Principles clinico -pharmaceutical - PowerPoint Presentation

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Principlesclinico-pharmaceuticalapproach to the selection of drugsfor the treatment of allergic diseases

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ALLERGY IS A SITUATION FOR HUMANITY FOR ITS INABILITYThis disease is one of the most common on Earth. According to statistics, already today every fifth inhabitant of our planet suffers:every sixth American,every fourth German,from 5 to 30% of Ukrainian.And if the XX century was the century of cardiovascular diseases, then the XXI is predicted by WHO to become a century of allergy.This is facilitated by the following factors:- increased allergenic load on a person,- change its ability to respond to this load.The deteriorating ecological situation and, as a result, increased permeability for allergens of barrier tissues, inadequate nutrition, inadequate drug therapy, uncontrolled use of antibiotics, increased stress loads, sedentary lifestyle, changes in climate lead to the fact that the susceptibility of the human body to allergens, even those , which have always existed, is significantly increased.2

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In accordance with the definition of the concept of allergy, the group of allergic diseases includes such diseases, the mechanism of damaging action in which is associated with immediate-type hypersensitivity (ITH), delayed type hypersensitivity (DTH), or combinations thereof.       In the group of ITH (IgE-reactive) are the following diseases: atopic bronchial asthma, infectious-allergic bronchial asthma in children, anaphylactic shock, hay fever, urticaria, Quincke's edema, allergic rhinitis and conjunctivitis, a significant part of the drug and food allergies.       The group of DTH (Th1-reactin) includes: allergic contact dermatitis, infectious-allergic bronchial asthma in adults, some forms of drug and food allergies; HRT-mediated granulomatous processes: leprosy, tuberculosis, brucellosis, tularemia, iersiniosis, pseudotuberculosis, sarcoidosis, Crohn's disease, leishmaniasis.

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Аtopic dermatitis- a chronic allergic skin disease, the development of which is associated with both hereditary predisposition and the impact of a number of unfavorable environmental factors

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Allergic rhinitis Allergic rhinitis is characterized by watery discharge from the nose, difficulty in nasal breathing, sneezing, itching in the nose, decreased sense of smell

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Allergic conjunctivitis The main manifestations of allergic conjunctivitis include itching in the eye area, a feeling of "sand" in the eyes, lacrimation, photophobia, burning eyes, redness and swelling of the eyelids

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Pollinosis The name "pollinosis" comes from the Latin word pollen - pollen, as the disease causes pollen of plants. Once, hay fever was called hay fever, believing that the cause of the disease is hay

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Hives, urticaria This appearance on the skin of blisters of different sizes, similar to rashes after nettle burn, accompanied by skin itching

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Food allergy People with food allergies experience a worsening of their well-being after eating certain foods that others do not cause negative reactions

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Immunogenetic studies have brought the base under a hereditary predisposition to allergic diseases (atopy). The existence of a genetic system of non-specific regulation of the level of IgE, carried out by the genes of the excess immune response by Ih-genes (immune hyperresponse) is proved. These genes are associated with antigens of the main histocompatibility complex A1, A3, B7, B8, Dw2, Dw3 and a high IgE level is associated with haplotypes A3, B7, Dw2 (Marsh D.C. et al., 1982). There is evidence of a predisposition to specific allergic diseases, and this predisposition is supervised by different antigens of the HLA system, depending on nationality. So, for example, a high predisposition to

pollinosis in Europeans is associated with the antigen HLA-B12; the Kazakhs - with HLA-DR7; among Azerbaijanis - with HLA-B21 (Balabolkin

, 1998). At the same time,

immunogenetic

studies in allergic diseases can not yet be concrete guidelines for clinicians and require further development.

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"As with other types of allergies, with food allergies, the quality of the allergen is crucial, but in food allergens one should not underestimate their number. The prerequisite for the development of the reaction is the excess of the threshold dose of the allergen, which happens with a relative excess of the product with respect to the digestive capacity of the gastrointestinal tract "(L. Jaeger, 1990).        This is an important thesis, since it makes it possible to identify individuals with various digestive disorders in the risk group and to correct digestive disorders in curative and prophylactic programs for food allergies.        Almost any food product can be an allergen, however, cow's milk, chicken eggs, seafood (cod, squid, etc.), chocolate, nuts, vegetables and fruits (tomatoes, celery, citrus fruits), seasonings and spices, yeast, flour are the most allergenic. .

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According to the data of Studenikin and II Balabolkin (1998), a cross allergy within a single botanical family is possible: citrus fruits (oranges, lemons, grapefruits); pumpkin (melon, cucumber, zucchini, pumpkin); mustard (cabbage, mustard, cauliflower, Brussels sprouts); Solanaceae (tomatoes, potatoes); pink (strawberries, strawberries, raspberries); plum (plum, peaches, apricots, almonds), etc.          You should also focus on meat products, especially on poultry meat. Although these products do not have a big sensitizing activity, however, antibiotics are included in the diet of birds before slaughtering, and they can cause allergic diseases associated not with food, but with drug allergies. As for flour, more often flour becomes an allergen by inhalation, and not by ingestion through the mouth.

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Allergens of house dust. These allergens are most significant for allergic diseases of the respiratory system, in particular, bronchial asthma. The main allergens of household dust are the chitinous cover and the products of the livelihood of Dermatophagoides pteronyssimus and Derm. Farinae. These pincers are widely distributed in beds, carpets, upholstered furniture, especially in old houses and old bedding.        The second most important allergens of home dust are allergens of molds (more often Aspergillus, Alternaria, Penicillium, Candida). These allergens are most often associated with raw unventilated rooms and the warm season (April-November); they are also part of the allergen of library dust.        The third most important in this group are allergens of domestic animals, and the most sensitizing ability is possessed by cat allergens (dandruff, wool, saliva).

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Allergens- foreign substances, which, entering the body, become the main cause of allergic reactions

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Vegetative allergens. They are primarily related to the pollen, and the main place belongs to pollen, and pollen ragweed, wormwood, swans, hemp, timothy, rye, plantain, birch, alder, poplar, hazel are the most common etiologic factor of pollinosis.        According to the data of M. Ya. Studenikin and I. I. Balabolkin (1998), the common antigenic properties (cross-allergy) are pollen of cereals, mallow, polynia, ambrosia, sunflower; pollen of birch, alder, hazel, poplar, aspen. These authors also note the antigenic relationship between the pollen of birch, cereals and apples.

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Since medications are usually relatively simple chemical compounds, they act as haptenes, connecting with the body's proteins to complete antigen. In this regard, the allergenicity of medicinal substances depends on a number of conditions:        1) the ability of a drug or its metabolites to be conjugated to a protein,        2) the formation of a strong bond (conjugate) with the protein, resulting in the formation of a complete antigen.         It is this circumstance that determines a fairly frequent cross-sensitization of drugs.         L.V. Luss (1999) cites such data: penicillin cross-reacts with all penicillin series preparations, cephalosporins, sultamycillin, sodium nucleate, enzyme preparations, a number of food products (mushrooms, yeast and products on yeast basis, kefir, kvass, champagne ); sulfanilamides cross react with novocaine, ultracaine, anesthesin, antidiabetic agents (diabeton), triampur, paraaminobenzoic acid; Analgin cross-reacts with non-steroidal anti-inflammatory drugs, acetylsalicylic acid derivatives and

salicylates, food products containing tartrazine, etc.

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In this connection, another circumstance is important.      Simultaneous administration of two or more drugs can affect the metabolism of each of them, violating it.      The violation of the metabolism of drugs that do not have sensitizing properties can cause allergic reactions to them.      L. Yeager (1990) cited this observation: the use of antihistamines in some patients caused an allergic reaction in the form of agranulocytosis.

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It is important to give clinical guidelines that allow differential diagnosis of drug allergy and pseudoallergia.       Pseudoallergia often occurs in women after 40 years on the background of diseases that disrupt the metabolism of histamine or the sensitivity of receptors to BAS (pathology of the liver and biliary tract, gastrointestinal tract, neuroendocrine system). The background for the development of pseudoallergies are also polypharmacy, oral administration of drugs for ulcerative, erosive, hemorrhagic processes in the mucosa of the gastrointestinal tract; dose of the drug is not appropriate for the age or weight of the patient, inadequate therapy for the current disease, changes in the pH of the medium and the temperature of solutions administered parenterally, simultaneous administration of incompatible drugs (L.V. Luss, 1999).

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Typical clinical signs of pseudoallergia are: the development of the effect after the initial administration of the drug, the dependence of the severity of clinical manifestations on the dose and mode of administration, the frequent absence of clinical manifestations with repeated administration of the same drug, the absence of eosinophilia.

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Previously, bacterial allergy was associated with delayed type hypersensitivity, since high allergic activity of nucleoprotein fractions of the microbial cell was established.        However, back in the 1940s Swineford O. and Holman J. J. (1949) showed that polysaccharide fractions of microbes can cause typical IgE-dependent allergic reactions. Thus, bacterial allergy is characterized by a combination of delayed and immediate reactions and this served as the basis for including specific immunotherapy (SIT) in the treatment of allergic diseases of the bacterial nature.        At present, "neisserial" bronchial asthma, "staphylococcal" infectious-allergic rhinitis, etc. are singled out. A practical doctor should know that it is not enough to establish the infectious-allergic nature of the disease (for example, bronchial asthma), it is also necessary to decipher what kind of conditionally pathogenic flora determines allergization. Only then, applying in the complex treatment of SIT of this allergovaccine, you can get a good therapeutic effect.

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Complaints typical of allergic diseases appear either in a completely healthy person, or, if the patient, then can not be explained by the peculiarities of his pathology. Common manifestations: chills, fever, agitation, weakness, dizziness, migraine-like syndrome, pallor of the skin, lowering of arterial pressure, itching, burning, sneezing, enlarged lymph nodes. Local manifestations. Most often they are manifested by complaints from the skin, gastrointestinal tract, mucous nasopharynx, bronchial tree, mouth and joints. Skin manifestation: redness and dryness of the cheeks, itching, burning, photosensitivity, sensitivity to cold, skin rashes (erythema, papules, blisters, maculopapular rashes, maculopapular eruptions, coripiform, scarlet-like, etc.). All skin rashes are often accompanied by itching and burning, however, not necessarily. Typically, this resembles a nettle burn.

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Gastrointestinal tract: flatulence, pain and burning in the abdomen, unstable or frequent loose stools, constipation, nausea, vomiting, stomach or intestinal colic, reactive pancreatitis. Eye symptomatology: foreign body sensation in the eye, itching, burning, lacrimation, eyelid puffiness, eyelid dermatitis, blepharitis, conjunctivitis, keratitis, uveitis, scleritis, etc.       Symptomatology from the mucous nasopharynx, bronchial tree and oral cavity: sore throat, itching, burning, sneezing, coughing or dry cough, copious watery, often foamy discharge from the nose, swelling of the nasal mucosa, nasopharynx, nasopharyngeal gland; difficulty breathing, bronchospasm, geographical language (a reliable sign of an allergic disease).       Pain in the joints and muscles is quite an alarming symptom, since they testify to the systemic nature of allergic diseases. Quite often these complaints are encountered with drug and food allergies.

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In the clinical picture of HIT, two phases are distinguished: early and late.      The early phase is clinically manifested in a few minutes (up to 30 minutes) after contact with the allergen and also quickly stops (not more than an hour). At the heart of this phase, the above-mentioned SNT mechanisms associated with the release of BAS and the development of pathophysiological disorders (vasodilation, increased permeability, edema, mucus hyperplasia, smooth muscle spasm), which are clinically manifested by erythema, intestinal colic, bronchospasm, edema, blisters, mucous segregated, itching, burning, etc.

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In the clinical picture of HIT, two phases are distinguished: early and late.               The late phase begins in 2-6 hours and lasts 1-2 days. At the heart of this phase, the so-called "allergic inflammation," where the main actors are neutrophils and eosinophils, infiltrating the lesion, releasing proteolytic enzymes (extracellular cytolysis) under the influence of which the kinins are formed, the complement system is activated to form anaphylotoxins, the blood coagulation system is activated , its aggregate state (microthrombi) is disturbed. Production of activated mast cells and leukocyte-migrant cytokines (IL-1, IL-6, TNF, chemokines, GM-CSF) promotes leukocyte infiltration and maintenance of inflammation (A.A .Yarilin, 1999).

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Conditionally allergic diseases can be divided into systemic and local.       The main place of localization of mast cells - serous membranes, spleen, epithelium and submucosal layers of the gastrointestinal, respiratory and urogenital tracts; skin, connective tissue of capillary couplings. If the clinical symptomatology of an allergic disease comes from several places of mast cell localization, then one speaks of a systemic allergic disease. Clinically, this manifests itself in various combinations of the nasopharynx, skin, gastrointestinal tract, etc. With local allergic diseases, clinical symptoms only occur from individual loci of fixation of mast cells (rhinitis, conjunctivitis, urticaria, gastritis, etc.).       The only exception is the clinical symptomatology, which comes from the location of mast cells in the connective tissue of capillary couplings. It is always a systemic allergic disease, because it is based on vasculitis, which manifests itself in maximum expression with anaphylactic shock.

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Frequent objective signs of allergic diseases are eyelid hyperemia and edema of their skin, edema and congestion hyperemia, eyeballs.Almost mandatory objective signs of allergic diseases are swelling and swelling of mucous membranes; and also serous or foamy discharge (more often from the nose). Changes in mucous membranes with allergic diseases are typical: the mucous membranes are swollen with a marble shade, often cyanotic, edema of the posterior arch, tongue, posterior pharyngeal wall with multiple clusters of lymphoid tissue. For mucous membranes of the lower and middle nasal conchas, the presence of white spots (spots Voyachek). It is important to remember that in the first year of life there can not be hypertrophy of adenoids - their increase in this period is a consequence of edema accompanying allergic diseases. Once again, attention should be paid to the "geographical" language - a reliable sign of allergic diseases.

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Objective signs on the part of the broncho-pulmonary system: more often dry, sometimes small- and medium-bubbling rales, an easy boxed tint of percussion sound.With palpation of the abdominal cavity tend to be soreness in the upper half of the abdomen, spasms of the jejunum, as gastrointestinal variants of allergy are more often manifested by jejunitis, duodenitis, gastritis, bulbitis, esophagitis. Reduced blood pressure, tachycardia, elevated body temperature are also frequent objective manifestations of allergic diseases.It should be emphasized again that these clinical signs are important in the diagnosis of allergic diseases only when they appear in healthy individuals or when these clinical signs can not be explained by the patient's existing disease.

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There are three directions in the diagnosis of allergic diseases:- nosological diagnosis, or clinical identification of an allergic disease;- pathogenetic diagnosis, or determination of the characteristics of DIT or HIT;- etiological diagnosis, or determination of the causative factor of DIT or HIT.

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At present, the problem of isolating at-risk groups of allergic diseases has not received its worthy development and the clinical guidelines for identifying at-risk groups are rather meager:-- genealogical anamnesis;-- family history;-- neonatal pathology.

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Prognostic role of IgE level in children and adults (according to Humburger).Age Level of

IgE

in

IU

/

l

Probability of allergic diseases in %.

Up to 2 weeks

<0.5

12

>0.5

45

Up to 3 years

6

5

6-15

20

16-60

35

>60

~100

Children and adults

60

8

61-210

22

211-450

36

>450

~100

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Differential diagnosis of DIT and HIT based on a comprehensive assessment of immunological tests. Immunological testsDIT

HIT

Number of

eosinophils

+

Number of

basophils

+

Number of

monocytes

+

CD4

+-

+

CD8

-

CD20

+

+-

CD23

+

IgA

-

IgE

+

IgG

-

IgG4

-

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Differential diagnosis of DIT and HIT based on a comprehensive assessment of immunological tests(continuation) Immunological tests

DIT

HIT

IL

-2

+

IL

-4

+

IL

-5

+

+

IL

-12

+

IF

-

gamma

+

FNT-alpha

+

FNT-beta

+

+ increase in the indicator; - decrease in the indicator

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In 1952, Parrot and Urquia revealed the ability of healthy people's blood serum to bind free histamine and called this property histamine-pexy.They proposed a method for quantitatively taking into account this phenomenon, which they called a histaminopex index (HPI), and it was found that a decrease in HPI below 30% indicates an allergic condition. Later, their data were confirmed by numerous researchers and HPI became widely used in the diagnosis of allergic diseases.

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In 1961, Mikol, Renoux, Merklen discovered an antihistamine factor (AHF), which reflected another side of the binding of blood serum histamine, because the histamine-serum ability of the serum was lost upon heating for two hours at a temperature of 56 ° C; while the ability of the blood serum to agglutinate the histamine-laden particles of latex, which is the basis of the determination of the AHF, was completely preserved.The titer of the AHF below 1/160 was characteristic for allergic diseases.

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At the basis of etiological diagnostics is an attempt with paraclinical tests to establish a specific antigen causally significant for the development of this particular allergic disease.       All paraclinical tests used for these purposes can be divided into two large groups:-- Diagnostic tests in vivo;-- Diagnostic tests in vitro.

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Diagnostic tests in vivo.These include skin tests and provocative tests, which are conducted directly in the patient.Skin tests are divided into cutaneous (application, compress, drip, etc.), scarification tests, prick tests, modified prick test, intradermal tests.General conditions for carrying out all in vivo diagnostic tests - they should be conducted by professionals in specially equipped offices that allow for the provision of emergency care.

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Diagnostic tests in vivo.Skin tests are performed only during the remission of allergic disease; they are contraindicated in the acute period of any other (non-allergic) disease, during pregnancy, breast-feeding, in the first 2-3 days of the menstrual cycle; in the absence of a convincing anamnesis and preliminary examination, indicating the presence of an allergic disease.

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Provocative tests.They are used to confirm the causative significance of the allergen in cases of discrepancy in the history and skin tests.Categorically it is contraindicated to conduct provocative tests for non-specialists and in the absence of the possibility of providing emergency medical assistance, especially with inhalation provocations.Most often, the following variants of provocative samples are used: conjunctival, nasal, inhalation, oral. The indicator of a positive sample is an exacerbation of the symptoms of the corresponding allergic disease.

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The opposite provocative is a test with the exception of the alleged allergen established on the basis of an allergic medical history.This test should be carried out by every doctor, as reducing the clinical manifestations of an allergic disease when excluding the putative allergen not only confirms its etiological role in this disease, but also serves as a prognosis for the effectiveness of treatment.

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Diagnostic tests in vitro.From our point of view, these are the most effective and safe tests of etiologic diagnosis of allergic diseases, which in the future should replace in vivo tests except for the sample with the exception of the supposed allergen.The most widespread among these tests was a radioallergo-adsorbent test (RAAT). RAAT allows to measure the level of antibodies specific for allergens. The essence of the method is that if allergen-specific IgE antibodies are present in the blood, they bind to the corresponding allergens fixed on an inert matrix.

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Diagnostic tests in vitro.After the addition of radioactive anti-IgE antibodies, they bind to the formed allergen-IgE antibody complexes and allowance for radioactivity gives the level of allergen-specific IgE antibodies. RAAT allows to carry out allergodiagnosis in the acute stage of the disease; the test results are not affected by pharmaceuticals and other factors; there is a good correlation of the test with the severity of the disease.The main disadvantage of RAAT is its rather high cost. However, the appearance of various modifications of RAST (enzyme

allergoadsorbent test, fluorescent allergoadsorbent

test, combined allergic adsorbent test,

immunoperoxidase

system, etc.) allows us to hope for overcoming this shortcoming.

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Diagnostic tests in vitro.The Shelley test or an indirect basophil degranulation test was also widely used. The reaction is based on the basophilic binding of animals to Fc-fragments of IgE antibodies upon the addition of blood serum to patients with allergic diseases. After the addition of allergens specific for these IgE antibodies, the

basophils sensitized in this manner and the release of BAS are degranulated

. The reaction indicator is the percentage of

degranulated

basophils

.

In addition to these most common methods, passive

hemagglutination

(PHGA), precipitation, indirect

basophil

degranulation

test,

immunoblotting

method, allergen neutralizing serum activity, allergen-specific granulocyte damage response, etc. are used.

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SCHEME OF DEVELOPMENT OF ALLERGIC REACTION OF IMMEDIATE TYPE43

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CLASSIFICATION OF ANTI-ALLERGIC DRUGS The drugs used to suppress hyperimmune reactions of immediate type:1. Glucocorticoid preparations2. Stabilizers of membranes of mast cells (kromolin-sodium, ketotifen)3. Antihistamines (blockers of H1-histamine receptors):  - H1-antagonists of the 1st generation, which have a noticeable sedative effect; - H1-antagonists of the 2-nd generation, not giving a sedative effect in the recommended therapeutic dose, however, with an increase in the dose showing a sedative effect; - H1-antagonists of the 3-rd generation, not causing signs of sedation and when the therapeutic dose is exceeded.4. Leukotriene receptor antagonists (zafirlukast, montelukast), inhibitors of leukotriene synthesis (zileuton)5. Functional antagonists of mediators of allergy: adrenomimetics, m-cholinoblokars, antispasmodics.

44

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Means used to suppress hyperimmune states of delayed type.Cytotoxic agentsCyclosporinGlucocorticoidsImmunoglobulins antimitocyteNSAIDs45

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HISTAMINEis the main pathophysiological agent in the development of an allergic reaction of immediate type MAIN EFFECTS OF HYSTAMINE:An increase in the tonicity of smooth muscles of the bronchi, uterus, intestine;Spasm of large arteries and dilatation of capillaries (decrease of blood pressure);Increased vascular permeability;Increased gastric secretion;Stimulation of adrenal secretion of epinephrine and glucocorticoids.46

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Allergic reaction, accompanied by the development of nasal symptomsAllergic reaction developing in the respiratory tractEXAMPLES OF DEVELOPMENT OF AN ALLERGIC REACTIONS OF IMMEDIATE TYPE47

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10CLASSIFICATION OF ANTIHISTAMINE PREPARATIONS (H1-BLOCKERS)1 generation

2

generation

3

generation

Suprastin

(

chloropyramine

)

Dimedrol

(

diphenhydramine

)

Diazolin

(

mebhydroline

)

Tavegil

(

Clemastin

)

Pipolphen

(

diprazine

)

Claritin (

loratadine

)

Zirtek

(

cetirizine

)

Kestin

(

ebastin

)

Histalong

(

astemizole

)

Semprex

(

acrescine

)

Telfast

(

fexofenadine

)

Erius

(

desloratadine

)

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Mechanism of actionClassical H1-antagonists are competitive blockers of H1-receptors, so their binding to the receptor is reversible. To achieve the main pharmacological effect, it is necessary to use relatively high doses of such drugs, while undesirable side effects of classical H1-antihistamines are more easily and more often manifested.In addition, most of these drugs have a short-term effect, which means that they must be taken 3-4 times a day.Antihistamines of the second generation bind to H1-receptors uncompetitively. Such compounds can hardly be displaced from the receptor, and the ligand-receptor complex formed dissociates relatively slowly, which explains the longer action of these drugs.49

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The main side effects of antihistamine drugs of 1 st generation:- blockade of receptors of other mediators (for example, M-holinoretseptorov, which manifests itself in the form of dryness of the oral mucosa, nose, throat, bronchi, rarely - urination and blurred vision);- local anesthetic action;- Quinidine-like action on the heart muscle;- analgesic effect and enhancing action in relation to analgesics;- antiemetic action;- the effect on the central nervous system (sedation, impaired coordination, dizziness, lethargy, decreased ability to concentrate attention);- increased appetite;- Disorders from the digestive side (nausea, vomiting, diarrhea, loss of appetite, unpleasant sensations in epigastrium);- Tachyphylaxis (reduction of therapeutic effect with prolonged use).50

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Advantages of AHD of 2nd generation:very high specificity and high affinity for H1-receptors;fast start of action;sufficient duration of the main effect (up to 24 hours);absence of blockade of other types of receptors;Do not pass through the blood-brain barrier in therapeutic doses;Absence of dependence of absorption on food intake;absence of tachyphylaxis.51

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The main side effects of AHD of 2 nd generationIn therapeutic doses, these drugs have a good safety profile. However, when metabolism of these drugs is slowed down by liver enzymes (CYP3A4 of the cytochrome P450 system), unmetabolized initial forms accumulate, which leads to cardiac disturbance. This complication can occur in patients with impaired liver function, with the simultaneous use of macrolides, antifungal imidazole derivatives, other medications and food components that inhibit the oxygenase activity of the CYP3A4 cytochrome P450 system.This side effect is characteristic of terfenadine, astemizole and loratadine. Due to cardiotoxic effect in a number of countries, including Russia, astemizole and terfenadine are withdrawn from sale.The effects on the CNS of this group are extremely weak. Sedation is rare and only in individuals with high individual sensitivity to the medication.52

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Antihistamines of the 3rd generationIn therapeutic doses, drugs of the third generation cause sedative effect extremely rarely, it is not so pronounced as to cause the drug to be discontinued; apparently, only in patients with unusually high individual sensitivity does this side effect occur.Clinical trials of fexofenadine (Telfast) have shown that, in contrast to other third-generation AHD, fexofenadine has a true non-sedation: even two- and three-fold excess of the average therapeutic dose of the drug did not cause sedation.53

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CETIRYZINEin pharmacologically active doses, does not have a significant sedative effect, has an antiallergic effect and is devoid of any appreciable anticholinergic and antiserotonin action. Does not penetrate the blood-brain barrier.INDICATIONSTreatment of seasonal and chronic allergic rhinitis, allergic conjunctivitis, itching, chronic idiopathic urticaria and Quincke edema.METHOD OF ADMINISTRATION AND DOSESChildren from 2 to 6 years: 5 mg per day (10 drops) once or 5 drops in the morning and evening.Children from 6 to 12 years: 10 mg per day (1 tablet or 20 drops per day) once, or 1/2 tablet 2 times a day in the morning and in the evening.Adults and children 12 years and older: 10 mg per day (1 tablet or 20 drops) once.At present, there is no evidence of the need to reduce the dose in elderly patients with normal renal function. Patients suffering from kidney failure, the dose of the drug should be reduced by half.CONTRAINDICATIONSis contraindicated for persons with anamnestic data on the presence of a hypersensitivity reaction to any of the components of the dosage form.54

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SIDE EFFECT There are isolated reports of mild and rapid reactions in the form of headache, dizziness, drowsiness, dry mouth, agitation, gastrointestinal disorders.Hypersensitivity reactions in the form of skin reaction and vascular edema are extremely rare.A WARNINGAlthough the drug does not potentiate the effects of alcohol in therapeutic doses (at a blood plasma concentration of 0.8 g / l), nevertheless, caution should be exercised when taking them together.INTERACTIONUntil now, no information on possible interactions with other drugs has been obtained. According to the studies, neither diazepam nor cimetidine interacted with cetirizine. As with other antihistamines, it is recommended that you avoid alcohol abuse.55

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LORATADINEantihistamine long-acting drug that does not cause sedation Indications for usefor the elimination of seasonal and allergic rhinitis symptoms (such as sneezing, itching and rhinorrhea), allergic conjunctivitis;for the removal of symptoms of acute and chronic urticaria, Quincke's edema, other skin diseases of an allergic nature, allergic reactions to bites and stinging insects.It is used in the complex treatment of itching dermatoses (contact allergic dermatitis, chronic eczema, etc.). 56

Slide57

MODE OF APPLICATIONAdults and children weighing 30 kg or more: 1 tablet (10 mg) or 2 teaspoons (10 ml) of syrup once a day. Children 2 years and older with a weight of less than 30 kg: 1/2 tablet (5 mg) or 1 teaspoon (5 ml) syrup once a day.57

Slide58

Interaction with other drugsIn the study of the psychomotor function after joint intake of loratadine and alcohol, no potentiating effect on the effect of alcohol was revealed. An increase in loratadine concentrations in the plasma was observed when combined with ketoconazole, erythromycin and cimetidine, but without any clinical changes, including electrocardiogram.58

Slide59

Side effectThe incidence of adverse events with loratadine is the same as with placebo.These phenomena include: dry mouth, disorders of the gastrointestinal tract.In the conduct of controlled clinical trials in children, the above-mentioned side effects associated with treatment were as rare as with placebo.Contraindications: loratadine contraindicated if hypersensitivity to any of the components.59

Slide60

DesloratadineDesloratadine is the primary active metabolite of loratadine.10-20 times more active loratadine MECHANISM OF ACTIONAntiallergic activity due to stabilization of mast cells and basophilsAntihistamine effect due to a powerful blockade of H1-receptorsAnti-inflammatory activity by suppressing the release of pro-inflammatory cytokines and chemokines, migration and accumulation of eosinophils60

Slide61

INDICATIONS FOR USEUsed to quickly stop the symptoms of seasonal allergic rhinitis, such as sneezing, nasal discharge, itching and nasal congestion, itching and redness of the eyes, lacrimation, itching of the palate.Applied with chronic idiopathic urticaria for reducing and eliminating itching and rash61

Slide62

DOSAGE AND METHOD OF APPLICATIONAdults and adolescents from 12 years: one tablet of 5 mg per day, regardless of food intake. The drug is intended for oral administration. The tablet should be swallowed whole, not liquid, and washed down with water.INTERACTIONIn clinical studies, no signs of significant interaction between desloratadine and ketoconazole and erythromycin have been identified. Desloratadine did not increase the suppressive effect of alcohol on the psychomotor function.62

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Side effect Undesirable effects were compared in 659 patients who received desloratadine 5 mg and 661 patients who received a placebo. In clinical studies, the nature and frequency of adverse effects with desloratadine were generally comparable to those of placebo.In controlled and uncontrolled clinical trials desloratadine did not cause clinically significant adverse reactions, including those from the cardiovascular system. When administered at a recommended dose of 5 mg / day, the incidence of adverse events was 4% higher than in the placebo group. There was no increase in the frequency of drowsiness. Headache was observed in 2% of patients. Dry mouth and fatigue were rare.63

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FEXOFENADINE (TELFAST)Active metabolite of terfenadine ADVANTAGESthe last generation of antihistamines is characterized by rapid removal of allergic reactions;does not cause drowsiness, there is no need to change the dose in the elderly;there is no interaction with other medications, there is no addiction, its absorption is not reduced when taken with food, it is excreted from the body in an unchanged form.64

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Indications for use - seasonal allergic rhinitis, - chronic ideopathic urticaria.Method of administration and dose: is used in adults and children over 12 years - with seasonal allergic rhinitis - 120 mg once a day; - in chronic idiopathic urticaria - 180 mg once a day.Side effects (headache, drowsiness, nausea, dizziness) occur no more often than when taking a placebo.65

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GLUCOCORTICOIDSPreparations of glucocorticoids have antiallergic effect by affecting almost all stages of allergy developmentThe mechanism of their antiallergic effect is as follows:     - First, they have pronounced immunosuppressive properties, that is, they suppress the development of immune cells (lymphocytes, plasmocytes) and reduce the production of antibodies.     - Secondly, glucocorticoids prevent the degranulation (destruction) of mast cells and the isolation of allergic mediators from them.    - Thirdly, these drugs have an effect opposite to the effects of mediators of allergy (for example, reduce vascular permeability, increase blood pressure, etc.).66

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In this regard, glucocorticoids are highly effective in allergic disorders.However, the expressed side effect of glucocorticoids limits the area of ​​their use as antiallergic agents.Preparations of glucocorticoids are used mainly for severe (anaphylactic shock) and moderate severity (Quincke's edema, serum sickness) allergic reactions, as well as for severe progressive allergic and autoimmune diseases (bronchial asthma, collagenoses, etc.).In dermatological practice, preparations of glucocorticoids are relatively often applied topically with various allergic skin lesions (itching, eczema, dermatitis, etc.).67

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STABILIZERS OF MAST CELL MEMBRANES MAST CELL STABILIZERS-- Limit the release of contents from the granules of mast cells, thereby inhibiting the development of the pathophysiological stage of allergy-- Prevent the occurrence of allergic reactions of immediate and delayed type.68

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ANAPHYLACTIC SHOCK - an allergic reaction of an immediate type that occurs when the allergen is reintroduced into the body. It is characterized by rapidly developing predominantly common manifestations: a decrease in blood pressure and body temperature, a disruption of the function of CNS, an increase in vascular permeability, and spasm of smooth muscle of organs. - Anaphylactic shock can develop with the introduction of drugs into the body, the use of specific diagnostic methods and hyposensitization, as a manifestation of insect and very rarely food allergies.69

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CLINICThe first symptoms of a beginning anaphylactic shock are anxiety, a sense of fear, a throbbing headache, dizziness, noise in the ears, cold sweat.In some cases, a precursor of anaphylactic shock can be a pronounced pruritus with a subsequent rapid appearance of urticaria and Quincke edema.Often there are shortness of breath, a feeling of tightness in the chest, coughing (a consequence of bronchospasm or allergic edema of the larynx), as well as symptoms of impaired gastrointestinal function in the form of paroxysmal pains in the abdomen, nausea, vomiting, diarrhea.Possible mydriasis, foam from the mouth, cramps, involuntary defecation and urination, spotting from the vagina.70

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Urgent care:- stop and block the intake of the allergen into the body: cut off the injection or bite site of 0.3-0.5 ml of 0.1% solution of epinephrine in 3-5 ml of 0.9% sodium chloride solution;- When breathing is stopped or if it is inadequate, artificial ventilation is performed, conical tracheostomy is performed, oxygen supply is adjusted; - in the absence of pulsation on major trunk vessels (carotid or femoral), external cardiac massage is performed, they prepare everything necessary for defibrillation;- remove the electrocardiogram;- Introduce intravenously 0.3-1 ml of adrenaline solution in 10 ml of 0.9% sodium chloride solution. If necessary, the dose of adrenaline is repeated after 3-5 minutes. If i.v. fails, you can use the endotracheal tube, as well as inject adrenaline into the heart or root of the tongue;- with insufficient or short-term effect of adrenaline go to the drip introduction of the drug at a rate of 0.1 mg/ kg / minute.71

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At the same time, adjust the infusion therapy in 1-2 veins, especially for patients with typical and hemodynamic variants of anaphylactic shock:1. colloidal solutions (polyglucin, reopolyglucin) for the first ten minutes 50-200 ml, and then under the control of blood pressure, heart rate, black hole.2. Hypertensive 7.5% sodium chloride solution with or without the addition of colloids in a volume of 2-4 ml / kg body weight.3. Crystalloid solutions (0,9% sodium chloride solution, chlosol, disol, glucose solutions) for the first ten minutes 100-200 ml, and then under the control of blood pressure, heart rate, black hole. The anti-shock efficacy is lower than with the use of colloidal solutions.72

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intravenously injected glucocorticoid drugs: prednisolone 3-10 mg / kg body weight, 8-40 mg dexametasone or hydrocortisone 5-15 mg / kg body weight;an intravenous combination of H1 and H2 receptor blockers is administered: -- 1. blockers of H1 receptors: diprasine (pipolphen) 2.5% -2-4 ml, dimedrol 1%, tavegil 0.1% or suprastin solution 2.5% 2-4 ml (suprastin can not be administered for allergies to euphyllin). -- 2. blockers of H2 receptors: cimetidine 10% or cinamete of 2-4 ml.73

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SYMTOMATIC THERAPYwith bronchospasm, which is not stopped by epinephrine, against the background of stable hemodynamics intravenous eufyllin 2.4% is administered at a dose of 5-6 mg / kg of body weight for 20 minutes, after which they switch to a maintenance dose of 1 mg / hour;- with convulsions and excitation intravenously administered seduxen 0,5% -2-6 ml or other benzodiazepines;- with anaphylactic shock caused by penicillin, administer 1 000 000 penicillinase intramuscularly in 2 ml of 0.9% sodium chloride solution.74

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Classification of immunity-enhancing agentsDrugs of nonspecific active stimulating immunotherapy:a) lipopolysaccharides and autolysates of bacteria: prodigiosan; pyrogenal; ribomunyl;b) synthetic substances: thymogen; levamisole; sodium nucleate, pentoxyl, methyluracil;c) vegetable origin: immunal (purple Echinacea juice); echinacea drops;Drugs of adaptive stimulating nonspecific immunotherapy:     preparations of lymphoid tissue (thymus, bone marrow, spleen): thymalin; splenin.Drugs of substitution immunotherapy, compensating the lack of factors of the immunity system: normal human immunoglobulin (intraglobin, octagam, pentaglobin); roncoleukin (recombinant yeast human interleukin-2).

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Mechanism of actionLipopolysaccharides and autolysates of bacteria (prodigiosan, pyrogenal, etc.) cause a hyperergic reaction of the organism, stimulating immunogenesis by activating macrophages and enhancing the formation of interferons. When topical application of the postisan increases the resistance of tissues to the effects of pathogenic microflora76

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LEVAMIZOLincreases the number of T-lymphocytes, their blastogenesis and activity (selectively), increases the activity of phagocytes, stimulates the production of interferons.It is believed that levamisole is able to strengthen the weakened response of cellular immunity, cause oppression to be excessively strong and not to affect the normal.77

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Interferon preparations and interferonogens (stimulants of interferon production) as immunomodulating and immunostimulating agents were included in the arsenal of antiviral and anti-blast drugs.78

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Medicines of adaptive stimulating nonspecific immunotherapyThe mechanism of action consists in the perception by immunocompetent cells of nonspecific stimulating signals from hormones and other factors of the immunity system introduced from the outside.Such effects are characteristic of the hormones of the thymus, bone marrow, spleen.Preparations from them regulate the amount, proliferation, migration and cooperation of T and B lymphocytes, stimulate the reactions of cellular and humoral immunity, increase the production of lymphokines, including interferon, enhance phagocytosis.79

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Indications: Immunostimulants use:  with prolonged infectious and infectious-inflammatory diseases;sluggish regenerative processes (chronic purulent and purulent-necrotic conditions, burn disease, trophic ulcers, severe trauma);after chemotherapy or radiotherapy in cancer patients, lymphoproliferative diseases (lympho-neukemia, lymphogranulomatosis), multiple sclerosis, psoriasis.80

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Some drugs (typical immunomodulators) are more widely used in auto-allergic (autoimmune) diseases (levamisole, subreum - with rheumatoid arthritis) or even exogenous allergies (pyrogenal - in bronchial asthma, urticaria).Preparations of this group are contraindicated in pregnancy81