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Drug disease

Drug disease is a manifestation of hypersensitivity to drugs or individual intolerance to drugs. There are two forms of drug disease: 1) drug allergy - the main, most common form; at the same time, either the drug itself, or its transformation products, bind to the serum or tissue proteins of the body and form a complete antigen that causes the formation of allergic antibodies; 2) idiosyncrasy, develops as a result of genetically determined defects of enzymes metabolizing the administered drug. Often this enzymatic defect contributes to the development and allergic reaction. Other types of drug-induced reactions should be distinguished from drug disease (toxic effect due to overdose, side effects of the therapeutic drug, such as candidosis, in patients who received antibiotics).

Manifestations of drug disease are diverse. All organs and systems of the body can be affected. Medicinal diseases can be divided according to the speed of development and the course into 3 groups: 1) reactions that develop instantaneously or within one hour after the drugs enter the body and usually proceed with acute anaphylactic shock (see Anaphylaxis ), urticaria (see) , Quincke swelling (see), an attack of bronchial asthma (see), hemolytic anemia (see); 2) reactions of the subacute type occur within the first days after the drug administration: agranulocytosis and thrombocytopenia (see), systemic capillary toxicosis (see Vasculitis, hemorrhagic), fever, allergic rhinitis ; 3) late type reactions that develop several days and weeks after drug administration: serum sickness (see), allergic vasculitis and purpura, allergic dermatitis, inflammatory processes in the joints, lymph nodes and internal organs (allergic hepatitis, nephritis , encephalomyelitis ). In addition, drug disease is manifested by exacerbations of the underlying disease. The most dangerous acute manifestations of drug disease.

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In principle, any drug may be an allergen, that is, it may cause sensitization of the body and the development of a drug disease. However, with different drugs, this ability is expressed differently. With repeated courses of treatment with the same drug, especially with the introduction of antitoxic serums, the frequency of medicinal diseases, as a rule, increases. Medical and pharmacy workers display drug allergy three times more often than the rest of the population.

It is easy to make a diagnosis if the drug disease occurs immediately after taking the medication. In other cases, you need to collect a thorough history of the patient. The use of skin tests for the diagnosis of drug disease is not recommended. Introduction to the skin of the most minimal amounts of drugs, such as an antibiotic, in sensitive patients can cause anaphylactic shock. The diagnosis is confirmed if, after drug withdrawal, the symptoms of the drug disease disappear.

Treatment . To stop the further introduction of the drug, and with the rapid development of drug disease, if possible, to stop the further flow of the allergen into the blood; if a drug disease is caused by subcutaneous or intramuscular injection of drugs, then, if possible, put a tourniquet above the injection site. At the injection site immediately enter 0.5 ml of 0.1% solution of adrenaline. In shock, subcutaneously inject 0.5 ml of 0.1% adrenaline solution, and in severe cases, intravenously in 10-20 ml of 40% glucose solution. If the blood pressure does not recover, repeat the adrenaline injection. In the absence of improvement, drip intravenous administration of norepinephrine (5 ml of a 0.2% solution diluted in 500 ml of a 5% glucose solution and injected at a rate of 40–50 drops per minute). When symptoms of bronchospasm enter slowly intravenously 10 ml of 2.4% solution of aminophylline .

For any manifestations of a rapidly developing drug disease, especially for cutaneous, intramuscularly antihistamines should be administered: 1-2 ml of a 2.5% solution of pipolfen, or 1-2 ml of a 2% solution of suprastin (can be carefully administered intravenously), or 5 ml of a 1% solution of Dimedrol . Subacute and late drug disease is best treated with corticosteroids ( prednisone , triamcinolone , dexamethasone, hydrocortisone acetate ) orally or intramuscularly. With timely treatment, the prognosis is favorable.

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Prevention . General measures: 1) not to prescribe drugs where there is no need for this (for example, antibiotics for influenza); 2) do not prescribe intravenous injections where intramuscular or subcutaneous injection is sufficient; 3) the first injection of the drug, especially antibiotics, should be done in the shoulder area, so that in the event of the development of an acute drug disease it was possible to impose a tourniquet proximal to the injection; 4) in treatment rooms, have separate syringes and needles for each group of chemically related antibiotics; eliminate the habit of removing excess solution from the syringe directly into the air, as this leads to the spraying of medication, which can contribute to the sensitization of health workers and patients and cause the development of drug disease; 5) patients with allergies to drugs should not be placed in the ward next to patients receiving these drugs. Individual prophylaxis: 1) to ask the patient whether he received this drug earlier and how his patient was transferred; 2) to find out whether the patient suffers from any allergic diseases, since such patients often develop drug disease; 3) to make notes in the history of the disease on allergy to the drug; 4) warn the patient not to take this drug in the future.

Drug disease [morbus medicamentosus; synonym drug allergy (allergia medicamentosa)] - manifestations of sensitization to certain drugs in certain individuals with increased immunological reactivity. The basis of a medicinal disease, like allergies (see) in general, is the reaction of a drug - an antigen with a specific antibody.

Simple chemicals can either directly act as antigens (A.M. Bezredka, 1928) and as haptens [after binding to whey protein into complex antigens, Landsteiner (K. Landsteiner)] or alter the antigenic properties of body tissues by damaging cellular elements. Medicines with allergenic properties include benzene and pyrimidine derivatives with NH 2 , NO 2 side chains and others.

Drug allergy, as well as any other, manifests itself in two types of reactions: 1) an immediate “blistering” or anaphylactic reaction with the presence of specific antibodies (reagins) in blood serum detected by various immunological methods — by agglutination with serum of patients in suspension of indifferent particles loaded antigen; precipitation, etc .; 2) delayed, "tuberculin" reaction of the nature of cellular hypersensitivity with the clinical syndrome of the "ninth day erythema." The second type of reaction is characterized by the formation of intradermal granulomas on the administration of a drug (antigen) in the absence of circulating antibodies. The presence of cellular antibodies can be shown in the experiment with the transfer of lymphocytes and other similar complex methods. Drug allergies to a particular drug can be expressed by an immediate “blistering” or anaphylactic reaction, followed by the development of granulomas, vasculitis, etc., as is the case with serum sickness, with which the drug disease has many other similarities.

Drug allergies have become more frequently observed due to the widespread use of highly antigenic drugs - arsenobenzenes, which cause individual hypersensitivity to nitritoid crises, hemorrhagic encephalitis, etc .; amidopirin (pyramidone), a well-known “provocateur” agranulocytosis; mercury diuretic, causing allergic hemorrhagic vasculitis; sulfa drugs with complications such as acute hemolysis, vasculitis, up to periarteritis nodosa; penicillin, thiouracil, butadion, PAS and others.

Clinical manifestations of a medicinal disease include medicinal rashes, medicinal fever (“paradoxical” fever with quinine intolerance), medicinal arthritis, etc., as well as cases of sudden, as if causeless death from shock (for example, immediately after lubrication of the tonsils with an ordinary solution silver nitrate). E. A. Arkin (1901) for the first time combined the drug rash and other symptoms, often repeating the clinical manifestations of an infectious disease, into the concept of a medicinal disease, opposing it to drug poisoning. The name of a medicinal disease, i.e., drug allergy, cannot be extended to other important side effects of drugs - specific toxicosis, dysbacteriosis, etc. For example, leukopenia or aplastic anemia can have not only an immunocytopenic, but also a cytotoxic or anti-metabolite mechanism (as with chloramphenicol).

The shock characteristic of an immediate reaction usually occurs in the next few minutes after the administration of the drug, often parenteral and especially intravenous; manifested by tightness in the chest, asphyxiation, cyanosis (sometimes after the initial sharp hyperemia of the face - "nitritoid crisis"), tachycardia with arrhythmia, collapse, convulsions, stupor, sometimes the development of angioedema, quickly occurring, often in the first 5-15 minutes, death (anaphylactic death). On the section they find bronchospasm, distention of the lungs, the overflow of blood vessels of the abdominal cavity. In milder cases, an immediate reaction, especially with intravenous drug administration, is only expressed by itching, urticaria, sneezing, chills, fever.

A slow reaction (“erythema of the ninth day”) usually occurs 5–9 days after the start of treatment and lasts about 1–2 weeks, expressed as a general reaction cyclically proceeding in the form of generalized dermatitis such as urticaria, etc., itching, fever, joint damage, adenopathy , vasculitis, serositis, damage to the blood, nervous and other systems.

There may be a local reaction of the contact type in the form of a nettle blister or erythema at the site of subcutaneous or intramuscular drug administration, edema of the tongue or pharynx when the drug is administered by inhalation, etc., or a resorptive response in the form of an increase in the inflammatory process in the lungs with hemoptysis, tissue necrosis for example with pneumonia. Drug disease in individual patients may manifest as an isolated, as if independent, lesion of one or another organ - skin with bark-, scarlet-like, smallpox-like exanthema, purpura, erythema nodosum, exfoliative dermatitis; lungs with eosinophilic volatile infiltrate, asthma, vascular interstitial pneumonia; blood lesion with agranulocytosis, aplastic or hemolytic anemia; Hearts with plasma cell eosinophilic myocarditis, etc .; liver with eosinophilic, cholestatic or severe parenchymal hepatitis; kidney with nephritis or nephrotic syndrome; nervous system with polyneuritis, encephalitis, etc., as well as in the form of lymphadenopathy and hepatolienolimine adenopathy such as reticulosis, systemic vasculitis such as hemorrhagic or nodular periarteritis with lesions of many organs, etc.

Drug disease usually proceeds cyclically, quickly ending in recovery from drug withdrawal; However, repeating, as a rule, with the new use of the same medicine, often in stereotypical form (fixed erythema, drug agranulocytosis, etc.), the drug disease can take a chronic course, not only due to repeated exposure to a specific allergen, but also a different nature (the phenomenon of parallelergy), which is especially clearly observed in drug asthma and drug dermatitis. In the section, the diagnosis of a delayed-type medicinal disease is confirmed by the lesion of the corresponding organ in the form of allergic myocarditis, pulmonary vasculitis with pneumonitis, hemorrhagic encephalitis, necrotizing gastritis, colitis, subacute nephritis, aplastic bone marrow, etc.

Diagnosis. Drug disease is still not widely recognized, often in the presence of skin rashes, urticaria, pruritus, fever, eosinophilia, leukopenia, arising in clear connection with the reception of the most highly sensitizing agents. Drug allergies can, however, also manifest themselves as isolated tachycardia, isolated arterial hypotension, accelerated ESR, globulin shifts and other diverse symptoms after the introduction of even the most common drugs. A runny nose for iodine, also known for individual intolerance to quinine, sulfa drugs, butadion, etc .; infiltrates from camphor oil injections, accompanied by high blood eosinophilia; sudden death after intravenous administration of usual doses of sulfobromphthalein, dioderast, etc. Allergic, including fatal, reactions can also occur on low-toxic drugs like penicillin, amidopyrine (pyramidone), atofan, which have been used for years in medicine without any special side effects.

Disease allergies predispose diseases that are accompanied by significant immunological rearrangement (infections, collagenosis, etc.) and require the systematic, often prolonged use of active drugs. At the same time, manifestations of drug allergy in such cases are more difficult to recognize. For example, in patients with tuberculosis treated with PASK, or in patients with heart failure, receiving mercuzale, hemorrhagic vasculitis, leukopenia, eosinophilia can be a manifestation of both the underlying disease and drug intolerance. However, at present, such complications are more often due to drug allergy.

The diagnosis of a medicinal disease often reinforces the cessation of fever and other symptoms with the discontinuation of a suspect in poor tolerability. Allergy skin tests are practically little reliable and far from indifferent for the patient. Detection of specific antibodies and other similar complex diagnostic methods are available only to research laboratories. In some cases, the drug disease may remain unrecognized neither in life nor in the section.

Treatment and prevention. At the first signs of anaphylactic shock, adrenaline is immediately injected subcutaneously or intramuscularly, and even (slowly) with an intravenous dose of 0.3–0.5 ml of a 0.1% solution, if necessary again, aminophylline (aminophylline), 0.24–0.48 g intravenous, hydrocortisone 50 mg in 1 liter of saline intravenously; oxygen therapy, artificial respiration, usual stimulants and desensitizing agents - Dimedrol, 5 ml of 1% solution intramuscularly, novocaine are also used. In each case of medication use, especially parenteral, in case of suspicion of individual intolerance, it is recommended to have a syringe with adrenaline solution ready; in addition, parenteral administration of the drug should be in the distal part of the limb, so that if necessary it can be possible to delay the flow of the drug into the general bloodstream by constricting the limb of a patient with a cord above the injection site.

In severe drug disease occurring in a delayed type, it is most advisable to use prednisone or other corticosteroids in medium doses for quite a long time; treatment with the drug that caused the drug disease must be stopped.

Lighter desensitizing agents are also used: diphenhydramine, diprazin (pipolfen), etizin, novocaine, acetylsalicylic acid (aspirin), calcium chloride, amidopyrine (pyramidone), analgin (if there is no leukopenia), not forgetting that each of them can turn in turn cause allergies. They also seek to destroy, neutralize, or rather remove the pathogenic medicine from the body.

For the prevention of drug disease is extremely important not to abuse drugs, especially in individuals with allergic diathesis; it is necessary to clarify in detail in each patient the presence of at least small signs of intolerance to one or another medicine.

People suspected of sensitization to the drug, but with persistent indications for treatment with this agent, are given a minimum dose (for example, 1/100 treatment), avoiding parenteral, especially intravenous, administration as far as possible; treatment is carried out under the protection of corticosteroids. Specific desensitization can be performed very rarely.