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Lecture notes, cheat sheets
Internal illnesses. Drug disease (lecture notes)
Directory / Lecture notes, cheat sheets Table of contents (expand) LECTURE No. 46 Drug disease is associated with the production of antibodies or the appearance of T-lymphocytes specific for the drug or its metabolites. The first report of drug allergy or serum sickness caused by the administration of horse serum appeared more than 100 years ago. Until the end of the 1930s. (appearance of sulfonamides) complications of drug treatment were observed in 0,5-1,5% of patients. Currently, drug allergy only in patients who are in the hospital occurs in 15-30% of cases. Reasons for development include repeated use of intolerable drugs: penicillins, chymopapain, immune sera, live viral vaccines, barbiturates, sulfonamides, quinidines, quinine, allopurinol, iodine preparations, hydralazine, timolol, propranolol, cromolyn, nitrofurantoin, isoniazid, gold preparations, carbamazepine, methyldopa , phenacetin, heparin, phenylbutazone, antithyroid drugs, aspirin, indomethacin, opioids, halothane, penicillinamine. Ways of formation There are 5 types of drug allergic reactions based on the classification of F. Gell and R. Coombs (1964): 1) anaphylactic: sensitization of the body is associated with hyperproduction of cytophilic IgE, which are quickly fixed by the Fc fragment on tissue basophils - mast cells, to a lesser extent on eosinophils and other cells; this is accompanied by a low plasma IgE concentration. When each antigen molecule binds to two IgE molecules (with an obligatory excess of antibodies), a large amount of biologically active substances is released on the surface of the mast cell; 2) cytotoxic: sensitization is characterized by the production of antibodies against antigens that are direct or secondary components of cell membranes; antibodies are IgJ, less often - IgM. The immunoglobulin molecule binds to an antigen located in the cell membrane, the Fab fragment; free Fc-fragment, its CH2 domain bind complement with the formation of a membrane attack complex, perforation of the cell membrane and its subsequent lysis; 3) immunocomplex: occurs when pathogenic circulating immune complexes (CIC) appear in the plasma; pathogenicity is acquired with the insolubility of the CEC, in the case of complement deficiency, or in violation of their normal clearance by RES cells; 4) cellular (delayed-type hypersensitivity): occurs on allergens that are part of large molecules, which are then phagocytosed by macrophages, without damaging antigenic determinants; they are expressed on the macrophage membrane and combined with their own cellular antigen of the HLA-D clone; information from the antigen on the macrophage is read by T-lymphocytes, a protein is synthesized that is complementary to the antigen structure with its expression on the lymphocyte membrane; 5) immunological stimulation: is a variant of the type 2 reaction, develops when antibodies to cell receptors appear; Immunoglobulin binds to the Fab fragment receptor and activates complement, but the resulting membrane attack complex only stimulates this receptor and the specific function of the cell. Classification. Complications associated with infusion, transfusion, and therapeutic injections include: 1) anaphylactic shock associated with the introduction of serum; 2) vascular complications associated with infusion, transfusion and therapeutic injection. The rate of development of allergic reactions. Early allergic reactions (urticaria and anaphylactic shock) develop within 30 minutes after repeated administration of the drug. Delayed allergic reactions (urticaria, itching, bronzospasm, laryngeal edema) develop 2-72 hours after repeated use of the drug. Late allergic reactions (maculopapular rash, urticaria, arthralgia, fever) develop no earlier than 72 hours after repeated administration of the drug. Clinical manifestations. Allergic reactions of immediate type. Caused by many drugs, most often penicillins, develop within 30 minutes after drug administration. Urticaria, Quincke's edema, bronchospasm, anaphylactic shock appear. Rarely, with the introduction of penicillins, Stevens-Johnson syndrome, Lyell's syndrome, interstitial nephritis, systemic vasculitis, hemolytic anemia, neutropenia, neuritis can develop. Cytotoxic allergic reactions. With this form, hematological disorders develop: autoimmune hemolytic anemia, thrombocytopenia, agranulocytosis. The kidneys are affected: with interstitial nephritis caused by methicillin, antibodies to the basement membrane of the renal tubules appear. Immune complex allergic reactions. Most often caused by penicillins, heterologous sera. Serum sickness symptoms usually appear 1-3 weeks after serum administration. Urticaria, maculopapular rash, fever, arthralgia (large joints) develop, lymph nodes may increase, glomerulonephritis, peripheral neuropathy, systemic vasculitis, acute inflammatory demyelinating polyradiculoneutropathy may occur. It is possible to develop drug-induced lupus syndrome, vasculitis with symptoms of fever, hemorrhagic rash, more often on the legs, with damage to the kidneys and lungs. Delayed allergic reactions. These include allergic contact dermatitis (after topical application of drugs), acute pneumonitis, interstitial pneumonitis, encephalomyelitis, interstitial nephritis, drug-induced hepatitis, vasculitis. Acute and interstitial pneumonitis is characterized by fever, dyspnea, cough, eosinophilia, limited or extensive opacities in the lungs, pleural effusion, and respiratory failure. RџSЂRё additional diagnostic study skin tests are used: 1) in allergic reactions of the immediate type: intradermal injection of the antigen is manifested by hyperemia and a blister at the injection site due to degranulation of mast cells and the release of inflammatory mediators; 2) in delayed-type allergic reactions, skin tests have no diagnostic value; Application tests reveal sensitization to drugs for topical use only. The level of specific IgE is determined with the production of a radioallergosorbent test or a histamine release reaction by mast cells. Immunological determination of specific IgJ and IgM to drugs, fixed in tissues or circulating immune complexes (CIC) is performed. To identify sensitized T-lymphocytes, the reaction of lymphocyte blast transformation (RBTL) is performed or cytokine production is evaluated. This method is more sensitive than RBTL. Provocative tests allow you to establish a connection between the use of the drug and the occurrence of an allergic reaction. Due to the high risk of developing severe allergic reactions, samples are used very rarely, only in a hospital. Complications. These include allergy to drug metabolites, pseudo-allergic reactions. Differential diagnostics. Should be carried out with the primary side effect of the drug, which develops when using drugs in therapeutic doses and is associated with their direct effect on target organs. It is necessary to exclude the secondary side effect of the drug as a complication of drug treatment that is not associated with the direct effect of drugs on target organs. You must also exclude: 1) idiosyncrasy, a qualitatively altered response to the drug, due to non-immune mechanisms; 2) drug intolerance - the appearance of side effects when prescribing drugs in low doses; 3) toxic manifestations that develop with an overdose of the drug; 4) systemic lupus erythematosus; 5) vasculitis; 6) dermatitis, skin diseases. Treatment. First of all, the drug that caused the allergic reaction is canceled. In case of a type I allergic reaction, epinephrine, H1blockers, with allergic reactions II, III and IV types - corticosteroids. RџSЂRё anaphylactic shock it is necessary to quickly assess the patency of the respiratory tract, indicators of external respiration and hemodynamics. The patient should be laid on his back with raised legs. When breathing and blood circulation stop, immediately begin cardiopulmonary resuscitation. A tourniquet is applied above the injection site, every 10 minutes it is loosened for 1-2 minutes. A solution of adrenaline 1: 1000 is injected subcutaneously into the shoulder or thigh: for adults - 0,3-0,5 ml, for children - 0,01 ml / kg, if necessary, the administration is repeated after 15-20 minutes. The injection site of the injected allergenic drug (with the exception of the head, neck, hands and feet) is chipped with 0,1-0,3 ml of adrenaline solution 1: 1000. In case of arterial hypotension, 1 ml of adrenaline solution 1: 1000 is diluted in 10 ml of saline, the resulting solution 1:10 is given intravenously over 000-5 minutes. After that, if necessary, an infusion of adrenaline 10: 1 can be carried out. For this, 1000 ml of adrenaline 1: 1 is diluted in 1000 ml of a 250% glucose solution. The initial rate of administration is 50 μg / min, in the absence of side effects, the rate increases to 1 μg / min. With coronary heart disease, atherosclerosis of the cerebral vessels in the elderly, side effects of the action of adrenaline may appear. With cyanosis and severe shortness of breath, oxygen is inhaled at a moderate or high rate (5-10 l / min.) Using a mask or nasal catheter. In chronic obstructive pulmonary diseases, oxygen inhalations are contraindicated, since they lead to depression of the respiratory center. To prevent the recurrence of symptoms of an anaphylactic reaction, N1blockers: diphenhydramine - 1-2 mg / kg intravenously (for 5-10 minutes), intramuscularly or orally. A single dose should not exceed 100 mg. Then the drug is taken at 25-50 mg orally every 6 hours for 2 days. Additionally, N2- histamine receptor blockers: cimetidine is used at a dose of 300 mg (children 5-10 mg / kg) intravenously slowly, intramuscularly or orally every 6-8 hours, ranitidine at a dose of 50 mg intravenously slowly or intramuscularly every 6-8 hours or 150 mg orally every 12 hours (children 2-4 mg / kg). If arterial hypotension and respiratory failure persist, the patient is transferred to the intensive care unit, where the following medical measures are taken: 1) intravenous fluid infusion through a catheter with a maximum diameter: 5% glucose solution in 0,45% sodium chloride solution - 2000-3000 ml / m2 per day. Within 1 hour, 500-2000 ml of liquid is injected, for children - up to 30 ml / kg. With persistent arterial hypotension, physiological saline, albumin, colloidal solutions are also used; 2) β is used for bronchospasm2- adrenostimulants: 0,5-1,0 ml of 0,5% salbutamol solution; while maintaining bronchospasm, aminophylline 4-6 mg/kg is administered intravenously over 15-20 minutes; 3) in the absence of the effect of the treatment, adrenostimulants are prescribed: norepinephrine intravenously, 4-8 mg of norepinephrine is dissolved in 1000 ml of a 5% glucose solution in water or saline, the maximum injection rate should not exceed 2 ml / min if the patient takes glucagon , β-blockers are additionally prescribed 5-15 mcg / min intravenously; 4) instead of norepinephrine, dopamine may be prescribed, more often in patients with heart failure: 200 mg of dopamine is dissolved in 500 ml of a 5% glucose solution, administered intravenously at a rate of 0,3-1,2 mg / kg per hour; 5) with a pronounced edema of the upper respiratory tract, tracheal intubation or tracheostomy is indicated; 6) corticosteroids are prescribed early, as they prevent the recurrence of symptoms: hydrocortisone is administered at a dose of 7-10 mg / kg intravenously, then 5 mg / kg intravenously every 6 hours, the duration of treatment is not more than 2-3 days; 7) after stabilization of the condition, the administration of liquid and medication continues for up to several days (depending on the severity of the condition). Flow. depending on the type of allergic reaction. Recovery is complete. Death from severe anaphylactic reactions occurs within the first 30 minutes. Complications include the development of myocardial infarction and stroke. Forecast. With an allergic reaction of type I in case of untimely resuscitation, the prognosis is unfavorable, with allergic reactions of types II, III and IV - favorable. Prevention. It is necessary to conduct a mandatory collection of an allergic history, to exclude drugs that often cause allergies. When prescribing drugs, possible cross-reactions should be taken into account, more often developing: 1) between penicillins and cephalosporins; 2) various aminoglycosides (such as streptomycin, kanamycin, neomycin, gentamicin); 3) para-aminobenzene derivatives (such as sulfonamides, sulfonylurea derivatives, thiazide diuretics, procaine, acetylsalicylic acid). If it is impossible to cancel or replace the drug, provocative tests with a gradual increase in its doses must be carried out. Usually, the route of administration of the drug is used, which is supposed to be the main one. The drug in increasing doses is prescribed every 15 minutes (Bezredka method). With the development of an anaphylactic reaction during a provocative test, the drug is abandoned. In life-threatening conditions and the development of an anaphylactic reaction to the drug during a provocative test, when it is impossible to replace the drug with another, desensitization is performed. For mild to moderate local reactions, the drug is re-introduced at the same dose that caused the reaction, after which the dose is gradually increased. With an anaphylactic or severe reaction, the dose of the drug is reduced, and then increased more smoothly. Author: Myshkina A.A. << Back: Allergy
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