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Drug allergy

Throughout all history the mankind searched for means to cure illnesses, to alleviate suffering, prolong life. At first empirical, then the scientific way selected and estimated a large quantity of substances of a natural and chemical origin. The data about negative by-effects as a whole useful substances in parallel collected.

At a modern level of development of a society we can speak about the developed system of rendering of medical aid which includes activity of the diplomaed experts who are engaged in treatment of patients in specialized establishments, and functioning of the developed pharmaceutical industry. Many scientific research institutes develop and study new medical products.

Certainly, exist dieto - both the physiotherapy and other methods of treatment of disease, but use of medical products is still priority. Application of modern medicines rescues from many serious illness (and postoperative complications), promotes growth of life expectancy of people.

Penicillin reception in 1942 has rescued millions human lives. Streptomycin application has allowed to cure many forms of a tuberculosis. All over the world hundreds tons of antibiotics are developed. Pride of a medical science is also synthesis of chemotherapy, applied in oncology, and also the vasodilating means used in cardiology.

The doctor-professional can spend scientifically well-founded therapy only. He should think how to secure the patient against complications. The doctor should own methods of diagnostics, treatment and preventive maintenance of complications, to inform the patient on possible by-effects.

The doctor-professional can spend scientifically well-founded therapy only. He should think how to secure the patient against complications. The doctor should own methods of diagnostics, treatment and preventive maintenance of complications, to inform the patient on possible by-effects.

Proceeding from modern representations about mechanisms of collateral actions of medicines, it is possible to make the following classification scheme.

  1. Toxic reactions:
    • Overdose.
    • Toxic reactions from the therapeutic doses, connected with delay of a metabolism of medicines.
    • Toxic reactions in connection with functional insufficiency of a liver, kidneys.
    • The remote toxic effects (teratogenicity, carcinogenicity).
  2. Superinfections and dysbacterioses.
  3. The Reactions connected with a massive bacteriolysis under operation of the medicine (reaction of Jarisha-Gersgejmera, etc.)
  4. The Reactions caused by special sensitivity of subpopulation:
    • The unusual reactions which distinct from pharmacological, are caused, possibly, enzymopathia, and pseudo-allergic reactions.
    • Allergic reactions.
  5. Psychogenic reactions.

Toxic action of medical products can be the general or local with primary defeat of separate bodies. For example, monomycinum, streptomycin can cause toxic damage of acoustical nerves.

Now we want to talk about the allergic complications caused by medical products. The medicinal and medicamentous allergy is the secondary raised specific immune reaction to the medical products, accompanied by the general or local clinical displays. It develops only at repeated introduction of preparations. Pseudo-allergic reactions to medicines are clinically identical allergic are nonspecific (without antibodies) the raised reactions to preparations.

There are two categories of patients. At one medicinal allergy arises as complication at treatment of any disease. At others is the occupational disease, being the basic, and it is frequent also the unique reason of time or changeable invalidity. As occupational disease a medicinal allergy arises at almost healthy faces owing to long contact to medicines and medicines (doctors, staff nurses, pharmacists, workers of factories of medical preparations).

Among urban population the medicinal allergy meets more often at women — 30 women and 14 men on 1000 persons (in countryside accordingly 20 and 11). More often the medicinal allergy is observed at persons at the age of 31-40 years. In 40-50 % of cases the reason of allergic reactions are antibiotics.

The risk of development of an allergy to a medicine makes 1-3 %. Therefore it is possible to allocate principal causes of development of an allergy to medicines:

  • The hereditary, genetically caused predisposition;
  • Presence of other kinds of an allergy (bacterial, pollen, food, etc.);
  • Long application by patients (at healthy — contact) medical products, especially repeated courses;
  • Application of depots-preparations;
  • Simultaneous appointment of a great number of medical products from different groups which products of a metabolism can strengthen allergenic action each other;
  • Physical and chemical structure, high activity of a preparation.

Four types of immunological mechanisms of damage of fabrics can participate in development of allergic reactions to medicines.

Accordingly these mechanisms of display of a medicinal allergy can be divided into following kinds:

  1. Immediate.
  2. Cytotoxic. Usually it hematologic reactions (a haemolytic anemia, leukopenia, a thrombocytopenia).
  3. Immunokompleksnyj type. A typical example is the syndrome serum illnesses.
  4. Slowed down — caused by cellular type of hypersensitivity.

Reactions of the first type — anaphylactics (IqE-dependent).

Immediate allergic reactions develop quickly, from several seconds (anaphylactic shock) till 12 o'clock (small tortoiseshell), and more often in 30 minutes.

The clinical picture of reaction of the first type can be expressed in the form of medicinal anaphylactic shock, an attack of a bronchial asthma, a rhinitis, conjunctivitis (St. Claire's disease), the small tortoiseshell and a hypostasis of Kvinke.

The slowed down allergic reactions develop in 24-72 hours and are caused by interaction of allergen with T-limfotsitami.

Reactions of the slowed down type are observed at an allergic contact dermatitis, at formation of the infiltrates induced by medicines, in various bodies and fabrics.

The majority of clinical displays of a medicinal allergy is accompanied by presence of the mixed reactions of various types. So, shock, the small tortoiseshell, a bronchospasm can be accompanied by reactions both the first, and the third type, in pathogenesis of hematologic infringements participate cytotoxic and immunocomplex mechanisms.

Unlike true allergic reactions at the pseudo-allergic there are no antibodies and immune T-limfotsity.

Pseudo-allergic reactions can be observed at primary introduction in an organism radiopaque substances, local anesthetics, opiates, neuromuscular blocking agent and other preparations.

Almost all medical products can induce allergic reactions. Some medicines, being squirrels, glycoproteins and other difficult biological molecules (vaccines, whey, antibodies and etc.) alien (an animal, microbic) origins, easily are induced by the immune answer and allergic reactions. Obligate allergens is antiwhey (tetanus, antidiphtherial, against a gas gangrene, the Siberian ulcer, poison of snakes). Hormones and enzymes, squirrels and polypeptides of an animal (insulin, corticotropin, a cyto-poppy, cytochrome With, etc.) and microbic (streptodecasum) origins can similarly operate.

Other, simple chemical molecules of small molecular weight — haptens — aren't capable to start the immune answer independently.

However, incorporating to squirrels, polysaccharides, lipids and other macromolecules-carriers of an organism, modify them, creating high-immunogenic complexes.

The big problem are cross reactions to medicines and medicines.

The general determinants are available for penicillin and cephalosporins. Other example — novocaine and sulfanilamidies — close antigene properties also have.

Recently the allergy to latex that is connected with expansion of the use of products from this material is even more often described, on the average it makes 5,8 % — in hospital, 25 % — in stomatologic offices.

By-effects from disinfectants can develop from local irritating, toxic and contact allergenic actions on a skin and aerosol — on mucous membranes of respiratory ways, eyes.

Clinical displays of an allergy to medicines are various on localization, weight, a current.

Clinical forms (on localization and involving of bodies and systems):

  1. Generalized:
    • anaphylactic's shock;
    • serum illness and serum similar a syndrome (skin-form of a medicinal allergy);
    • Fever;
    • Generalized vasculitis in a combination to other defeats.
  2. Localized (organ and system):
    • Skin defeats;
    • toxicoderma with defeat of an internal (a syndrome of Lajella, Stevens-Johnson);
    • hematologic defeats;
    • vasculitis;
    • visceral (internal);
    • Mucous membranes and respiratory system;
    • Nervous system.

As diagnostic criteria following signs serve:

  • Establishment of communication of clinical displays with drug intake.
  • Softening or disappearance of symptoms after cancellation.
  • The personal on allergy personal and family anamnesis.
  • Good shipping of a preparation in the past.
  • Exception of other kinds of collateral action (toxic, pharmacological, and so forth).
  • Presence of the latent period of a sensitization — not less than 7 days.
  • Similarity of clinical symptoms to allergy displays, but not with other effect.
  • Positive allergological and immunological tests.

If in the anamnesis there are accurate instructions (or records in the history of illness) on an allergy to a preparation and the medicines having cross-reacting general determinants, to the patient it is impossible to enter it and to put provocative tests (skin, etc.) with this preparation it is not recommended. Probably laboratory inspection. It is extremely necessary, if the anamnesis isn't clear (the patient doesn't remember, on what preparation there was a shock) or it it is impossible to collect (unconsciousness).

During the sharp period of allergic disease specific tests quite often happen negative, and testing of allergens for patients can strengthen an aggravation. Therefore such inspection spend usually in remission. As alternative to tests for the patient laboratory inspection serves. Allergologichesky inspection includes two kinds of methods:

Laboratory methods which should precede tests for the patient;

Provocative tests for the patient.

At an estimation of results of inspection always it is necessary to remember that at the positive laboratory and-or provocative test at the patient reaction to the examinee a preparation is possible its replacement, hence, is necessary. In case of negative tests (especially if it is put one) reaction possibility isn't excluded.

Laboratory methods of diagnostics of a medicinal allergy

Allergenspetsifichesky laboratory methods are the cores for diagnostics of many kinds of an allergy, including medicinal.

The general indications for application of laboratory methods of revealing of a medicinal allergy:

  • Patients with intolerance of medicines;
  • Patients with burdened allergic anamnesis (wolferine);
  • Patients with a professional allergy (for diagnosis and employment statement);
  • Not clear cases for diagnostics, suspicions on visceral forms of a medicinal allergy;
  • Necessity of an exception of pseudo-allergic reactions at introduction of medicines and medicines the patient with predisposition to them;
  • Desire of the patient and-or the doctor (before medicine introduction, operation, etc.).

Obligatory indications for preliminary laboratory inspection of patients on shipping of medicines:

  • Shock, heavy toxicoderma in the anamnesis on an unknown preparation and necessity of medicinal therapy;
  • Intolerance of medicines at children of early age and adults when skin tests are negative on a histamine;
  • At extensive defeats of a skin (heavy toxicoderma) and necessities of selection of transferable preparations (antibiotics, etc.);

Specific methods of allergy diagnosis are directed on:

  • Revealing of free antibodies in whey of blood and secrets;
  • Detection of the antibodies connected with leukocytes (basophiles, neutrophils, platelet, etc.);
  • Definition T-limfotsitov, sensitized to allergen.

Complex of the laboratory methods providing reliable diagnostics of an allergy

Skin tests not always give trustworthy information about presence of a medicinal allergy and they can't be used at the expressed defeats of a skin, and also at anaphylactic shock or possibility of its development in connection with not clear anamnesis. At children of early age, sometimes at older persons at drug allergy skin tests are negative. Therefore laboratory methods of revealing of an allergy on safety and use possibility during any period of disease remain preferable. Application of a complex of laboratory methods for authentic diagnostics of a medicinal allergy is necessary. For this purpose at Institute of allergology and clinical immunology we have developed reports of the minimum and maximum complex of laboratory methods.

The report of a full complex of the methods providing diagnostics of all kinds of hypersensitivity, includes:

  • Revealing of reactions anaphylactic, IgE-dependent type;
  • Definition of the IgE-antibodies connected with basophiles;
  • Registration immunocomplex reactions;
  • Definition of reaction of the cytotoxic and intermediate (delayed) type;
  • Diagnostics of the cellular-mediated, T-cellular and slowed down reactions;

For the purpose of preventive maintenance of complications to reveal a sensitization to a medicine which is necessary for entering to the patient, use various provocative tests: skin, hypoglossal, oral, intranasal, inhalation, etc. However it is necessary to consider possibility of complications and shock reactions even on preparation micrograms.

Positive skin tests specify in sensitization presence to allergen. The latent, clinically not shown sensitization is possible. On the other hand, skin tests can be negative and in the presence of allergy clinic. Only at coincidence of results of skin tests to the anamnesis, clinic and the laboratory data etiological the diagnosis becomes doubtless.

Relative contra-indications to skin tests:

  • During the sharp period of allergic and any another of average weight or a serious illness; at an easy current the question dares individually, taking into account possible complications;
  • During pregnancy, feeding of the child and first two-three days of a menstrual cycle;
  • In the absence of the convincing anamnesis and the pilot survey testifying about allergological character of disease.

However in need of introduction of a medicine with the burdened or not clear anamnesis it is necessary for patient to put test after an exception of allergenicity of a preparation in laboratory tests.

On character of displays and possible consequences even mild cases of medicinal allergic reactions potentially pose threat of life of the patient. It is connected with possibility of fast generalization of process in the conditions of relative insufficiency of spent therapy, its delay in relation to progressing allergic reaction. Propensity to progressing, process weighting, occurrence of complications — characteristic feature of an allergy in general, but especially medicinal. From these positions therapy of a medicinal allergy is a complex of the urgent actions including various means depending on weight of process and presence of specific and nonspecific complications and syndromes.

As a rule, at all displays of a medicinal allergy it is necessary to cancel all earlier applied preparations as and in cases of seeming evidence of the reason — reaction to directly entered preparation — it is possible that it was a consequence before accepted in of a preparation or entered even some days ago. Therefore leave only the preparations necessary under vital indications (insulin — sick of a diabetes, an antibiotic — at a sepsis and etc.).

Patients to a medicinal allergy quite often have a food allergy. Therefore the basic hypoallergenic diet in which carbohydrates are limited is necessary for them and all products of extreme flavoring sensations (salty, sour, bitter, sweet), and also smoked products, spices are excluded, etc. In the presence of a food allergy the diet is appointed elimination. Plentiful drink of water and tea, but not the difficult painted drinks (an allergy to dyes) is shown.

In some cases it is required to solve urgently a question on possibility of use of those or other preparations. Such estimation is expedient for spending since the laboratory tests which result can be received within 1 hour.

Treatment subacute and chronic forms of a medicinal allergy has the features. Usually they meet as consequence of occupational disease at medics, pharmacists, working the medical industry. In these cases therapy, that is an exception of contact with cause-significant allergens — employment of patients is necessary elimination. It warns at them process progressing, development of a polyvalent allergy to other groups of allergens, allows to keep work capacity, though and with partial loss of professional suitability (especially at nurses). In an aggravation of the given form of an allergy in treatment use antihistamines, other antimediators, including their prolonged forms. The given contingent of patients accepts antirelapse therapy.

One of the reasons of high frequency of allergic reactions to medicines — ignoring of measures of preventive maintenance.

Gathering allergic history is the first stage of preventive maintenance of drug allergy. The patient without the anamnesis burdened by an allergy: in the past had no any allergic diseases and well transferred all medical products, foodstuff, contacts to household chemical substances or never earlier accepted medicines. Such patient can to be surveyed.

Patients with the burdened anamnesis, on the contrary, demand inspection for the purpose of diagnostics of the latent predisposition or an obvious allergy. On degree of risk they can be divided into three groups. We consider that all expediently originally to survey laboratory about shipping of the preparations necessary for treatment.

The factors promoting occurrence of a medicinal allergy at children, are:

  • Genetic predisposition;
  • Atopic illnesses;
  • Previous infections;
  • palindromic a candidiasis;
  • immunodeficiency a condition;
  • Anomalies of the constitution of development in the form of an ekssudativno-catarrhal diathesis;
  • System diseases of mother;
  • Artificial feeding;
  • intermittent drug intake, an inhalation way of introduction;
  • Dysbacterioses;
  • helminthiasis;
  • Allergy to vaccines;
  • endocrine infringements;
  • fermentopathy congenital and got genesis;
  • highly allergenic properties of medicines;
  • A unilateral food of mother during pregnancy, predilection for products with food dyes, stabilizers and preservatives;
  • gestosis I and II half of pregnancy.

Diagnostics of a medicinal allergy at children begins with detailed studying allergic the anamnesis: the current of pregnancy of mother of the child, presence gestosis pregnancy, predilection for any foodstuff, a food unilaterality, presence of professional harm, drug intake is analyzed during pregnancy, a current of sorts with application of medicamentous stimulation and anesthesia, a current of the early neonatal period of adaptation of the newborn, use of any medicines, including the woman in childbirth concerning the complicated postnatal condition, feeding of the child by the chest milk, the adapted or not adapted dairy mixes. Terms of introduction of fruit and vegetable juice, reaction to them, reaction of the child to various kinds of a feeding up (occurrence of a rash, a skin itch, change of character of a chair and etc.) Presence of collateral reaction to vaccination, reactions of the child to the various medicines used at diseases, time of their occurrence (on the first introduction or reception, for 7-14th day of application), severity level — locality or systemic allergic reaction, and also adequacy of reaction of biological liquids — blood, urine, a saliva, transudate, a spinno-brain liquid and etc.

Hereditary predisposition to a medicamentous allergy and allergological to diseases in general is without fail established. It is necessary to find out feature of reaction to stings of insects, to define provoking and aggravating factors (for example, weather conditions, reception of the products concerning strong food allergens, contact to chemical and household substrata, contact to animals, computer presence in premises of the child, the animals, blossoming plants, communication with catarrhal diseases, virus infections and etc.). After diagnosis specification pass to purposeful clinical inspection of the child.

Complexes of laboratory methods and skin tests which well correlate with the anamnesis and the clinical data are applied to diagnostics of a medicinal allergy at children.

Experts of institute of allergology and clinical immunology own all methods of diagnostics and treatment of a medicinal allergy, we give special attention to laboratory diagnostics, as to the most sparing, perspective and informative method of diagnostics, especially at its complex carrying out.

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