Antihistamines 2nd generation presentation. Antiallergic drugs
INTRODUCTION
Antihistamines are commonly called drugs that block H1 and H2 histamine receptors.
Histamine, this most important mediator of various physiological and pathological processes in the body, was chemically synthesized in 1907. Subsequently, it was isolated from animal and human tissues (Windaus A., Vogt W.). Even later, its functions were determined: gastric secretion, neurotransmitter function in the central nervous system, allergic reactions, inflammation, etc. Almost 20 years later, in 1938, the first substances with antihistamine activity were created (Bovet D, Staub A.). And already in the 60s, the heterogeneity of histamine receptors in the body was proven and three of their subtypes were identified: H1, H2 and NZ, differing in structure, localization and physiological effects that occur during their activation and blockade. From this time on, an active period of synthesis and clinical testing of various antihistamines began.
Numerous studies have shown that histamine, acting on receptors in the respiratory system, eyes and skin, causes characteristic allergy symptoms, and antihistamines that selectively block H1-type receptors are able to prevent and relieve them. Drugs that block H1-histamine receptors are used to treat allergic diseases. Agents that block H2-histamine receptors reduce secretion and are used as antiulcer drugs.
Most of the antihistamines used have a number of specific pharmacological properties that characterize them as a separate group. These include the following effects: antipruritic, decongestant, antispastic, anticholinergic, antiserotonin, sedative and local anesthetic, as well as prevention of histamine-induced bronchospasm. Some of them are caused not by histamine blockade, but by structural features.
1. HISTAMINE
Histamine (Histaminum) (4-(2-Aminoethyl)-imidazole, or -imidazolyl-ethylamine) is a biogenic compound formed in the body by decarboxylation of the amino acid histidine. Histamine is found in mast cells, basophils, and leukocytes.
Histamine is one of the endogenous mediators involved in the regulation of vital functions of the body and plays an important role in the pathogenesis of a number of painful conditions.
Under normal conditions, histamine is found in the body predominantly in a bound, inactive state. During various pathological processes (anaphylactic shock, burns, frostbite, hay fever, urticaria and other allergic diseases), as well as when certain chemicals enter the body, the amount of free histamine increases. In this case, histamine causes spasm of smooth muscles (including bronchial muscles), dilation of blood vessels and a decrease in blood pressure, an increase in capillary permeability and, as a result, tissue swelling. Histamine causes increased secretion of gastric juice.
With intradermal and subcutaneous administration of histamine, after a few seconds, redness, local swelling, and a feeling of pain and itching develop at the injection site. These symptoms are based on local dilation of capillaries, increased vascular permeability and irritation of sensitive nerve endings.
Histamine is a natural ligand of specific histamine (H) receptors localized in various organs and tissues. There are 3 subtypes of histamine receptors: H1, -, H2, -, H3, receptors.
H1 receptors are localized in the bronchi and intestines (when they are excited, the smooth muscles of these organs contract), in the blood vessels (vasodilation occurs). H2 receptors are located on the parietal cells of the stomach (when stimulated, the secretion of hydrochloric acid increases). The central nervous system contains H1, H2 and H3 receptors. Together with H1 receptors, H2 receptors play a role in the development of allergic and immune reactions. H2 receptors are also involved in the mediation of excitation in the central nervous system.
The first substances with antihistamine activity were created in 1936. In the 60s, a period of active synthesis and clinical testing of various antihistamines began. Recently, great importance has been attached to the stimulation of H3 receptors in the mechanism of the central action of histamine, and a search is underway for drugs that activate and inhibit the functions of this group of receptors.
Antihistamines that block H1-histamine receptors are used to treat allergic diseases. Antihistamines that block histamine H2 receptors are used as antiulcer drugs.
2. H1-HISTAMINE RECEPTOR BLOCKERS
Antihistamines that block H1 receptors are used for immediate allergic reactions: urticaria, itching, allergic conjunctivitis, angioedema (Quincke's edema), allergic rhinitis, etc. These drugs block H1 histamine receptors in organs and tissues and make them insensitive to free histamine. They have virtually no effect on the release of free histamine.
Rice. 1. Scheme of development of an immediate allergic reaction and the direction of action of antiallergic drugs.
When foreign substances - antigens - act on the body, the humoral immune system is activated and antibodies (immunoglobulins E) are formed, which are fixed on mast cells. When this antigen re-enters the body, it interacts with IgE antibodies on the surface of mast cells. This causes degranulation of mast cells and the release of mediators of allergy and inflammation from them: histamine, bradykinin, prostaglandins, slow-reacting substance of anaphylaxis, etc. As a result of the action of allergy mediators on tissues and organs, allergic reactions develop, which can manifest themselves in the form of bronchospasm, dilation of capillaries and redness of the skin, increased capillary permeability and the development of edema, decreased blood pressure, etc.
Most antihistamines that block H1 receptors are chemically related to fat-soluble amines, which have a similar structure. The core (R1) is represented by an aromatic or heterocyclic group and is linked via a nitrogen, oxygen or carbon molecule to an amino group. The core determines the severity of antihistamine activity and some of the properties of substances.
There are several classifications of antihistamines, although none of them is generally accepted. According to their chemical structure, antihistamines are divided into several groups (ethanolamines, ethylenediamines, alkylamines, derivatives of alphacarboline, quinuclidine, phenothiazine, piperazine and piperidine). The most popular classification is based on the time of creation: first and second generation drugs. First generation drugs are also commonly called sedatives (based on the dominant side effect) in contrast to non-sedating second generation drugs. Currently, it is customary to distinguish the third generation: it includes fundamentally new drugs - active metabolites, which, in addition to the highest antihistamine activity, exhibit the absence of a sedative effect and the cardiotoxic effect characteristic of second-generation drugs.
2.1. FIRST GENERATION ANTIHISTAMINES
All first-generation antihistamines (sedatives) are highly soluble in fats and, in addition to H1-histamines, also block cholinergic, muscarinic and serotonin receptors. As competitive blockers, they reversibly bind to H1 receptors, which necessitates the use of fairly high doses. The following pharmacological properties are most characteristic of them:
The sedative effect is determined by the fact that most first-generation antihistamines, easily soluble in lipids, penetrate well through the blood-brain barrier and bind to H1 receptors in the brain. The degree of manifestation of the first generation sedative effect varies between drugs and in different patients from moderate to severe and increases when combined with alcohol and psychotropic drugs. Some of them are used as sleeping pills. Psychomotor agitation rarely occurs (more often in moderate therapeutic doses in children and in high toxic doses in adults). Because of the sedative effect, most medications should not be used while performing tasks that require alertness. All first-generation drugs potentiate the effect of sedatives and hypnotics, narcotic and non-narcotic analgesics, monoamine oxidase inhibitors and alcohol.
Atropine-like reactions (due to the anticholinergic properties of the drugs) are manifested by dry mouth and nasopharynx, urinary retention, constipation, tachycardia and visual disturbances. These properties can be useful for rhinitis, but can increase airway obstruction in bronchial asthma (due to increased sputum viscosity), cause exacerbation of glaucoma and prostate adenoma, etc.
They have antiemetic and anti-sickness effects, reduce the symptoms of parkinsonism - thanks to the central anticholinergic effect of the drugs.
May cause a transient decrease in blood pressure in sensitive individuals.
A local anesthetic (cocaine-like) effect is characteristic of most antihistamines.
Tachyphylaxis (decreased antihistamine activity): with long-term use, medications must be changed every 2-3 weeks.
The therapeutic effect occurs relatively quickly, but is short-lived (effective within 4-5 hours).
Some first-generation antihistamines are included in combination medications used for colds, motion sickness, as sedatives, sleeping pills and other components.
The most commonly used is diphenhydramine , chloropyramine, clemastine, cyproheptadine, promethazine, fencarol and hydroxyzine.
1) Diphenhydramine, best known in our country under the name diphenhydramine.
DIMEDROL (Dimcdrolum).
2-Dimethylaminoethyl ether benzhydrol hydrochloride, or N,N1-dimethyl-2-(diphenylmethoxy)ethylamine hydrochloride:
SYNONYMS: Allergies, Alledryl, Allergan, Allergin, Allergival, Amidryl, Bcnadryl, Benzhydraminum, Diabenyl, Dimedryl, Dimidril, Diphenhydramine, Diphenhydramine Hydrochloride, Restamin, etc.
White fine-crystalline powder with a bitter taste; causes numbness of the tongue. Hygroscopic. Easily soluble in water, very easily in alcohol.
Diphenhydramine is one of the first antihistamines (a first-generation drug) that has found widespread use in medical practice since the 1950s. Despite the emergence of a number of new antihistamines, diphenhydramine has not lost its importance to this day.
It is a blocker of histamine H1 receptors and has pronounced antihistamine activity. It has a local anesthetic effect and relaxes smooth muscles. Shows moderate antiemetic effect.
Diphenhydramine is well absorbed when taken orally. Penetrates the blood-brain barrier. An important feature of diphenhydramine is its sedative effect: in appropriate doses it has a hypnotic effect.
Diphenhydramine is used mainly in the treatment of urticaria, hay fever, serum sickness, hemorrhagic vasculitis (capillary toxicosis), vasomotor rhinitis, angioedema, pruritic dermatoses, acute iridocyclitis, allergic conjunctivitis and other allergic diseases; allergic complications from taking various medications (including antibiotics), blood transfusions and blood-substituting fluids, and the use of enzyme and other drugs.
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Medicines are compounds used to treat and prevent diseases. For example: nitroglycerin aspirin salol glutamic acid anesthesin novocaine n-aminosalicylic acid
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From history Medicinal substances have been known since very ancient times. For example, in Ancient Rus', male fern, poppy and other plants were used as medicine. And until now, 25-30% of various decoctions, tinctures and extracts of plant and animal organisms are used as medicines. Recently, biology, medical science and practice are increasingly using the achievements of modern chemistry. A huge number of medicinal compounds are supplied by chemists, and new advances have been made in the field of drug chemistry in recent years.
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From history Plants in various forms (decoctions, tinctures), dried insects, and animal organs were used for treatment.
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With the development of scientific knowledge, individual, pure substances were obtained from natural sources. For example, alkaloids, hormones, vitamins, etc. were obtained this way.
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Medicinal substances can be divided into two large groups: inorganic and organic. Both are obtained from natural raw materials and synthetically. The raw materials for the production of inorganic preparations are rocks, ores, gases, water from lakes and seas, and chemical waste. The raw materials for the synthesis of organic drugs are natural gas, oil, coal, shale and wood. Oil and gas are a valuable source of raw materials for the synthesis of hydrocarbons, which are intermediate products in the production of organic substances and medicines. Petroleum jelly, petroleum jelly, and paraffin obtained from petroleum are used in medical practice.
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Synthetic drugs 1887 – phenacetin 1896 – pyramidon 20th century. – veronal Appeared in the 19th century.
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Modern medicines according to the nature of the action they have on the body Antimicrobial Cures: sore throat, pneumonia, scarlet fever and other infectious diseases Painkillers (aspirin, paracetamol, analgin) Affecting the heart and blood vessels (nitroglycerin, anaprilin, dibazol) Antihistamines (suprastin, diphenhydramine; treatment allergic diseases) Antitumor (dactinomycin, mitomycin) Psychopharmacological (clozapine, dicarbine, thioridazine)
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Antimicrobial drugs Furacilin Indications: purulent wounds; burns II–III degree; conjunctivitis; boils of the external auditory canal; osteomyelitis; acute external and otitis media; stomatitis; gingivitis; minor skin damage (including abrasions, scratches, cracks, cuts)
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Painkillers Analgin Indications: headache; toothache; neuralgia; postoperative pain; febrile conditions in infectious and inflammatory diseases. Indications: pain syndrome of various localizations (joint, muscle, headache, toothache); febrile conditions. Aspirin
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Affecting the heart and blood vessels Nitroglycerin Dibazol Indications: Attacks of angina Indications: Arterial hypertension, spasm of arteries, spasm of smooth muscles of internal organs (peptic ulcer of the stomach and duodenum, intestinal colic) diseases of the nervous system
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Antihistamines Indications: urticaria; serum sickness; allergic rhinitis; conjunctivitis; contact dermatitis; skin itching; acute and chronic eczema; atopic dermatitis; food and drug allergies; allergic reactions to insect bites. Suprastin Indications: Allergic diseases; allergic dermatoses; peptic ulcer of the stomach and duodenum; Insomnia; seasickness; radiation sickness; Diphenhydramine
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Antitumor drugs Mitomycin Indications: Stomach cancer, pancreatic cancer, esophageal cancer, liver cancer, bile duct cancer, colon and rectal cancer, malignant tumors of the head and neck,
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Psychopharmacological drugs Dikarbin Indications: Schizophrenia, alcoholic psychosis, withdrawal syndrome Indications: insomnia, Anxiety, neuroses, depression, psychopathy in excited patients, aggressiveness, dysphoria. Clozapine
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Medicines Causal (act directly on the disease, eliminating it) quinacrine (affects the causative agent of malaria) cardiac drugs (returns the diseased heart muscle to normal strength) Symptomatic (without eliminating the disease, they destroy only the deviations from the norm caused by it) aspirin (reduces t) pyramidon (eliminates neuralgic pain)
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Sleeping pills Substances that induce sleep belong to different classes, but the best known are derivatives of barbituric acid. Its derivatives are called barbiturates. All barbiturates depress the nervous system. Amytal has a wide range of sedative effects. In some patients, this drug relieves inhibitions associated with painful, deeply buried memories. The human body becomes accustomed to barbiturates through frequent use as sedatives and sleep aids, so people using barbiturates find that they need increasingly larger doses. Diphenhydramine is widely used as a sedative and hypnotic. It is not a barbiturate, but belongs to ethers.
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Sulfamide drugs Streptocide, norsulfazole, sulfadimezin, etazol, sulfadimethoxine are easily absorbed, quickly accumulate in the required concentrations in the blood, and are used in the treatment of infectious diseases. Phthalazole, phthazine - are difficult to absorb, remain in the intestines for a long time in high concentrations, are used for infectious diseases of the gastrointestinal tract
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Sulfa drugs Absorption and rate of excretion from the body determine the dose and frequency of drug administration. Sulfa drugs that stay in the body for a long time can be used once a day. The time of taking the medicine depends on the chemical properties of the substance: before or after meals. In the practice of treating diseases, the phenomenon of microorganisms becoming accustomed to the drug has been discovered, i.e. The usual medications no longer work, and the disease is more difficult to treat, so it is necessary to update the medications.
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1. You must strictly follow the instructions. This is especially true when it comes to the relationship between medication and food. Not only the effectiveness of treatment, but also the condition of the digestive and excretory systems will depend on strict adherence to this requirement. After all, there are practically no medications that need to be taken on an empty stomach. 2. Self-medication is not allowed. Most patients consider themselves the best doctor. And of course, they treat themselves, taking medications on the recommendation of friends. Rules for taking medications
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3. Take medications at regular intervals. It is known that the concentration of drugs in the blood is highest after taking the drug, then, with each passing hour, it gradually decreases. If you leave long intervals between medications, a period will come when the concentration of the drug in the blood will be very low. Therefore, they need to be taken 2, 4, 6 times a day, and the intervals between doses should be even. Rules for taking medications
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4. What time of day is best to take medications? The pain is worst at night, so it is very important to take painkillers in the evening. It is advisable to take vasodilators in the morning. Indeed, during this period the danger of myocardial infarction reaches its peak. But in the evening, the doses of these medications can be reduced without any health consequences. Antirheumatic drugs should also be taken in the evening. This will reduce joint pain and improve joint mobility after sleep. Also in the evening, but late, you need to take antiallergic medications, since it is at night that the body produces the least amount of the hormone that inhibits allergic reactions. Considering that gastric juices are very aggressive at night, it is most advisable to take medications against gastric and duodenal ulcers in large doses shortly before bedtime. Several rules for taking medications
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6. If several medications are prescribed, they must be taken separately. Even the most harmless medications for the body when taken in one gulp, i.e., taking several drugs at the same time, will put a lot of stress on the stomach and liver. This means that taking medications should be spaced out so that the interval between doses is at least 30 minutes. Rules for taking medications
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7. When using tablets, you must chew them. An exception to this rule is tablet and powder medications that are in gelatin capsules, shells, wafers, the purpose of which is to protect the digestive tract from irritation. It is recommended to chew the remaining tablets, even if they are very bitter, then they will begin to be absorbed in the mouth and will continue to be rapidly absorbed in the stomach without losing their medicinal properties, which will allow the therapeutic effect to be achieved more quickly. Rules for taking medications
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8. Medicines must be taken with water. Even miniature tablets need to be washed down, since a high concentration of the active substance can harm the stomach. It is best to take medications with warm boiled water. It is not allowed to drink it with juices, carbonated water, milk (unless provided for in the instructions), kefir, etc. After all, milk and kefir, even low-fat ones, contain fat that envelops the tablets, preventing them from being absorbed completely and without delay. Rules for taking medications
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10. Due to the fact that medications are foreign and toxic to the body, their correct dosage is very important! Rules for taking medications
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Emergency conditions in allergology Lecturer - professor, doctor of medical sciences. Nedelskaya S.N. ZDMUSlide 2
Urticaria (urticaria) is a disease characterized by the appearance on the skin of itchy spots, papules or blisters, quite clearly contoured, ranging in size from a few millimeters to ten or more centimeters. The rash appears quickly, the elements can merge and spread over the entire surface of the body. The elements persist for several hours, then gradually disappear and reappear elsewhere. If urticarial lesions persist for more than 24 hours, a diagnosis of urticarial vasculitis or delayed pressure urticaria should be considered.
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Angioedema is an acutely developing and relatively quickly passing swelling of the skin, subcutaneous tissue and/or mucous membranes ICD-10: T78.3 Angioedema D84.1 Defect of the complement system
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The etiological factors for the development of urticaria (K) and allergic edema (AO) are: Food or injection allergens (medicines, food products) latex
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substances that act directly on mast cells - opiates, radiopaque agents curare, tobaccocurine chloride, substances that interfere with the metabolism of arachidonic acid, aspirin, NSAIDs, some cyclooxygenase-2 inhibitors, physical stimuli, heat and cold, vibration, contact with water, pressure, sunlight, ultraviolet, physical exercise (cholinergic)
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idiopathic Urticaria Other: nutritional supplements Separately, there is a hereditary variant of Urticaria.
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Treatment Goal – relief of manifestations of acute urticaria and selection of adequate therapy Indications for hospitalization – severe forms of OK, AO of the larynx with a risk of asphyxia, all cases of anaphylactic reaction Non-drug treatment: hypoallergenic diet, keeping a food diary, patient education
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Drug treatment Antihistamines H1-histamine blockers of the 1st, 2nd and 3rd generations Glucocorticoids: prednisolone 2-3-5 mg/kg body weight Sorbents
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Lyell's syndrome (toxic-allergic bullous epidermal necrolysis) The most severe form of LA Most often its development is caused by antibiotics, barbiturates, analgesics and NSAIDs Development is often preceded by an acute infectious process, for which the drug that caused the syndrome was prescribed
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Clinic The disease develops within a few hours or days after taking the drug Prodromal period in the form of fever, weakness, headache and myalgia, skin hyperesthesia, itching of the conjunctiva Hyperthermia up to 39-40 C, a spotted and/or petechial rash appears, there may be urticaria or blisters Often the first rashes appear on the mucous membranes of the mouth, nose, genitals, and sometimes the eyes. Over the course of several days, erythroderma develops, against the background of which detachment of the epidermis begins with the formation of erosions
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Positive Nikolsky symptom Pain is sharply expressed in areas of rashes and erosions The condition progressively worsens, symptoms of dehydration occur The course of the disease resembles a burn disease (a symptom of burned skin) Damage to the mucous membranes is typical in 90% (e) The prognosis depends on the prevalence of necrosis Mortality reaches 30%
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Treatment In the intensive care unit The primary task is to maintain water-electrolyte and protein balance, treat the affected erosive surfaces Antibiotics and glucocorticosteroids 5-15 mg/kg Locally – corticosteroid aerosols, antibacterial lotions on wet areas, solcoseryl ointment or cream, panthenol
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Stevens-Johnson syndrome The most severe form of bullous polymorphic exudative erythema, in which, along with skin lesions, there is damage to the mucous membranes of at least 2 organs Cause - penicillins, NSAIDs, anticonvulsants
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Anaphylactic shock Asphyxial Hemodynamic Abdominal Cerebral Mixed By type of course Acute benign Acute malignant Protracted Recurrent Abortive
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Emergency assistance: stop administering the drug that caused the allergic reaction. Lay the patient down, turn his head to the side, extend the lower jaw, and fix the tongue. Provide access to fresh air or inhale humidified oxygen. It is necessary to stop further entry of the allergen into the body:
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When introducing an allergen parenterally: prick the injection site (bite) crosswise with a 0.1% solution of adrenaline 0.1 ml/year of life in 5 ml saline. solution and apply ice to it, apply a tourniquet (if localization allows) proximal to the site of allergen introduction for 30 minutes, without squeezing the artery, if an allergic reaction occurred to the administration of penicillin, inject 1 million units. penicillinase in 2 ml. physical IM solution
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When introducing the allergen dropwise into the nose or eyes, rinse the latter with copious amounts of running water; If the allergen is administered orally, rinse the patient’s stomach if the condition allows. Immediately administer intramuscularly: 0.1% adrenaline solution at a dose of 0.05-0.1 ml/year of life (no more than 1 ml) and 3% solution r prednisolone at a dose of 5 mg/kg into the muscles of the floor of the mouth Antihistamines: 1% diphenhydramine solution 0.05 ml/kg 9no more than 0.5 ml - for children under 1 year old and 1 ml - over a year old) or 2% r -p suprastin 0.1-0.15 ml/year of life) The use of pipolfen is contraindicated due to its significant hypotensive effect! Mandatory monitoring of pulse, respiration and blood pressure!
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After completing the priority measures, provide access to the vein and inject a 0.1% adrenaline solution in a stream at a dose of 0.05-0.1 ml/year of life in 10 ml saline. sodium chloride solution Introduce intravenous glucocorticoids: 3% prednisolone solution 2-4 mg/kg (in 1 ml - 30 mg) or Hydrocortisone 4-8 mg/kg (in 1 ml suspension - 25 mg) or 0 .4% dexamethasone solution 0.3-0.6 mg/kg (4 mg in 1 ml) Start IV infusion therapy with 0.9% sodium chloride solution or Ringer's solution at the rate of 20 ml/kg for 20-30 minutes. In the future, if there is no stabilization of hemodynamic parameters, a colloid solution (reopolyglucin) at a dose of 20 ml/kg. The volume and speed of infusion is determined by the value of blood pressure, central venous pressure and the patient’s condition.
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If blood pressure becomes low, alpha-adrenergic agonists are administered intravenously every 10-15 minutes until the condition improves 0.1% solution of adrenaline 0.05-0.01 ml/year of life (total dose up to 5 mg) or 0.2 % solution of norepinephrine - 0.1 ml/year of life (no more than 1 ml) or 1% solution of mezaton 0.1 ml/year of life (no more than 1 ml) If there is no effect, titrated intravenous administration of dopamine dose of 8-10 mcg/kg/min under the control of blood pressure and heart rate For bronchospasm and other respiratory disorders: Carrying out oxygen therapy Administer 2.4% aminophylline solution 0.5-1 ml/year of life (no more than 10 ml) intravenously in a stream of 20 ml saline. solution Remove accumulated secretions from the trachea and oral cavity If stridor breathing appears and there is no effect from complex therapy, immediate intubation, and in some cases, for health reasons, conicotomy. Questions that a doctor should ask before prescribing any medicine Does the patient himself or his relatives suffer from any allergic disease? Has the patient previously received this drug, and has he had any allergic reactions to its use? What drugs were the patient treated for a long time and in large doses? Did the patient receive injections of serums and vaccines? Does the patient have mycosis of the skin and nails (athlete's foot, trichophytosis). Does the patient have professional contact with medications? Does contact with animals cause exacerbation of the underlying disease or the appearance of allergic symptoms? Prevention of drug allergies Before prescribing any drug, the doctor must answer the following questions: Is this medicine really necessary for the patient? What will happen if it is not prescribed? What do I want to achieve by prescribing this drug? What are its side effects?
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Primary prevention, prevention of the development of LA: Avoid polypharmacy, doses of drugs should correspond to the age and weight of the patient, strict adherence to the instructions for the method of drug administration. Secondary prevention, prevention of LA in people suffering from allergic diseases. Patient education - the doctor gives the patient a leaflet “Passport of a patient with an allergic disease”
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The term “antihistamines” refers to drugs that block H1-histamine receptors, and drugs that act on H2-histamine receptors (cimetidine, ranitidine, famotidine, etc.) are called H2-histamine blockers. The former are used to treat allergic diseases, the latter are used as antisecretory agents.
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Histamine
Histamine, this most important mediator of various physiological and pathological processes in the body, was chemically synthesized in 1907. Subsequently, it was isolated from animal and human tissues (Windaus A., Vogt W.). Even later, its functions were determined: gastric secretion, neurotransmitter function in the central nervous system, allergic reactions, inflammation, etc. Almost 20 years later, in 1936, the first substances with antihistamine activity were created (Bovet D., Staub A.). And already in the 60s, the heterogeneity of histamine receptors in the body was proven and three of their subtypes were identified: H1, H2 and H3, differing in structure, localization and physiological effects that occur during their activation and blockade.
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Histamine
Numerous studies have shown that histamine, acting on receptors in the respiratory system, eyes and skin, causes characteristic allergy symptoms, and antihistamines that selectively block H1-type receptors are able to prevent and relieve them.
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According to one of the most popular classifications, antihistamines, based on the time of creation, are divided into first and second generation drugs. First generation drugs are also commonly called sedatives (based on the dominant side effect) in contrast to non-sedating second generation drugs. Currently, it is customary to distinguish the third generation: it includes fundamentally new drugs - active metabolites, which, in addition to the highest antihistamine activity, exhibit the absence of a sedative effect and the cardiotoxic effect characteristic of second-generation drugs.
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Classification
1st generation antihistamines Diphenhydramine (diphenhydramine) Clemastine (tavegil) Chloropyramine (suprastin) Mebhydrolin (diazolin) Quifenadine (fencarol) Promethazine (diprazine, pipolfen) Hydroxyzine (atarax) Cyproheptadine (peritol) Trimeprazine (teralen)
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2nd generation atigistamsinic drugs Acrivastine (Semprex) Astemizole (Gismanal) Dimetindene (Fenistil) Oxatomide (Tinset) Terfenadine (Bronal, Histadine) Azelastine (Allergodil) Levocabastine (Histimet) Mizolastine Loratadine (Claritin) Epinastine (Alesion) Ebastine (Kestin) Bamipin (soventol
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3rd generation antihistamines Cetirizine (Zyrtec) Fexofenadine (Telfast)
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First generation antihistamines (sedatives).
All of them are highly soluble in fats and, in addition to H1-histamine, also block cholinergic, muscarinic and serotonin receptors. As competitive blockers, they reversibly bind to H1 receptors, which necessitates the use of fairly high doses. The following pharmacological properties are most characteristic of them.
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The sedative effect is determined by the fact that most first-generation antihistamines, easily soluble in lipids, penetrate well through the blood-brain barrier and bind to H1 receptors in the brain. Perhaps their sedative effect consists of blocking central serotonin and acetylcholine receptors. Some of them are used as sleeping pills (doxylamine). Rarely, instead of sedation, psychomotor agitation occurs (more often in moderate therapeutic doses in children and in high toxic doses in adults). Because of the sedative effect, most medications should not be used while performing tasks that require alertness. All first-generation drugs potentiate the effect of sedatives and hypnotics, narcotic and non-narcotic analgesics, and alcohol.
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The anxiolytic effect characteristic of hydroxyzine may be due to the suppression of activity in certain areas of the subcortical region of the central nervous system.
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The antiemetic and anti-motion sickness effect is also likely associated with the central anticholinergic effect of the drugs. Some antihistamines (diphenhydramine, promethazine, cyclizine, meclizine) reduce the stimulation of vestibular receptors and inhibit the function of the labyrinth, and therefore can be used for movement disorders.
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Atropine-like reactions associated with the anticholinergic properties of drugs are most typical for ethanolamines and ethylenediamines. Manifested by dry mouth and nasopharynx, urinary retention, constipation, tachycardia and visual impairment. These properties ensure the effectiveness of the drugs under discussion for non-allergic rhinitis. At the same time, they can increase obstruction in bronchial asthma (due to an increase in sputum viscosity), cause exacerbation of glaucoma and lead to bladder outlet obstruction in prostate adenoma, etc.
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A number of H1-histamine blockers reduce the symptoms of parkinsonism, which is due to the central inhibition of the effects of acetylcholine.
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The antitussive effect is most characteristic of diphenhydramine; it is realized through a direct effect on the cough center in the medulla oblongata.
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The antiserotonin effect, primarily characteristic of cyproheptadine, determines its use for migraine.
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The α1-blocking effect of peripheral vasodilation, especially that of phenothiazine antihistamines, may lead to a transient decrease in blood pressure in sensitive individuals.
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A local anesthetic (cocaine-like) effect is characteristic of most antihistamines (occurs due to a decrease in membrane permeability to sodium ions). Diphenhydramine and promethazine are stronger local anesthetics than novocaine. At the same time, they have systemic quinidine-like effects, manifested by prolongation of the refractory phase and the development of ventricular tachycardia.
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Tachyphylaxis: a decrease in antihistamine activity with long-term use, confirming the need to alternate medications every 2-3 weeks. It should be noted that first-generation antihistamines differ from the second generation in their short duration of action with a relatively rapid onset of clinical effect. Many of them are available in parenteral forms. All of the above, as well as low cost, determine the widespread use of antihistamines today.
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Indirect administration of 1st generation antihistamines
Many of the qualities that were discussed allowed “old” antihistamines to occupy their niche in the treatment of certain pathologies (migraines, sleep disorders, extrapyramidal disorders, anxiety, motion sickness, etc.) not related to allergies. Many first-generation antihistamines are included in combination drugs used for colds, as sedatives, hypnotics and other components. The most commonly used are chloropyramine, diphenhydramine, clemastine, cyproheptadine, promethazine, fenkarol and hydroxyzine.
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Chloropyramine
Chloropyramine (suprastin) is one of the most widely used sedative antihistamines. It has significant antihistamine activity, peripheral anticholinergic and moderate antispasmodic effects.
Effective in most cases for the treatment of seasonal and year-round allergic rhinoconjunctivitis, Quincke's edema, urticaria, atopic dermatitis, eczema, itching of various etiologies; in parenteral form - for the treatment of acute allergic conditions requiring emergency care.
Provides a wide range of therapeutic doses used.
It does not accumulate in the blood serum, therefore it does not cause an overdose with long-term use.
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Suprastin is characterized by a rapid onset of effect and short duration (including side effects). In this case, chloropyramine can be combined with non-sedating H1-blockers in order to increase the duration of the antiallergic effect. Suprastin is currently one of the best-selling antihistamines in Russia. This is objectively due to the proven high efficiency, controllability of its clinical effect, the availability of various dosage forms, including injectable ones, and low cost.
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Clemastine (tavegil)
Clemastine (tavegil) is a highly effective antihistamine, similar in action to diphenhydramine. It has high anticholinergic activity, but penetrates the blood-brain barrier to a lesser extent. It also exists in injection form, which can be used as an additional remedy for anaphylactic shock and angioedema, for the prevention and treatment of allergic and pseudoallergic reactions. However, hypersensitivity to clemastine and other antihistamines with a similar chemical structure is known.
Diphenhydramine, best known in our country as diphenhydramine, is one of the first synthesized H1 blockers. It has fairly high antihistamine activity and reduces the severity of allergic and pseudo-allergic reactions. Due to its significant anticholinergic effect, it has an antitussive, antiemetic effect and at the same time causes dryness of the mucous membranes and urinary retention. Due to its lipophilicity, diphenhydramine produces pronounced sedation and can be used as a hypnotic.
It has a significant local anesthetic effect, as a result of which it is sometimes used as an alternative in case of intolerance to novocaine and lidocaine.
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Cyproheptadine
Cyproheptadine (peritol), along with an antihistamine, has a significant antiserotonin effect. In this regard, it is mainly used for some forms of migraine, dumping syndrome, as an appetite enhancer, and for anorexia of various origins. It is the drug of choice for cold urticaria.
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Promethazine
Promethazine (pipolfen) - a pronounced effect on the central nervous system determined its use in Meniere's syndrome, chorea, encephalitis, sea and air sickness, as an antiemetic. In anesthesiology, promethazine is used as a component of lytic mixtures to potentiate anesthesia.
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Quifenadine
Quifenadine (fenkarol) - has less antihistamine activity than diphenhydramine, but is also characterized by less penetration through the blood-brain barrier, which determines the lower severity of its sedative properties. In addition, fenkarol not only blocks histamine H1 receptors, but also reduces the content of histamine in tissues. May be used in cases of developing tolerance to other sedating antihistamines.
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Hydroxyzine
Hydroxyzine (atarax) - despite the existing antihistamine activity, it is not used as an antiallergic agent. It is used as an anxiolytic, sedative, muscle relaxant and antipruritic agent.
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Thus, first-generation antihistamines, which affect both H1 and other receptors (serotonin, central and peripheral cholinergic receptors, α-adrenergic receptors), have different effects, which has determined their use in a variety of conditions. But the severity of side effects does not allow them to be considered as the first choice drugs in the treatment of allergic diseases. The experience gained in their use allowed the development of unidirectional drugs - the second generation of antihistamines
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Second generation antihistamines (non-sedating).
Unlike the previous generation, they have almost no sedative and anticholinergic effects, but are distinguished by their selectivity of action on H1 receptors. However, they exhibit a cardiotoxic effect to varying degrees. The most common properties for them are the following.
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High specificity and high affinity for H1 receptors with no effect on choline and serotonin receptors. Rapid onset of clinical effect and duration of action. Prolongation can be achieved due to high protein binding, accumulation of the drug and its metabolites in the body and slow elimination.
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Absence of tachyphylaxis with long-term use.
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Minimal sedative effect when using drugs in therapeutic doses. It is explained by weak passage of the blood-brain barrier due to the structural features of these drugs. Some particularly sensitive individuals may experience moderate drowsiness, which is rarely a reason to discontinue the drug.
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The ability to block potassium channels in the heart muscle, which is associated with prolongation of the QT interval and cardiac arrhythmias. The risk of this side effect increases when antihistamines are combined with antifungals (ketoconazole and intraconazole), macrolides (erythromycin and clarithromycin), antidepressants (fluoxetine, sertraline and paroxetine), when drinking grapefruit juice, as well as in patients with severe liver dysfunction.
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There are no parenteral forms, but some of them (azelastine, levocabastine, bamipin) are available in forms for topical use.
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Terfenadine
Terfenadine is the first antihistamine without an inhibitory effect on the central nervous system. Its creation in 1977 was the result of a study of both the types of histamine receptors and the features of the structure and action of existing H1 blockers, and marked the beginning of the development of a new generation of antihistamines. Currently, terfenadine is used less and less, which is associated with an increased ability to cause fatal arrhythmias associated with prolongation of the QT interval (torsade de pointes).
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Astemizole
Astemizole is one of the longest-acting drugs in the group (the half-life of its active metabolite is up to 20 days). It is characterized by irreversible binding to H1 receptors. It has virtually no sedative effect and does not interact with alcohol. Since astemizole has a delayed effect on the course of the disease, its use in acute processes is inappropriate, but may be justified in chronic allergic diseases. Since the drug tends to accumulate in the body, the risk of developing serious heart rhythm disturbances, sometimes fatal, increases. Due to these dangerous side effects, the sale of astemizole in the United States and some other countries has been suspended.
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Akrivastine
Akrivastine (Semprex) is a drug with high antihistamine activity with minimally expressed sedative and anticholinergic effects. A feature of its pharmacokinetics is its low level of metabolism and lack of accumulation. Acrivastine is preferable in cases where there is no need for constant antiallergic treatment due to the rapid achievement of effect and short-term action, which allows the use of a flexible dosing regimen.
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Dimetenden
Dimethenden (fenistil) is closest to first-generation antihistamines, but differs from them in having a significantly less pronounced sedative and muscarinic effect, higher antiallergic activity and duration of action.
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Loratadine
Loratadine (Claritin) is one of the most widely purchased second-generation drugs, which is understandable and logical. Its antihistamine activity is higher than that of astemizole and terfenadine, due to greater binding strength to peripheral H1 receptors. The drug has no sedative effect and does not potentiate the effect of alcohol. In addition, loratadine practically does not interact with other drugs and does not have a cardiotoxic effect. The following antihistamines are topical drugs and are intended to relieve local manifestations of allergies.
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Levocabastine
Levocabastine (Histimet) is used as eye drops to treat histamine-dependent allergic conjunctivitis or as a spray for allergic rhinitis. When applied topically, it enters the systemic bloodstream in small quantities and does not have undesirable effects on the central nervous and cardiovascular systems.
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Azelastine
Azelastine (allergodil) is a highly effective treatment for allergic rhinitis and conjunctivitis. Used as a nasal spray and eye drops, azelastine has virtually no systemic effect. Another topical antihistamine, bamipin (Soventol) in the form of a gel, is intended for use in allergic skin lesions accompanied by itching, insect bites, jellyfish burns, frostbite, sunburn, and mild thermal burns.
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Third generation antihistamines (metabolites).
Their fundamental difference is that they are active metabolites of previous generation antihistamines. Their main feature is their inability to influence the QT interval. Currently there are two drugs - cetirizine and fexofenadine.
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Cetirizine
Cetirizine (Zyrtec) is a highly selective antagonist of peripheral H1 receptors. It is an active metabolite of hydroxyzine, which has a much less pronounced sedative effect. Cetirizine is almost not metabolized in the body, and the rate of its elimination depends on renal function. Its characteristic feature is its high ability to penetrate the skin and, accordingly, its effectiveness in treating skin manifestations of allergies. Cetirizine showed no arrhythmogenic effects on the heart either experimentally or clinically.
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Fexofenadine
Fexofenadine (Telfast) is the active metabolite of terfenadine. Fexofenadine does not undergo transformations in the body and its kinetics does not change with impaired liver and kidney function. It does not enter into any drug interactions, does not have a sedative effect and does not affect psychomotor activity. In this regard, the drug is approved for use by persons whose activities require increased attention. A study of the effect of fexofenadine on the QT value showed, both experimentally and in the clinic, a complete absence of cardiotropic effects when using high doses and long-term use. Along with maximum safety, this drug demonstrates the ability to relieve symptoms in the treatment of seasonal allergic rhinitis and chronic idiopathic urticaria.
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So, in the doctor’s arsenal there is a sufficient number of antihistamines with various properties. It must be remembered that they provide only symptomatic relief for allergies. In addition, depending on the specific situation, you can use both different drugs and their varied forms. It is also important for the doctor to remember the safety of antihistamines.
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WHERE DOES HISTAMINE COME FROM? Histamine is a biogenic amine that occupies one of the central places in inflammatory reactions, in an immediate allergic reaction. Histamine in the body is synthesized from histidine, an amino acid, which is a constituent component of protein. It is found in almost all organs, tissues, fluids and secretions of the body, but also it is unknown whether it is contained in bone and cartilage tissue. Its concentration is greatest in organs in contact with the external environment: skin (mainly in the epidermis), gastrointestinal tract, lungs [Weisfeld I.L., Kassil G.N., 1981] One of the important depots of histamine are mast cells and basophils , where it accumulates in granules. Damage to mast cells leads to the transition of histamine to an active form and release into the general bloodstream, where it exerts its physiological effect.
“FOOD” HISTAMINE (pseudo-allergy) alcoholic beverages (especially red wine, some beers and sake) cheese (with a long ripening period) smoked meat and sausages fish and seafood (especially if they are canned or stored in brine) yeast coffee and soy cocoa , beans and tofu wheat flour pickled vegetables strawberries, kiwi, as well as bananas, citrus fruits, pears and pineapples long-term stored foods at insufficiently low temperatures foods that stimulate the production of endogenous (internal) histamine - eggs, strawberries. foods with lots of additives that destroy mast cells
FACTORS LEADING TO ACTIVATION AND RELEASE OF HISTAMINE trauma burns stress some medications immune complexes radiation exposure allergic reactions with damage to mast cells by the antigen-antibody complex
BIOLOGICAL EFFECT OF HISTAMINE Spasm of smooth (involuntary) muscles in the bronchi and intestines (this manifests itself, respectively, in abdominal pain, diarrhea, and respiratory distress). The release of the “stress” hormone adrenaline from the adrenal glands, which increases blood pressure and increases heart rate. Increased production of digestive juices and mucus secretion in the bronchi and nasal cavity. The effect on blood vessels is manifested by a narrowing of large and expansion of small blood vessels, and an increase in the permeability of the capillary network. The consequence is swelling of the mucous membrane of the respiratory tract, hyperemia of the skin, the appearance of a papular (nodular) rash on it, a drop in pressure, and headache. Histamine in the blood in large quantities can cause anaphylactic shock, in which convulsions, loss of consciousness, and vomiting develop against the background of a sharp drop in blood pressure.
HISTORICAL BACKGROUND 1907 – synthesis of histamine 1920 – the role of histamine in allergic reactions is shown 1942 – the first antihistamine for humans is synthesized 1966 – the heterogeneity of histamine receptors is proven 1977 – a 2nd generation antihistamine is synthesized
HISTAMINE RECEPTORS H 1 receptors are found in the cells of smooth (involuntary) muscles, the inner lining of blood vessels and in the nervous system. Their irritation causes external manifestations of allergies (bronchospasm, swelling, skin rashes, abdominal pain, etc.). The action of antiallergic drugs - antihistamines is to block H1 receptors and eliminate the influence of histamine on them. H 2 receptors are found in the membranes of the parietal cells of the stomach (those that produce hydrochloric acid). Drugs from the H 2 blocker group are used in the treatment of gastric ulcers because they suppress the production of hydrochloric acid. H 3 receptors are located in the nervous system, where they take part in the conduction of nerve impulses.
HISTORICALLY, THE term “antihistamine” drugs refers to drugs that block H 1 -histamine receptors (used to treat allergic diseases). Medicines that act on H 2 -histamine receptors (cimetidine, ranitidine, famotidine, etc.) are called H 2 - histamine blockers and are used as antisecretory agents.
MEDIATORS OF ALLERGIC REACTIONS Biogenic amines (histamine, serotonin) Leukotrienes Prostaglandins Kinins Chemotactic factors Cationic proteins, etc. In recent years, new drugs with antimediator effects have been synthesized and tested - leukotriene receptor antagonists (zafirlukast, montelukast), 5-lipoxygenase inhibitors (zeliuton), ical agents. However, drugs with antihistamine action have found the most widespread use in clinical practice.
MECHANISM OF ACTION OF ANTIHISTAMINES Antihistamines block the effect of histamine on H1 receptors, but are not able to displace histamine bound to the receptor. H1 blockers are most effective in preventing immediate allergic reactions, and in the event of a developed reaction, they prevent the release of new portions of histamine.
CLASSIFICATION OF ANTIHISTAMINES According to one of the most popular classifications, antihistamines are divided into first and second generation drugs based on the time of creation. First generation drugs are also commonly called sedatives (based on the dominant side effect), in contrast to non-sedating second generation drugs. Currently, it is customary to distinguish the third generation: it includes fundamentally new drugs - active metabolites, which, in addition to the highest antihistamine activity, exhibit the absence of a sedative effect and the cardiotoxic effect characteristic of second-generation drugs
CLASSIFICATION OF ANTIHISTAMINES First generation antihistamines (sedatives). All of them are highly soluble in fats and, in addition to H1-histamine, also block cholinergic, muscarinic and serotonin receptors. As competitive blockers, they reversibly bind to H1 receptors, which necessitates the use of fairly high doses.
1st GENERATION ANTIHISTAMINES Chloropyramine hydrochloride (suprastin) Diphenhydramine (diphenhydramine) Promethazine hydrochloride (pipolfen) Clemastine fumarate (tavegil) Dimetindene maleate (fenistil) Khifenadine (fenkarol)
SIDE EFFECTS OF 1st GENERATION ANTIHISTAMINES Sedative effect (binding with H1 receptors of the brain and blocking central serotonin and acetylcholine receptors - potentiate the effect of sedative and hypnotic drugs, narcotic and non-narcotic analgesics, monoamine oxidase inhibitors and alcohol) Anxiolytic effect (suppression of activity in certain areas subcortical region of the central nervous system) Atropine-like reactions (dry mucous membranes, urinary retention, constipation, tachycardia, visual impairment) Antiemetic and anti-sickness effect (central anticholinergic effect) Antitussive effect (direct effect on the cough center in the medulla oblongata) - diphenhydramine Antiserotonin effect (for migraine) - cyproheptadine
SIDE EFFECTS OF 1st GENERATION ANTIHISTAMINES Transient decrease in blood pressure in sensitive individuals (peripheral vasodilation) Local anesthetic (cocaine-like) effect (reduced membrane permeability to sodium ions) Systemic quinidine-like effect (extension of the refractory phase and development of ventricular tachycardia) Tachyphylaxis (decreased anti histamine activity with long-term use , requiring changes in medications every 2–3 weeks)
ADVANTAGES OF 1st GENERATION ANTIHISTAMINES Short duration of action Relatively quick onset of clinical effect Release in parenteral forms Low cost Niche in the treatment of certain pathologies (migraine, sleep disorders, extrapyramidal disorders, anxiety, motion sickness, etc.) not related to allergies Quite a few first generation antihistamines are included in combination drugs used for colds, as sedatives, hypnotics and other components
For ARVI (drugs with anticholinergic effects have a “drying” effect on the mucous membranes): Pheniramine (Avil); + paracetamol + ascorbic acid (Fervex). Promethazine (Pipolphen, Diprazin); + paracetamol + dextromethorphan (Coldrex Nite). Chloropyramine (Suprastin). Chlorphenamine; + paracetamol + ascorbic acid (Antigrippin); + paracetamol + pseudoephedrine (Theraflu, Antiflu); + biclotymol + phenylephrine (Hexapneumine); + phenylpropanolamine (CONTAC 400); + phenylpropanolamine + acetylsalicylic acid (HL-cold). Diphenhydramine (Dimedrol).
To suppress cough: Diphenhydramine (Dimedrol) Promethazine (Pipolphen, Diprazin) To correct sleep disorders (improves falling asleep, depth and quality of sleep, but the effect lasts no more than 7-8 days): Diphenhydramine (Dimedrol); + paracetamol (Efferalgan Nightcare). To stimulate appetite: Cyproheptadine (Peritol); Astemizole (Hismanal). To prevent nausea and dizziness caused by labyrinthitis or Meniere's disease, as well as to reduce the symptoms of motion sickness: Diphenhydramine (Dimedrol) Promethazine (Pipolphen, Diprazin)
For the treatment of vomiting of pregnant women: Diphenhydramine (Dimedrol) For potentiation of the action of analgesics and local anesthetics (premedication, component of lytic mixtures): Diphenhydramine (Dimedrol) Promethazine (Pipolphen, Diprazin) For the treatment of minor cuts, burns, insect bites (the effectiveness of topical use of drugs is strictly not proven, use is not recommended for > 3 weeks due to increased risk of local irritation): Bamipin (Soventol).
SECOND GENERATION ANTIHISTAMINES (NON-SEDATIVE) Unlike the previous generation, they have almost no sedative and anticholinergic effects, and are distinguished by their selectivity of action on H1 receptors. But they have a cardiotoxic effect to varying degrees
PROPERTIES OF ANTIHISTAMINES OF THE II GENERATION High specificity and high affinity for H1 receptors with no effect on choline and serotonin receptors Rapid onset of clinical effect and duration of action Minimal sedation when using drugs in therapeutic doses No tachyphylaxis with long-term use No inactivation of the drug by food Ability to block potassium channels of the heart muscle (prolongation of the QT interval and cardiac arrhythmia). The risk of this side effect increases when antihistamines are combined with antifungals (ketoconazole and intraconazole), macrolides (erythromycin and clarithromycin), antidepressants (fluoxetine, sertraline and paroxetine) when drinking grapefruit juice in patients with severe liver dysfunction
ACTIVE END METABOLITES OF II GENERATION DRUGS (III generation) the first was cetirizine (analergin, Zyrtec, Zodak, Letizen, Cetrin) is slightly metabolized does not interact with drugs that inhibit the cytochrome P 450 system does not have side effects on the cardiovascular system is able to suppress not only early, but also late phases of the allergic response (reduces nasal congestion); the half-life of cetirizine in adults after a single dose of 10 mg of the drug is 7–11 hours; traces of the cetirizine metabolite appear in the plasma after 10 hours. Cetirizine is characterized by a low volume of distribution and high ability to penetrate into skin during a course of treatment, a constant plasma concentration is achieved within 3 days, and with further use the drug does not accumulate and the rate of elimination does not change
ALLERGIC DISEASES in children Frequency in Russia is more than 30% Bronchial asthma - from 2% to 10% Allergic rhinitis - more than 14% Atopic dermatitis in children 10 -28% Urticaria 15.3 -31%
Atopic march is the sequential development of clinical symptoms of an atopic disease, when some symptoms become more pronounced, while others decline1 Atopic dermatitis in early childhood Allergic rhinitis (in 15.0% -45.0% of patients) Bronchial asthma (in 40. 0% - 43. 0%) 1. J M. Spergel and A. S. Paller Atopic dermatitis and atopic march. J Allergy Clin Immunol Dec 2003, 112; 6: 118 -126.
MAIN INDICATIONS FOR PRESCRIBING ANTIHISTAMINES Allergic rhinitis Hay fever Atopic dermatitis Chronic urticaria Quincke's edema Prevention of complications in ASIT Pseudo-allergy Bronchial asthma? Acute respiratory diseases?
ANTIHISTAMINES AND BRONCHIAL ASTHMA Not being a first-line drug, the latest generation antihistamines are indicated for patients with bronchial asthma with concomitant allergic diseases (allergic rhinitis, atopic dermatitis, etc.) ARIA
It is recommended to prescribe antihistamines to all patients with ARVI if they have allergic diseases or are at high risk of developing them. . . But it is undesirable to use 1st generation antihistamines. National scientific and practical program “Acute respiratory diseases in children: treatment and prevention” 2002.
ANTIHISTAMINES IN CHILDREN WITH ALLERGIES (LAST GENERATION!) Cetirizine (Zyrtec, drops) – from 6 months. Cetirizine (zodak, parlazine) - from 1 year Deslorotadine (erius, syrup) - from 1 year Levocetirizine (xysal, drops) - from 2 years Lorotadine (Claritin, syrup) - from 2 years Fexofenadine (Tefast, tablet) - from 6 years
DISADVANTAGES OF 1ST GENERATION ANTIHISTAMINES IN CHILDREN Sedative effect – drowsiness, disruption of sleep-wake cycles, increased convulsive threshold. Impaired cognitive functions - decreased ability to think, delayed development of the emotional sphere, decreased memory, reduced ability to learn: children began to do worse at school and learn worse; IQ index decreases. Short duration of action Tachyphylaxis Binding of M-cholinergic receptors. Dryness is very dangerous in bronchial asthma and acute respiratory infections. These drugs should absolutely not be used for acute respiratory infections. Cardiotoxicity and arrhythmogenicity in overdose due to muscarinic action. There have been many publications on the association of deaths from arrhythmias, especially in children due to the greater possibility of overdose with low body weight.
CONSENSUS ON THE RISKS ASSOCIATED WITH THE USE OF 1ST GENERATION H1-HISTAMINES Should not be prescribed to infants under 6 months of age Antihistamines to children under 6 years of age 1st generation antihistamines FDA up to 6 months of age any H1-histamine blockers are not recommended
Zodak is a drug for allergies of the latest generation, which begins to act within 20 minutes. The effect of the drug Zodak lasts for 24 hours. Age Daily Frequency Drops Tablets 5 drops dose 1 – 2 years 2.5 mg X 1 day per day 2 – 6 years 5 mg 2.5 mg X 2 times / day or 5 mg X 10 drops 1 time / day Over 6 years old 10 mg X 1 time / day 20 drops 1 tablet.
Begins to act within 12 minutes!* Age Daily dose Multiplicity Tablets Over 6 years 5 mg 1 tablet. 5 mg X 1 time per day
Telfast/Allegra is the original allergy drug of the latest generation, which is effective for 24 hours and has no sedative effect! Active ingredient: Fexofenadine Tablets Age Indications Frequency, dosage 120 mg 12 years Seasonal allergic rhinitis 120 mg (1 tablet) X 1 time per day 180 mg 12 years Chronic idiopathic urticaria 180 mg (1 tablet) X 1 time per day