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In the XX century. side effects of drugs and drug disease continue to be the most pressing medical and social problems.

According to the WHO, drug side effects are currently ranked 5th in the world after cardiovascular, oncological, lung diseases and injuries.

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Causes of drug disease

The reason for the annual steady increase in cases of drug side effects and drug disease is:

• violation of the ecology of the environment;
• the presence in food of pesticides, preservatives, antibiotics and hormonal agents;
• the duration of the course of treatment with drugs (PM) for many diseases;
• polypharmacy (against the background of stress, urbanization, chemicalization of industry, agriculture and everyday life);
• self-treatment;
• the irresponsibility of state policy in the sale of medicines (without prescriptions);
• pharmacological boom (growth in the production of branded drugs, generics, dietary supplements).

The pharmaceutical boom is evidenced by the use of more than 7,000 drugs in 15,000 dosage forms in the pharmaceutical market of Ukraine, produced in 76 countries of the world. These data are confirmed by the volume of pharmacy sales of drugs of domestic and foreign production in monetary terms, in kind and in dollar terms.

Of all manifestations of side effects of drugs, according to the Ukrainian Center for the Study of DPLS, 73% are allergic reactions, 21% are side effects associated with the pharmacological action of drugs, and 6% are other manifestations. In dermatovenereology, among the most frequently recorded manifestations of side effects of drugs, the following are noted:

• true allergic reactions (drug and serum sickness) - 1-30%;
• toxic allergic reactions - 19%;
• pseudo-allergic reactions - 50-84%;
• pharmacophobia - no data.

Despite the existence of problems of side effects of drugs and drug disease, there is still a lot of unresolved and debatable in them: the lack of official statistics, the lack of a unified view of their terminology and classification, the lack of correspondence between the domestic terminology of true allergic reactions to drugs and the ICD-10 terminology. revision, issues of diagnosing side effects of drugs and drug disease, and in particular, the advisability of skin tests with drugs before surgery and starting antibiotic therapy, issues of drug disease therapy.

At present, official statistics are only the tip of the iceberg, since they are practically not kept.

There is no generally accepted classification of side effects of drugs. The main approaches (etiological and clinical-descriptive), which were previously used in the preparation of classifications, were not applicable in this case, since it is known that the same drug can cause a different clinical picture and vice versa. Therefore, the basis of the current classifications of side effects of drugs is most often put on the pathogenetic principle. Modern ideas are most consistent with the classification, which distinguishes:

• pharmacological side effect;
• toxic side effect;
• side effect due to a violation of the immune system;
• pseudo-allergic reactions to drugs;
• carcinogenic effect;
• mutagenic action;
• teratogenic effect;
• side effects due to massive bacteriolysis or changes in the ecology of microbes (Yarish-Herxheimer reaction, candidomycosis, dysbacteriosis);
• drug dependence (drug addiction and substance abuse, tolerance, withdrawal syndrome, psychogenic reactions and psychophobia).

In clinical practice, of all types of side effects of pharmacotherapy, reactions caused by a violation of the body's immune system, the so-called true allergic reactions, are most widely used. However, the question of their terminology is still debatable. If E. A. Arkin (1901), E. M. Tareev (1955), E. Ya. Severova (1968), G. Mazhdrakov, P. Pophristov (1973), N. M. Gracheva (1978) manifestations of true allergic reactions to medications were called "drug disease", regarding it as an analogue of "serum sickness", then other researchers - drug allergy, toxidermia. Meanwhile, according to many years of clinical observations and experimental studies conducted by our institute, there is reason to consider true allergic reactions to drugs not as a symptom or syndrome, but as an independent multifactorial disease - as a second disease that develops against the background of any pathological process and repeated use average therapeutic doses of drugs, due not so much to the pharmacological characteristics of the drug, but to the characteristics of the patient's immune system and his constitutional and genetic predisposition. The results of the conducted studies indicate that with the development of a drug disease, all body systems are involved in the pathological process, despite the fact that clinically the disease can occur with a predominant lesion of one of them, most often the skin. That is why drug disease, along with clinicians of all specialties, is of particular interest primarily to dermatologists.

The development of a drug disease is based on immunological mechanisms that are fully consistent with the patterns of any other allergic reactions to an antigen. Therefore, in the course of a drug disease, as in the course of any allergic process, three stages are distinguished: immunological, pathochemical and pathophysiological (or the stage of clinical manifestations). The features of the drug disease are manifested only in the immunological stage and consist in the fact that at this stage the drug from the hapten turns into a full-fledged antigen, against which p-lymphocytes begin to produce antibodies and sensitized lymphocytes in large quantities. The more antigen enters the body, the higher the concentration of antibodies and sensitized lymphocytes becomes. Morphologically and functionally, sensitized cells do not differ from normal ones, and a sensitized person is practically healthy until the allergen enters his body again and antigen-antibody reactions occur, accompanied by a massive release of mediators and pathophysiological disorders.

The development of an allergic process in a drug disease, as a rule, proceeds according to four types of allergic reactions. At the same time, IgE-dependent degranulation is initiated only by specific allergens, which already in the body bind to IgE molecules fixed on the surface of basophils and mast cells due to a special high-affinity receptor for the IgE Fc fragment. In turn, the binding of a specific allergen to IgE generates a signal that is transmitted through receptors and includes the biochemical mechanism of activation of both membrane phospholipids with the production of inositol triphosphate and diacylglycerol, and phosphokinase, followed by phosphorylation of various cytoplasmic proteins. These processes change the ratio of cAMP and cGMP and lead to an increase in the content of cytosolic calcium, which promotes the movement of basophil granules to the cell surface. The membranes of the granules and the cell membrane merge, and the contents of the granules are ejected into the extracellular space. In the process of degranulation of peripheral blood basophils and mast cells, which coincides with the pathochemical stage of an allergic reaction, mediators (histamine, bradykinin, serotonin), as well as various cytokines, are released in large quantities. Depending on the localization of antigen-antibody complexes (IgE mast cells or peripheral blood basophils) on a particular shock organ, various clinical manifestations of a drug disease may develop.

Unlike a drug disease, pseudo-allergic reactions do not have an immunological stage, and therefore their pathochemical and pathophysiological stages proceed without the participation of allergic IgE antibodies with excessive release of mediators, which occurs in a non-specific way. Three groups of mechanisms take part in the pathogenesis of this excessive non-specific release of mediators in pseudo-allergy: histamine; violations of the activation of the complement system; metabolic disorders of arachidonic acid. In each case, the leading role is assigned to one of these mechanisms. Despite the differences in the pathogenesis of the drug disease and pseudo-allergic reactions, in the pathochemical stage, both in one and in the other case, the same mediators are released, which causes the same clinical symptoms and makes their differential diagnosis extremely difficult.

In drug disease, in addition to changes in immune homeostasis, neuroendocrine regulation, processes of lipid peroxidation and antioxidant protection are violated. In recent years, the role of the peripheral link of the erythron in the pathogenesis of drug disease has been studied, which made it possible to identify an increase in the heterogeneity of the population of circulating erythrocytes with a predominance of their macroforms, a change in the barrier functions of erythrocyte membranes, a redistribution of potassium-sodium gradients between plasma and erythrocytes, manifested by the loss of excess potassium and increased entry into cells of sodium ions and indicating a violation of the ionotransport function of erythrocytes. At the same time, the dependence of indicators characterizing the physicochemical properties of erythrocytes on the clinical symptoms of a drug disease was revealed. The analysis of these studies indicates that erythrocytes are a sensitive link in the peripheral erythron system in the mechanisms of the development of a drug disease, and therefore their morphometric parameters, as well as the functional state of their membranes, can be included in the algorithm for examining patients. These data were the basis for the development of biophysical methods for the rapid diagnosis of a drug disease, based on measuring the levels of ultrasound absorption by erythrocytes, as well as assessing the erythrocyte sedimentation rate in the presence of putative drug allergens, which compare favorably with traditional immunological tests, as they are more sensitive and allow diagnosis in 20-30 minutes.

In the pathogenesis of drug disease, the role of endogenous intoxication syndrome has been established, as evidenced by the high level of peptides of medium molecules, as well as their chromatographic analysis, the appearance of fraction A with subfractions Al, A2, A3, which are absent in practically healthy people. The structure of the genes that control the mechanisms of the pharmacological reaction and are responsible for the synthesis of immunoglobulins E and the development of sensitization is changing. At the same time, favorable conditions for the development of sensitization occur mainly in individuals with a special phenotype of enzyme systems, for example, with reduced activity of liver acetyltransferase or the enzyme glucose-6-phosphate dehydrogenase of erythrocytes, so now, more than ever, it is extremely important to study the pathogenesis of a drug disease phenotype - external manifestations of the genotype , i.e., a combination of signs in individuals who are prone to developing allergic reactions to drugs.

The variety of immunological types in drug disease is expressed by the polymorphism of clinical manifestations - generalized (multisystemic) lesions (anaphylactic shock and anaphylactoid conditions, serum sickness and serum-like diseases, lymphadenopathy, drug fever)

• with predominant skin lesions:
• often found (like urticaria and Quincke's edema; pink deprivation of Zhiber, eczema, various exanthemas),
• less common (like erythema multiforme exudative; cystic eruptions resembling Dühring's dermatitis; vasculitis; dermatomyositis), rare (Lyell's syndrome; Stevens-Johnson syndrome);
• with a primary lesion of individual organs (lungs, heart, liver, kidneys, gastrointestinal tract);
• with a predominant lesion of the hematopoietic organs (thrombocytopenia, eosinophilia, hemolytic anemia, agranulocytosis);
• with a predominant lesion of the nervous system (encephalomyelitis, peripheral neuritis).

However, there is still no unified view on the clinical classification of a drug disease.

The absence in the ICD-10 of a term that combines the manifestations of true allergic reactions to drugs indicates, firstly, a discrepancy between international and our terminology, and secondly, it actually does not allow statistics to be made and forces us to study the prevalence of side effects of pharmacotherapy mainly by negotiability.

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Diagnosis of drug disease

With a characteristic allergic history and typical clinical manifestations, the diagnosis of a drug disease is not difficult. The diagnosis is confirmed quickly and easily when there is a temporary relationship between medication and the development of an allergic process, the cyclical course of the process and its rather rapid remission after the withdrawal of a poorly tolerated drug. Meanwhile, there are often difficulties in the differential diagnosis of a drug disease and the underlying disease, for which it is often taken as a complication, since the skin symptoms of a drug disease are very similar to the clinic of many true dermatoses, some infectious diseases, as well as toxic and pseudo-allergic reactions.

In view of the foregoing, a phased diagnosis of a drug disease is applied:

• evaluation of data of allergic anamnesis and clinical criteria of drug disease;
• evaluation of the results of clinical and laboratory examination;
• assessment of a specific immunological examination in order to identify the etiological factor of the allergic process;
• differential diagnosis between true and pseudo-allergic reactions to drugs;
• differential diagnosis of drug disease and toxic reactions;
• differential diagnosis of a drug disease and some infectious diseases (measles, scarlet fever, rubella, chicken pox, secondary early fresh and recurrent syphilis);
• differential diagnosis of drug disease and true dermatoses;
• differential diagnosis of drug disease and psychogenic reactions (psychophobia).

Diagnosis of true and pseudo-allergic reactions is based mainly on subjective criteria for their differences (with pseudo-allergy, according to the allergological history, there is no period of sensitization; the duration of pseudo-allergic reactions is short-term; there are no repeated reactions when using chemically similar drugs). Of the objective differential diagnostic criteria, one can rely only on the results of test-tube specific immunological tests, which, as a rule, are negative in case of pseudo-allergic reactions to drugs.

The toxic side effects of drugs are indicated by:

• drug overdose; cumulation of drugs due to impaired elimination due to liver and kidney failure; a statement of fermentopathy, in which there is a slowdown in the metabolism of therapeutic doses of drugs.
• Psychophobia is evidenced by a positive intradermal test with saline.
• Most discussions arise when making an etiological diagnosis of a drug disease.
• As a rule, the etiological diagnosis of a drug disease is carried out using:
• provocative tests (sublingual test, nasal test, skin tests);
• specific immunological and biophysical tests.

Of the provocative tests, sublingual, nasal and conjunctival tests are relatively rarely performed, for which, however, cases of allergic complications have not been described. Traditionally, step-by-step staging of drip, application, scarification and intradermal tests is more widely used, the diagnostic value of which has been debatable for several decades. Along with opponents of the use of skin tests for the purpose of predicting and diagnosing a drug disease, even those who are guided by their formulation recognize their inappropriateness, associated with a danger to the life of the patient and low information content due to the development of false positive and false negative reactions. Meanwhile, in recent years, a draft new order has been issued to improve the diagnosis of a drug disease, in which the emphasis of diagnosis continues to be on skin tests.

The most common causes of false-positive skin test reactions are: increased sensitivity of skin capillaries to mechanical irritation; non-specific irritating effect of allergens due to their improper preparation (the allergen must be isotonic and have a neutral reaction); the difficulty of dosing the injected allergen; sensitivity to preservatives (phenol, glycerin, merthiolate); meta-allergic reactions (positive reactions in a certain season of the year with allergens to which patients do not react at other times of the year); the presence of common allergenic groups between some allergens; use of non-standardized solutions for diluting drugs.

Of the causes of false-negative reactions, the following are known: the absence of the necessary drug allergen; loss of allergenic properties of the medicinal product due to its long and improper storage or in the process of dilution, since there are still no standardized medicinal allergens; lack or decrease in the sensitivity of the patient's skin, caused by:

• lack of skin-sensitizing antibodies;
• an early stage in the development of hypersensitivity;
• depletion of the stock of antibodies during or after an exacerbation of the disease;
• decrease in skin reactivity associated with impaired blood supply, edema, dehydration, exposure to ultraviolet radiation, advanced age;
• taking patients immediately before testing antihistamines.

An important factor limiting the use of skin tests with drugs is their relative diagnostic value, since the registration of their positive results to a certain extent indicates the presence of an allergy, and negative ones do not in any way indicate the absence of an allergic condition in a patient. This fact can be explained by the fact that, firstly, most drugs are haptens - inferior allergens, which become complete only when they bind to blood serum albumins. That is why it is not always possible to recreate a reaction on the skin that is adequate to what is happening in the patient's body. Secondly, almost all drugs in the body undergo a series of metabolic transformations, while sensitization develops, as a rule, not to the drug itself, but to its metabolites, which can also be stated as a negative reaction to the tested drug.

For the production of skin tests, in addition to their low information content and relative diagnostic value, there are many other contraindications, of which the main ones are: the acute period of any allergic disease; a history of anaphylactic shock, Lyell's syndrome, Stevens-Johnson syndrome; acute intercurrent infectious diseases; exacerbation of concomitant chronic diseases; decompensated conditions in diseases of the heart, liver, kidneys; blood diseases, oncological, systemic and autoimmune diseases; convulsive syndrome, nervous and mental diseases; tuberculosis and the turn of tuberculin tests; thyrotoxicosis; severe form of diabetes; pregnancy, breastfeeding, the first 2-3 days of the menstrual cycle; age up to three years; the period of treatment with antihistamines, membrane stabilizers, hormones, bronchospasmolytics.

One of the important points limiting the use of skin tests is the impossibility of predicting the development of side effects not mediated by immunoglobulin E with their help. in any modification, it can be administered with only one drug per day, and its diagnostic value is limited to a short period of time. Obviously, taking into account all the shortcomings of skin tests with drugs, they were not included in the diagnostic standards, i.e., in the list of mandatory methods for examining patients with acute toxic-allergic reactions to drugs recommended by the Institute of Immunology of the Ministry of Health of the Russian Federation and the Russian Association of Allergists and clinical immunologists. Meanwhile, in numerous publications not only of the past, but also of recent years, including the legislative documents of Ukraine, skin tests continue to be recommended both for the purpose of making an etiological diagnosis of a drug disease, and for the purpose of predicting it before starting treatment, especially before injection. antibiotic therapy. Thus, according to the order of the Ministry of Health and the Academy of Medical Sciences of Ukraine dated April 2, 2002 No. 127 “On organizational measures for the introduction of modern technologies for the diagnosis and treatment of allergic diseases” and the annex No. 2 attached to it in the form of an Instruction on the procedure for diagnosing drug allergies in all medical In prophylactic institutions, when prescribing treatment to patients with the use of injectable antibiotics and anesthetics, skin tests are required to prevent complications of pharmacotherapy. According to the instructions, the antibiotic is diluted with a certified solution so that 1 ml contains 1000 IU of the corresponding antibiotic. A skin test is placed in the forearm area, after wiping the skin with a 70% ethanol solution and retreating 10 cm from the elbow bend, with an interval of 2 cm between the samples, and simultaneously with no more than 3-4 drugs, and also in parallel with the positive ( 0.01% histamine solution) and negative (dilution liquid) controls. It is recommended to perform mainly a prick test, which, unlike a scarification test, is more unified, specific, aesthetic, economical, less dangerous and traumatic. In order to further increase the information content of skin testing, a rotational prick test is shown, the essence of which is that after a skin prick, a special lancet is fixed for up to 3 s, and then it is freely rotated 180 degrees in one direction and 180 degrees in another. The reaction is taken into account after 20 minutes (with a negative reaction - there is no hyperemia, with a doubtful reaction - hyperemia of 1-2 mm, with a positive reaction - 3-7 mm, with a positive reaction - 8-12 mm, with a hyperergic reaction - 13 mm and more).

In the Instructions on the procedure for diagnosing drug allergies, in addition to the debatable question of the eligibility of using skin tests with drugs for this purpose, there are many other controversial points regarding the technology of their setting. Thus, according to the instructions, a provocative skin test can be performed in the event of an allergic reaction according to the reagin type, while laboratory tests are indicated with the development of a reaction according to cytotoxic and immunocomplex types, and laboratory tests and application tests are indicated with the development of a delayed-type hypersensitivity reaction. However, as clinical observations show, it is simply impossible to predict in advance the type of allergic reaction in a patient with an uncomplicated allergic history, if this reaction suddenly develops, before starting injectable antibiotic therapy.

No less controversial is the indication that skin testing can be performed simultaneously with 3-4 drugs, since there are opposing opinions on this subject, according to which only one drug can be skin tested on the same day.

The possibility of implementing the postulate of the instruction that skin testing with drugs should be carried out under the supervision of an allergist or doctors who have undergone special allergological training, including measures to provide resuscitation to patients with anaphylaxis, raises doubts. There are a limited number of such specialists in Ukraine, represented only by doctors of city and regional allergological offices and hospitals, and therefore, skin tests with drugs in all medical institutions, according to regulatory documents, will be performed, as it was before, by untrained medical workers. In fact, the normative document on the organization of an allergological service in Ukraine has no economic basis for its implementation, since, taking into account the economic situation in the country, it is currently just as unrealistic to train specialists competent in allergology for all medical institutions, as it is to provide these institutions with tools and standardized drug kits for screening diagnostics.

Taking into account all the shortcomings and contraindications of skin tests, as well as the annual increase in allergic and pseudo-allergic reactions to drugs, it is debatable whether they should be administered with antibiotics before injecting antibiotic therapy, both in patients with widespread dermatoses with a complicated course of pyoderma, and in patients with infections, sexually transmitted, in the acute or subacute period of their disease. Meanwhile, despite all the contraindications and the danger of skin tests, as well as their low information content, legislative documents relating to the dermatovenereological service continue to insist on the advisability of their setting before starting antibiotic therapy, as evidenced by the draft new order on improving diagnosis of a drug disease, in which the emphasis is still on skin testing.

From our point of view, since the formulation of skin tests with drugs has many contraindications and limitations, and is also dangerous for the life of patients and is often fraught with the possibility of obtaining false positive and false negative results, it is more expedient to use specific immunological tests when conducting etiological diagnostics. The attitude to them, as well as to skin tests, is no less controversial because of their shortcomings: the duration of the test; lack of standardized diagnostic drug allergens; difficulties in acquiring the necessary material base (vivarium, radioimmune laboratory, luminescent microscope, enzyme immunoassay analyzer, test systems, etc.). In addition, it should be taken into account that there are still no standardized diagnostic drug allergens, as a result of which it is necessary to work with allergens characterized by different physicochemical parameters, for which it is not always possible to select the optimal concentrations, as well as their solvents. Therefore, in recent years, biophysical methods for the rapid diagnosis of a drug disease have been developed, allowing etiological diagnosis to be carried out within 20–30 minutes, while almost all specific immunological tests require a long time to complete.

Of such biophysical methods for the etiological rapid diagnosis of a drug disease, developed at the Institute of Dermatology and Venereology of the National Academy of Medical Sciences of Ukraine, the following should be noted, based on the assessment:

• the maximum intensity of ultra-weak luminescence of blood serum, previously incubated with the alleged drug allergen and induced by hydrogen peroxide;
• the rate of onset of erythrocyte hemolysis in the presence of suspected drug allergens;
• erythrocyte sedimentation rate in the presence of suspected drug allergens;
• the level of ultrasound absorption in erythrocytes previously incubated with a suspected drug allergen.

Along with this, the institute has developed diagnostic devices for etiological express diagnostics by evaluating: erythrocyte sedimentation rate (together with the National Technical University of Radio Electronics); the level of ultrasound absorption by erythrocytes pre-incubated with the alleged drug allergen (together with the Kharkov Instrument-Making Plant named after T. G. Shevchenko).

Automated information systems (AIS), developed jointly with Kharkiv National Polytechnic University and Kharkiv Institute of Radio Electronics, are of great help in the early diagnosis of a drug disease, which allow: to identify risk groups; to quantify the degree of risk of allergic dermatosis morbidity for each subject separately; assess the psycho-emotional state of workers and employees of enterprises; conduct automated professional selection of applicants for work; keep records of production-related and occupational allergic diseases; analyze the effectiveness of preventive measures; give recommendations on the choice of an individual preventive complex, depending on the state of immune homeostasis and the adaptive-compensatory capabilities of the body.

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Treatment of drug disease

Treatment of a drug disease is difficult due to frequent polysensitization even to corticosteroids and antihistamines. It is built on the basis of data on pathogenetic mechanisms and taking into account the state of the individual. Treatment of a drug disease is carried out in two stages. At the first stage of treatment, measures are taken to remove the patient from an acute state, in which the most effective way is to remove the drug to which the patient is sensitized from the body and the environment, as well as to exclude its further intake, which is not always realistic. The main drugs for acute manifestations of a drug disease in modern conditions continue to be corticosteroids. An important place in therapy is occupied by antihistamines and measures aimed at normalizing the water-electrolyte-protein balance by introducing detoxification solutions (isotonic solution, reopoliglyukin, hemodez) and diuretics (lasix, furosemide, etc.). Meanwhile, the lack of modern injectable hyposensitizing drugs creates difficulties in intensive care for patients with anaphylactic shock.

An important place in the treatment of a drug disease with acute clinical manifestations is occupied by external therapy. In addition to lotions, corticosteroid ointments and creams are widely used, the effectiveness of which depends not only on the active corticosteroid, but also on its basis. Advantan, elokom, celestoderm B creams deserve special attention, and in case of infection - celestoderm with garamycin, diprogent.

The second stage of treatment begins at the stage of remission, during which the whole complex of measures is carried out, aimed at changing the reactivity of the patient and preventing him from relapses in the future. With polysensitization to drugs, which is often combined with food, bacterial, pollen, solar and cold allergies, nonspecific therapy is indicated, which is used as traditional desensitizing agents (corticosteroids and antihistamines, calcium, sodium, etc.). Of the antihistamines, preference is given to drugs of the second (claritin, semprex, gistalong) or third (telfast, histafen, xizal) generation, which have a high affinity and strength of binding to HI receptors, which, along with the absence of a sedative effect, allows the use of drugs once a day. during the day, for a long time without changing to another alternative antihistamine. For patients with a history of recurrent drug disease, the third-generation antihistamines Telfast, Histafen, Xizal, which are devoid of side effects of second-generation drugs - effects on the central nervous and cardiovascular systems, have now become the drug of choice.

Enterosorption is successfully used (activated carbon, sorbogel, polyphepan, enterodes, etc.).

Based on the data on the neurohumoral regulation of immunogenesis processes, adrenoblocking drugs are used - domestic adrenoblockers - pyrroxane and butyroxane, acting selectively on adrenergic neurons concentrated in the hypothalamus.

Taking into account the role of the autonomic nervous system in the mechanisms of the development of a drug disease, the appointment of quateron (daily dose of 0.04-0.06 g) is effective, which acts normalizing in dysfunction of the autonomic nervous system due to the blockade of H-cholinergic receptors of autonomic nodes. Effective preparations of the antioxidant series (vitamins A, E, C, etc.), acupuncture and its variety - qigong therapy. A wider use of other non-drug and physiotherapeutic methods of treatment is shown, such as electrosleep, microwave therapy on the adrenal region, magnetotherapy, ultrasound therapy, UHF therapy, drug electrophoresis, psychotherapy, hypnosis, climatotherapy, hypothermia, etc.

Of the new methods of treatment of a drug disease developed at the Institute, it should be noted:

• a complex-sequential method, which consists in the sequential effect of a complex of medicines on various levels of body integration, starting from the higher parts of the central nervous system and ending with the organs of immunogenesis;
• a method for the treatment of patients with allergic dermatosis with a burdened allergic history, which includes the appointment of ultrasound on the site of the projection of the adrenal glands, which differs in that an alternating magnetic field with an intensity of 1-2 W/cm2 is additionally administered daily to the thymus gland for 10 minutes, in a constant mode, at the same time, ultrasound is prescribed every other day, using an emitter with a diameter of 4 cm, a labile technique, a pulsed mode, an intensity of 0.4 W/cm2, the duration of the procedure is 5 minutes on each side until the onset of clinical remission;
• a method for treating patients with allergies to drugs, including the appointment of a complex of pharmacological agents and physiotherapeutic influences, which differs in that in case of true allergy, the immunological conflict is normalized by the appointment of magnetotherapy according to the transcerebral method and ultrasound on the area of ​​the thymus projection, which alternate every other day with microwave therapy on the area of ​​the cervical sympathetic nodes and ultrasound on the site of the projection of the spleen, and in case of pseudo-allergy, cortico-hypothalamic-pituitary relationships and liver function are corrected by the appointment of magnetotherapy on the collar zone and ultrasound on the site of the projection of the liver, the level of histamine - with antihistamines, the level of unsaturated fatty acids - with calcium antagonists, and complement activity - inhibitors of proteolysis, repeating the treatment regimen until the onset of clinical remission;
• a method for the treatment of patients with allergic dermatosis with a burdened allergic history, including the appointment of ultrasound on the projection area of ​​the adrenal glands, which differs in that additional supracubital laser irradiation is performed for 15 minutes at a laser power of 5 to 15 W, alternating these procedures every other day, and an alternating magnetic field with an intensity of 1-2 W for 10 minutes is administered daily to the thymus gland in a constant mode until the onset of clinical remission;
• a method for the treatment of dermatoses with a burdened allergic history, including pharmacological agents, which differs in that electrosonphoresis with pyrroxane (with concomitant hypertension) or butyroxane (with concomitant hypotension and normal pressure) is additionally prescribed every other day, and on unoccupied days - microwave therapy for projection adrenal glands;
• a method for the treatment of dermatoses with a burdened allergic history, including pharmacological agents, which is characterized in that high-frequency electrotherapy is additionally prescribed to the projection of the adrenal glands, which is alternated with electrosleep, while on the days of the electrosleep, ultraphonophoresis of tocopherol acetate is additionally prescribed to the projection of the liver;
• a method for the treatment of dermatosis with a burdened allergic history, including pharmacological agents, which is characterized in that additional local hypothermia is prescribed, alternating with low-temperature effects on 3-4 BAPs of general and segmental-reflex action, while the temperature of exposure during the course of therapy is reduced from + 20 up to - 5 degrees Celsius, and the exposure period is increased from 1 to 10 minutes.

As for the use of new technologies in the treatment of a drug disease with polysensitization in its remission stage, the applicator for resonant correction of information-exchange loads "AIRES" can be considered as a means of choice, if the body is considered an organ that perceives and transmits a continuous flow of information, and a drug disease - the result of an information failure.

Considering a drug disease as a disruption of protective and adaptive mechanisms and a violation of adaptation (disadaptation), which is accompanied by structural and functional changes at all levels, and above all, disorders of the neuroendocrine and immune systems, which are the pathogenetic basis for the development of the disease, in recent years, interest in the problem of immunotherapy has increased, i.e., prescribing to patients a complex of drugs that actively affect the immune reactivity of the body, depending on the identified violations in one or another link of immunity.

If we consider a drug disease as a chronic relapsing process and the associated stress caused by a violation of adaptation, then it entails the occurrence of physical and psychological changes with the development of signs characteristic of chronic fatigue syndrome with asthenic symptoms, reducing the quality of life of patients and requiring rehabilitation measures, during which it is advisable to give preference to non-drug methods or their combination with hyposensitizing agents.

Summarizing all of the above, it should be noted that, along with the progress on the problem of drug disease, there are still many unresolved issues. Thus, the issue of working with the International Medical Statistical Classification of Diseases of the Tenth Revision (ICD-10) remains open. There are no official statistics on the prevalence of a drug disease, which makes it impossible to analyze its dynamics by region, makes it difficult to carry out preventive, anti-relapse, and rehabilitation measures among patients and risk groups. Difficulties in the differential diagnosis of a drug disease and true dermatoses (urticaria, vasculitis, eczema, etc.), some infectious diseases (scarlet fever, measles, rubella, scabies, recurrent syphilis, etc.), psychogenic and pseudo-allergic reactions to drugs create a situation , in which it is difficult for a practitioner to make a correct diagnosis, and therefore patients with a drug disease are often registered under other diagnoses. The situation is aggravated by the fact that even if, based on the data of the allergic anamnesis and the clinic, there is a suspicion that the patient has developed a drug disease, then most of the doctors cannot confirm their clinical diagnosis with the results of specific immunological tests due to the fact that in many medical institutions are simply not engaged in etiological diagnostics.

Of the debatable issues, one can point to the lack of a unified view of the terminology and classification of a drug disease, as well as the expediency or lack thereof of setting up skin tests with drugs before surgery and starting antibiotic therapy. The questions of consensus of dermatologists and allergists on the management of patients with drug disease and other allergic dermatoses are subject to no less discussion. It is known that the functional duty of allergists is to identify the etiological factor of allergies and their treatment mainly with specific allergens. However, long-term observations show that the specific treatment of a drug disease and allergic dermatoses is practically not used at present. Specific diagnostics to identify the drug responsible for the development of an allergic condition is important, but still auxiliary. Leading in the diagnosis of a drug disease, along with the data of an allergic history, is the clinic. Therefore, for patients with a drug disease with predominantly skin manifestations, which are recorded most often, the leading specialist is a dermatologist, since only he is able to make a differential diagnosis of clinical manifestations that resemble any true dermatosis. An allergist, even a qualified one who does not have knowledge of dermatology, can misinterpret clinical manifestations and mistake a skin or infectious disease for a medicinal disease.

Prof. E. N. Soloshenko. Drug disease in the problem of side effects of drugs: current state // International Medical Journal - No. 3 - 2012

medicinal disease

Recently, there has been increasing talk about the fact that drugs can cause or exacerbate the symptoms of almost any disease.

In serious scientific publications, research data is published confirming the general harmful effects of drugs on sick people. So, scientists conducted a study, as a result of which it turned out that drugs every year cause the death of about 100 thousand people, and also lead to the development of serious diseases in more than 2 million people. This phenomenon is called drug disease.

Scientific studies also show that in about half of the cases, the negative effects of the use of drugs appeared due to the intake of unreasonably high doses, which is the mistake of doctors. In addition, some patients simply do not inform their physicians about the presence of allergic reactions to certain drugs. Often drugs are prescribed without taking into account the individual characteristics of the patient.

So, according to ongoing studies, in the United States, about half of both children and adults, doctors still prescribe them for viral diseases that do not require the use of antibiotics, for example, for a cold.

Studies conducted by scientists from the Medical Department of Harvard University have shown that about 20% of hospitalized patients take drugs prescribed by a doctor to their detriment. The reason for this is often an overdose. According to the researchers, doctors overestimate the doses to play it safe. Of the patients studied, none died, but about 30% of them received complications after treatment in the hospital.

The most common complications caused by inappropriate medication are diarrhea, dehydration, and weakness. These consequences could have been avoided in about 60% of cases if medical staff were more attentive to patients.

[!] The word "medicine" comes from the Greek word "pharmakeia", which translates as both "medicine" and "poison".

Doctors are too quick to prescribe medicines. So, when complaining of insomnia, more than 60% of doctors prescribed sleeping pills to patients, while the cause of this condition could be strong tea or coffee at night, daytime sleep, lack of exercise, etc. When people complained of pain in the abdomen and data of endoscopic examination, speaking of diffuse irritation of the walls of the stomach, about 65% of doctors prescribe them drugs from the group of H2-histamine blockers, such as ranitidine. However, in many cases, the same coffee, smoking, stress, uncontrolled intake of aspirin, etc. are the cause of pain in the abdomen. In all these cases, it would be more correct to identify and try to eliminate the real causes, or at least reduce their influence.

It is not uncommon in medical practice that there are cases when a disease occurs as a reaction to taking some medicine. In this case, the appointment of another drug to eliminate the disease that has arisen is fraught with negative consequences. Unfortunately, doctors spend little time on finding out all the factors that led to the onset of a particular disease. Too often, people take medication in situations where medication could have been avoided by other therapies, or at the very least by significantly reducing the amount of medication they take.

[!] 10 times more people die from drug side effects than from surgical errors.

Researchers at the Universities of Toronto and Harvard have discovered a phenomenon they call the appointment cascade. It consists in the fact that when a side effect occurs in a person after taking a drug, the doctor mistakenly interprets it as a symptom of a new disease and prescribes another drug for its treatment, which can also cause side effects and be interpreted in his own way. turn, as a sign of another disease. Thus, drugs are prescribed in a cascade that are not so much effective for the patient as harmful.

For example, the use of antidepressants, antipsychotics, and antihistamines can impair bowel motility, prompting a physician to prescribe laxatives. The use of cardiotropic drugs can lead to symptoms similar to those of Parkinson's disease, resulting in the prescription of drugs to treat parkinsonism. Common symptoms such as depression, insomnia, sexual dysfunction, arrhythmias, heart problems and pressure drops can also be caused by medication. At the same time, tranquilizers and sleeping pills used to treat these symptoms cause severe side effects, negatively affecting the functioning of the central nervous system (CNS). Antihypertensive drugs and agents used to treat cardiac arrhythmias and gastrointestinal disorders can also lead to severe side effects.

[!] The old Russian word "potion" means both a medicinal and a poisonous drink.

Against the backdrop of widespread advertising of therapy exclusively with drugs, even the doctors themselves, taking the patient, are in a hurry to decide what should be prescribed to him, and not how to help at all. As a result, in most cases, other treatments, such as lifestyle changes or a therapeutic diet, are not taken into account.

The reason for the problem of drug disease is that in the modern world, powerful chemicals are used as medicines. Their high biological activity sometimes makes it impossible to determine the boundary between the maximum effective and toxic doses, sometimes the difference between them is too small.

In addition, every drug without exception has at least some side effect, and there are contraindications to it. So, even the most seemingly safe drugs are actually harmful. For example, aspirin can cause a lot of trouble for those who have a tendency to bleed or suffer from peptic ulcers of the stomach or intestines. In these people, aspirin use can cause serious illness and sometimes death.

Aspirin can also provoke asthma attacks in people who are predisposed to this disease. In children, aspirin can cause Reye's syndrome, especially in infections where parents most often give the drug to relieve fever. Meanwhile, Reye's syndrome very often leads to death. This list of contraindications refers to a drug that is considered more or less safe!

[!] From 3 to 5% of all admissions of patients to hospitals are caused by side effects of drugs.

Similarly, any other drug can not only cause side effects, but also lead to death. However, in the annotations to medicines, they do not always write about side effects. This mainly applies to small drug manufacturers. So it is advisable to purchase drugs from large, well-known pharmaceutical companies that try to give, as a rule, complete information about their products.

But the danger of improper use of the drug also lies in the fact that the side effect is not always associated with an excess of the dose. Side effects are different, for example in the form of allergic reactions. Even the smallest amount of the drug can lead to serious consequences. An overdose usually causes toxic reactions, which are more pronounced, the more a person exceeds the allowable dose for treatment.

The reason for the emergence of drug disease is also the fact that many drugs are often incompatible with each other. The chemicals that make up the drugs, entering the body and mixing, begin to interact with each other, leading to unpredictable consequences. Different drugs, when interacting, change the effect of other drugs. But in hospitals, they often prescribe 5-10, and sometimes up to 40 medications. The effect of so many drugs is simply impossible to describe.

It is not always possible to do without drugs, especially for serious diseases, but any person should know the rules of "drug safety".

From the book Plants are your friends and foes author Rim Bilalovich Akhmedov

56. DRAWING LETTERS For many years of acquaintance with it, I have become convinced that this most valuable medicinal plant has not yet received due wide recognition. But it was not in vain that the people used to say in ancient times: sell a coat - buy a letter.

From the book Thyroid Diseases. Choosing the right treatment, or How to avoid mistakes and not harm your health author Julia Popova

63. MEDICINAL VERBENA In ancient times, magical properties were attributed to it, supposedly protecting from the evil eye, damage and curses. It was believed that it cures all diseases. Now vervain is rarely used, as there are more effective remedies for treating the liver,

From the book Hospital Pediatrics: Lecture Notes author N. V. Pavlova

65. MEDICINAL VERONICA Veronica grass in the form of infusions and decoctions is popular in folk medicine for memory loss, dizziness, and diseases caused by weight lifting. Veronica treats diseases of the liver, kidneys, spleen, bladder, stomach ulcers. She finds

From the book Internal Medicine: Lecture Notes author

165. BUYED MEDICINAL This plant has long attracted my attention with a touch of some kind of mystery. The stem is not straight, but bent in a semi-arc, as if it carries a heavy burden. The leaves lined up as if in a queue - they rise from the root to the top in a uniform sequence and

From the book Internal Diseases author Alla Konstantinovna Myshkina

185. MEDUNIA MEDINIA In folk medicine, lungwort is considered one of the best remedies for children's tuberculosis. Lungwort is popularly treated with bronchitis, pharyngitis, bronchial asthma, pneumonia, inflammation of the kidneys, hemorrhoids, inflammatory female diseases, and also drink

From the book Medicines That Kill You author Liniza Zhuvanovna Zhalpanova

186. MELISSA MEDICINAL Preparations from lemon balm leaves are valued primarily as an effective sedative. With heart disease, shortness of breath disappears, tachycardia attacks stop, pain in the heart area disappears. Melissa is especially useful for elderly patients

From the book Handbook of Sane Parents. Part two. Urgent care. author Evgeny Olegovich Komarovsky

Diffuse toxic goiter (Graves' disease, Graves' disease, Perry's disease) This is one of the most famous and common diseases of the thyroid gland, familiar to many from photographs from school anatomy textbooks, which showed faces with bulging eyes.

From the book Thyroid Diseases. Treatment without errors author Irina Vitalievna Milyukova

LECTURE № 14

From the book Sugar-Reducing Plants. No to diabetes and overweight author Sergey Pavlovich Kashin

LECTURE No. 46. Drug disease Drug disease is associated with the production of antibodies or the appearance of T-lymphocytes specific to the drug or its metabolites. The first report of drug allergy or serum sickness caused by administration

From the book Allergy. Folk methods of treatment author Yuri Mikhailovich Konstantinov

55. DRUG DISEASE (DIAGNOSTICS, COMPLICATIONS, TREATMENT) Skin tests are used in diagnostic testing: 1) in case of immediate allergic reactions: intradermal injection of an antigen is manifested by hyperemia and a blister at the injection site

From the author's book

Drug-Associated Disease In recent years, there has been increasing talk that drugs can cause or exacerbate the symptoms of almost any disease. Reputable scientific publications publish research data confirming the overall harmful effects

From the author's book

11.13. MOTION SICKNESS (MOTION SICKNESS, SEASICKNESS) Motion sickness is a condition manifested by weakness, dizziness, increased salivation, sweating, nausea and vomiting. Occurs with prolonged irritation of the vestibular apparatus (when traveling, flying and

From the author's book

Diffuse toxic goiter (Basedow's disease; Graves' disease) This is the most common cause of thyrotoxicosis, although diffuse toxic goiter is not a common disease. Nevertheless, it occurs quite often, in about 0.2% of women and in 0.03% of men -

From the author's book

From the author's book

From the author's book

Drug Allergies Allergies are the scourge of our time, and of course, they also manifest themselves in relation to drugs. At the same time, the occurrence of allergy symptoms in response to the administration of drugs is observed not only in those who are prone to allergies, although they, of course, have a frequency of such reactions.

Medical disease. (LB)

The question of the theoretical risk that a doctor takes on with any treatment, including drugs, has gained particular notoriety in connection with the complications observed in recent years. Professor Georgiy Mandrakov says this: “A medicine is a symbol of the goals pursued by medicine and the opportunities it has to achieve these goals.”

At the present time we have at our disposal a huge number of drugs, we have the most powerful specific drugs, the use of which cures and brings millions of people back to life. However, the widespread use of drugs, the appointment of maintenance and continuous therapies for certain diseases (collagenosis, blood diseases) led to the appearance of many side effects of drugs. Before our eyes, diseases that were previously very rare (candidiasis, deep mycoses) are becoming more frequent, and new still little-known pathological conditions are emerging. So, as you already understood from the introductory speech, the topic of today's lecture is LB.

We need to address the following questions today:

definition of the concept, its legitimacy.

to analyze the issues of etiology and pathogenesis.

focus on the features of drug allergies.

focus on classification

analyze the clinic of LB, the defeat of individual organs and systems in LB

Dismantle the clinic of anaphylactic shock - as the most formidable form of LB

LB diagnostic methods

Treatment and prevention of LB

The term LB was first proposed in 1901 by the Russian scientist Arkin Efim Aronovich (he noticed that when rubbing a sulfuric mercury ointment in a patient, along with a rash, severe signs of damage to the whole organism appeared (anorexia, asthenia, fever, dyspeptic disorders, etc.) From here he naturally expressed the opinion that this disease, which is caused by a medicinal substance and in it the rash plays the role of only an external manifestation.These medicinal lesions cannot be called rashes, as it would be wrong to call measles papular, and scarlet fever - an erythematous rash.

The first half of the 20th century was characterized by advances in chemotherapy. The arsenal of treatment included derivatives of quinoline, benzene, pyrozol, sulfanilamide drugs, antibiotics. At the same time, more and more descriptions of complications from their use accumulated in medical practice. Generalization of these data showed that these complications are completely different in terms of the mechanism of occurrence, pathological changes and clinical manifestations.

A greater variety of complications of drug therapy did not allow them to be brought to a single nosological form, but it was quite obvious that the effect of a drug on the body is a complex biological phenomenon due to many mechanisms, i.e. the concept of drug side effects.

A.N. Kudrin in 1968 at the 1st International Symposium on Side Effects of Drugs, all drug complications are divided into the following groups:

true drug side effects

toxic effects of drugs

complications associated with sudden drug withdrawal

individual intolerance to the drug

Let's dwell on these concepts.

Under side effects of drugs - understand the undesirable effect of the drug, due to its structure and properties that it has on the body along with its main actions.

Toxic effects of drugs - may be due to an overdose, accelerated saturation of the body, rapid administration of medium and even minimal doses, insufficient function of the excretory organs (CRF) or a violation of their neutralization processes in the body (with primary liver failure).

Complications due to rapid drug withdrawal (withdrawal syndrome, obstinence) - with the rapid cancellation of some potent drugs, painful symptoms occur that are difficult to tolerate by patients, including withdrawal syndrome. it is characterized by an exacerbation of those symptoms, for the elimination of which treatment was carried out.

Individual intolerance to drugs - is expressed in an unusual perverse reaction of the body to the usual doses of drugs that are harmless to most people. Individual intolerance is a disease of altered reactivity of the organism. Individual intolerance includes idiosyncrasy and an allergic reaction.

Idiosyncrasy - this is a genetically determined, peculiar response to this medicine when it is first taken. The cause of idiosyncrasy is an insufficient amount or low activity of enzymes. For example, a lack of the enzyme glucose-6-phosphate-DH in response to taking certain drugs (quinidine, CA drugs, aspirin, pyrazalone, antibiotics) leads to the development of hemolytic anemia.

allergic reactions This is the most common cause of drug intolerance. The term "allergy" was first introduced by the Viennese pediatrician Pirket in 1906. ALLERGY is currently understood as an altered sensitivity of the body to the action of a given substance, either paraspecifically or due to hereditary high sensitivity of the body. LB is one of the most significant clinical forms of the body's allergic reaction to medications.

Continuing the development of the doctrine of LB Landsteiner, who experimentally proved the antigenicity of simple chemical compounds and thereby strengthened the theoretical basis for the unity of the mechanisms of the body's response to non-protein substances. In our country, the nosological outline of LB was substantiated by Tareev E.M. at the same time, the discussion about the legitimacy of the use of the term LB is still ongoing. Authors such as Ado V.A., Bunin propose the term LB to denote the entire group of undesirable consequences of active drug therapy, i.e. use it as a group, not a nosological concept.

However, to date, a sufficient number of convincing and indisputable facts have been collected confirming the nosological outline of this disease (these are the works of Severova, Nasonova, Semenkov, Mondrakov).

So, one hundred is understood by LB?

LB - this is a peculiar, persistent non-specific reaction of the body that occurs when using therapeutic or permissive (small) doses of drugs and manifests itself in a variety of clinical syndromes. The frequency of LB according to domestic authors is 7-15%, according to foreign authors 18-50%.

Etiology.

In fact, any drug can lead to drug allergies. The most common cause of LB is antibiotics (33%). Of these, penicillins account for about 58.7%, BICILLINS 18.5%, streptomycin 15%. In second place are serums and vaccines - 22.8%, 3 - tranquilizers 13.6%, 4-hormones - 10%, 5 - analgesics, SA drugs, in sixth - antispasmodics - 2.7% and anesthetics - quinine, quinidine, SG, gold preparations, salicylates, vitamins, etc.

The frequency of lesions as a result of pharmacotherapeutic agents, in addition to the therapeutic properties of the drug itself and the body's response to their use, depends on many other factors:

uncontrolled use of drugs by both doctors and patients themselves

LB most often occurs in an organism previously affected by the disease, the underlying disease changes the reactivity of the body, and the altered reactivity causes unexpected effects when using drugs.

an important reason for the development of LB is polypharmacy, which creates conditions for polyvalent sensitization

An undoubted role is played by nutrition, which, when using drugs, can change the reactivity of the body and the tolerance of drugs.

Age plays an important role in the occurrence of LB. It has long been known that children are more sensitive to barbiturates, salicylates, and in the elderly - to SH. This is due to insufficient development in childhood, a decrease in old age - enzyme systems involved in the breakdown and neutralization of certain substances.

the question of drug genetic lesions and the genetic conditionality of a number of drug lesions is important.

the degree and rate of sensitization of the body partly depends on the route of administration of drugs. So, local applications and inhalations most often cause sensitization. With i.v. administration, the sensitization of the body is less than with i.m. and i.v. injections.

Pathogenesis. As we have already agreed, LB is one of the clinical forms of drug allergy. Most drugs are simple chemical compounds. They are incomplete antigens (haptens) that can react with antibodies present in the body, but they themselves cannot cause their formation. Drugs become full-fledged antibodies only after binding to proteins in body tissues. In this case, complex (conjugated) antigens are formed, which cause sensitization of the body. Other drugs already without splitting play the role of haptens (levomycitin, erythromycin, diacarb). When re-introduced into the body, these haptens can often combine with the formed antibodies or sensitized leukocytes already on their own without prior binding to proteins. These areas may be the same for different drugs. They got the name common or cross-reactive determinants. Therefore, with sensitization to one drug, allergic reactions may occur to all other drugs that have the same determinant. Drugs that share a common determinant:

penicillin (natural, semi-synthetic - oxacillin, carbenicillin, cephalosporins), a common determinant for them is the beta-lactam ring. If the patient has a positive allergic reaction to natural penicillins, then he should not be prescribed beta-lactams (ceporin, etc.)

novocaine, para-aminosalicylic acid, SA, have a common determinant - aniline (phenylamine)

oral hypoglycemic drugs (butamide, bucarban, chlorpropamide), dysuric thiazides (hypothiazide, furosemide), carbanhydrase inhibitors (diacarb) have a common determinant - the benzene-sulfonamide group.

neuroleptics (aminosine), antihistamines (diprazine, pipolfen), methylene blue, antidepressants (fluorocyzine), coronary dilators (chloracizine, nanachlosine), antiarrhythmics (ethmozine), etc. have a common determinant - the phenothiazene group

sodium or potassium iodine, Lugol's solution, iodine-containing contrast agents - iodine.

That is why most patients experience polyvalent sensitization to several drugs.

So, for the development of LB (allergy) 3 steps are necessary:

converting a drug into a form that can react with proteins

with body proteins to form a complete antigen

the immune response of the body to this complex, which has become foreign in the form of the formation of antibodies through the formation of immunoglobulins.

Thus, under the influence of drugs, a specific immunological restructuring of the body occurs. There are the following stages of allergic manifestations:

preimmunological - the formation of complete (complete) allergens (antigens)

immunological - an antigen-antibody reaction occurs on the territory of the shock organs. This reaction is strictly specific and is caused only by the introduction of a specific allergen.

pathochemical - as a result of the formation of an antigen-antibody complex, up to 20 biologically active substances (histamine, heparin, serotonin, kinin) are released. The reaction is not specific.

pathophysiological - manifested by the pathogenetic action of biologically active substances on various organs and tissues.

There are allergic reactions of immediate and delayed types. An immediate type reaction is associated with the presence of circulating antibodies in the blood. This reaction occurs 30-60 minutes after drug administration and is characterized by an acute manifestation: local leukocytosis, eosinophilia. A delayed-type reaction is due to the presence of antibodies in tissues and organs, accompanied by local lymphocytosis, occurs 1-2 days after taking the drug. This classification is based on the time of occurrence of the reaction after the administration of the drug. However, it does not cover the entire variety of manifestations of allergies. Therefore, there is a classification of allergic reactions according to the pathogenetic principle (Ado 1970, 1978). All allergic reactions are divided into true (actual allergic reactions) and false (pseudo allergic reactions, not immunological). True are subdivided into chimergic (B-dependent) and kitergic (T-dependent), depending on the nature of the immunological mechanism. True allergic reactions have an immunological stage in their development, false ones do not. Chimergic allergic reactions are caused by the reaction of an antigen with an antibody, the formation of which is associated with B-lymphocytes, kytergic - by the combination of an allergen with sensitized lymphocytes.

Features of drug allergies:

its dependence on the type of drug or on the so-called sensitization index. For example, phenyethylhydantoin almost always causes allergies (sensitization index 80-90%, for penicillin - 0.3-3%)

The development of a drug allergy depends on the individual abilities of the organism, in which genetic factors play an important role. For example, children are less likely to suffer from drug allergies than adults. More often, drug allergy develops in patients (i.e., against the background of the underlying disease) than in healthy people. Patients with SLE are particularly prone to drug allergies. Bronchial asthma often develops in people with a deficiency of Ig E, prostaglandins, etc.

For the development of drug allergy, prior sensitization, especially with substances of a protein nature, is of great importance.

the predominant localization of the allergic reaction, regardless of the method of drug administration: SA, gold - damage the bone marrow, soybeans of heavy metals - toxic-allergic hepatitis.

CLASSIFICATION OF LB: according to the severity of occurrence, 2 forms are distinguished:

Sharp forms

anaphylactic shock

bronchial asthma

acute hemolytic anemia

angioedema

vasomotor rhinitis

lingering forms

serum sickness

drug vasculitis

Lyell's syndrome, etc.

According to the severity of the course, 3 degrees are distinguished

mild (itching, angioedema, urticaria) symptoms disappear 3 days after the appointment of antihistamines

moderate severity (urticaria, eczematous dermatitis, erythema multiforme, fever up to 39, poly- or monoarthritis, toxic-allergic myocarditis). Symptoms disappear after 4-5 days, but require the appointment of glucocorticoids in an average dose of 20-40 mg.

the severe form is manifested by anaphylactic shock, exfoliative dermatitis, Lyell's syndrome, and lesions of internal organs (myocarditis with rhythm disorders, nephrotic syndrome) are attached. All symptoms disappear 7-10 days after the combined appointment of not only glucocorticoids, but also immunomodulators, antihistamines.

Early manifestations of LB are very diverse and not very specific, which often makes it difficult to assess them correctly. Among them, there is a general deterioration in well-being, malaise, weakness, apathy, usually unexplained by the course of the underlying disease. there may be a headache, dizziness, dyspeptic disorders, etc. The clinical syndromes of LB are also extremely diverse. Figuratively speaking, Polosukhina says that the manifestations of LB are diverse and unexpected. Of the many syndromes described, we will focus only on those that are of the greatest clinical importance, as often occurring or severe, life-threatening.

Anaphylactic shock.

For the first time, the concept of "anaphylaxis" was formulated in 1902 by Richet and Portier, as an unusual reaction of the body of dogs to the repeated administration of an extract from akpenib tentacles. In 1905, Sakharov described a similar reaction to repeated administration of horse serum in guinea pigs.

Anaphylaxis is the opposite of the body's defense against toxic products.

Anaphylactic shock is a type of drug allergy of the immediate type that has arisen on the repeated administration of a drug into the patient's body. The cause of anaphylactic shock can be all currently used drugs. Most often, anaphylactic shock develops on the introduction of antibiotics (penicillin 0.5-16%). The dose of penicillin that causes shock can be extremely small. For example, a case of shock to traces of penicillin in a syringe, which remained in it after the syringe used to administer penicillin to one patient, was washed, boiled, and injected with another drug to a patient sensitive to penicillin, is described. There are described cases of anaphylactic shock on the introduction of x-ray contrast agents, relaxants, anesthetics, vitamins, insulin, trypsin, parathyroid hormones. Anaphylactic shock is characterized by a sharp drop in vascular tone that occurs in direct connection with the administration of a drug and leads to life-threatening circulatory and necrotic changes in the tissues of vital organs - the brain, heart, kidneys, etc.

Drug-induced anaphylactic shock occurs 3-30 minutes after drug administration. Clinical signs are varied. Depending on the severity, there are 3 degrees of anaphylactic shock. The severity of shock is due to the degree of circulatory disorders and respiratory function. With a mild course of anaphylactic shock, a short prodromal period of 5-10 minutes is observed, which is characterized by the appearance of itching, urtic rash, skin hyperemia, Quincke's edema, laryngeal edema with hoarseness up to aphonia. Patients have time to complain of pain in the chest, dizziness, lack of air, blurred vision, numbness of the fingers, tongue, lips, pain in the abdomen, lumbar region.

Objectively: pallor of the skin, cyanosis, thready pulse, bronchospasm with distant wheezing, vomiting, loose stools. HELL 60\30 - 50\0 mm Hg heart sounds are barely audible, extrasystoles.

In moderate ANAPHILAX SHOCK, certain symptoms are harbingers: weakness, anxiety, fear, dizziness, heart pain, vomiting, heartburn, suffocation, urticaria, Quincke's edema, convulsions. This is followed by loss of consciousness, cold sticky sweat, pale skin, cyanosis, dilated pupils, thready pulse, arrhythmic, blood pressure is not determined, tonic and clonic convulsions, nasal, uterine and ventricular bleeding, due to the activation of fibrinolysis and the release of heparin by mast cells.

SEVERE ANAPHILAX SHOCK is characterized by the absence of a prodromal syndrome, sudden loss of consciousness, convulsions, and death.

According to the leading syndrome in the clinical picture, 5 variants of anaphylactic shock are distinguished:

hemodynamic

asphyxial

cerebral

abdominal

thromboembolic

The post-shock period lasts 3-4 weeks. Patients who have undergone shock for a long time feel weakness, memory impairment, headache. They may also be disturbed by pain in the heart, shortness of breath, tachycardia, due to the development of myocarditis and myocardial damage, symptoms of kidney damage (increased blood pressure, nocturia, hematuria, proteinuria), liver - liver enlargement, jaundice, itching. In the post-shock period, myocardial infarction, hemolytic anemia, thrombocytopenia, agranulocytosis, meningoencephalitis, polyarthritis, and arachnoiditis may develop. The cause of death in anaphylactic shock can be:

acute vascular insufficiency

asphyxia due to laryngeal edema, bronchospasm

thrombosis of cerebral and cardiac vessels

hemorrhages in vital organs - goal. Brain

over the past 3-5 years, the frequency of deaths in anaphylactic shock is 0.4 per 1 million population per year (from penicillin 1 death per 7.5 million injections, radiopaque substances are about 9 per 1 million urological examinations.

SERUM DISEASE.

This is a fairly common drug disease syndrome. Currently, there are more than 30 drugs that can cause serum sickness. this syndrome is similar to true serum sickness caused by heterolytic or homologous sera, there are mild, severe and anaphylactic forms of serum sickness. The development of an acute reaction is preceded by an incubation period of 7-10 days from the moment of administration of the drug. The prodromal period is characterized by hyperemia, hyperesthesia of the skin, an increase in blood pressure, and rashes at the injection sites.

acute period. It is characterized by fever up to 39-40, polyarthralgia, profuse urtic and severely itchy rash. The rash can be erythematous, papular, papulovesicular, hemorrhagic in nature, polyarthritis, Quincke's edema appear, myocarditis, polyneuritis, diffuse glomerulonephritis, and hepatitis are often diagnosed. The acute period lasts 5-7 days, in severe cases up to 2-3 weeks. Complications are rare. The clinical picture in serum sickness with repeated administration of the drug depends on the period that has elapsed since the first administration. If this period is 2-4 weeks, then serum sickness develops immediately after drug administration and proceeds severely in the form of edema, inflammation of the Arthus phenomenon at the injection sites and fever, rash, arthralgia or anaphylactic shock.

Urticaria and angioedema are characterized by a monomorphic rash, the primary element of which is a wheal, which is an acute swelling of the papillary dermis. The disease begins suddenly with intense itching of the skin. Then, in places of itching, hyperemic areas of the rash appear, protruding above the surface. If the total duration is more than 5-6 weeks, then they speak of a chronic form of urticaria capable of recurrence with painful itching, the addition of a papular rash, abscesses and other elements.

Quincke's edema is characterized by swelling of the dermis and subcutaneous tissue and even sometimes extends to the muscles. Quincke's edema is a giant urticaria. Local lesions are observed in places with loose fiber, the favorite localization is the lips, eyelids, mucous membranes of the oral cavity (tongue, soft palate, tonsils). Dangerous is Quincke's edema in the larynx, which occurs in 25% of all cases. If laryngeal edema occurs - hoarseness of voice, "barking" cough, then difficulty in breathing, inspiratory-expiratory dyspnea, noisy stridar breathing, cyanosis of the face, patients rush about, restless. If the edema spreads to the trachea, bronchi, then bronchospastic syndrome develops and death from asphyxia. With mild and moderate severity, laryngeal edema lasts from 1 hour to a day. After the acute period subsides, hoarseness of voice, sore throat, shortness of breath remain for some time, dry rales are heard in the lungs. With the localization of edema on the mucous membranes of the gastrointestinal tract, an abdominal syndrome begins with nausea, vomiting, acute pain joins, first local, then throughout the abdomen, accompanied by flatulence, increased peristalsis. During this period, a positive Shchetkin-Blumberg symptom may be observed. The attack ends with profuse diarrhea. Abdominal edema in 30% is accompanied by skin manifestations. With the localization of edema on the face, serous meninges may be involved in the process with the appearance of meningeal symptoms and convulsions.

Thus, the clinical picture and the severity of the process is determined by the localization of the pathological process and the degree of its intensity. Skin lesion is the most common form of LB, characterized by various lesions: itching, erythematous rash, maculopapular, morbilliform, eczema-like rash, exudative erythema multiforme, exfoliative dermatitis, Lyell's syndrome, etc. Usually, rashes appear 7-8 days after the start of medication. Most often they are caused by SA drugs, erythromycin, gentamicin, barbiturates, gold preparations. The rash disappears 3-4 days after the drug is discontinued.

Of all the skin manifestations of LB, I would like to dwell on Lyell's syndrome. Lyell's syndrome - This is toxic epidermal necrolysis - a severe bullous disease with a total lesion of the skin and mucous membranes. The disease begins acutely within a few hours or days after taking drugs (amidopyrine, aspirin, bucarban, a\b, analgesics), sometimes suddenly as an acute febrile infectious disease. blisters the size of a walnut appear, which burst, forming erosions, later merge, occupy large areas on the skin of the trunk, limbs, necrotic epithelium, torn away, forms large areas without a protective cover of the epithelium with the development of toxemia and death of patients from sepsis.

MEDICINAL VASCULITIS refers to systemic vasculitis - a group of diseases, which are based on a generalized lesion of arteries and veins of various calibers with secondary involvement of internal organs and tissues in the process. The relationship of systemic vasculitis with medication was proven by Tareev. Drug-induced vasculitis is more likely to develop in individuals with a burdened allergic history. More than 100 drugs are known to cause systemic vasculitis. Medicinal vasculitis (arteritis, capillaritis, venulitis, phlebitis, lymphanaitis) rarely represent independent diseases, more often they are one of the components of another pathological process. Drug-induced vasculitis has an acute and subacute course, may recur, but usually does not progress. The process is temporary and ends with complete recovery. The disease proceeds according to the type of hemorrhagic vasculitis (Schonlein-Genoch disease), necrotizing vasculitis, Wegener's granulomatosis, Mashkowitz's syndrome, thromboangiitis obliterans, etc.

The most extensive group (up to 90% of all cases of L. b.); toxic L. b. and teratogenic L. 6. (causing a violation of the development of the embryo). Sometimes there is a combined effect - toxin-allergic. Allergy from drugs is progressively increasing due to a sharp increase in the production of various types of drugs (antibiotics, hormonal and other synthetic drugs), as well as an increase in the number of allergens (synthetic substances, various dusts, new types of nutrients, etc.). Allergic conditions to allergens that do not have the properties of drugs (for example, to food - strawberries, eggs, etc.) create nonspecific hypersensitivity to drugs. A hereditary-constitutional predisposition to allergies can also be of known importance.

Allergens can be drugs, products of their oxidation and decay. Drugs or their metabolic products usually combine in the body with blood proteins (albumins); these connections also are the allergens causing L..

Clinical picture L. b. may be expressed by a local inflammatory process in areas of the skin in contact with the drug (drug contact dermatitis). A very heavy expression of L. b. - anaphylactic shock (see Anaphylaxis). L. b. it can manifest itself in the form of hemorrhage, purpura (hemorrhages on the skin and in internal organs), acute urticaria, bronchial asthma, etc. Prevention of drug allergies: administration of drugs with great caution to those suffering from allergies, refraining from administering drugs to which there is an allergy. Treatment of drug allergies is carried out depending on its manifestations.

The toxic effect of drugs also manifests itself in various forms. In large doses (non-therapeutic) many drugs are toxic. Certain drugs (for example, some antitumor and other drugs) have a teratogenic effect, that is, they cause malformations of the embryo. The teratogenic effect of the foreign hypnotic drug thalidomide (Germany), which was removed in the 1960s, is known. 20th century from production. The "thalidomide catastrophe" prompted intensive study of the teratogenic effects of drugs in order to prevent these complications.

Lit.: Ado A. D., General Allergology, M., 1970; Allergy to medicinal substances. [Sat. Art.], trans. from English, M., 1962.

A. D. Ado.

Great Soviet Encyclopedia. - M.: Soviet Encyclopedia. 1969-1978 .

See what "drug disease" is in other dictionaries:

DRUG DISEASE, a term denoting various manifestations of hypersensitivity (drug allergies) or individual intolerance (idiosyncrasy) of drugs and other types of side effects of drugs ... Modern Encyclopedia

The term, which does not have a strictly scientific content, characterizes various manifestations of hypersensitivity (drug allergy) or individual intolerance (idiosyncrasy) of drugs and other types of side effects ... ... Big Encyclopedic Dictionary

Conventional name for a group of diseases characterized mainly by various manifestations of hypersensitivity (drug allergy) or individual intolerance (idiosyncrasy) of drugs. * * * MEDICINAL… … encyclopedic Dictionary

Conv. the name of a group of diseases characterized by 1l. arr. dec. manifestations of hypersensitivity (drug allergies) or individual intolerance (idiosyncrasy) of drugs. funds… Natural science. encyclopedic Dictionary

The characteristic appearance of the fingers in Raynaud's disease (phenomenon P ... Wikipedia

ILLNESS HIGH ALTITUDE- honey. Altitude sickness is a condition caused by a lack of 02 at high altitude, ranging from mild discomfort to death. Caused by low partial pressure of inhaled oxygen, characterized by nausea, headache… Disease Handbook

PARKINSON'S DISEASE- honey. Parkinson's disease is an idiopathic slowly progressive degenerative disease of the central nervous system characterized by slowness of movement, muscle rigidity, tremor at rest, and impaired postural reflexes. At the heart of the disease is defeat ... ... Disease Handbook

CROHN'S DISEASE- honey. Crohn's disease is a nonspecific inflammatory lesion of various parts of the gastrointestinal tract of unknown etiology, characterized by segmentation, recurrent course with the formation of inflammatory infiltrates and deep longitudinal ulcers, often ... ... Disease Handbook

DISEASE LMRBURG-VIRAL- honey. Marburg disease is a severe, acute, and often fatal viral hemorrhagic fever. The main factor of pathogenesis is platelet dysfunction with the development of hemorrhagic shock. Pathogen. Enveloped rod-shaped branching virus... Disease Handbook

DIVERTICULAR INTESTINAL DISEASE- honey. Diverticular bowel disease is a disease characterized by the formation of diverticula in the intestinal wall; possible development of diverticulosis and diverticulitis (see Diverticular disease). The frequency of diverticular disease of the colon ... ... Disease Handbook

Books

• Internal illnesses. Textbook in two volumes. + CD , Valentin Moiseev , Anatoly Martynov , Nikolai Mukhin , 1866 pp. The textbook presents current data on the etiology, pathogenesis, diagnosis, clinical picture, treatment and prevention of diseases of internal organs. Diseases are listed by... Category: Textbooks for universities Publisher: GEOTAR-Media, Producer: GEOTAR-Media,
• Internal illnesses. Textbook for students of dental faculties of medical universities , Leshchenko V. I. , Nadinskaya M. Yu. , Okhlobystin Alexey Viktorovich , Podymova S. D. , The textbook presents modern data on the etiology, clinical manifestations, diagnosis, treatment and prevention of major diseases internal organs. Also considered are such ... Category:

Lecture
Viktorova I.A., head of Department of Internal Diseases and Polyclinic Therapy, MD, Professor

medicinal disease

- nosological form, which has a clear etiology, pathogenesis and a polymorphic clinical picture, manifests itself after the use of drugs in therapeutic doses.
A synonym for the term is a side effect of drugs.
The term was proposed in 1901 by the domestic scientist E.A. Arkin

Pathogenesis

I. Individual reactions of the body to the drug
Pharmacological idiosyncrasy
Functional insufficiency of the organs that excrete the drug (liver, kidneys)
Premorbid allergic reaction due to previous sensitization by the mechanism of HRT and HNT - 79% of cases

The pathogenesis of drug disease

Hypersensitivity of immediate type
Anaphylaxis (antibodies to JgE) - shock, Quincke's edema.
Anaphylactic reaction (antibodies with cytotoxic properties) - hemolytic anemia, thrombocytopenia, leukopenia
Occurrence of antigen-antibody complexes with compliment fixation - drug vasculitis
Delayed type hypersensitivity
Interaction of antigen with lymphocytes without a compliment and CEC - medicinal dermatitis

Pathogenesis

II. Side effects of the pharmacological action of drugs
Allergic contact dermatitis with local therapy in the form of ointments, drops, aerosol, iontophoresis;
Mutagenic action - congenital deformities;
Substitutive-complimentary action: abstinence in the treatment of drugs, withdrawal syndrome in the treatment of corticosteroids, anticoagulants;
Violation of the natural microflora of the body in the treatment of antibiotics and sulfonamides.

Thomas Quasthoff

Alison Lapper

thalidomide

Pathogenesis

III. Corticovisceral reactions - psychogenic vomiting, palpitations, dizziness, pathomymia (artificial reproduction of rashes, ulcers, bruises).

medical statistics

Every 10th bed in the therapeutic departments is occupied by patients who have been "affected" by the doctors' attempt to heal them.
The drug disease develops in 16% of previously healthy individuals and 18-30% of patients treated with chemotherapy drugs.
Economic losses from the negative effects of drugs are equivalent and even exceed those from infectious diseases.

Everyday chemicalization of household and industrial spheres.
An increase in the number of synthetic drugs.
Insufficient knowledge of health workers about the side effects of drugs and their prescription in the absence of indications. At least 95% of drugs, especially antibiotics, are used without sufficient justification.
Self-treatment.
Prevalence of maintenance therapy.
Polypharmacy (polytherapy) for non-severe, easily reversible diseases. 20% of pharmacotherapy complications are due to drug interactions.

With the simultaneous use of 16 drugs, the frequency of drug disease increases to 60%.
Polypharmacy is widespread; excessive therapeutic measures are often mistakenly considered not as shortcomings of the doctor's activity, but as his achievements.

Etiology of drug disease

Any drugs cause the development of a drug disease.
In practice, whole-virion vaccines, sera, novocaine, antibiotics, and analgesics most often cause LP.
According to A.S. Lopatina, 1992
antitumor antibiotics - 62%, anti-tuberculosis drugs - 28%, antibiotics - 16%, antipsychotics - 10%.

Clinic for drug disease

Fast type reaction
Anaphylactic shock, urticaria, angioedema, bronchospastic syndrome
Subacute reaction
Drug fever, agranulocytosis, erythroderma, papular exanthema
delayed reaction
Serum sickness, vasculitis, pancytopenia, arthritis, lymphadenitis, internal organ damage

Anaphylactic shock

Deaths - 0.4 per 1 million population per year.
Most often cause penicillin, radiopaque substances with parenteral use of drugs, but development from oral administration is possible. Anaphylactic reactions have been described with the use of insulin, pituitary hormones, trypsin, ACTH, heparin, pertussis, typhoid and influenza vaccines, and diphtheria toxoid.

Anaphylactic shock

Occurs after 3-30 minutes. after the introduction of the drug into a sensitized organism. With latently flowing sensitization (among healthcare workers), it occurs when injections are made for the first time, inhalations, or when the drug comes into contact with the skin.

Clinical options:

Asthmatic (bronchospasmic)
Hemodynamic (collaptoid)
Abdominal
infarction-like
Cerebral (stroke-like with psychomotor disorders)
Edema-urticarial

Anaphylactic shock

Light ASh: short prodromal period (5-10 min.): itching, urticaria-like rashes, erythema, burning sensation, Quincke's edema, including in the larynx. Patients have time to complain about their feelings: chest pain, dizziness, headache, fear of death, lack of air, cramping pain in the abdomen.
On examination: pallor, cyanosis, bronchospasm in the lungs, lack of consciousness, blood pressure 60/30 mm Hg, thready pulse 120-150 per minute, muffled heart sounds.

Anaphylactic shock

Moderate AS: Blood pressure is not determined, involuntary urination, defecation, tonic and clonic convulsions, nasal and gastrointestinal bleeding.

Anaphylactic shock

Heavy AS. Lightning-fast development of the clinical picture: sudden loss of consciousness, severe cyanosis, foam at the mouth, dilated pupils, convulsions, heart sounds are not heard, blood pressure is not determined, in the absence of immediate resuscitation, death occurs.

occurs in 65% of drug-induced patients
Peculiarities:
polymorphism, the occurrence after 5 minutes (acute type reaction), at 6–12 and even 40 days after taking drugs (at the initial dose), often accompanied by itching.

Quincke's edema and urticaria evidence of a pronounced degree of sensitization to the drug. They can lead to asphyxia, cause a clinic of Meniere's syndrome, an acute abdomen, etc.
Angioedema of the lips. Urticaria on penicillin

Arthus-Sakharov phenomenon- compaction, redness at the site of repeated intramuscular, s / c administration of the drug (reminiscent of a post-injection abscess), which pushes for unnecessary surgical intervention.

Chronic discoid lupus erythematosus. Skin lesion in the form of a "butterfly", lip lesion.

localized erythema- a signal of sensitization to sulfonamides; scarlet fever, morbilliform rash- on the intake of vitamins of group B, quinine; "butterfly" on the face- for aspirin, novocaine, novocainamide.

Drug damage to the oral mucosa

Allergic contact dermatitis especially in the practice of physiotherapists, mucous eye damage allergic nature - in the practice of an oculist.

Skin lesions - pemphigus.

Mucosal lesions in drug-induced lupus erythematosus: hyperemia and atrophy

Pemphigus vulgaris: on the lips and oral mucosa

Lyell's syndrome – toxic epidermal necrolysis, "scalded skin syndrome"

It occurs more often in women 40-60 years old after the use of sulfonamides, antibiotics, NSAIDs, the combined use of antibiotics with analgin, intravaginal contraceptives, often against the background of diabetes mellitus, sepsis, malignant lymphoma.
Generalized pruritic erythema with acute development of blisters in the epidermis, followed by desquamation, as with burns of the II-III degree. At the same time, mucous membranes and internal organs are affected, secondary sepsis develops.
Fatal outcome with damage to 80% of the skin surface.

Multimorphic exudative erythema Stevenson-Johnson - erosive-hemorrhagic lesions of the skin and mucous membranes in the form of keratitis, conjunctivitis, urethritis, vaginitis. Lethality 25%.

Multimorphic exudative erythema Stevenson-Johnson

Alopecia areata

More than 300 different medicinal substances can cause hair loss, on the basis of which several thousand preparations are produced.
Alopecia is a common side effect of chemotherapy.

"serum" disease

injection site rash, fever, lymphadenopathy, arthritis, myocarditis, nephritis.

In 87% of patients with drug disease.
Anemia
Hemolytic in connection with a direct damaging effect on red blood cells (nitrous oxide) or the formation of antibodies (penicillin, salazopyridazine, dopegyt).
Aplastic(in the presence of a certain genetic predisposition) - chloramphenicol, butadione, sulfonamides, etc.
Megaloblastic(folic acid deficiency) when taking tuberculostatic drugs, anticonvulsants.

Violation of leukopoiesis
Leukopenia and / or agranulocytosis - sulfonamides, pyrazolone preparations, tuberculo- and cytostatics;
Leukocytosis, often with eosinophilia (antibiotics, hormones), leukocytosis with monocytosis.

Thrombocytopathy (thrombocytopenia)
Rare, associated with damage to progenitor cells (megakaryocytes) or platelets themselves directly or through the development of antibodies (curantil, quinidine, heparin, gold preparations).

medicinal fever

In 10% of inpatients, the rise in temperature is associated with taking medications.
This is a source of diagnostic errors, regarded by doctors as an exacerbation of the infection, which dictates the appointment of antibacterial agents at the time when they should be canceled.

medicinal fever

Diagnostics:
Appearance on days 7-14 of treatment;
Disappearance less than 48-72 hours after discontinuation of the "culprit" drug;
The absence of diseases that can explain the increase in body temperature;
Most often occur during treatment with penicillin, cephalosporins, less often - sulfonamides, barbiturates, quinine;
Rarely - the only manifestation of LB.

1. Pneumonitis, alveolitis, pulmonary hypereosinophilia (antibiotics, sulfonamides, isoniazid);
2. Violation of the innervation of the lungs: blockade of the respiratory center (narcotic analgesics, sedatives, tranquilizers); blockade of neuromuscular synapses (aminoglycosides);

3. Damage to the pleura: serositis, lupus syndrome, eosinophils in the pleural fluid (antibiotics, methotrexate); fibrosis (propranolol);
4. Respiratory tract lesions: bronchospasm (NSAIDs, beta-blockers, penicillin, pancreatin, vitamin B1, etc.);

5. Vascular damage: thromboembolism, thrombosis (sex hormones); pulmonary hypertension; pulmonary vasculitis (nitrofurans, penicillin, glucocorticosteroids);
6. Non-coronary pulmonary edema (NSAIDs, lidocaine, methotrexate, opiates, radiopaque agents, cordarone).
7. Candidiasis: exhaustion, fever, hemoptysis, eosinophilia.

Drug-induced liver injury

The list of drugs that cause liver damage in 1992 included 808 drugs.
Mechanisms of damage to the liver tissue
Direct toxic effect on hepatocytes with their subsequent necrosis;
Violation of bilirubin metabolism;
Sinus dilatation and veno-occlusion;
Immunological reactions (HRT, GNT).

Classification of drug-induced liver lesions

Acute hepatitis (dopamine, halothane, etc.)
Fatty degeneration (tetracyclines, amiodarone)
Fibrosis (methotrexate, vit. A, arsenic preparations)
Chronic active hepatitis (nitrofurans, methyldopa, halothane, paracetamol, isoniazid)
Hepatocyte necrosis (paracetamol, halothane)
Cholestasis (sex hormones, contraceptives, methyltestosterone, cyclosporine A, erythromycin)
Tumors (estrogen)
Hypersensitivity reactions (sulfonamides, quinidine, allopurinol)
Vascular damage (cytostatics, sex hormones)

Damage to the nervous system (15%)

Drowsiness, depression (clofellin, rauwolfia preparations).
Hallucinations (cardiac glycosides).
Headaches.
epileptiform seizures.

Joint damage - 20%

drug arthritis accompanies serum sickness, less often - AS, Quincke's edema, drug-induced bronchial asthma (penicillin antibiotics, tetracyclines, vaccines, sera, sulfonamides).
medicinal gout due to:
a) taking drugs - sources of exogenous purines (pancreatin, liver preparations), b) inhibition of purine secretion in the distal tubules of the kidneys (diuretics, salicylates in small doses).
Pyrophosphate arthropathy(thyroid hormones)
SLE syndrome- more often in older men on hydralazine (apressin), novocainamide, isoniazid.
Joint damage, like drug fever, is a source of diagnostic errors and a reason for unreasonable drug therapy.

Drug-induced kidney injury

Interstitial nephritis (NSAIDs, antibiotics, analgesics)
Glomerulonephritis (apressin, D-penicillamine)
Acute renal failure
Acute urolithiasis (vitamin D, ascorbic acid, cytostatics + diuretics, calcium preparations)
Chronic drug nephropathy (NSAID)
Papillary necrosis (iodine preparations, verografin)
Acute hemoglobinuric nephrosis (delagil)
Tubulointerstitial nephropathy
allergic cystitis, urethritis

Drug-induced lesions of the gastrointestinal tract

Functional Disorders
Ulcerative lesions of the stomach and intestines
Allergic lesions of the small intestine
Dysbacteriosis, mycosis
Pancreatitis

Collapse (beta-blockers, aminosine, procainamide)
Drug vasculitis (antibiotics, sulfonamides, butadione, serums)
Arrhythmias:
ventricular extrasystole (norepinephrine + strophanthin)
blockade, asystole (butadione, procainamide)
excitability dysfunction (strophanthin)
Cardialgia

Pericarditis (eufillin)
Infection of the endocardium and valves (glucocorticoids, cytostatics, immunosuppressants)
Coronaritis (oral contraceptives, gold preparations, calcium chloride, radiopaque agents)
Myocarditis (tetanus toxoid, toxoid, analgin, novocaine, penicillin antibiotics).

Diagnosis of drug disease

Careful history taking, mainly of allergies and medications.
Clinic.
Frequent combination of these symptoms (syndromes).
Rapid positive dynamics after discontinuation of the drug (exception - damage to the kidneys, liver, fever).
Allergist examination.

Formulation of the diagnosis of a drug disease

Disease name
Severity
Stage of the disease
Main manifestations or syndromes
List intolerable drugs
Features of the process flow
Example:
Drug-induced disease, severe course, necrotizing vasculitis, agranulocytosis. cholestatic hepatitis. Sensitization to butadione.

"The best
medicine
for the patient
- good doctor
M.V. Chernorutsky

The main role in the prevention of drug disease is played by a highly educated doctor

OUTCOMES

recovery - in 81%;
transition to a chronic course 13%. An example of a chronic course of LB is BA, recurrent agranulocytosis, chronic drug-induced hepatitis, chronic interstitial nephritis;
residual effects after a protracted course of drug allergy with irreversible effects: myocardial cardiosclerosis, pneumosclerosis, adhesive conjunctivitis;
mortality of patients - 6.3%; causes - anaphylactic shock, hypoplastic anemia, agranulocytosis, hemorrhagic encephalitis, myocarditis, vasculitis.