migration and platelet aggregation, suppression of ICAM-1 expression by epithelial cells.
Many authors, both foreign and domestic, consider cetirizine to be the standard of modern AGP. It is one of the most studied antihistamines, which has been proven to be effective and safe in many clinical studies. For patients who respond poorly to other antihistamines, cetirizine is recommended. Cetirizine fully complies with the requirements for modern AGP.
For cetirizine, the elimination half-life is 7–11 hours, the duration of the effect is 24 hours, after a course of treatment, the effect lasts up to 3 days, with prolonged use - up to 110 weeks, no addiction is observed. The duration of the effect of cetirizine (24 hours) is explained by the fact that the effect of AGP is determined not only by the concentration in the plasma, but also by the degree of binding to blood plasma proteins and receptors.
Cetirizine is practically not metabolized in the liver and is excreted mainly by the kidneys, therefore it can be used even in patients with impaired liver function. But for patients with renal insufficiency, a dose adjustment of the drug is required.

Cetrin - effective quality generic cetirizine at an affordable price
Currently, of the cetirizine preparations, in addition to the original (Zyrtec), 13 generic preparations (generics) from different manufacturers are registered. The question of the interchangeability of generics of cetirizine, their therapeutic equivalence to the original drug and the choice of the optimal agent for the treatment of allergic diseases is relevant. The stability of the therapeutic effect and the therapeutic activity of the reproduced drug are determined by the characteristics of the technology, the quality of active substances and the spectrum of excipients. The quality of drug substances from different manufacturers can vary significantly. Any change in the composition of excipients may be accompanied by pharmacokinetic abnormalities (decreased bioavailability and side effects).
A generic drug must be safe to use and equivalent to the original drug. Two medicinal products are considered bioequivalent (pharmacokinetically equivalent) if, after administration by the same route (for example, by mouth) in the same dose and regimen, they have the same bioavailability (the proportion of the drug that entered the bloodstream), the time to reach the maximum concentration and the level of this concentration in the blood, elimination half-life and area under the time-concentration curve. The listed properties are necessary for the proper efficacy and safety of the drug.
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.
Bioequivalence studies have become mandatory for drug registration since 2010. The FDA (Food and Drug Administration, USA) annually publishes and publishes the "Orange Book" with a list of drugs (and their manufacturers) that are considered therapeutically equivalent to the original.
In addition, it is important to pay attention to compliance with international manufacturing standards (GMP) in the manufacture of drugs. Unfortunately, so far not all manufacturers (especially domestic ones) have production that meets the requirements of GMP, and this may affect the quality of drugs, and therefore the effectiveness and safety of generics.
Thus, when choosing generics, there are a number of reliable guidelines: the credibility of the manufacturer, compliance with GMP, inclusion in the FDA's Orange Book. All of these criteria are fully met by the drug Cetrin by Dr. Reddy's Laboratories Ltd. Cetrin is manufactured by an international pharmaceutical company with GMP certified manufacturing sites. It is bioequivalent to the parent drug and is listed in the FDA's Orange Book as a proven therapeutic equivalence drug. In addition, Tsetrin has a long-term successful experience of application on the territory of Russia and a large own evidence base.
In a comparative study of the therapeutic efficacy and pharmacoeconomics of cetirizine preparations from different manufacturers in the treatment of chronic urticaria, it was shown that the largest number of patients who achieved remission were in the groups receiving Zyrtec and Cetrin, while the best results in terms of economic efficiency were demonstrated by Cetrin therapy.
The long history of using Tsetrin in the domestic clinical practice has proven its high therapeutic efficacy and safety. Cetrin is a drug that meets the practical need of clinical medicine for an effective and safe antihistamine drug available to a wide range of patients.

Literature

1. Georgitis J.W. 1, Stone B.D., Gottschlich G. Nasal inflammatory mediator release in ragweed allergic rhinitis: correlation with cellular influx into nasal secretions // Int Arch Allergy Appl Immunol. 1991. Vol. 96 (3). P. 231-237.
2. Ray N.F., Baraniuk J.N., Thamer M., Rinehart C.S., Gergen P.J., Kaliner M., Josephs S., Pung Y.H. // J Allergy Clin Immunol. 1999 Mar. Vol. 103 (3 Pt 1) P. 408-414.
3. Skoner D.P. 1, Gentile D.A., Fireman P., Cordoro K., Doyle W.J. Urinary histamine metabolite elevations during experimental influenza infection // Ann Allergy Asthma Immunol. 2001 Oct. Vol. 87 (4). R. 303-306.
4. Kondyurina E.G., Zelenskaya V.V. Antihistamines in the control of atopic diseases in children // BC. 2012. T. 20. No. 2. P. 56–57.
5. Gushchin I.S. Prospects for improving the antiallergic action of H1-antihistamines // Attending physician. 2009. No. 5.
6. Tillement J.P. The advantages for an H1 antihistamine of a low volume of distribution // Allergy. 2000. Vol. 55 (suppl 60). R. 17-21.
7. Gillman S., Gillard M., Strolin Benedetti M. The concept of receptor occupancy to predict clinical efficacy: a comparison of second generation H1 antihistamines // Allergy Asthma Proc. 2009. Vol. 30. P. 366–376.
8. Dinh Q.T., Cryer A., ​​Dinh S. et al. Transcriptional up-regulation of histamine receptor-1 in epithelial, mucus and inflammatory cells in perennial allergic rhinitis // Clin Exp Allergy. 2005. Vol. 35. R. 1443-1448.
9. Hiroyuki Mizuguchi 1. Shohei Ono 1. Masashi Hattori 1. Hiroyuki Fukui I. Inverse Agonistic Activity of Antihistamines and Suppression of Histamine H1 Receptor Gene Expression // J Pharmacol Sci. 2012. Vol. 118. P. 117-121.
10. Grant J.A., Danielson L., Rihoux J.P. et al. A double-blind, single-dose, crossover comparison of cetirizine, ebastine, epinastine, fexofenadine, terfenadine, and loratadine versus placebo: suppression of histamine-induced wheal and flare response for 24 h in healthy male subjects // Allergy. 1999. Vol. 54. P. 700–707.
11. Bachert C., Maspero J. Efficacy of second-generation antihistamines in patients with allergic rhinitis and comorbid asthma // J. Asthma. 2011. Vol. 48 (9). P. 965-973.
12. Weber-Schoendorfer C., Schaefer C. The safety of cetirizine during pregnancy. A prospective observational cohort study // ReprodToxicol. 2008 Sep. Vol. 26 (1) R. 19–23.
13. Gillard M., Christophe B., Wels B. et al. H1 antagonists: receptor affinity versus selectivity // Inflamm Res. 2003. Vol. 52 (suppl 1). R. 49-50.
14. Emelyanov A.V., Kochergin N.G., Goryachkina L.A. History and modern approaches to the clinical use of antihistamines // Clinical Dermatology and Venereology. 2010. No. 4. P. 62–70.
15. Golightly L.K., Greos L.S: Second-generation antihistamines: actions and efficacy in the management of allergic disorders // Drugs 2005. Vol. 65. P. 341–384.
16. Dos Santos R.V., Magerl M., Mlynek A., Lima H.C. Suppression of histamine- and allergen-induced skin reactions: comparison of first- and second-generation antihistamines // Ann Allergy Asthma Immunol. 2009 Jun. Vol. 102 (6). R. 495-499.
17. Revyakina V.A. Antihistamines in the practice of an outpatient doctor // Attending physician. 2011. Vol. 4. R. 13–15.
18. Tataurschikova N.S. Modern aspects of the use of antihistamines in the practice of a general practitioner // Farmateka. 2011. No. 11. P. 46–50.
19. Kareva E.N. The quality of the drug // Russian medical news. 2014. V. 19.No. 4. P. 12–16.
20. Open randomized crossover study of comparative pharmacokinetics and bioequivalence of drugs Cetrin, tablets 0.01 (Dr. Reddy's Laboratories LTD, India) and Zyrtec tablets 0.01 (UCB Pharmaceutical Sector, Germany). SPb., 2008.
21. Nekrasova E.E., Ponomareva A.V., Fedoskova T.G. Rational pharmacotherapy of chronic urticaria // Ros. allergological journal. 2013. No. 6. P. 69–74.
22. Fedoskova T.G. Antihistamines: myths and reality // Effective pharmacotherapy. 2014. No. 5. P. 50–56.

A rare child is not allergic to various pathogens, some react painfully to certain foods from birth, others to cosmetics or flowering plants, but thanks to the new generation of medicines - antihistamines for children, serious complications can be avoided. If you take timely measures to eliminate children's allergies, then acute processes will not turn into a state of chronic ailments.

What are antihistamines

A group of modern drugs that suppress the action of histamine (a neurotransmitter) are called antihistamines. When an allergen is exposed to the body, a neurotransmitter or an organic compound, histamine begins to be released from connective tissue cells that are part of the immune system. When a neurotransmitter interacts with specific receptors? swelling, itching, rash, and other manifestations of allergies often occur. Antihistamines are responsible for blocking these receptors. Today there are four generations of these drugs.

Antiallergic drugs do not completely cure the disease. They do not particularly affect the cause of the allergy, but only help to cope with unpleasant signs... Such medications can be prescribed to patients of any age, even one-year-olds and infants. Antihistamines are prodrugs. This means that when ingested, they begin to transform into active metabolites. An important property of these funds is the complete absence of a cardiotoxic effect.

Indications for use

When teething occurs, special antiallergic medications can be used to neutralize a possible allergic reaction before vaccination. Besides, indications for the use of such funds are:

• hay fever (hay fever);
• Quincke's edema;
• year-round, seasonal allergic reactions (conjunctivitis, rhinitis);
• itchy skin in chronic infectious diseases;
• previously observed complex manifestations of allergies or symptoms of anaphylactic shock;
• atopic dermatitis, eczema, dermatosis, urticaria and other skin rashes;
• individual predisposition to allergies;
• deterioration of the child's condition with chronic ailments of the respiratory tract (laryngitis, laryngeal stenosis, allergic cough);
• a high rate of eosinophils in the blood;
• insect bites;
• swelling of the mucous membranes of the nose, mouth;
• acute manifestations of allergy to drugs.

Classification

Antiallergic drugs, depending on the characteristics of the chemical composition, can be divided into groups:

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

Modern medicine offers a huge number of classifications of antiallergic drugs, but none of them is generally accepted. A wider application in clinical practice has received the classification of medicines by the time of their creation or by generations, which are currently distinguished by 4: 1 - sedatives, 2nd generation - non-sedative, 3 and 4 - metabolites.

Generations of antihistamines

The very first anti-allergic drugs appeared in the 30s of the 20th century - they were drugs of the 1st generation. Science is constantly moving forward, so over time, similar tools of the second, third and fourth generations were developed. With the advent of each new drug, the strength and number of side effects decreases, and the duration of exposure increases. Below is a table of 4 generations of anti-allergic drugs:

Generation	The main active ingredient	Characteristic	Names
1	Diphenhydramine, diphenhydramine, diprazine, clemastine, hifenadine	They have a sedative effect and are characterized by short-term effects. Diphenhydramine is often prescribed for hay fever, allergic dermatosis. Medications cause tachycardia and vestibulopathy.	Psilo-balm, Suprastin, Tavegil, Diazolin
2	Azelastine, Ebastine, Astemizole, Loratadine, Terfenadine	Not sedatives. There is no influence on the heart. Only one dose per day is needed, long-term use is possible.	Claritin, Kestin, Rupafin, Cetrin, Ketotifen, Fenistil, Zodak
3	Cetirizine, Fexofenadine, Desloratadine	Active metabolites, do not affect the functioning of the heart. Rarely cause dryness of the mucous membranes of the mouth.	Ksizal, Allegra, Desloratadin, Cetirizin, Telfast, Fexofast
4	Levocetirizine, desloratadine	Modern means that instantly affect the body. 4th generation drugs quickly block histamine receptors, effectively eliminate allergy symptoms.	Ksizal, Glenzet, Erius, Ebastin, Bamipin, Fenspirid

Antiallergic drugs for children

The choice of antihistamines should be made by a physician. Self-medication will only aggravate the resulting allergic reaction and cause undesirable consequences. Parents often use creams for first aid. They can be smeared with a reaction to vaccination. Other forms: drops, tablets, syrup, suspension should be used after consulting a specialist. The pediatrician will select the dosage taking into account the severity of the allergy and the age of the baby.

Up to a year

Usually, pediatricians prescribe new generation drugs for infants, since the second and the first are capable of causing side effects: headache, drowsiness, suppression of activity, respiratory depression. Doctors often do not recommend taking antihistamines for babies, but sometimes in acute situations they are simply necessary. The best remedies for young patients are:

• Suprastin solution. It is used to treat rhinitis, urticaria, acute allergic dermatitis. It relieves itching well, accelerates the process of getting rid of skin rashes. Approved for the treatment of infants (from the age of 30 days). The children's dose is one fourth of the ampoule 2 times a day. Rarely, a medicine can cause nausea, stool disturbance, and dyspepsia. Suprastin is dangerous when taken more than one ampoule.
• Fenistil drops. A popular allergy remedy for children is used to treat rubella, chickenpox. In addition, it is often drunk for contact dermatitis, sunburn, insect bites. Antihistamine drops for children Fenistil at the very beginning of treatment can cause drowsiness, but after a few days this effect disappears. The medicine has side effects: dizziness, muscle spasms, swelling of the oral mucosa. Children under one year old are prescribed 10 drops once a day, but not more than 30.

From 2 to 5 years old

When a child grows up, the range of medicines expands, although many well-known drugs are still contraindicated, for example, Suprastin and Claritin in tablets, Azelastin drops. The most popular medicines used from 2 to 5 years of age are:

• Cetrin drops. It is used for food allergies, for the treatment of conjunctivitis and rhinitis. The advantage of using the drug is its long-term effect. Drops must be taken only once a day. Side effects: anticholinergic effects, drowsiness, headache.
• Erius. This allergy syrup for children is one of the most popular. It belongs to the 3rd generation drugs. Helps to relieve allergic symptoms and alleviate the general condition of the patient. Not addictive. Erius syrup is useful for rhinitis, hay fever, allergic conjunctivitis, urticaria. Side effects: nausea, headache, diathesis, diarrhea.

6 years and older

As a rule, from the age of 6, a specialist can prescribe 2nd generation antihistamines for children. A child at this age is already able to take a tablet form, therefore allergists often prescribe Suprastin in tablets. For allergic rhinitis and conjunctivitis, Allergodil drops are used. Besides, patients over 6 years old can take:

• Tavegil. Recommended for hay fever, dermatitis, allergic insect bites. Among the anti-allergic drugs, Tavegil is considered the safest. Therapy for children from 6 to 12 years old involves the following intake of the drug - half a capsule in the morning and in the evening. The tablets should be drunk regularly before meals, preferably at the same time. They should be taken with caution in patients with glaucoma. Tavegil causes a deterioration in the clarity of perception of visual images.
• Zyrtec. These non-hormonal tablets have anti-inflammatory and anti-exudative effects. The advantage of using the drug is its use in the combined treatment of bronchial asthma. Children from 6 years old can drink half a tablet 2 times a day. Side effects: itching, rash, malaise, asthenia.

Which antihistamines are best for a child

Unstable children's immunity often contributes to the appearance of allergic reactions. Modern antihistamines for children help to cope with negative symptoms... Many pharmaceutical companies produce anti-allergic drugs in children's dosage in the form of syrup, drops, suspension. This makes it easier to take and does not make the baby averse to treatment. Often, your doctor may prescribe an antihistamine in the form of a gel or cream to treat local inflammation. They are used externally for allergic skin reactions to insect bites.

Usually, antihistamines for newborns are allowed in the form of syrup or oral drops, and they should not use the drugs of the old generation (1st) due to sedation and high toxicity. The dosage of medicines also depends on the severity of the symptoms and the patient's body weight. Antiallergic drugs of the 3rd generation are recommended for children from one year old. Pills are more suitable for an older child. It is also possible to use antiallergenic local remedies: nasal sprays, eye drops, gels, creams, ointments.

Pills

The most common form of release of anti-allergenic drugs is tablets. A child can take them only from the age of 3, but often at this age the baby is not yet able to swallow the medicine. Therefore, tablets can be given in crushed form by diluting them with water. Popular tablet formulations are:

• Loratadin. Second generation drug. Helps to quickly eliminate unpleasant symptoms of allergic rhinitis, reactions to pollen and flowering plants. It is used in the treatment of urticaria, bronchial asthma. A single dose of 5 mg is recommended for children from two years of age. Teenagers - 10 mg. Side effects: fever, blurred vision, chills.
• Diazolin. Helps with seasonal allergic rhinitis and cough. It can be prescribed during chickenpox, urticaria, and conjunctivitis caused by pollen. The maximum daily dose of Diazolin for patients from 2 to 5 years old is 150 mg. It is not recommended to take pills for heart problems.

Drops

This form is convenient for use in small children, it is easily dosed using a special bottle. As a rule, for newborns, doctors try to prescribe antihistamines in drops. The most famous means are:

• Zodak. The tool has an anti-exudative, antipruritic, anti-allergic effect, prevents the further development of the disease. The action of the drug begins within 20 minutes after ingestion and lasts throughout the day. Dosage for children from one year old: 2 times a day, 5 drops. Rarely, with the use of drops, nausea and dry mouth occur. Patients with liver disease should drink them with caution.
• Fenkarol. The drug relieves spasms, reduces suffocation, quickly extinguishes the negative manifestations of allergies. Patients under three years old are recommended to give 5 drops 2 times a day. Fenkarol is prescribed for chronic and acute hay fever, urticaria, dermatosis (psoriasis, eczema). Side effects: headache, nausea, dry mouth.

Syrups

Most antihistamines for children come in pills, but some have alternatives in syrup form. Most of them have an age limit of up to two years. The most popular antihistamine syrups are:

• Claritin. Has a long-term anti-allergic effect. The tool is suitable for eliminating acute symptoms, preventing severe relapses. After oral administration, the medicine will take effect in 30 minutes. Claritin is prescribed for seasonal or year-round rhinitis, allergic conjunctivitis. Rarely, drowsiness and headache may appear while taking the medication.
• Gismanal. The drug is prescribed for allergic skin reactions, for the treatment and prevention of angioedema. Doses of the drug: patients from 6 years old - 5 mg once a day, younger than this age - 2 mg per 10 kg. Rarely, the medication can cause nausea, headache, and dry mouth.

Ointments

Antiallergic baby ointments are a large group of medicines intended for topical use. Antihistamine ointments are applied to the affected area of ​​skin manifestations of allergies. The most famous are:

• Bepanten. Ointment that stimulates tissue regeneration. Used to care for babies, skin irritations, diaper dermatitis, to relieve dry skin. Rarely, Bepanten with long-term treatment causes itching and hives.
• Gistan. Non-hormonal antihistamine cream. It contains components such as string extract, violets, calendula. This topical medicine is used for allergic skin reactions and as a topical anti-inflammatory agent for atopic dermatitis. Contraindications: you cannot use the ointment for children under one year old.

Overdose of antihistamines in children

Abuse, misuse, or long-term therapy with antiallergic drugs can lead to overdose, which often manifests itself in the form of increased side effects. They are only temporary and disappear after the patient stops taking the medication or is prescribed an acceptable dose. Usually, overdose in children may develop:

• severe drowsiness;
• overstimulation of the central nervous system;
• dizziness;
• hallucinations;
• tachycardia;
• excited state;
• fever;
• convulsions;
• impaired renal function;
• dry mucous membranes;
• dilated pupils.

The price of antihistamines for children

Any anti-allergic medicines and their analogues can be purchased at a pharmacy without a prescription or ordered online. Their cost depends on the manufacturer's firm, dosage, form of release, pricing policy of the pharmacy and the region of sale. Approximate prices for antiallergic drugs in Moscow are presented in the table:

The presence of many undesirable effects in 1st generation antihistamines has become the reason for the search for new blockers of H1-histamine receptors. In 1977, the first antihistamine drug appeared, which had the ability to suppress skin allergies and at the same time practically did not have a sedative effect. This marked the beginning of going out to the clinic antihistamines of the 2nd generation.

2nd generation antihistamines include:

• Loratadin (Claritin);
• Terfenadine (Trexil, Taldan, Histadil, Bronal);
• Astemizole (Astemisan, Gismanal, Histalong);
• Akrivastin (Semprex);
• Cetirizine (Cetrin, Zyrtec);
• Ebastin (Kestin);
• Fexofenadine;
• Azelastine;
• Levocabastine (Histimet).

Features of 2nd generation antihistamines:

• Fast onset of action;
• High affinity for H1-histamine receptors;
• Duration of action (12-24 hours);
• Do not block other receptors;
• Lack of sedation;
• Lack of dependence on meal time;
• Lack of addiction with prolonged use;
• Possibility of combination with CNS depressants and alcohol;
• Lack of influence on the cardiovascular system, urine-genital organs, stomach, intestines, vision, mucous membranes.

In most cases, it is not the 2nd generation antihistamines themselves that have antihistaminic activity, but their metabolites, which explains the different efficacy of the drugs in different individuals.

The accumulation of the original substance, which is associated with a pronounced metabolic disorder, has an extremely negative effect on the body. A cardiotoxic effect sets in.

It was found that terfenadine and astemizole in high concentrations led to cardiac arrhythmias up to sudden death.

Risk factors that can increase the blood concentration of 2nd generation antihistamines:

• Overdose;
• Alcohol abuse;
• Liver dysfunction;
• Taking some antibiotics (macrolides) - erythromycin, clarithromycin;
• Taking antimycotic drugs - itroconazole, fluconazole, ketoconazole, niconazole.

Antihistamines of the 2nd generation: a list

Currently, in the special literature, opinions differ as to which antiallergic drugs should be classified as the second and third generation. In this regard, the list of 2nd generation antihistamines will have its own characteristics, depending on the point of view of modern pharmacists.

By what criteria are antihistamines classified into the second group?

According to the first point of view, second-generation drugs are all those anti-allergic drugs that are devoid of sedation because they do not enter the brain through the blood-brain barrier.

The second and most common point of view is that the second generation of antihistamines should include only those that, although they do not affect the nervous system, are capable of causing changes in the heart muscle. Medicines that do not act on the heart and nervous system have been classified as the third generation of antihistamines.

According to the third point of view, only one drug with antihistaminic properties, ketotifen, belongs to the second generation, because it has a membrane stabilizing effect. And all those drugs that stabilize the mast cell membrane, but do not cause sedation, make up the third generation of antihistamines.

Why are antihistamines so named?

Histamine is an essential substance that is predominantly found in the mast cells of connective tissue and blood basophils. Released under the influence of various factors from these cells, it binds to the H 1 and H 2 receptors:

• H 1 -receptors, when interacting with histamine, cause bronchospasm, contraction of smooth muscles, expand capillaries and increase their permeability.
• H 2 -receptors stimulate an increase in acidity in the stomach, affect the heart rate.

Indirectly, histamine can cause severe itching, stimulating the release of catecholamines from adrenal cells, increasing the secretion of the salivary and lacrimal glands, and accelerating intestinal motility.

Antihistamines bind to H 1 and H 2 receptors and block the action of histamine.

List of drugs of the second group

According to the most common classification of antihistamines, the second generation includes:

All of these drugs do not enter the brain and therefore do not induce sedation. However, the possible development of cardiotoxic action limits the use of this group of drugs in the elderly and those who suffer from heart disease.

Enhances myocardial damage when treated with second-generation antihistamines, the simultaneous administration of antifungal agents and some antibiotics, for example, clarithromycin, erythromycin, itraconazole and ketoconazole. You should also refrain from consuming grapefruit juice and antidepressants.

Dimetindene (fenistil)

It is available in the form of drops, gel and capsules for oral administration. It is one of the few drugs that can be used in children in the first year of life, with the exception of the neonatal period.

Fenistil is well absorbed internally and has a pronounced antiallergic effect, lasting after 1 dose for about 6-11 hours.

The drug is effective for pruritus, eczema, drug and food allergies, insect bites, itchy dermatoses and exudative-catarrhal diathesis in children. Its other purpose is to remove mild household and sunburns.

Features of the application. It is one of the few second-generation drugs that still crosses the blood-brain barrier, so it can slow down the response while driving. In this connection, it should be prescribed with extreme caution to drivers, and even more so not to use it during work that requires a quick reaction.

When applying the gel to the skin, protect the area from direct sunlight.

Dimetindene is contraindicated during the first trimester of pregnancy and in the neonatal period. It is used with caution in the second and third trimesters of pregnancy, with prostate adenoma, angle-closure glaucoma.

Loratadin (claritin, lomilan, lotaren)

Like other drugs in this group, it effectively treats all kinds of allergic diseases, especially allergic rhinitis, conjunctivitis, nasopharyngitis, angioedema, urticaria, endogenous itching. The drug is available in the form of tablets and syrup for oral administration, and is also part of multicomponent antiallergic gels and ointments for local treatment.

Effective for pseudo-allergic reactions, hay fever, urticaria, itchy dermatoses. As an aid, it is prescribed for bronchial asthma.

Features of the application. May cause sedation in the elderly, not recommended during pregnancy and breastfeeding. Many drugs reduce the effectiveness of loratadine or increase its side effects, so you should definitely consult your doctor before taking it.

Ebastin (Kestin)

Also belongs to the group of second generation antihistamines. Its distinctive feature is the lack of interaction with ethanol, so it is not contraindicated for the use of medicines containing alcohol. Simultaneous administration with ketoconazole increases the toxic effect on the heart, which can lead to fatal consequences.

Ebastine is prescribed for allergic rhinitis, urticaria and other diseases accompanied by excess histamine release.

Cyproheptadine (peritol)

This drug for the treatment of allergic reactions can be prescribed to children from 6 months. Like other drugs in this group, cyproheptadine has a strong and long-term effect, eliminating allergy symptoms. A distinctive feature of peritol is the relief of migraine headaches, a sedative effect, a decrease in excess secretion of growth hormone in acromegaly. Cyproheptadine is prescribed for toxicoderma, neurodermatitis, in the complex therapy of chronic pancreatitis, serum sickness.

Azelastine (allergodil)

This drug works well for allergy manifestations such as allergic rhinitis and conjunctivitis. Available as a nasal spray and eye drops. In pediatrics, it is prescribed for children from 4 years old (eye drops) and from 6 years old (spray). The duration of the course of treatment with azelastine, on the recommendation of a doctor, can last up to 6 months.

From the nasal mucosa, the drug is well absorbed into the general bloodstream and has a systemic effect on the body.

Acrivastin (Semprex)

The drug weakly penetrates the blood-brain barrier, therefore it does not have a sedative effect, however, vehicle drivers and those whose work requires quick and accurate action should refrain from taking it.

Acrivastin differs from other representatives of this group in that it begins to act within the first 30 minutes, and the maximum effect on the skin is observed within 1.5 hours after ingestion.

Drugs of the second group, about which there is disagreement in scientific circles

Mebhydrolin (diazolin)

Most experts classify diazolin as the first generation of antihistamines, while others, due to the minimally pronounced sedative effect, classify this agent as the second. Be that as it may, diazolin is widely used not only in adults, but also in pediatric practice, being considered one of the most inexpensive and available medicines.

Desloratadine (edem, erius)

It is most often referred to as the third generation of antihistamines because it is an active metabolite of loratadine.

Cetirizine (zodak, cetrin, paralazin)

Most researchers classify this drug as the second generation of antihistamines, although some confidently classify it as the third, because it is an active metabolite of hydroxyzine.

Zodak is well tolerated and rarely causes side effects. It is available in the form of drops, tablets and syrup for oral administration. With a single dose of the drug, it has a therapeutic effect throughout the day, so it can be taken only once a day.

Cetirizine relieves allergy symptoms, does not cause sedation, prevents the development of smooth muscle spasm and swelling of surrounding tissues. It is effective for hay fever, allergic conjunctivitis, urticaria, eczema, and removes itching well.

Features of the application. If the drug is prescribed in large doses, then you should refrain from driving vehicles, as well as work that requires a quick response. When used together with alcohol, cetirizine can increase its negative effects.

The duration of the course of treatment with this drug can be from 1 to 6 weeks.

Fexofenadine (Telfast)

Most researchers also belong to the third generation of antihistamines, because it is an active metabolite of terfenadine. It can be used by those whose activities are related to driving vehicles, as well as those suffering from heart disease.

• Allergy 325
  • Allergic stomatitis 1
  • Anaphylactic shock 5
  • Hives 24
  • Quincke's edema 2
  • Pollinosis 13
• Asthma 39
• Dermatitis 245
  • Atopic dermatitis 25
  • Neurodermatitis 20
  • Psoriasis 63
  • Seborrheic dermatitis 15
  • Lyell's syndrome 1
  • Toxidermia 2
  • Eczema 68
• General symptoms 33
  • Runny nose 33

Full or partial reproduction of site materials is possible only if there is an active indexed link to the source. All materials presented on the site are for informational purposes only. Do not self-medicate, recommendations should be given by the attending physician during an in-person consultation.

2nd generation antihistamines

Learn more about smoking

Which twin smokes?

Lines around lips

Pale skin color

Base material

II generation antihistamines

At the end of the 70s of the last century, H1 antagonists of the second generation entered the pharmaceutical market, which have a number of advantages, including a high affinity for H1 receptors. That is why II generation H1 antagonists in therapeutic doses do not antagonize such mediators as acetylcholine, catecholamines, dopamine, and, as a result, do not give many side effects inherent in I generation H2 antagonists.

In 1977, the first reports of terfenadine appeared, in subsequent years other compounds (astemizole, cetirizine, loratadine, acrivastine, ebastine, fexofenadine, desloratadine) became known, which had a pronounced antihistamine effect and did not have a noticeable central action. These drugs were named II generation H1 antagonists (Table 6).

Table 6... H1 antagonists of the second generation

Most of these drugs have the following benefits:

1. high specificity and high affinity for H1-histamine receptors;
2. rapid onset of action;
3. long duration of the antihistamine effect (up to 24 hours);
4. lack of blockade of other types of receptors;
5. lack of penetration through the blood-brain barrier in therapeutic doses;
6. lack of connection between absorption and food intake (except for astemizole);
7. lack of tachyphylaxis.

H1 antagonists are well absorbed from the gastrointestinal tract when taken orally, the peak concentration in the blood after 2 hours. Most of the II generation H1 antagonists, with the exception of fexofenadine and cetirizine, undergo hepatic metabolism with the formation of active compounds. The antihistamine effect of most drugs is due to the accumulation of active metabolites in the blood in sufficient concentration. The synthesis of metabolites is carried out by the CYPZA4 isoenzyme of the cytochrome P450 system.

The elimination of H1 blockers and their metabolites is via the kidneys and liver. When liver function is impaired, the concentration of these drugs in the blood increases.

The rate of elimination of drugs from the blood varies widely from several hours for terfenadine to several days for astemizole. The half-life of drugs increases with age.

The maximum antihistamine effect of H1 receptor blockers is observed several hours after the peak of drug concentration in the blood and continues, even if their concentration in serum is low, probably due to the action of active metabolites

They differ from other II generation antihistamines: cetirizine (active metabolite of hydroxyzine), desloratadine (active metabolite of loratadine) and acrivastine. The concentration of arivastine in the blood reaches a maximum within 1 hour, desloratadine - after 1.3-3.7 hours, their antihistaminic effect is manifested within 30 minutes after ingestion.

Desloratadine (Erius) is the most powerful of the existing antihistamines, possessing antihistamines, anti-allergic and anti-inflammatory effects in therapeutic doses. Its affinity for H1 receptors is 25-1000 times higher than that for other H1 blockers and is combined with the ability to inhibit the production of proinflammatory mediators. The benefits of desloratadine over other antihistamines for allergic rhinitis and idiopathic urticaria have been proven in clinical trials, including several multicenter, double-blind studies, involving a total of about 48,000 patients. Desloratadine does not have sedative and anticholinergic effects, does not cause lengthening of the QT interval on the ECG and does not lead to the development of arrhythmias, does not enter into clinically significant interactions with other drugs, alcohol, grapefruit juice, and the heart. The drug is well tolerated by patients of all age categories, including the elderly and children 2-5 years old.

Metabolized drugs - ebastine, terfenadine, loratadine - are also fast-acting, their active metabolites quickly accumulate in the blood. The concentration in the blood of astemizole and its active metabolite (desmetilastemizole) reaches a maximum 4 hours after taking the drug. A constant plasma concentration of unchanged astemizole and astemizole, together with its active metabolite, is achieved only after 1 week and 4 weeks, respectively, after starting the drug intake. Astemizole begins to act slowly, and the maximum effect occurs with a delay.

Features of metabolism and pharmacokinetics of H1-antagonists and their metabolites determine other clinical features of drug action. In particular, different pharmacological efficacy in different individuals may be associated with the individual characteristics of drug metabolism.

Indications for the appointment of II generation H1 antagonists:

1. perennial allergic rhinitis;
2. seasonal allergic rhinitis;
3. itchy dermatoses (histamine-mediated) (urticaria, Quincke's edema, atopic dermatitis).

The possibility of using H1-antagonists of the second generation in bronchial asthma is being studied. This is due to the following facts:

1. the obvious role of histamine in the development of an asthma attack in bronchial asthma;
2. H1-antagonists of the second generation do not have side effects that limit their use in bronchial asthma (do not cause dryness of mucous membranes and worsening of viscous sputum discharge);
3. due to their high affinity for H1 receptors, they can effectively block these receptors.

In particular, on the example of a clinical study of desloratadine in allergic rhinitis in combination with bronchial asthma, it was shown that, in addition to the positive dynamics of symptoms of allergic rhinitis, desloratadine reduces asthma symptoms (a decrease in the total index of bronchial asthma symptoms). The average number of inhalations of β2-agonists decreased at the 1st week by 14%, at the 2nd week - by 7%, at the 3rd and 4th weeks - by 12% and 10%, respectively.

It was found that in patients with bronchial asthma, H1-antagonists of the second generation have a bronchodilator effect, reduce bronchial hyperreactivity to histamine (but not acetylcholine), exercise, cold air, and inhibit the early phase of asthmatic reaction caused by inhalation of allergens. The use of cetirizine at a dose of 10 mg / day for 6 weeks significantly reduces the severity of symptoms of bronchial asthma and concomitant allergic rhinitis.

Nevertheless, the assessment of the results of the use of II generation H1 antagonists is controversial. A number of authors consider the use of these drugs in bronchial asthma insufficiently effective.

In double-blind, placebo-controlled, randomized trials, it has been proven that desloratadine (Erius) effectively relieves nasal and non-nasal symptoms in allergic rhinitis. Unlike other antihistamines, it provides a stable, statistically significant reduction in swelling and nasal congestion. Desloratadine reliably relieves symptoms in patients with seasonal allergic rhinitis and concomitant bronchial asthma, has an anti-inflammatory effect on the bronchial mucosa, leading to an improvement in the course of bronchial asthma, maintaining FEV1 and reducing the need for β2-agonists. Its effectiveness in this category of patients is comparable to that of montelukast. More than 91% of patients and doctors who participated in clinical trials of desloratadine rate its effectiveness as excellent and good; more than 98% believe that the drug is excellent or well tolerated.

The development of tachyphylaxis has not been described for any II generation H1-antagonist.

The absence of sedation or extremely weak manifestations of it is one of the important advantages of these drugs. The effect of the second generation H1-histamine blockers on psychomotor functions, cognitive abilities and functional skills was also studied. For this, a number of tests were used (sleep latency test, Stanford sleepiness scale, test for staying awake, test for replacing numbers with symbols - taking into account the speed of information processing, test for performing a series of additions and subtractions, test for psychomotor reaction). In terfenadine and astemizole, the presence of arrhythmogenic activity was established, which is manifested by an extension of the QT interval, the appearance of a bidirectional fusiform ventricular extrasystole (“pirouette syndrome” - torsade de pointes), atrioventricular blockade and blockade of the legs of the His bundles.

The likelihood of an increase in the QT interval is increased with electrolyte disturbances, in people with heart disease (ischemia, myocarditis, cardiomyopathy), with an increase in the level of antihistamines in the blood (due to overdose, liver dysfunction, alcohol abuse, interactions with certain medications).

The known arrhythmogenic effects of terfenadine and astemizole served as the basis for refusal to re-register in a number of countries and withdraw them from the pharmacy network in Russia, too, according to the decision of the Pharmaceutical Committee. It has been shown that the QT interval can also increase ebastine, but in doses significantly higher than therapeutic.

Medicines that are pharmacologically active substances that are not metabolized by the liver and do not possess cardiotoxicity are characterized by a high safety profile, which indicates that these medicines are promising. Examples of such compounds are fexofenadine (an active metabolite of terfenadine), desloratadine (an active metabolite of loratadine), norastemizole (an active metabolite of astemizole).

Contraindications and warnings

Contraindications to the use of H1-blockers of the II generation:

Experts from the European Academy of Allergology and Clinical Immunology formulated the following recommendations for the safe use of antihistamines.

1. Do not exceed the prescribed dose of H1-antagonists.
2. Avoid prescribing drugs that compete with antihistamines for hepatic metabolism when using antihistamines that involve cytochrome P450 in the metabolism (Table 6).
3. H1-antagonists should be prescribed with greater caution in patients with liver diseases and cardiac arrhythmias (prolongation of the QT interval, ventricular tachycardia, atrioventricular blockade).
4. In the same group of patients, preference should be given to drugs that are not metabolized in the liver (fexofenadine, desloratadine).

The CYP3A4 system takes part in the metabolism of antihistamines and a number of other drugs competing with them for biotransformation in the liver; some substances are its inhibitors (Table 7). The simultaneous appointment of these drugs with H1-blockers (terfenadine, astemizole) leads to the accumulation of starting substances in the blood and the development of a cardiotoxic effect.

The concentration of drugs in the blood is increased:

The risk of prolongation of the QT interval increases with the simultaneous administration of astemizole, terfenadine, ebastine with:

1. antiarrhythmic drugs (quinidine, sotalol, disopyramide);
2. psychotropic drugs (phenothiazines, tricyclic and tetracyclic antidepressants);

antibacterial agents (erythromycin, pentamidine, trimethoprim, sulfamethoxazole); antihistamines (astemizole, terfenadine, ebastine).

Table 7. Interaction of drugs and the cytochrome P450 system (CYP ZA4 isoenzyme)

metabolizable CUR ZA4

SUR ZA4 inhibitors

Analgesics: codeine, fentanyl, paracetamol

Antifungal agents: ketoconazole,

Local anesthetics: lidocaine, propafenone,

Antibacterial agents: erythromycin,

Anticonvulsants: carbazepine,

clarithromycin, ciprofloxacin, sparfloxacin

Antidepressants: fluoxetil, fluvoxamide,

Antidepressants: amitriptyline, clopyramine,

Antivirals: indinavir,

Lipid-lowering: lovastin, simvastatin,

Some drugs of other groups: cimeti-

Antihypertensives: felodipine, nifedipine,

din, diltiazem, bromocriptine, amiodarone

Cytostatics: cyclophosphamide, tamoxifen,

Protease inhibitors: indavir, saquinavir

Sedatives: midazolam, triazolam

Steroids: dexamethasone, estradiol,

Miscellaneous: cisapride, dapsone, glibenclamide,

omeprazole, ziuleton, rifampicin, quinidine

Goryachkina JI.A., Moiseev S.V. The role of desloratadine (Erius) in the treatment of allergic diseases. Clinical pharmacology and therapy. No. 5, 2001; 10: 79-82.

Gushchin I.S. Allergic inflammation and its pharmacological control. M .: Farmarus print, 1998; 246.

Gushchin I.S. Prospects for the treatment of allergic diseases: from antihistamines to multifunctional antiallergic drugs. IX Russian National Congress “Man and Medicine”. M., 2002; 224-232.

Pytskiy V.I., Adrianova N.V., Artomasova A.B. Allergic diseases. M .: Triada-X, 1999; 128.

ARIA: Allergic rhinitis and its effect on bronchial asthma. Allergology. No. 3, 2001; 47-56.

Come J.M., Holgate S.T. Histamine and H1-receptor antagonists in allergic disease / Ed. F.E.R. Simons. Marcel Dekker, Ink. 1996; 251-271.

Passalacqua G., Bousquet J., Bachet C. et al. Allergy. No. 10, 1996; 51: 666-675.

Simons F., Simons R., Simons K.J. Pharmacokinetic optimization of histamine H: -receptor antagonist therapy.

Clin. Pharmacokinetics. 1991; 21: 372-393.

Post Views: 921