Non-narcotic analgesics, non-steroidal anti-inflammatory and antipyretic drugs. Clinical pharmacology of the most commonly used antipyretics Analgesics Antipyretics Side effects

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All drugs in this group are inhibitors of the enzyme cyclooxygenase (COX), which acts on arachidonic acid to form important mediators of inflammation and pain - prostaglandins and thromboxanes. Most representatives of this group of agents non-selectively inhibit both forms of the enzyme: type I cyclooxygenase (COX-I) constitutively presented in many cells, as well as type II cyclooxygenase (COX-Il) induced by inflammation and pain. One of the main side effects of NSAIDs is their ulcerogenic effect, due to a decrease in the production of gastroprotective prostaglandins in the gastric mucosa, which is associated with inhibition of COX-1 activity.

A newer NSAID, celecoxib (Celebrex), is a highly selective COX-P inhibitor and therefore does not cause gastric ulceration.

In dentistry, this group of drugs is used orally, as well as parenterally for toothache, neuralgia and myalgia. maxillofacial region, arthritis of the temporomandibular joint, lupus erythematosus and other collagenoses. Ketorolac tromethamine has the maximum analgesic effect (for some pains, it is only 3 times inferior to morphine), however, as an analgesic, this drug is not recommended for long-term (more than 5 days) administration due to a possible ulcerogenic effect on the stomach even with parenteral administration.

When taking high doses of salicylates (acetylsalicylic acid, etc.), one should also take into account the possibility of bleeding (decrease in the production of thromboxane A2) and reversible toxic effects on auditory nerve. Long-term use of pyrazolone derivatives can cause hematopoiesis suppression (agranulosis, aplastic anemia), which can be manifested by ulceration of the oral mucosa.

As local analgesics and anti-inflammatory agents in dentistry, mafenamine sodium salt and benzydamine are used, which also inhibit COX, locally reduce the production of prostaglandins and reduce their edematous and algogenic effects. Systemic toxicity at local application these funds are not listed.

Aminophenazone(Aminophenazone). Synonyms: Amidopyrine (Amidopyrinum), Amidazophene (Amidazophen).

pharmachologic effect: has antipyretic, analgesic and anti-inflammatory effect. Unlike narcotic analgesics, it does not have a depressing effect on the respiratory and cough centers, does not cause euphoria and drug dependence phenomena.

Indications: in the conditions of an outpatient appointment, they are prescribed for removal pain of various origin (myositis, arthritis, neuralgia, headache and toothache etc.) and in odontogenic inflammatory processes.

Mode of application: inside 0.25-0.3 g 34 times a day (maximum daily dose - 1.5 g).

Side effect: with individual intolerance, the development of anaphylactic reactions and the appearance of skin rashes. Causes oppression of hematopoietic organs (agranulocytosis, granulocytopenia).

Contraindications: individual intolerance and diseases of the hematopoietic system.

Release form: powder, tablets of 0.25 g in a package of 6 pcs. Amidopyrine is part of complex tablets (Piranal, Pirabutol, Anapirin), which are prescribed depending on the pharmacological action of the components that make up their composition. When taking combination tablets, you may experience Side effect characteristic of their constituent components.

Storage conditions: in a place protected from light. List B.

Acetylsalicylic acid(Acidum acetylsalicylicum). Synonyms: Aspirin (Aspirin), Plidol 100/300 (Plidol 100/300), Acenterin (Acenterin), Anapyrin (Anapyrin), Apo-Asa (Apo-Asa), Aspilyte (Aspilyte), Acylpyrine (Asu 1 pyrin), Kolfarit (Colfarit), Magnyl (Magnyl), Novandol (Novandol).

pharmachologic effect: non-steroidal anti-inflammatory agent. It has antipyretic, analgesic and anti-inflammatory effects, and also inhibits platelet aggregation. The main mechanism of action of acetylsalicylic acid is the inactivation of the cyclooxygenase enzyme, as a result of which the synthesis of prostaglandins is disrupted.

Indications: in dental practice, it is prescribed for pain syndrome of low and moderate intensity of various genesis (arthritis of the temporomandibular joint, myositis, trigeminal and facial neuralgia, etc.) and as a symptomatic agent in the treatment of odontogenic inflammatory diseases.

Mode of application: appoint inside 0.25-1 g after meals 34 times a day. Drink plenty of fluids (tea, milk).

Side effect: possible nausea, anorexia, epigastric pain, diarrhea, allergic reactions, long-term use - dizziness, headache, reversible visual impairment, tinnitus, vomiting, impaired rheological properties and blood clotting, ulcerogenic effect.

Contraindications: peptic ulcer stomach and duodenum, individual intolerance, blood diseases, impaired renal function, pregnancy (I and III trimesters). For children under 2 years of age, the drug is prescribed only for life Indications m. With caution prescribed for liver diseases.

Release form: acetylsalicylic acid - tablets of 0.1; 0.25; 0.5 g

Aspirin - coated tablets, 325 mg, in a package of 100 pcs.

Plidol - tablets of 100 mg, in a package of 20 pcs and 300 mg, in a package of 500 pcs.

Acenterin - enteric tablets of 500 mg, in a package of 25 pcs.

Anopirin - "buffer" tablets, enteric-coated, 30, 100 and 400 mg, in a package of 10 and 20 pcs.

Apo-Asa - tablets of 325 mg, 1000 pcs in a pack.

Acylpyrine - tablets of 500 mg, 10 pcs in a pack.

Aspilight - film-coated tablets, 325 mg, in a package of 100 pcs.

Kolfarit - tablets of 500 mg, in a package of 50 pcs.

Magnil - tablets of 500 mg, in a package of 20, 50 and 100 pcs.

Novandol - tablets of 300 mg, in a package of 10 pcs.

Storage conditions: at room temperature, protected from light.

Benzydamine(Benzydamine). Synonyms: Tantum (Tantum), Tantum Verde (Tantum verde).

pharmachologic effect: a representative of a new class of non-steroidal anti-inflammatory drugs of the indazole group for topical and systemic use. Anti-inflammatory analgesic action due to a decrease in the synthesis of prostaglandins and stabilization of neutrophil cell membranes mast cells, erythrocytes and platelets. Benzydamine does not irritate tissues and does not have an ulcerogenic effect when used systemically. When applied to mucous membranes, it promotes re-epithelialization.

Indications: when used systemically, it is indicated as an anti-inflammatory and analgesic agent in surgery, orthopedics, dentistry, otorhinolaryngology, gynecology, pediatrics.

In dentistry, the drug benzydamine tantum verde is used topically (with proven clinical efficacy) for symptomatic therapy in inflammatory diseases of the oral mucosa with pain syndrome - acute and chronic herpetic oral lesions of the mucous membrane, catarrhal stomatitis, recurrent aphthous stomatitis, red lichen planus, desquamative gloss, non-specific forms of stomatitis, as well as for the treatment of periodontal disease, oral candidiasis (in combination with anti-candidiasis drugs), reducing pain after tooth extraction and injuries oral cavity.

Mode of application: locally - 15 ml of tantum verde solution is used to rinse the mouth 4 times a day. When rinsing, do not swallow the solution. The duration of treatment depends on the severity of the inflammatory process. With stomatitis, the approximate duration of the course is 6 days. Aerosol "Tantum Verde" is used for irrigation of the oral cavity, 4-8 doses every 1.5-3 hours. This dosage form is especially convenient for use in children and postoperative patients who are unable to rinse. For children aged 6-12 years, an aerosol is prescribed in 4 doses, and at the age of up to 6 years - 1 dose for every 4 kg of body weight (no more than 4 doses) every 1.5-3 hours. 34 times a day.

Systemically: Tantum tablets for oral administration are prescribed for adults and children over 10 years old, no 1 pc (0.05 g) 4 times a day. Contraindications: at topical application- individual intolerance to the drug. The rinse solution is not recommended for use in children under 12 years of age. Systemic use - pregnancy, lactation, phenylketonuria.

Side effect: when applied topically, numbness of the tissues of the oral cavity or a burning sensation, allergic reactions are rarely noted.

Interaction with other drugs: not noted.

Release form:

1) liquid for rinsing the mouth and throat - 0.15% solution of benzydamine hydrochloride in a 120 ml vial.

Other Ingredients: Glycerol, Saccharin, Sodium Bicarbonate, Ethyl Alcohol, Methylparaben, Polysorbitol;

2) aerosol in vials of 30 ml (176 doses), containing 255 mcg of benzydamine hydrochloride in 1 dose;

3) oral lozenges containing 3 mg of benzydamine hydrochloride (20 per pack);

4) tablets for oral administration containing 50 mg of benzydamine hydrochloride.

Storage conditions: at room temperature.

diclofenac(Diclofenac). Synonyms: Diclonate P (Diclonat P), Dicloreum (Dicloreum), Apo-Diklo (Apo-Diclo), Veral (Veral), Voltaren (Voltaren), Diclac (Diclac), Diclobene (Diclobene), Diclomax (Diclomax), Diclomelan ( Diclomelan), Diklonak (Diclonac), Dicloran (Dicloran), Revodina (Rewodina), Rumafen (Rheumafen).

pharmachologic effect: non-steroidal anti-inflammatory agent. Is an active substance a large number medicines, produced in the form of tablets (see synonyms).

It has an anti-inflammatory, analgesic and moderate antipyretic effect due to the inhibition of the synthesis of prostaglandins, which play a major role in the pathogenesis of inflammation, pain and fever.

Indications: pain syndrome after traumas, operations. Inflammatory edema after dental operations.

Mode of application: administered orally at 25-30 mg 2-3 times a day (maximum daily dose - 150 mg). For children over 6 years of age and adolescents, the daily dose - 2 mg / kg of body weight - is divided into 3 doses.

Side effect: possible nausea, anorexia, pain in the epigastric region, flatulence, constipation, diarrhea, as well as dizziness, agitation, insomnia, fatigue, irritability; in predisposed patients - edema Contraindications: gastritis, peptic ulcer of the stomach and duodenum, hematopoietic disorders, pregnancy, hypersensitivity to diclofenac. Do not administer to children under 6 years of age.

: simultaneous reception with acetylsalicylic acid leads to a decrease in its concentration in plasma. Reduces the effect of diuretics.

Release form: retard tablets, pack of 20 (each tablet contains 100 mg of diclofenac sodium); solution for injection in ampoules of 3 ml, in a package of 5 pcs (in 1 ml - 50 mg of diclofenac sodium).

Dicloreum - tablets of 50 mg, in a package of 30 pcs; retard tablets 100 mg, pack of 30; solution for injections of 3 ml in ampoules, in a package of 6 pcs (1 ml contains 25 mg of diclofenac sodium).

Storage conditions: in a dry, cool place.

Ibuprofen(Ibuprofenum). Synonyms: Apo-ibuprofen (Apo-lbuprofen), Bonifen (Bonifen), Burana (Burana), Ibupron (Ibupron), Ibusan (Ibusan), Ipren (Ipren), Markofen (Marcofen), Motrin (Motrin), Norswel (Norswel) , Paduden.

pharmachologic effect: has anti-inflammatory, antipyretic and analgesic properties. The antipyretic effect is superior to phenacetin and acetylsalicylic acid. The latter is inferior to ibuprofen and analgesic action. The mechanism of action is associated with the inhibition of prostaglandins. Analgesic effect occurs 1-2 hours after taking the drug. The most pronounced anti-inflammatory effect is observed after 1-2 weeks of treatment.

Indications: used for arthralgia of the temporomandibular joint of rheumatic and non-rheumatic origin (arthritis, deforming osteoarthrosis), myalgia, neuralgia, postoperative pain.

Mode of application: appoint inside after eating 0.2 g 3-4 times a day. Daily dose - 0.8-1.2 g.

Side effect: possible occurrence of heartburn, nausea, vomiting, sweating, skin allergic reactions, dizziness, headache, gastric and intestinal bleeding, edema, color vision disorders, dry eyes and mouth, stomatitis.

Contraindications: peptic ulcer of the stomach and duodenum, ulcerative colitis, bronchial asthma, parkinsonism, epilepsy, mental illness, pregnancy and lactation, hypersensitivity to ibuprofen. Use with caution in persons of operator professions, with violations of blood clotting, liver and kidney function.

Interaction with other drugs: the drug enhances the effect of sulfonamides, difenin, indirect anticoagulants.

Release form: tablets of 0.2 g, film-coated. Storage conditions: in a dry, dark place. List B.

Indomethacin(Indometacin). Synonyms: Indobene (Indobepe), Indomelan (lndomelan), Indomin (lndomin), Indotard (1pdotard), Metindol (Metindol), Elmetatsin (Elmetacin).

pharmachologic effect: has anti-inflammatory, antipyretic and analgesic properties. The antipyretic effect is superior to phenacetin and acetylsalicylic acid. The latter is inferior to indomethacin and analgesic action.

Indications: recommended for arthritis and arthrosis of the temporomandibular joint of various origins; as a short term addition to complex therapy myalgia and neuropathy; with pain syndrome and inflammation after dental surgical interventions. It can also be used for reactive hyperemia of the pulp after tooth preparation for fixed dentures or an extensive filling, inlay.

Mode of application: administered orally during or after meals 34 times a day, starting from 0.025 tons. Depending on tolerance, the dose is increased to 0.1-0.15 g per day. The course of treatment is 23 months. With hyperemia of the pulp, the drug is used for 57 days. It can be used as an ointment, which is rubbed into the joint area 2 times a day.

Side effect: possible occurrence of stomatitis, ulceration of the mucous membrane of the stomach, intestines, pain in the epigastric region, dyspeptic symptoms, gastric and intestinal bleeding, headache, dizziness, hepatitis, pancreatitis, allergic reactions, agranuloiitosis, thrombocytopenia.

Contraindications: not recommended for gastroduodenal ulcers, bronchial asthma, blood diseases, diabetes, individual intolerance, during pregnancy and lactation, mental illness, in children under 10 years of age.

Interaction with other drugs: in combination with salicylates, the effectiveness of indomethacin decreases, its damaging effect on the gastric mucosa increases. The effect of the drug is enhanced when combined with glucocorticoids, pyrazolone derivatives.

Release form: dragee 0.025 g; tubes with 10% ointment. Storage conditions: in a dry, cool place. Ketoprofen (Ketoprofen). Synonyms: Ketonal (Ketonal), Pro-, Phenide (Profenid), Fastum (Fastum).

pharmachologic effect: has anti-inflammatory, antipyretic and analgesic effect, inhibits platelet aggregation. The mechanism of action is associated with a decrease in the synthesis of prostaglandins. The anti-inflammatory effect is noted. begins at the end of the first week of treatment.

Indications: symptomatic treatment of inflammatory and inflammatory-degenerative diseases of the joints. Pain syndrome of various origins, including postoperative post-traumatic pain.

Mode of application: administered orally, in a daily dose of 300 mg in 23 doses. Maintenance dose - 50 mg 3 times a day. Locally apply the gel, which is applied to the affected surface 2 times a day, long and gently rubbed, after rubbing, you can apply a dry bandage.

Side effect: during treatment with the drug, nausea, vomiting, constipation or diarrhea, gastralgia, headache, dizziness, drowsiness may occur. When prescribing the gel - itching skin rash at the site of application of the drug.

Contraindications: when taken orally - diseases of the liver, kidneys, gastrointestinal tract, pregnancy and lactation, age up to 15 years, hypersensitivity to ketoprofen and salicylates. With topical application of the gel - dermatoses, infected abrasions, wounds.

Interaction with other drugs: when administered simultaneously with anticoagulants, the risk of bleeding increases.

Release form: coated tablets, 100 mg, in a package of 25 and 50 pcs; retard tablets 150 mg, pack of 20 Gel in tubes of 30 and 60 g (1 g contains 25 mg active substance), cream in tubes of 30 and 100 g (1 g contains 50 mg of the active substance).

Storage conditions: in a dry, cool place.

Ketorolac tromethamine(Ketorolac tromethamine). Synonym: Ketanov.

pharmachologic effect: non-narcotic analgesic with a very strong analgesic effect and moderate anti-inflammatory and antipyretic properties. It is a derivative of pyrrolopyrole. In terms of analgesic activity, it surpasses all known non-narcotic analgesics, with intramuscular and intravenous administration at a dose of 30 mg causes an analgesic effect equivalent to the effect of intramuscular injection of 12 mg of morphine. It inhibits the cyclooxygenase pathway of arachidonic acid metabolism, reducing the production of prostaglandins, mediators of inflammation and pain. Unlike narcotic analgesics, it has a peripheral effect, does not depress the central nervous system, respiration, cardiac activity and other autonomic functions. Does not cause euphoria and drug dependence. Ketorolac is not characterized by tolerance. Like other non-steroidal anti-inflammatory drugs, it inhibits platelet aggregation, prolongs the mean bleeding time. The duration of action for intramuscular and oral administration is 46 hours.

Indications: used for short-term pain relief with severe and moderate pain syndrome, after operations in the maxillofacial region, with traumatic injuries of bones and soft tissues, toothache, including after dental interventions, arthrosis of the temporomandibular joint, oncological pain.

Mode of application: the first dose (10 mg) for the relief of acute severe pain is administered intramuscularly. If necessary, a subsequent dose (10-30 mg) is administered every 45 hours. The maximum daily dose of the drug for any route of administration for adults is 90 mg, in elderly patients it should not exceed 60 mg. The maximum duration of ketorolac injection is 2 days. After cupping acute pain and with a pain syndrome of moderate intensity, the drug can be administered orally at 10 mg (one tablet) every 46 hours. The duration of use with enteral administration should not exceed 7 days.

Side effect: Ketorolac is well tolerated. In rare clouds, nausea, vomiting, diarrhea, headache, and sweating may occur. As with other non-steroidal anti-inflammatory drugs, irritation of the gastric mucosa, exacerbation of peptic ulcer, and gastrointestinal bleeding are possible. These phenomena are characteristic mainly for enteral administration.

Contraindications: Do not administer during pregnancy, lactation, and patients under the age of 16 years. Contraindicated in peptic ulcer of the stomach and duodenum, especially in the acute stage, individual intolerance to non-steroidal anti-inflammatory drugs, including "aspirin asthma". Use with caution in diseases of the liver and kidneys, and it is necessary to reduce the dosage.

Interaction with other drugs: well combined with morphine and other narcotic analgesics, which allows for postoperative pain to reduce the dosage of narcotic analgesics by 1/3. This combination does not enhance the inhibitory effect of narcotic analgesics on breathing. Ketorolac can potentiate the effects of indirect anticoagulants by displacing them from their association with plasma proteins. High doses of salicylates can increase the level of the free fraction of ketorolac in plasma and enhance its effect, while a decrease in the dosage of the drug is necessary.

Release form: coated tablets, pack of 10 pcs (1 tablet contains 10 mg of ketorolac tromethamine); ampoules and syringe-tubes of 1 ml of a solution containing 30 mg of ketorolac tromethamine.

Storage conditions: in a place protected from light at room temperature.

Metamizole sodium(Metamizoli sodium). Synonyms: Analgin (Analginum), Baralgin M (Baralgin M), Nebagin (Nebagin), Optalgin-Teva (Optalgin-Teva), Spasdolzin (Spasdolsin), Toralgin (Toralgin).

Formacological action: is a derivative of pyrazolone. It has a pronounced analgesic and antipyretic effect. The analgesic effect is due to the suppression of the biosynthesis of a number of endogenous substances (endoperoxides, bradykinins, prostaglandins, etc.). It prevents the conduction of painful extero- and proprioceptive impulses along the Gaulle and Burdach bundles and increases the excitability threshold at the level of the thalamus. The antipyretic effect is due to the suppression of the formation and release of pyrogenic substances.

Indications: in dental practice, it is prescribed as an anesthetic (toothache, myositis, neuritis and neuralgia of the trigeminal and facial nerve, pain after tooth extraction and filling root canal, alveolitis and other odontogenic inflammatory diseases, postoperative period, painful medical manipulations, etc.), anti-inflammatory and antipyretic agent for feverish conditions, including those of odontogenic origin. Used for premedication with other analgesics, tranquilizers and hypnotics.

Mode of application: when taken orally, a single dose for adults - 200-500 mg (maximum - 1 g); for children aged 23 years 100-200 mg, 57 years 200 mg, 8-14 years 250-300 mg. Multiplicity of appointment - 2-3 times a day.

Intramuscularly or intravenously slowly, adults are prescribed 1-2 ml of a 25% or 50% solution 23 times a day. Children are parenterally prescribed at a dose of 50-100 mg per 10 kg of body weight. Long-term use of the drug requires monitoring of the picture of peripheral blood.

Side effect: when applied, skin rash, chills, dizziness may occur; there may be changes in the blood (leukopenia, agranulocytosis). With intramuscular injection, infiltrates are possible at the injection site.

Contraindications: pronounced disorders of the kidneys and liver, blood diseases, hypersensitivity to pyrazolone derivatives. Use with caution during pregnancy, children in the first 3 months of life.

Release form: tablets of 0.5 g with a risk for children, in a package of 10 pcs, an analgin solution for injection in ampoules of 1 and 2 ml, 10 pcs in a package (1 ml - 250 mg of the active substance).

Storage conditions: in a dry, cool place.

Mefenamin sodium salt (Mephenaminum sodium).

pharmachologic effect: has a local anesthetic and anti-inflammatory effect, stimulates the epithelization of the damaged oral mucosa.

Indications: used in the treatment of periodontal diseases and ulcerative lesions of the oral mucosa, as well as in the treatment of traumatic complications caused by various designs of dentures.

Mode of application: used in the form of a 0.1-0.2% aqueous solution for application 1-2 times a day or 1% paste, which is injected into the dentogingival pockets after 1-2 days (68 sessions per course). The solution and paste are prepared immediately before use. As the basis for the preparation of the paste, isotonic sodium chloride solution and white clay are used.

Side effect: when using solutions with a concentration above 0.3% or a paste with a concentration of more than 1%, there may be irritation of the oral mucosa.

Contraindications: individual intolerance.

Release form: powder 3 kg in plastic bags.

Storage conditions: in a dry, dark place. List B,

Nabumeton(Nabumeton). Synonym: Relafen.

pharmachologic effect: non-steroidal anti-inflammatory drug, inhibits the synthesis of prostaglandins. It has anti-inflammatory, analgesic and antipyretic effects.

Indications: in dentistry it is used as a symptomatic remedy in the complex treatment of diseases of the temporomandibular joint.

Mode of application: appoint inside 1 g 1 time per day, regardless of the meal.

Side effect: possible sleep disorders, headache and dizziness, blurred vision, shortness of breath, pain in the epigastric region, changes in the picture of peripheral blood, urticaria.

Contraindications: hypersensitivity to the drug and other NSAIDs, pregnancy and lactation, gastrointestinal diseases and impaired renal function. Not intended for children

Interaction with other drugs: do not prescribe with drugs that have a high binding to plasma proteins.

Release form: Relafen [Smith Klein Beecham| : film-coated tablets, beige, in a package of 100 and 500 pcs (1 tablet contains 750 mg of nabumetone); coated tablets, white color, in a package of 100 and 500 pieces (1 tablet contains 500 mg of nabumetone).

Storage conditions: in a dry, cool place.

Naproxen(Naproxen). Synonyms: Apo-naproxen (Aro-pargohep), Daprox Entero (Daprox Entero), Naprobene (Naprobene), Apranax (Apranax), Naprios (Naprios), Pronaxen (Pronahep), Naprosyn (Narposyn), Sanaprox (Sanaprox).

pharmachologic effect: is a derivative of propionic acid, has anti-inflammatory, analgesic and antipyretic effects. Suppresses the synthesis of inflammatory mediators and prostaglandins, stabilizes lysosome membranes, prevents the release of lysosomal enzymes that cause tissue damage during inflammatory and immunological reactions. Relieves pain, including joint pain, reduces swelling. The maximum anti-inflammatory effect is achieved by the end of the 1st week of treatment. With prolonged use, it has a desensitizing effect. Reduces platelet aggregation.

Indications: used for arthritis, including the temporomandibular joint ( rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, articular syndrome with gout, pain in the spine), myalgia, neuralgia, traumatic inflammation of the soft tissues and the musculoskeletal system. As an adjuvant, it is used for infectious and inflammatory diseases of the upper respiratory tract, headache and toothache.

Mode of application: administered to adults orally in a daily dose of 0.5-1 g, in two divided doses. The maximum daily dose is 1.75 g, the maintenance daily dose is 0.5 g. It is also used as rectal suppositories at night (1 suppository each containing 0.5 g of the drug). When administered rectally, toxic effects on the liver are excluded.

Side effect: with prolonged use, dyspeptic symptoms (pain in the epigastric region, vomiting, heartburn, diarrhea, bloating), tinnitus, dizziness are possible. In rare cases, there are thrombocytopenia and granulocytopenia, Quincke's edema, skin rash. When using suppositories, local irritation is possible.

Contraindications: fresh peptic ulcer of the stomach, "aspirin" asthma, hematopoietic disorders, severe disorders of the liver and kidneys. Use with caution during pregnancy. Do not appoint children under one year.

Interaction with other drugs: reduces the diuretic effect of furosemide, potentiates the effect of indirect anticoagulants. Antacids containing magnesium and aluminum reduce the absorption of naproxen from the gastrointestinal tract.

Release form: tablets of 0.125; 0.25; 0.375; 0.5; 0.75; 1 g; rectal suppositories of 0.25 and 0.5 g.

Storage conditions: List B.

Niflumic acid(niflumic acid). Synonym: Donalgin.

pharmachologic effect: non-steroidal anti-inflammatory agent for oral administration, which has anti-inflammatory and analgesic effects.

Indications: pain with fractures of the jaws, dislocations and subluxations of the temporomandibular joint, soft tissue injuries of the maxillofacial region, periostitis, arthritis, osteoarthrosis, pain dysfunction of the joint, as well as pain syndromes after tooth extraction, various dental procedures, etc.

Mode of application: administered orally 1 capsule 3 times a day during or after meals. The capsule is swallowed whole, without chewing. In severe cases, especially with exacerbation of chronic inflammatory processes, the daily dose can be increased to 4 capsules. After the onset of clinical improvement, the maintenance daily dose is 1-2 capsules per day.

Side effect: possible nausea, vomiting, diarrhea, sometimes stomach pain.

Contraindications: pregnancy, diseases of the liver, kidneys, peptic ulcer of the stomach and duodenum. It is not recommended to prescribe to children, as well as in case of hypersensitivity to the drug.

Interaction with other drugs: simultaneous reception of donalgin and glucocorticosteroids allows you to reduce the dose of the latter. In patients taking indirect anticoagulants, it is necessary to constantly monitor the prothrombin index.

Release form: gelatin capsules, pack of 30 pcs (1 capsule contains 250 mg of niflumic acid).

Storage conditions: in a dry, cool place.

Paracetamol(Paracetamol). Synonyms: Brustan (Brustan), Dafalgan (Dafalgan), Ibuklin (Ibuclin), Kalpol (Calpol), Coldrex (Coldrex), Panadein (Panadeine), Panadol (Panadol), Plivalgin (Plivalgin), Saridon (Saridon), Solpadein (Solpadeine) ), Tylenol (Tylenol), Efferalgan (Efferalgan).

pharmachologic effect: It is an analgesic, anti-inflammatory and antipyretic agent. Inhibits the synthesis of prostaglandins, which are responsible for the early stages of the inflammatory response and the sensation of pain. It inhibits the hypothalamic center of thermoregulation, which is manifested by an antipyretic effect. It is a metabolite of phenacetin, but differs from the latter in significantly lower toxicity, in particular, it forms methemoglobin much less often and does not have a pronounced nephrotoxic property. Unlike other non-steroidal anti-inflammatory drugs (salicylates, oxicams, pyrazolones, propionic acid derivatives), it does not irritate the gastric mucosa and does not inhibit leukopoiesis.

Indications: used for arthritis and arthrosis of the temporomandibular joints, myalgia, neuralgia, inflammatory diseases dental system. It is used for pain syndrome of low and medium intensity with inflammation, fever, infectious and inflammatory diseases, in combination with codeine (Panadeine) - for migraine.

Mode of application: administered orally alone or in combination with phenobarbital, caffeine, etc. in tablets or powders for adults at a dose of 0.2-0.5 g, for children from 2 to 5 years old - 0.1-0.15 g each, 6-12 years - 0.15-0.25 g per reception 23 times a day.

Side effect: generally well tolerated. With prolonged use in high doses, a hepatotoxic effect is possible. Rarely causes thrombocytopenia, anemia and methemoglobinemia, allergic reactions.

Contraindications: individual intolerance to the drug, blood diseases, severe liver dysfunction.

Interaction with other drugs: in combination with antispasmodics relieves spastic pain, with caffeine, codeine, antipyrine, the toxicity of paracetamol decreases and increases therapeutic effect mixture components. In combination with phenobarbital, methemoglobinemia may increase. The combination with phenylephrine hydrochloride helps to reduce swelling of the nasal mucosa with colds and flu.

The half-life of paracetamol increases with the simultaneous use of barbiturates, tricyclic antidepressants, and also with alcoholism. Analgesic activity may decrease with long-term use of anticonvulsants.

Release form: tablets of 0.2 and 0.5 g. In addition to monocomponent preparations of paracetamol, paraceta is currently the most common.

Panadol soluble (Panadol soluble) - tablets of 0.5 g;

Panadol baby and infant (Panadol baby end infant) - suspension in vials containing 0.024 g of paracetamol in 1 ml;

Panadol-extra (Panadol extra) - tablets containing 0.5 g of paracetamol and 0.065 g of caffeine;

Panadeine (Panadeine) - tablets of 0.5 g of paracetamol and 8 mg of codeine phosphate;

Solpadeine (Solpadeine) - soluble tablets containing 0.5 g of paracetamol, 8 mg of codeine phosphate, 0.03 g of caffeine.

From these drugs in dentistry with pain syndrome of moderate intensity (pain after tooth extraction, with pulpitis, periodontitis), preference can be given to fast-acting and active drugs containing, in addition to paracetamol, codeine and caffeine - Panadeine and Solpadeine. Caffeine has the ability to enhance the analgesic effect of paracetamol and other non-narcotic analgesics. Codeine, being a weak agonist of opiate receptors, also significantly potentiates and prolongs the analgesic effect. The drugs are prescribed for adults 1-2 tablets up to 4 times a day. The drugs are safe, well tolerated and can be prescribed to patients with comorbidities such as diseases of the gastrointestinal tract and bronchial asthma. They are contraindicated in severe violations liver and kidney function, as well as children under the age of 7 years. Despite the minimal content of codeine, the possibility of addiction should be borne in mind.

Brustan (Brustan): tablets containing 0.325 g of paracetamol and 0.4 g of ibuprofen. The drug is indicated for adults with pain syndrome of moderate intensity (traumatic pain, dislocations, fractures, postoperative pain, toothache). As an analgesic for adults, the drug is prescribed 1 tablet 34 times a day. Side effects: see Ibuprofen.

Plivalgin (Plivalgin): tablets containing 0.21 g of paracetamol, 0.21 g of propyphenazone, 0.05 g of caffeine, 0.025 g of phenobarbital, 0.01 g of codeine phosphate. The drug is indicated for pain of moderate intensity. Adults appoint a single dose of 2-6 tablets per day. Contraindicated in severe liver diseases, blood diseases, pregnancy, lactation, hypersensitivity to the components of the drug.

Storage conditions: in a dry, dark place. Piroxicam. Synonyms: Apo-piroxicam (Apo-piroxicam), Piricam (Piricam), Pirocam (Pirocam), Remoxicam (Remoxicam), Sanicam (Sanicam), Hotemin (Hotemin), Erazon, (Erason), Felden (Feldene).

pharmachologic effect: is a derivative of the oxicam class, has anti-inflammatory, analgesic and antipyretic effects. It inhibits cyclooxygenase and reduces the production of prostaglandins, prostacyclins and thromboxane, reduces the production of inflammatory mediators. After a single application, the effect of the drug lasts one day. Analgesic action begins 30 minutes after taking the drug.

Indications: used for arthralgia (rheumatoid arthritis, osteoarthritis, including arthritis of the temporomandibular joint, ankylosing spondylitis, gout), myalgia, neuralgia, traumatic inflammation of soft tissues and the musculoskeletal system, acute infectious and inflammatory diseases of the upper respiratory tract.

Mode of application: administered orally 1 time per day at a dose of 10-30 mg. Higher doses can be used in acute severe cases such as gout attacks. At the same time, it is possible intramuscular injection at a dose of 20-40 mg 1 time per day until the relief of acute events, after which they switch to maintenance therapy with tablets. The drug is also administered rectally in the form of suppositories, 20-40 mg 1-2 times a day.

Side effect: When ingested in high doses, nausea, anorexia, abdominal pain, constipation, diarrhea are possible. The drug can cause erosive and ulcerative lesions of the gastrointestinal genesis. Rarely, toxic effects on the kidneys and liver, oppression of hematopoiesis, adverse effects from the central nervous system - insomnia, irritability, depression. When applied rectally, irritation of the rectal mucosa is possible.

Contraindications: erosive and ulcerative lesions of the gastrointestinal tract in the acute phase, severe violations of the liver and kidneys, "aspirin" asthma, hypersensitivity to the drug, pregnancy, lactation.

Interaction with other drugs: enhances the side effects of other non-steroidal anti-inflammatory drugs. The toxicity of piroxicam increases when taken simultaneously with indirect anticoagulants.

Release form: tablets of 0.01 and 0.02 g; solution in ampoules (0.02 g in 1 ml and 0.04 g in 2 ml). Rectal suppositories by 0.02 g

Storage conditions: list B.

Sulindak(Sulindac). Synonym: Clinoril (Clinoril).

pharmachologic effect: is a derivative of indenacetic acid, an indene derivative of indomethacin. However, it is devoid of some of the side effects of this drug. In the body, it forms an active metabolite - sulfide. It has anti-inflammatory, analgesic and antipyretic effects. Reduces the synthesis of prostaglandins and inflammatory mediators, reduces the migration of leukocytes to the area of ​​inflammation. Compared to salicylates, it rarely causes side effects from the gastrointestinal tract, does not cause headaches, which are characteristic of indomethacin. Reduces joint pain at rest and during movement, eliminates swelling. The maximum anti-inflammatory effect develops by the end of the 1st week of treatment.

Indications: see Piroxicam.

Mode of application: administered orally in a daily dose of 0.2-0.4 g in 1 or 2 doses. The maximum daily dose is 0.4 g. If necessary, reduce the dose. Take the drug with liquid or food. With acute gouty arthritis average duration treatment is 7 days.

Side effect: as a rule, the tolerability of the drug is satisfactory. The most common disorders of the gastrointestinal tract: nausea, anorexia, epigastric pain, constipation, diarrhea. In rare cases, erosive and ulcerative lesions of the stomach and bleeding occur. Possible sleep disturbances, kidney function, paresthesia, changes in the blood picture.

Contraindications: do not use during pregnancy, lactation, in childhood (up to 2 years), with erosive and ulcerative lesions of the gastrointestinal tract in the acute phase, "aspirin" asthma, individual intolerance to non-steroidal anti-inflammatory drugs.

Interaction with other drugs: increases the effect of anticoagulants of indirect action.

Release form: tablets of 0.1; 0.15; 0.2; 0.3 and 0.4 g.

Storage conditions: list B.

Phenylbutazone(Phenylbutazone). Synonym: Butadion (Butadionum).

pharmachologic effect: has analgesic, antipyretic and anti-inflammatory effect.

By anti-inflammatory activity significantly superior to amidopyrine, is one of the main non-steroidal anti-inflammatory drugs. Butadione is an inhibitor of prostaglandin biosynthesis, and more powerful than acetylsalicylic acid.

Indications: used for the treatment of inflammatory diseases of periodontal tissues, with symptoms of xerostomia in patients with rheumatism, lupus erythematosus, acute purulent-inflammatory diseases of the maxillofacial region, neuritis and neuralgia, arthritis of the temporomandibular joint, burns of 1 and II degrees of a small area, inflammation skin at the site of intramuscular and intravenous injections, traumatic injuries of soft tissues.

Mode of application: administered orally and topically as an ointment. Inside take during or after a meal. The dose for adults is 0.1-0.15 g 4-6 times a day. Maintenance daily dose - 0.2-0.3 g. Children from 6 months are prescribed 0.01-0.1 g 34 times a day (depending on age). The course of treatment lasts 25 weeks or more. Locally use "Butadiene Ointment", containing 5% butadione. The ointment is applied to the oral mucosa or injected into periodontal pockets for 20 minutes daily until exudative phenomena are eliminated.

Side effect: when taken orally, fluid retention, nausea, vomiting, pain in the stomach (associated with ulcerogenic action), skin rashes and other skin allergic reactions, leukopenia and anemia, hemorrhagic manifestations are possible. Hematological changes and allergic reactions are indications for discontinuation of the drug.

Contraindications: peptic ulcer of the stomach and duodenum, diseases of the hematopoietic organs, leukopenia, impaired liver and kidney function, circulatory failure, disorders heart rate hypersensitivity to pyrazolones.

Interaction with other drugs: Maybe combined application with other non-steroidal anti-inflammatory drugs. Able to delay the release of various drugs (amidopyrine, morphine, penicillin, oral anticoagulants, antidiabetic drugs) by the kidneys. When prescribing butadione, it is recommended to limit the introduction of sodium chloride into the body.

Release form: tablets of 0.15 g, film-coated, in a package of 10 pcs (in 1 tablet - 50 mg of phenylbutazone): butadiene ointment 5% in tubes of 20 g.

Storage conditions: in a place protected from light.

Flurbiprofen(Flurbiprofen). Synonyms: Anseid (Ansaid), Flugalin (Flugalin).

pharmachologic effect: has a pronounced analgesic, anti-inflammatory and antipyretic activity. The mechanism of action is associated with inhibition of the cyclooxygenase enzyme and inhibition of prostaglandin synthesis.

Indications: symptomatic therapy for diseases of the temporomandibular joint and soft tissue injuries of the maxillofacial region.

Mode of application: administered orally at 50-100 mg 23 times a day with meals.

Side effect: Dyspepsia, heartburn, diarrhea, abdominal pain, headache, nervousness, sleep disorders, allergic skin reactions may occur.

Contraindications: diseases of the gastrointestinal tract in the acute phase, bronchial asthma, vasomotor rhinitis, intolerance to acetylsalicylic acid, as well as pregnancy and lactation. Use with caution in diseases of the liver and kidneys, arterial hypertension, chronic heart failure.

Interaction with other drugs: when used together with anticoagulants, there is an increase in their action, with diuretics - a decrease in their activity.

Release form: tablets of 50 and 100 mg, in a package of 30 pcs.

Storage conditions: in a dry, cool place.

The dentist's guide to medicines
Edited by Honored Scientist of the Russian Federation, Academician of the Russian Academy of Medical Sciences, Professor Yu. D. Ignatov

Summary

Non-opioid analgesics (antipyretic analgesics) are widely used in pediatric practice. When choosing drugs of this group for prescribing to children, it is especially important to focus on highly effective drugs with the lowest risk of adverse reactions. Today, only paracetamol and ibuprofen fully meet these requirements. They are officially recommended by WHO as antipyretics for pediatric use. The possibilities of using these medicines in the practice of a general pediatrician (with the exception of pediatric rheumatology) are considered. The results of a study demonstrating the high antipyretic and analgesic efficacy of Nurofen for children (ibuprofen) in patients with acute infectious and inflammatory diseases of the respiratory tract and ENT organs are presented. In addition, the high safety of taking Nurofen was noted. It is emphasized that against the background of etiotropic and pathogenetic treatment, timely and adequate therapy with antipyretic analgesics brings relief to a sick child, improves his well-being and speeds up recovery.

Non-opioid analgesics (analgesics-antipyretics) are among the most widely used drugs in pediatric practice. They are distinguished by a unique combination of antipyretic, anti-inflammatory, analgesic and antithrombotic mechanisms of action, which makes it possible to use these drugs to alleviate the symptoms of many diseases.

Currently, there are several pharmacological groups of non-opioid analgesics, which are divided into non-steroidal anti-inflammatory drugs (NSAIDs) and simple analgesics (paracetamol). Paracetamol (acetaminophen) is not included in the group of NSAIDs, since it has practically no anti-inflammatory effect.

Mechanisms of action of non-opioid analgesics and features of their use in children

The main mechanism of action of antipyretic analgesics, which determines their effectiveness, is the suppression of the activity of cyclooxygenase (COX), an enzyme that regulates the conversion of arachidonic acid (AA) into prostaglandins (PG), prostacyclin and thromboxane. It has been established that there are 2 COX isoenzymes.

COX-1 directs the processes of AA metabolism to the implementation physiological functions- formation of PGs that have a cytoprotective effect on the gastric mucosa, regulate platelet function, microcirculation processes, etc. COX-2 is formed only during inflammatory processes under the influence of cytokines. During inflammation, AA metabolism is significantly activated, the synthesis of PG, leukotrienes increases, the release of biogenic amines, free radicals, NO increases, which determines the development early stage inflammatory process. Blockade of COX in the CNS by analgesics-antipyretics leads to an antipyretic and analgesic effect (central action), and a decrease in the content of PG in the inflammation zone leads to an anti-inflammatory effect and, due to a decrease in pain reception, to an anesthetic (peripheral action).

It is assumed that the inhibition of COX-2 is one of the important mechanisms of the clinical efficacy of analgesics, and the suppression of COX-1 determines their toxicity (primarily in relation to the gastrointestinal tract). In this regard, along with standard (non-selective) NSAIDs, which equally suppress the activity of both COX isoforms, selective COX-2 inhibitors were created. However, these drugs were not without side effects.

The analgesic, anti-inflammatory and antipyretic activity of non-opioid analgesics has been proven in numerous controlled trials that meet the standards of evidence-based medicine (level A). Worldwide, more than 300 million people consume NSAIDs annually. They are widely used in febrile conditions, acute and chronic pain, rheumatic diseases and in many other cases. It is noteworthy that most patients use over-the-counter dosage forms of these drugs.

Despite the high effectiveness of antipyretic analgesics, their use in children is not always safe. So in the 70s. of the last century, convincing evidence appeared that the use of acetylsalicylic acid (aspirin) in viral infections in children may be accompanied by Reye's syndrome, characterized by toxic encephalopathy and fatty degeneration internal organs, predominantly in the liver and brain. US restrictions on the use of acetylsalicylic acid in children resulted in a significant reduction in the frequency of Reye's syndrome from 555 in 1980 to 36 in 1987 and 2 in 1997. In addition, acetylsalicylic acid increases the risk of developing inflammatory changes in the gastrointestinal tract, disrupts blood clotting, increases vascular fragility, and in newborns it can displace bilirubin from its association with albumin and thereby contribute to the development of bilirubin encephalopathy. WHO experts do not recommend the use of acetylsalicylic acid as an antipyretic in children under 12 years of age, which is reflected in the Russian National Formulary (2000). By order of the Pharmacological Committee of the Ministry of Health of the Russian Federation of March 25, 1999, the appointment of acetylsalicylic acid in acute viral infections is allowed from the age of 15. However, under the supervision of a physician, acetylsalicylic acid in children can be used for rheumatic diseases.

At the same time, data were accumulating on the side effects of other antipyretic analgesics. Thus, due to its high toxicity, amidopyrine was excluded from the drug nomenclature. Analgin (metamisole) can inhibit hematopoiesis, up to the development of fatal agranulocytosis, which contributed to a sharp restriction in its use in many countries of the world (International Agranulocytosis and Aplastic Anaemi Study Group, 1986). However, in such urgent situations as hyperthermic syndrome, acute pain in postoperative period etc., not amenable to other therapy, parenteral use of analgin and metamizole-containing drugs is acceptable.

Thus, when choosing antipyretic analgesics for children, it is especially important to focus on highly effective drugs with the lowest risk of adverse reactions. Currently, only paracetamol and ibuprofen fully meet the criteria for high efficacy and safety and are officially recommended by the World Health Organization and national programs for use in pediatrics as antipyretics (WHO, 1993; Lesko S.M. et al., 1997; Practical recommendations for doctors of the Russian Association pediatric centers, 2000, etc.). Paracetamol and ibuprofen can be prescribed to children from the first months of life (from 3 months of age). Recommended single doses of paracetamol are 10-15 mg/kg, ibuprofen - 5-10 mg/kg. Re-use of antipyretics is possible not earlier than after 4-5 hours, but not more than 4 times a day.

It should be noted that the mechanism of action of these drugs is somewhat different. Paracetamol has an antipyretic, analgesic and very slight anti-inflammatory effect, since it blocks COX predominantly in the central nervous system and does not have a peripheral effect. Qualitative changes in the metabolism of paracetamol depending on the age of the child, which are determined by the maturity of the cytochrome P450 system, were noted. In addition, a delay in the excretion of the drug and its metabolites can be observed in violation of the functions of the liver and kidneys. A daily dose of 60 mg / kg in children is safe, but with its increase, a hepatotoxic effect of the drug may be observed. A case of fulminant hepatic insufficiency with hypoglycemia and coagulopathy is described in the case of chronic excess of the dose of paracetamol (150 mg/kg) by parents for several days. If a child has a deficiency of glucose-6-phosphate dehydrogenase and glutathione reductase, the appointment of paracetamol can cause hemolysis of erythrocytes, drug-induced hemolytic anemia.

Ibuprofen (Nurofen, Nurofen for children, Ibufen, etc.) has a pronounced antipyretic, analgesic and anti-inflammatory effect. Most studies show that ibuprofen is as effective for fever as paracetamol. Other studies have found that the antipyretic effect of ibuprofen at a dose of 7.5 mg/kg is higher than that of paracetamol at a dose of 10 mg/kg and acetylsalicylic acid at a dose of 10 mg/kg. This was manifested by a pronounced decrease in temperature after 4 hours, which was also observed in a larger number of children. The same data were obtained in a double-blind study in parallel groups of children from 5 months to 13 years of age with repeated administration of ibuprofen at doses of 7 and 10 mg/kg and paracetamol at a dose of 10 mg/kg.

Ibuprofen blocks COX both in the central nervous system and in the focus of inflammation, which determines the presence of not only an antipyretic, but also an anti-inflammatory effect. As a result, phagocytic production of acute phase mediators, including interleukin-1 (IL-1; endogenous pyrogen), is reduced. A decrease in the concentration of IL-1 contributes to the normalization of body temperature. Ibuprofen has a dual analgesic effect - peripheral and central. The analgesic effect is already manifested at a dose of 5 mg / kg, and it is more pronounced than that of paracetamol. This allows the effective use of ibuprofen for mild to moderate sore throat, acute otitis media, toothache, teething pain in infants, and for the relief of post-vaccination reactions.

Numerous multicenter studies have shown that among all antipyretic analgesics, ibuprofen and paracetamol are the safest drugs, the frequency of adverse events with their use was comparable, amounting to approximately 8-9%. Side effects when taking non-opioid analgesics are noted mainly from the gastrointestinal tract (abdominal pain, dyspeptic syndrome, NSAID-gastropathy), less often in the form of allergic reactions, a tendency to bleeding, and renal dysfunction is extremely rarely observed.

It is known that aspirin and NSAIDs can provoke bronchospasm in individuals with aspirin intolerance, as they inhibit the synthesis of PGE 2 , prostacyclin and thromboxanes and increase the production of leukotrienes. Paracetamol does not affect the synthesis of these mediators of allergic inflammation, however, bronchoconstriction is also possible when taking it, which is associated with the depletion of the glutathione system in the respiratory tract and a decrease in antioxidant protection. In a large international study, it was shown that when using ibuprofen and paracetamol in 1879 children with bronchial asthma, only 18 people were hospitalized (paracetamol - 9, ibuprofen - 9), which indicates the relative safety of these drugs in children with this disease. In bronchiolitis in children of the first 6 months of life, ibuprofen and paracetamol did not have a bronchospastic effect. Aspirin intolerance in children is quite rare, in these cases the use of NSAIDs is contraindicated.

Thus, ibuprofen and paracetamol are the drugs of choice in children as antipyretic and analgesics(with pain of moderate intensity), and ibuprofen is widely used for anti-inflammatory purposes. Below we present the main prospects for the use of these drugs in the practice of a general pediatrician (with the exception of the use of NSAIDs in pediatric rheumatology).

Mechanisms of fever in children and principles of antipyretic therapy

An increase in body temperature is common and one of the important symptoms diseases childhood. Fever in children is the most common reason for visiting a doctor, although parents often try to reduce elevated temperature bodies in children on their own, using over-the-counter antipyretic drugs. Issues of the etiopathogenesis of hyperthermia and modern approaches to the treatment of febrile conditions are actual problems of pediatrics to date.

It is known that the ability to maintain body temperature at a constant level, regardless of temperature fluctuations in the external environment (homoiothermy), allows the body to maintain a high metabolic rate and biological activity. Homoiothermia in humans is primarily due to the presence of physiological mechanisms of thermoregulation, i.e., the regulation of heat production and heat transfer. Control over the balancing of the processes of heat production and heat transfer is carried out by the thermoregulation center located in the preoptic region of the anterior part of the hypothalamus. Information about the temperature balance of the body enters the thermoregulation center, firstly, through its neurons, which respond to changes in blood temperature, and secondly, from peripheral thermoreceptors. In addition, the endocrine glands, mainly the thyroid gland and adrenal glands, are involved in the implementation of the hypothalamic regulation of body temperature. Due to the coordinated changes in heat production and heat transfer, the constancy of thermal homeostasis in the body is maintained.

In response to the impact of various pathogenic stimuli, a restructuring of temperature homeostasis occurs, aimed at increasing body temperature in order to increase the natural reactivity of the body. This rise in temperature is called a fever. The biological significance of fever is to increase immunological protection. An increase in body temperature leads to an increase in phagocytosis, an increase in the synthesis of interferons, activation and differentiation of lymphocytes, and stimulation of antibody genesis. Elevated temperature prevents the reproduction of viruses, cocci and other microorganisms.

Fever is fundamentally different from an increase in body temperature during overheating, which occurs with a significant increase in temperature. environment, active muscular work, etc. In case of overheating, the setting of the thermoregulation center to normalize the temperature is maintained, while in case of fever, this center purposefully rearranges the “setting point” to a higher level.

Since fever is a non-specific protective and adaptive reaction of the body, the causes that cause it are very diverse. Fever is most common in infectious diseases, among which acute respiratory diseases upper and lower respiratory tract. Fever of infectious origin develops in response to exposure to viruses, bacteria and their decay products. An increase in body temperature of a non-infectious nature can have a different genesis: central (hemorrhage, tumor, trauma, cerebral edema), psychogenic (neurosis, mental disorders, emotional stress), reflex (pain syndrome during urolithiasis), endocrine (hyperthyroidism, pheochromocytoma), resorptive (contusion, necrosis, aseptic inflammation, hemolysis), and also occurs in response to the administration of certain drugs (ephedrine, xanthine derivatives, antibiotics, etc.).

Each of the variants of fever has both general developmental mechanisms and specific features. It has been established that an integral component of the pathogenesis of fever is the reaction of peripheral blood phagocytes and/or tissue macrophages to infectious invasion or non-infectious inflammatory process. Primary pyrogens, both infectious and non-infectious, only initiate the development of fever by stimulating body cells to synthesize secondary pyrogen mediators. Primarily phagocytic mononuclear cells become the source of secondary pyrogens. Secondary pyrogens are a heterogeneous group of pro-inflammatory cytokines: IL-1, IL-6, tumor necrosis factor α, etc. However, IL-1 plays a leading, initiating role in the pathogenesis of fever.

IL-1 is the main mediator of intercellular interaction in the acute phase of inflammation. Its biological effects are extremely diverse. Under the action of IL-1, activation and proliferation of T-lymphocytes are initiated, the production of IL-2 is enhanced, and the expression of cell receptors is increased. IL-1 promotes the proliferation of B cells and the synthesis of immunoglobulins, stimulates the synthesis of proteins of the acute phase of inflammation ( C-reactive protein, complement, etc.), PG and precursors of hematopoiesis in the bone marrow. IL-1 has a direct toxic effect on cells infected with the virus.

IL-1 is also the main mediator in the mechanism of fever development, which is why it is often referred to in the literature as an endogenous or leukocyte pyrogen. Under normal conditions, IL-1 does not cross the blood-brain barrier. However, in the presence of inflammation (infectious or non-infectious), IL-1 reaches the preoptic region of the anterior hypothalamus and interacts with neuronal receptors of the thermoregulation center. At the same time, COX is activated, which leads to an increase in the synthesis of PGE 1 and an increase in the intracellular level of cAMP. An increase in the concentration of cAMP contributes to the intracellular accumulation of calcium ions, a change in the Na / Ca ratio and a restructuring of the activity of the centers of heat production and heat transfer. An increase in body temperature is achieved by changing the activity of metabolic processes, vascular tone, peripheral blood flow, sweating, synthesis of pancreatic and adrenal hormones, contractile thermogenesis (muscle tremor) and other mechanisms.

It should be especially noted that with the same level of hyperthermia, fever in children can proceed in different ways. So, if heat transfer corresponds to heat production, this indicates an adequate course of fever and is clinically manifested by the relatively normal state of health of the child, pink or moderately hyperemic skin color, moist and warm to the touch (“pink fever”). This type of fever often does not require the use of antipyretics.

In the case when, with increased heat production, heat transfer is inadequate due to impaired peripheral circulation, the course of fever is prognostically unfavorable. Clinically, severe chills, pallor of the skin, acrocyanosis, cold feet and palms (“pale fever”) are noted. Children with such a fever, as a rule, need the appointment of antipyretic drugs in combination with vasodilators and antihistamines(or neuroleptics).

One of clinical options An unfavorable course of fever is a hyperthermic state in young children, in most cases due to infectious inflammation, accompanied by toxicosis. At the same time, there is a persistent (6 or more hours) and significant (above 40.0 °C) increase in body temperature, accompanied by microcirculation disorders, metabolic disorders and progressively increasing dysfunction of vital organs and systems. The development of fever against the background of acute microcirculatory metabolic disorders underlying toxicosis leads to decompensation of thermoregulation with a sharp increase in heat production and inadequately reduced heat transfer. All this is associated with a high risk of developing metabolic disorders and cerebral edema and requires urgent complex emergency therapy.

In accordance with the WHO recommendations "Treatment of fever in acute respiratory infections in children" (WHO, 1993) and domestic recommendations, antipyretic drugs should be prescribed when the child's temperature exceeds 39.0 ° C when measured rectally. Exceptions are children at risk for febrile seizures or severe lung or cardiovascular systems and children of the first 3 months of life. In the national scientific and practical program "Acute Respiratory Diseases in Children: Treatment and Prevention" (2002), it is recommended to prescribe antipyretics in the following cases:

- previously healthy children - with a body temperature above 39.0 ° C and / or with muscle aches and headaches;

- children with febrile seizures in history - at a body temperature above 38.0-38.5 ° C;

- children with severe heart and lung diseases - at a body temperature above 38.5 ° C;

- children of the first 3 months of life - at a body temperature above 38.0 ° C.

As stated above, only paracetamol and ibuprofen are recommended by the World Health Organization and national programs as antipyretics in children.

Antipyretic therapy in children with allergic reactions and diseases

Allergic diseases in children are now widespread, their frequency is constantly increasing. Allergy, as a premorbid background, in this group of patients often determines the characteristics of the course of conditions that occur with fever and, in addition, increases the risk of hypersensitivity reactions to the medications used.

Fever in children with allergic diseases has its own characteristics. First, these patients have a tendency to pronounced and lingering current fever, which is due to a high level of IL-1 in patients with atopy and, consequently, a vicious pathological circle of its synthesis, especially during the acute period of an allergic reaction. Second, children who are predisposed to atopy are at high risk of developing a drug-induced fever (so-called allergic fever). Thirdly, it must be taken into account that against the background of exacerbation of allergies, there may be an increase in temperature of a non-infectious nature. The appointment of antipyretic drugs (analgesics-antipyretics) for children with allergic diseases and reactions requires strict medical supervision. Appropriate in complex treatment febrile conditions in children with allergic diseases include along with antipyretics and antihistamines.

Some aspects of acute pain therapy in pediatric practice

With the problem of treating acute pain of moderate intensity, a general pediatrician meets quite often. Pain in children often accompanies certain infectious and inflammatory diseases (acute otitis media, tonsillitis, pharyngitis, acute respiratory infections), occurs along with fever in the early post-vaccination period. Pain bothers babies during teething and older children after tooth extraction. Pain syndrome, even of slight intensity, not only worsens the child's well-being and mood, but also slows down reparative processes and, as a result, recovery. It is necessary to emphasize the main role of etiotropic and pathogenetic approaches in the treatment of diseases accompanied by pain. However, the result of therapy will be more successful if, along with pathogenetic methods of treating the disease, adequate anesthesia is used.

The mechanism of pain formation is quite complicated, but the most important role in it is played by substances of the prostaglandin and kinin series, which are direct neurochemical mediators of pain. Inflammatory edema, as a rule, exacerbates the pain syndrome. A decrease in the production of pain mediators and / or a decrease in receptor sensitivity (for example, due to blockade of pain receptors) determines the analgesic effects of therapy.

In the practice of a general pediatrician, the main drugs for the relief of acute pain of moderate intensity are non-opioid analgesics. Blockade with their help of COX in the central nervous system leads to an analgesic effect central genesis, and a decrease in the content of PG in the area of ​​inflammation leads to an anti-inflammatory effect and an analgesic peripheral effect due to a decrease in pain reception.

Clinical studies indicate that ibupofen and, to a lesser extent, paracetamol are the drugs of choice in the treatment of acute pain of moderate intensity in children. Timely and adequate accompanying analgesic therapy brings relief to a sick child, improves his well-being and contributes to a faster recovery.

Prevention and treatment of post-vaccination reactions in children

Post-vaccination reactions are the expected conditions indicated in the instructions for vaccines. They are quite common, they should not be confused with complications of vaccination, the development of which is most often unpredictable and reflects the individual reaction of the child or a violation of the vaccination technique. A well-known post-vaccination reaction in children is hyperthermia after immunization. In addition, pain of moderate intensity, hyperemia, swelling may appear at the injection site, which is also sometimes accompanied by fever, malaise and headache. Hyperthermia and local reactions after immunization are considered an indication for ibuprofen. Since post-vaccination reactions are predictable, when conducting DTP vaccinations it is appropriate to recommend prophylactic use of ibuprofen or paracetamol in the child for 1-2 days after vaccination.

Experience with Nurofen in children

In order to study the clinical efficacy of ibuprofen in children with infectious and inflammatory diseases accompanied by fever and / or pain, we conducted an open, uncontrolled study in which Nurofen for children (Boots Healthcare International, UK) was used in 67 children with acute respiratory viral infections. and in 10 children with angina aged 3 months to 15 years. In 20 patients, ARVI proceeded against the background of mild to moderate bronchial asthma without indications of aspirin intolerance, in 17 patients with broncho-obstructive syndrome, in 12 patients with manifestations of acute otitis media, in 14 patients it was accompanied by severe headache and/or muscle aches. In 53 children, the disease was accompanied by high fever requiring antipyretic therapy; Nurofen was prescribed to 24 patients with subfebrile temperature only for analgesic purposes. Nurofen suspension for children was used in a standard single dosage of 5 to 10 mg/kg 3-4 times a day, which is usually from 2.5 to 5 ml of suspension per dose (measuring spoons were used). Duration of taking Nurofen ranged from 1 to 3 days.

The study of the clinical condition of patients included an assessment of the antipyretic and analgesic effects of Nurofen, registration of adverse events.

In 48 children, a good antipyretic effect was obtained after taking the first dose of the drug. Most children were prescribed Nurofen for no more than 2 days. In 4 patients, the antipyretic effect was minimal and short-lived. Two of them were prescribed diclofenac, 2 others used parenteral lytic mixture.

The decrease in pain intensity after the initial dose of Nurofen was observed after 30-60 minutes, the maximum effect was observed after 1.5-2 hours. The duration of the analgesic effect ranged from 4 to 8 hours (group average 4.9 ± 2.6 hours).

Adequate analgesic effect of Nurofen was noted in the vast majority of patients. After the first dose of the drug, an excellent or good analgesic effect was achieved in more than half of the children, satisfactory - in 28%, and only 16.6% of patients had no analgesic effect. A day after the start of therapy, a good and excellent analgesic effect was noted by 75% of patients, a satisfactory relief of the pain syndrome was recorded in 25% of cases. On the 3rd day of observation, the children practically did not complain of pain.

It should be noted that Nurofen for children has good taste and is well tolerated by children. different ages. Side effects from the digestive organs, development of allergic reactions, intensification or provocation of bronchospasm were not noted. None of the patients discontinued Nurofen due to adverse events.

Conclusion

To date, ibuprofen and paracetamol are among the most popular drugs in pediatric practice. It is the first choice for children with fever and moderate pain, and ibuprofen is widely used as an anti-inflammatory agent. However, when prescribing any antipyretic analgesic, it is important to carefully determine the required dose and take into account all possible risk factors. Should be avoided combined drugs containing more than one antipyretic. The course use of antipyretics without specifying the causes of fever is unacceptable.

Our study showed that ibuprofen-containing drug Nurofen for children has a pronounced and rapid antipyretic and analgesic effect in patients with acute infectious and inflammatory diseases of the respiratory tract and upper respiratory tract. The use of the drug was effective and safe. Our experience shows that along with etiotropic and pathogenetic therapy of the disease, it is advisable to conduct rational accompanying therapy using antipyretic analgesics. With timely and adequate appointment, such therapy brings relief to a sick child, improves his well-being and contributes to a faster recovery.

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1. (Analgesics - antipyretics)

Key Features:

Analgesic activity is manifested in certain types of pain: mainly in neuralgic, muscle, joint pain, headache and toothache. With severe pain associated with injuries, abdominal operations, they are ineffective.

The antipyretic effect, which manifests itself in febrile conditions, and the anti-inflammatory effect, are expressed to varying degrees in different drugs.

Absence of a depressant effect on respiration and cough centers.

The absence of euphoria and phenomena of mental and physical dependence during their use.

Main representatives:

Derivatives of salicylic acid - salicylates - sodium salicylate, acetylsalicylic acid, salicylamide.

Pyrazolone derivatives - antipyrine, amidopyrine, analgin.

Derivatives of n-aminophenol or aniline - phenacetin, paracetamol.

By pharmaceutical action are divided into 2 groups.

1. Non-narcotic analgesics are used in everyday practice, they are widely used for headaches, neuralgia, rheumatoid pain, and inflammatory processes. Since they usually not only relieve pain, but also reduce body temperature, they are often called antiperitoneal analgesics. Until recently, amidopyrine (pyramidone), phenacetin, aspirin, etc. were widely used for this purpose;

In recent years, as a result of serious research, the possibility of a carcinogenic effect of these drugs has been discovered. In animal experiments, the possibility of a carcinogenic effect of amidopyrine with prolonged use, as well as its damaging effect on the hematopoietic system, was found.

Phenacetin may have a nephrotoxic effect. In this regard, the use of these drugs has become limited, and a number of finished drugs containing these drugs are excluded from the nomenclature of drugs (amidopyrine solutions and granules, amidopyrine with phenacetin, etc.). Novymigrofen, amidopyrine with butadione, etc. have been used so far. Paracetamol is widely used.

2. Non-steroidal anti-inflammatory drugs.

These drugs have, along with a pronounced analgesic effect and anti-inflammatory activity. The anti-inflammatory effect of these drugs is close in strength to the anti-inflammatory effect of steroid hormonal drugs. At the same time, they do not have a steroid structure. These are preparations of a number of phenylpropionic and phenylacetic acids (ibuprofen, ortofen, etc.), compounds containing an indole group (indomethacin).

The first representative of non-steroidal anti-inflammatory drugs was aspirin (1889), which is still one of the most common anti-inflammatory, analgesic and antipyretic drugs today.

Nonsteroidal drugs are widely used in the treatment of rheumatoid arthritis, ankylosing spondylitis and various inflammatory diseases.

There is no strict distinction between these groups of drugs, since both of them have significant antihypermic, decongestant, analgesic and antipyretic effects, that is, they affect all signs of inflammation.

Analgesics-antipyretics pyrozolone derivatives:

p-aminophenol derivatives:

3. Method for obtaining antipyrine, amidopyrine and analgin

There is much in common in the structure, properties, and biological activity of these preparations. In the ways of obtaining too. Amidopyrine is obtained from antipyrine, analgin from an intermediate product of the synthesis of amidopyrine - aminoantipyrine.

Synthesis can start from phenylhydrazine and acetoacetic ester. However, this method is not used. On an industrial scale, a method is used to obtain this group of compounds starting from 1-phenyl-5-methylpyrazolone-5, which is a large-tonnage product.

Antipyrine.

An extensive study of pyrozolone compounds and the discovery of their valuable pharmacological action are associated with synthetic research in the field of quinine.

In an effort to obtain tetrahydroquinoline compounds with antipyretic properties of quinine, Knorr in 1883 carried out the condensation of acetoacetic ester with phenylhydrozine, which exhibits a weak antipyretic effect, is poorly soluble in water; its methylation led to the production of a highly active and highly soluble preparation 1-phenyl-2,3-dimethylpyrosolone (antipyrine).

Taking into account the presence of keto-enol tautomerism of the AC ester, as well as tautomerism in the pyrazolone core, when considering the reaction between phenylhydrazine and AC ester, one can assume the formation of several isomeric forms of 1-phenyl-3-methylpyrazolone.

However, 1-phenyl-3-methylpyrazolone is known only in 1 form. Non-crystals, appearance temperature - 127 °C, boiling point - 191 °C.

The methylation process of phenylmethylpyrazolone can be represented through the intermediate formation of a quaternary salt, which, under the action of alkali, rearranges into antipyrine.

The structure of antipyrine was confirmed by a counter synthesis during the condensation of the enol form of acetoacetic ester or halide ester with methylphenylhydrazine, since the positions of both methyl groups are determined by the starting products.

It is not used as a production method, since the yield is low and synthesis products are inaccessible.

The reaction is carried out in a neutral environment. If the reaction is carried out in an acidic medium, then at a temperature, not alcohol is cleaved, but the second water molecule is formed, and 1-phenyl-3-methyl-5-ethoxypyrazole is formed.

To obtain 1-phenyl-3-methylpyrazolone, which is the most important intermediate in the synthesis of pyrazolone preparations, a method has also been developed that uses diketone

The properties of antipyrine - high solubility in water, reactions with methyl iodide, POCl3, etc. are explained by the fact that it has the structure of an internal quaternary base.

In the industrial synthesis of antipyrine, in addition to the importance of the conditions for conducting the main condensation between AC-ether and phenylhydrazine (choice of medium, neutral reaction, a small excess of FG, etc.), the choice of methylating agent plays a certain role:

Diazomethane is not suitable, since it leads to the o-methyl ester of the quaternary salt, which is also partially formed during methylation with methyl iodide.

It is better to use methyl chloride or bromide, dimethyl sulfate or, better, benzenesulfonic acid methyl ester for these purposes, since in this case there is no need for absorbing autoclaves (CH3Br - 18 atm .; CH3Cl - 65 atm.).

Purification of the resulting antipyrine is usually carried out by 2-3-fold recrystallization from water; vacuum distillation (200-205°C at 4-5 mm, 141-142°C in cathode glow vacuum) can be used.

Antipyrine - crystals of a slightly bitter taste, odorless, highly soluble in water (1:1), in alcohol (1:1), in chloroform (1:15), worse in ether (1:75). Gives all characteristic qualitative reactions to alkaloids. With FeCl3 gives an intense red color. A qualitative reaction to antipyrine is the emerald color of nitrosoantipyrine.

Antipyretic, analgesic, as a local hemostatic.

A wide variety of antipyrine derivatives have been studied.

Of all the derivatives, only amidopyrine and analgin proved to be valuable analgesics, superior in properties to antipyrine.

4. Antipyrine synthesis technology Description of the main stages of the process.

Phenylmethylpyrazolone is loaded into an oil-heated glass-lined reactor and dried in vacuum at 100°C until moisture is completely removed. Then the temperature is raised to 127-130 °C and benzosulfonic acid methyl ester is added to the phenylmethylpyrazolone solution. The reaction temperature is not higher than 135-140 °C. At the end of the process, the reaction mass is transferred to the mold, where a small amount of water is loaded and cooled to 10 °C. The precipitated antipyrine benzosulfonate is squeezed out and washed in a centrifuge. To isolate antipyrine, this salt is treated with an aqueous solution of NaOH, the resulting antipyrine is separated from the salt solution and reprecipitated in isopropyl alcohol, the antipyrine is purified by recrystallization from isopropyl alcohol. Available in powders and tablets of 0.25 g.

Amidopyrine.

If antipyrine was discovered during the study of the alkaloid quinine, then the transition from antipyrine to amidopyrine is associated with the study of morphine.

The establishment of the N-methyl group in the structure of morphine gave reason to believe that the analgesic effect of antipyrine can be enhanced by the introduction of another tertiary amino group into the nucleus.

In 1893 was synthesized - 4-dimethylaminoantipyrine - amidopyrine, which is 3-4 times stronger than antipyrine. In recent years, it has been used only in combination with other drugs, due to undesirable effects: allergies, hematopoiesis suppression.

1-Phenyl-2,3-dimethyl-4-dimethylaminopyrazolone-5 (in water 1:11).

Qualitative reaction with FeCl3 - blue-violet color. Getting amidopyrine.

A large number of methods have been developed for carrying out reduction and methylation processes. In production conditions, the following are preferred:

1. Use of antipyrine in the form of benzenesulfonic acid:

Nitrous acid, necessary for nitration, is formed in this case by the interaction of NaNO2 with benzenesulfonic acid associated with antipyrine.

The reduction of nitrosoantipyrine to aminoantipyrine (light yellow crystals with Tm. 109 °) is carried out in high yields using a sulfite-bisulfite mixture in an aqueous medium:

reaction mechanism.

There are developed methods for the reduction of nitrosoantipyrine with hydrogen sulfide, zinc (dust), in CH3COOH, etc.

Purification of aminoantipyrine and its isolation from various solutions is carried out through a benzylidene derivative (light yellow, shiny crystals, mp 172-173 ° C), it is easily formed by the interaction of aminoantipyrine with benzaldehyde:

benzylideneaminoantipyrine - is the starting product in the synthesis of analgin.

Methylation of the aminoantipyrine is most economically achieved with a CH2O-HCOOH mixture.

Mechanism of the methylation reaction:

With this method of methylation, the formation of quaternary ammonium compounds, which are formed when using halo-substituted dimethylsulfonate as a methylating agent, is avoided.

When using haloamine, the resulting quaternary compound can be converted in an autoclave.

To isolate and purify amidopyrine, repeated recrystallization from isopropyl or ethyl alcohol is used.

5. Antipyrine synthesis technology

Process chemistry

Description of the main stages of the process.

An aqueous suspension of the antipyrine salt is transferred to the neutralizer, cooled to 20°C, and a 20% NaNO2 solution is gradually added. The reaction temperature should not exceed 4-5 °C. The resulting suspension of emerald green nitrosoantipyrine crystals and washed with cold water. The crystals are loaded into the reactor, where the bisulfite-sulphate mixture is added. The mixture is first kept for 3 hours at 22-285°C, then for 2-2.5 hours at 80°C. the sodium salt solution is transferred to the hydrolyzer. An aminoantipyrine hydrolyzate is obtained, which is methylated in a reactor with a mixture of formaldehyde and formic acid. Amidopyrine is isolated from the formic acid salt by treating the salt solution at 50 °C with a soda solution. After neutralization, amidopyrine floats as an oil. The oil layer is separated and transferred to a neutralizer, where it is recrystallized from isopropyl alcohol.

Analgin.

Structural formula of analgin

1-Phenyl-2,3-dimethylpyrazolone-5-4-methylaminomethylene sulfate sodium.

Empirical formula - C13H16O4N3SNa · H2O - white, slightly yellowish crystalline powder, easily soluble in water (1:1.5), difficult in alcohol. The aqueous solution is clear and neutral to litmus. When standing, it turns yellow, without losing activity.

Analgin is the best drug among the compounds of the pyrazolone series. Surpasses all pyrazolone analgesics. Low toxicity. Analgin is part of many drugs

Its highest single dose is 1 g, the daily dose is 3 g.

The industrial synthesis of analgin is based on two chemical schemes.

2). Production method for obtaining from benzylideneaminoantipyrine.

Empirical formula - C13H16O4N3SNa · H2O - white, slightly yellowish crystalline powder, easily soluble in water (1:15), difficult in alcohol. The aqueous solution is clear and neutral to litmus.

Analgin is the best drug among the compounds of the pyrazolone series. Surpasses all pyrazolone analgesics. Low toxicity.

Description of the technological process.

Phenylmethylpyrazolone is loaded into an oil-heated glass-lined reactor and dried in vacuum at 100°C until complete removal of moisture. The temperature is raised to 127-130 °C and benzosulfonic acid methyl ester is added to the FMP solution. The reaction temperature is 135-140 °C. At the end of the process, the reaction mass is transferred to the mold, where a small amount of water is loaded and cooled to 10 °C. The precipitated antipyrine benzenesulfonate is washed on the filter and fed to the next reactor for carrying out the nitrosation reaction. There, the mixture is cooled to 20°C and a 20% NaNO2 solution is gradually added. The reaction temperature is 4-5 °C. The resulting suspension of emerald green crystals is filtered on a vacuum filter and washed with cold water. The crystals are loaded into the reactor, where a bisulfite-sulphate mixture is added, which is first kept for 3 hours at 22-25 °C, then for another 2-2.5 hours at 80 °C. The resulting salt is transferred to the saponification reactor, where it is treated with a NaOH solution, resulting in the formation of the disodium salt of sulfoaminoantipyrine.

The resulting salt is transferred to a reactor for methylation with dimethyl sulfate. DMS is fed into the reactor from the mernik. The reaction proceeds at 107-110 °C for 5 hours. Upon completion of the reaction, the reaction product is separated from Na2SO4 on filter 15. The sodium salt solution is pressed into the reactor and hydrolyzed with sulfuric acid at 85°C for 3 hours. At the end of the reaction, NaOH was added to the reaction mixture to neutralize the acid. The reaction temperature should not exceed 58-62 °C. The resulting monomethylaminoantipyrine is separated from Na2SO4 on a filter and transferred to the methylation reactor. Methylation is carried out with a mixture of formaldehyde and sodium bisulfite at 68-70 °C. As a result of the reaction, analgin is obtained, which is then purified.

The solution is evaporated. Analgin is recrystallized from water, washed with alcohol and dried.

Method II - through benzylideneaminoantipyrine ..

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Barbiturates as a class of sedatives used in medicine to relieve anxiety syndromes, insomnia and convulsive reflexes. History of discovery, use and pharmachologic effect derivatives of this drug, research methods.

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Acetylsalicylic acid, paracetamol, metamizole sodium and ibuprofen lead among all antipyretic analgesics in terms of the number of applications among Russian citizens. The task of the pharmacist or pharmacist is to pay attention to contraindications for use and side effects, some of which can turn into serious health problems.

Paracetamol, ibuprofen, metamizole sodium (Analgin) and acetylsalicylic acid (Aspirin) are included in pharmacological group non-steroidal anti-inflammatory drugs. For many years, they have been the most popular analgesics-antipyretics on the Russian pharmacological market.

Since the beginning of the 20th century, unconditional primacy over the next 100 years belonged to acetylsalicylic acid, and only at the end of the 90s of the last century, paracetamol-based drugs became more popular.

As of the beginning of 2017, over 400 paracetamol preparations, more than 200 preparations based on acetylsalicylic acid and more than one and a half hundred preparations based on metamizole sodium and ibuprofen were registered in Russia.

Taking analgesics-antipyretics: differences in properties and potential danger

All analgesics-antipyretics, which will be discussed in this article, differ from each other in painkillers,.

Thus, the anti-inflammatory effect of ibuprofen and paracetamol significantly exceeds that of acetylsalicylic acid and metamizole sodium, while metamizole sodium and ibuprofen are superior to other drugs in analgesic effect. The ability to reduce elevated body temperature in all four drugs is approximately the same.

These medicines can be easily purchased at any pharmacy without a doctor's prescription, which creates a false impression of their safety. They are in the medicine cabinet in almost every Russian family, but few people think that each of them has an impressive list of contraindications and side effects.