Nonsteroidal anti-inflammatory drugs in pediatric practice

Indications for use

NSAIDs are used for inflammatory diseases of connective tissue, which are accompanied by damage to joints, cartilage, tendons, ligaments - arthritis, arthrosis, osteochondrosis, spondyloarthritis, tendovaginitis, bursitis.

NSAIDs are used for conditions that are accompanied by mild or moderate pain: headache, dental, menstrual, muscle, joint, as well as pain due to muscle injuries, joints, ligament damage, neuralgia.

Together with narcotic analgesics, NSAIDs are used for multiple injuries and pain after surgery.

In combination with antispasmodics, analgesics-antipyretics are used for pain associated with spasm of smooth muscles - hepatic, renal, intestinal colic.

In addition, certain NSAIDs are used for elevated body temperature (fever) against the background of infectious inflammatory diseases of the upper respiratory tract and ENT organs (tonsillitis, sinusitis, sinusitis, otitis), lower respiratory tract (bronchitis, pneumonia), influenza and colds.

External anti-inflammatory therapy for atopic dermatitis in children

VC. KOTLUKOV

, Ph.D.,
T.V.
KAZYUKOVA , Doctor of Medical Sciences,
A.S.
HAYRAPETYAN ,
Russian National Research Medical University named after.
N.I. Pirogova, Moscow The article reflects the main etiopathogenetic mechanisms of atopic dermatitis in children. The rationale for local anti-inflammatory therapy with new generation topical glucocorticosteroids (Advantan) is presented.

One of the important functional systems of the human body, which allows us to achieve a primary balance with the environment, is the skin. Human skin is a protective organ due to its strength and ability to withstand stretching, pressure, and compression. In children, especially young children, this skin function is significantly weaker, as evidenced by its easier vulnerability and susceptibility to frequent infection, which is associated with insufficient keratinization of the stratum corneum, its thinness, and immaturity of local immunity. Skin is not only a protective covering, but also the largest organ in the human body. The functions of the skin are relatively numerous and important. In addition to barrier and protective, the skin in children performs excretory, receptor (tactile, temperature, superficial pain sensitivity), immune and thermoregulatory functions (implementation of heat transfer processes: conduction, radiation, convection and evaporation), and provides tissue respiration [1]. The surface of a child's skin is somewhat drier than that of adults and has a more pronounced tendency to peeling due to physiological parakeratosis and weaker functioning of the glandular apparatus of the skin. These features contribute to the occurrence of frequent pathological changes in the skin: dermatitis, erythema, diaper rash, etc.

The basic anatomical and physiological characteristics of children's skin largely determine the composition and use of products for the treatment of pathological changes and care for the skin of children. These features include: the relative looseness of the epidermis in children in the first months of life, which is combined with the thinness of the stratum corneum and the content of cells with nuclei (slight vulnerability and tendency of the skin to irritate when in contact with physical and chemical irritants); weak (unstable) connection between the epidermis and dermis (due to weakness of the basement membrane and smoothness of the dermal papillae); relatively low moisture (water) content and imperfect blood supply to the skin; poor level of development and functioning of the sweat glands (imperfect sweating); inadequate level of functioning of the sebaceous glands and a relatively high level of moisture evaporation through the thinned stratum corneum of the skin; lack of protection of the skin from external pathogenic microorganisms by a natural acidic environment in the first weeks and months of life (in newborns, the pH of the skin is about 6-7).

The barrier function of the child's skin allows it to retain moisture, electrolytes and protein, and also protect the child from the effects of mechanical, physical and bacterial factors. However, the thin and delicate stratum corneum is easily damaged at an early age, as a result of which it does not effectively protect the child’s body from the effects of external aggressive factors. The absence of elastic fibers in the first months of life, compensated by a very large amount of moisture, provides protection only from minor mechanical damage [2].

The skin of children in the first years of life is the main reservoir of moisture. It contains up to 17% of all fluid contained in the child’s body, which is important for water-salt metabolism. Liquid absorption by the skin is quite high due to the pronounced hydrophilic properties of the outer stratum corneum of the epidermis, as well as the higher permeability of thin, underdeveloped horny and granular layers. Additional factors for moisture absorption are the presence of numerous and wide vessels of the skin itself, as well as well-developed sebaceous glands [2, 3]. Among pathological skin lesions in children, dermatitis of both infectious and non-infectious origin is more common. Among them, atopic dermatitis (AD) occupies one of the leading places [4].

AD (ICD-10: L20) is a chronic recurrent inflammatory skin disease accompanied by itching, which in typical cases begins in early childhood, can continue or recur in adulthood and lead to physical and emotional maladaptation of the patient and his family members.

The prevalence of the disease has increased over the past three decades and in developed countries, according to various authors, is 10-15% in children under 5 years of age and 15-20% in schoolchildren. The reasons for the increase in incidence are unknown. On the other hand, in some agricultural regions of China, Eastern Europe and Africa, the incidence remains at the same level. It has been established that AD develops in 81% of children if both parents are sick, in 59% if only one of the parents is sick and the other has an allergic pathology of the respiratory tract, and in 56% if only one of the parents is sick.

AD in childhood and adulthood appears to be a single disease. AD in most cases develops in individuals with a hereditary predisposition and is often combined with other allergic diseases, such as bronchial asthma, allergic rhinitis, food allergies, as well as recurrent skin infections. In 2002, the International Expert Group on AD (USA) concluded that AD in childhood and adulthood appears to be a single disease, despite the fact that in the future genetic subtypes with different expression patterns may be identified. Experts emphasize a characteristic feature of the course of AD: since such patients have impaired skin barrier function and itching, therapy takes a symptomatic focus - moisturizing the skin and relieving itching [5]. Currently, external therapy is pathogenetically justified and necessary for a patient with AD. The main tactics of external therapy for AD is the prescription of topical corticosteroids (TCS) and symptomatic drugs in the form of various dermatological agents.

The skin barrier is basically that the epidermis protects the skin from exposure to antigens and environmental factors. The hydrolipid film, together with the saprophytic flora and acidic pH, prevents the proliferation of pathogenic agents; prevents water loss; allows the skin to breathe and secrete sebum. When the integrity of the film is violated, water loss occurs, the sensitivity of dry skin to the effects of irritants increases, the intensity of bacterial growth increases and antigens accumulate. Disruption of the lipid structure of the stratum corneum of the skin in AD is the main cause of xerosis and increased sensitivity of the skin to irritants and antigens [6]. The epidermis consists of cells that are connected to each other through a cementing substance, which includes lipids: ceramides, essential fatty acids, cholesterol, triglycerides, squalene. Ceramides serve as the main molecules that retain fluid in the extracellular space of the keratinized membrane. The development of the active phase of the disease is facilitated by a shift in pH to the alkaline side both in the lesions of the skin and in undamaged areas [7]. Keratinocytes in AD patients support the inflammatory immune response of the skin by producing chemotactic factors and cytokines that attract more T cells to the epidermis [6]. An important role in maintaining skin xerosis is played by the incomplete conversion of co-6 fatty acids (linolenic, y-linolenic and dihomo-y-linolenic) into prostaglandin E1 [6]. Clinical manifestations of AD in 45% of cases begin in children at the age of the first 6 months of life. More than 50% of children who were diagnosed with AD in the first 2 years of life, as a rule, do not have any signs of IgE sensitization (the so-called non-allergic form of AD), but later they show signs of sensitization. In 70% of cases, such children experience spontaneous remission of the disease before adolescence. Clinical symptoms of AD are age-related.

Stands out:

infant stage

- children aged 2-3 months. up to 2-3 years. Development of the type of childhood eczema is noted: hyperemia, swelling on the cheeks and forehead (except for the nasolabial triangle), extensor surfaces of the legs, shoulders, forearms, buttocks with exudation, serous and hemorrhagic crusts. There is a predominance of food allergens;

childhood stage

- children aged 2-3 to 12-13 years. During this period, the transition of childhood eczema to diffuse neurodermatitis is recorded with a chronic process. On the skin of the face and flexor surfaces of the joints, infiltrative papules, dryness, infiltration, cracks, and itching are detected. During this period, there is a predominance of aeroallergens;

adult stage

- teenagers aged 12-13 years and adults. Chronic inflammation without significant exacerbations is observed on the skin: diffuse neurodermatitis (infiltration of the trunk, arms, head, neck, lichenification); chronic eczema of the hands (adults). During this period, there is a predominance of psycho-emotional factors in maintaining the activity of the pathological process [8, 9].

If treatment is ineffective, AD is complicated by skin infections of bacterial, viral, and fungal etiologies. The persistent, relapsing course, ineffective treatment of AD forces the doctor to conduct a differential diagnosis with other diseases (for example, with primary immunodeficiencies - hyperIgE syndrome, Neferton syndrome, Wiskott-Aldrich syndrome; psoriasis).

Currently, the possibilities of external anti-inflammatory therapy for AD in children have expanded significantly compared to previous years. This is due both to the emergence of new drugs and to the receipt of new evidence-based information about the effectiveness and safety of external agents that were previously known. Until the end of the 1990s. the possibilities of external anti-inflammatory therapy were limited by the following points:

- persistent corticosteroid phobia, associated with the fact that fluorinated corticosteroids (fluocinolone acetonide, triamcinolone acetonide, etc.) were used for treatment in children, the uncontrolled use of which led to side effects and discrediting corticosteroid treatment; — lack of training in allergy and immunology among pediatricians, who regard AD as an exclusively dermatological problem; — limited arsenal and lack of knowledge of external corticosteroids approved for use in children; — unjustified classification of external anti-inflammatory drugs, including glucocorticosteroids, as purely symptomatic drugs included in therapy only if it is impossible to achieve remission through the use of traditional complex prescriptions (ointments, mash, creams, lotions), the prescription of enzymes, bacterial preparations and others methods of therapy.

The effectiveness of the use of external glucocorticosteroids for AD has been proven by many years of practice and numerous controlled studies. An important moment in the development of the possibilities of sound external therapy for AD in children was the appearance in Russia in the late 1990s. a corticosteroid drug for external use, approved for children from 4 months of age, methylprednisolone aceponate (Advantan). The appearance of this drug marked the beginning of overcoming persistent corticosteroid phobia among pediatricians. All corticosteroids, each of which has its own characteristics and capabilities, such as hydrocortisone butyrate, mometasone furoate, alklometasone, have become more widely used and more active. However, the possibilities for choosing the form of the drug were limited, since only the drug mometasone furoate had three release forms (lotion, cream, ointment), used depending on the activity and stage of allergic skin inflammation. However, mometasone furoate can only be used from 2 years of age, and the choice of the dosage form of a topical glucocorticosteroid from 4 months of age was limited. In connection with this, an important stage in the development of this area was the appearance of several forms of methylprednisolone aceponate (Advantan) (emulsion, cream, ointment, fatty ointment), which allowed the pediatrician to easily “maneuver” in the choice of therapy not only in children of older age groups, but also in young children.

The basis of the anti-inflammatory effect of glucocorticosteroids is the suppression of the activity of genes of cells involved in inflammation. This effect of corticosteroids extends both to cells located in the skin and to cells migrating into it under the influence of chemotactic factors produced at the site of inflammation [10]. This universal mechanism of the anti-inflammatory action of glucocorticosteroids determines the powerful anti-inflammatory activity and determines the effectiveness of external steroid therapy, which has been indisputably proven in the treatment of both acute and chronic allergic skin diseases. However, there are a number of factors that determine the effectiveness and safety of the use of external corticosteroids. These factors often remain beyond the attention of the attending physician, which can lead to both insufficiently active treatment and the occurrence of side effects. Assessing the effectiveness and safety of topical corticosteroids is of greatest importance in pediatric practice. In children, the skin has anatomical and physiological features that predispose to side effects of topical corticosteroid therapy. The main ones are a delicate and loose epidermis, a large number of superficially located blood vessels, and increased permeability of the vascular endothelium. Due to these features, the skin of children, compared to adults, is more sensitive to the effects of corticosteroids: drugs are absorbed into the bloodstream in greater quantities, which increases the possibility of increasing their concentration in the blood, and the risk of developing local side effects associated with the inhibition of collagen synthesis by corticosteroids increases. elastin in the skin, cell mitosis [10]. It must be remembered that not all existing glucocorticosteroid preparations for external therapy, even those successfully used in adult patients, are advisable for use in children. This does not mean that there are “bad” and “good” drugs, just that each of them has its own niche in the treatment of various inflammatory skin diseases. To date, external glucocorticosteroids with “increased safety” have been created and have undergone controlled clinical trials in pediatric practice, which are primarily recommended for the treatment of children with AD.

In Russian pediatric practice, as an unspoken standard, there is a provision that the duration of external glucocorticosteroid therapy should be limited to several days until a very pronounced exacerbation is eliminated. However, this position, unproven by clinical studies, currently requires discussion and revision due to the availability of corticosteroid drugs with increased safety. Clinical studies and long-term practice have confirmed that these drugs (methylprednisolone aceponate, alklometasone, mometasone furoate, hydrocortisone butyrate) can be used for up to 4 weeks if necessary. daily.

Moreover, some researchers, based on data on immunological abnormalities even in unaffected areas of the skin of patients with AD, believe that the use of topical corticosteroids as maintenance therapy can lead to a good result. There is very little information regarding this approach to treatment. In particular, Van Der Meer et al. found that after the complete disappearance of AD symptoms with a single daily use of a topical glucocorticosteroid, further administration of the drug 2 times a week made it possible to maintain remission for a longer period than in patients receiving placebo [11]. However, since this approach to long-term therapy, in particular AD, is not absolutely justified using controlled studies, currently the duration of topical steroid therapy is regulated only by the maximum allowable for a given drug in accordance with the patient’s age. And with the advent of the calcineurin inhibitor pimecrolimus, the need for attempts at maintenance therapy with glucocorticosteroids has significantly decreased.

In all cases, given that the pathogenesis of AD is based on allergic inflammation of the skin, it is obvious that anti-inflammatory treatment should be carried out until complete remission of the disease occurs.

Any focus of skin inflammation, even minimal activity, that persists after discontinuation of anti-inflammatory treatment is the basis for relapse of the disease.

However, the concept of remission for patients with AD is quite vague, since minimal symptoms of the disease can persist even after a long course of anti-inflammatory treatment.

It is not uncommon for a situation where, despite long-term use of external anti-inflammatory drugs, complete remission does not occur. In such cases, long-term maintenance treatment is necessary, the drug and regimen of which are selected individually.

If a patient has severe AD and has to use topical corticosteroids for a long time, the possibility of both local and systemic side effects of such treatment should be taken into account. This side effect is due to the fact that these drugs inhibit not only the synthesis of pro-inflammatory cytokines, but also normal cell mitosis, which slows down their reproduction and proliferation. In addition, under the influence of corticosteroids, the synthesis of collagen and elastin fibers slows down.

There are various forms of Advantan available on the pharmaceutical market.

Advantan emulsion

. Base: oil in water emulsion, 67.5% water. The main properties are: the ability to evaporate water and eliminate weeping and swelling; does not stain clothes; without greasy shine.

Indications for use: skin diseases amenable to treatment with GCS for external use. Acute conditions: contact dermatitis on the face or with pronounced weeping on any part of the skin, including photodermatitis, sunburn, dermatitis on mucous membranes, skin reaction to insect bites. Chronic conditions: atopic dermatitis, mainly up to 2-3 years; dermatosis on the mucous membranes.

Advantan cream

. Base: oil in water emulsion, 60% water. The main properties are: promotes the evaporation of water and eliminates swelling, maintains normal skin moisture, softens the skin.

Indications for use: skin diseases amenable to treatment with GCS for external use. Acute conditions - contact dermatitis in any area: acute/subacute course without pronounced weeping; toxicoderma. Chronic conditions - eczema without pronounced infiltration: dyshidrotic (true), paratraumatic, seborrheic; atopic dermatitis in adolescents.

Advantan ointment

. Base: water-in-oil emulsion, 30% water. The main properties are: inhibits water evaporation and prevents the development of dryness; softens the skin.

Indications for use: skin diseases amenable to treatment with GCS for external use - eczema with infiltration: true, numular, varicose, pruriginous; lichen planus (adolescents, adults); lupus erythematosus; psoriasis; polymorphic photodermatosis.

Advantan fatty ointment

. Base: anhydrous, 0% water. The main properties are: the occlusive effect prevents water evaporation and increased skin dryness; enhances the penetration of the drug into the skin; softens the skin.

Indications for use: skin diseases amenable to treatment with GCS for external use - true (tilotic) eczema of the hands; atopic dermatitis in adults such as limited neurodermatitis and eczema of the hands; limited neurodermatitis; palmoplantar psoriasis.

During the clinical use of Advantan in 115 children suffering from AD, no adverse events were identified. Advantan quickly relieved exacerbations of AD of varying severity [12]. The obtained data are presented in Figure 1

.

The results of AD treatment with Advantan emulsion in 27 children aged 2 months to 4 years are presented in Figure 2

[13]. Figure 2. Dynamics of clinical symptoms of atopic dermatitis in children treated with Advantan emulsion.

Advantan almost completely eliminated the symptoms of AD of any severity within 7 days.

Thus, treatment of AD should begin with properly selected basic therapy, since the results of modern studies prove the important role of the use of topical glucocorticoids (TGCS) in the acute and chronic phases of AD. In general, adequate use of TGCS significantly increases the effectiveness of complex therapy for AD and the quality of life of such patients. In addition, timely administration of TGCS with a pronounced anti-inflammatory effect can significantly reduce the amount of drug therapy.

Literature

1. Studenikin V.M. Baby skin care: more gentle, even more gentle. Pharmaceutical Journal, 2007, 40: 16-17. 2. Stroud C.E. A pediatrician`s view of the newborn baby and its epidermis. Cur. Med. Res. Opin., 1982, 7: 29-32. 3. Kretchmer N, Quilligan EJ, Johnson JD. Prenatal and perinatal biology and medicine. Gordon & Breach Science Publ, 1997. 4. Balabolkin I.I. Modern concept of pathogenesis and therapy of atopic dermatitis in children: Modern problems of allergology, clinical immunology and immunopharmacology. M.: Medicine, 1998: 113-119. 5. Balabolkin I.I., Macharadze D.Sh. External therapy of atopic dermatitis in children (hydration, moisturizing preparations). Pediatrics named after G.N. Speransky, 2005, 3: 78-84. 6. Novak N, Bieber J, Leung D. Am. Acad. Dermatol., 2003, 48: 352-358. 7. Gfesser M, Rakoski L, Ring J. Br. J Dermatol 1996, 135: 560-565. 8. Ivanov O.L. Skin and venereal diseases: textbook. M., 2006. 9. Macharadze D.Sh. Atopic dermatitis in children. 2005. 10. Macharadze D.Sh. Atopic dermatitis in children. M.: GEOTAR-Media, 2007: 384. 11. Van Der Meer JB, Glazenburg EJ, Mulder PG et al. The management of moderate to severe atopic dermatitis in adults with topical fluticasone propionate. Br J Dermatol 1999, 140: 114-1121. 12. Korotky N.G. et al. Clinical effectiveness of various dosage forms of methylprednisolone aceponate in the treatment of chronic inflammatory skin diseases. Issues of modern pediatrics, 2005, 4, 3: 87-90. 13.Dr. Angel Vera Casano, Dr. Jordi Rex Cavalle: Monografia de Dermatologia. 2002, XV (6): 399-408.

Source:

Medical Council, No. 14, 2014

pharmachologic effect

NSAIDs block the enzyme cyclooxygenase (COX), which is involved in the formation of special mediators (transmitters) of inflammation, pain and fever - prostaglandins.

COX exists in two forms: COX-1 (or physiological - is formed in the body normally; is responsible for blood flow in the kidneys, the formation of protective mucus in the stomach, blood clotting, uterine tone) and COX-2 (or pathological - appears in the body only when inflammation; responsible for the development of edema, pain, increased body temperature).

Valuable pharmacological effects of NSAIDs (anti-inflammatory, antipyretic, analgesic) are associated with inhibition of COX-2, and negative side effects (formation of stomach ulcers, thrombosis or bleeding, impaired renal function, weakness of labor) are associated with inhibition of COX-1.

Classification of non-steroidal anti-inflammatory drugs

NSAIDs are classified according to the degree of selectivity of their action on COX, as well as according to their chemical structure:

• Non-selective inhibitors of COX-1 and COX-2 (non-selectively block both COX-1 and COX-2 to the same extent): salicylates: acetylsalicylic acid, lysine acetylsalicylate;
• acetic acid derivatives: diclofenac, indomethacin, aceclofenac, etodolac, amtolmetin guacil;
• propionic acid derivatives: ibuprofen, naproxen, ketoprofen, flurbiprofen, dexibuprofen, dexketoprofen;
• fenamates: mefenamic acid.

Nonsteroidal anti-inflammatory drugs in pediatric practice

Nonsteroidal anti-inflammatory drugs (NSAIDs) or drugs (NSAIDs) are widely used in pediatrics. These drugs are characterized by the ability to inhibit cyclooxygenase (COX), the enzyme responsible for the synthesis of prostaglandins [1].

As is known, NSAIDs are represented by the following classes of pharmacological substances: salicylates (acetylsalicylic acid, etc.), pyrazolidones (phenylbutazone), derivatives of indoleacetic (indomethacin, etc.) and phenylacetic (diclofenac) acids, oxicams (peroxicam, etc.), derivatives of propionic acid (ibuprofen, etc.), alkalones (nabumetone), sulfonamide derivatives (nimesulide, etc.), anthranilic acid derivatives (mefenamic acid, etc.), pyrazolones (metamizole, etc.), paraaminophen derivatives (paracetamol, etc.), derivatives heteroarylacetic acid (ketorolac) [2, 3].

The Federal Guide to the Use of Medicines (formulary system) (2011) and other pharmaceutical reference books present a number of NSAIDs, including the following (in alphabetical order): aminophenazone, aceclofenac, acetylsalicylic acid, diclofenac, diflunisal, ibuprofen, indomethacin, ketoprofen, ketorolac, clofezone, lornoxicam, meloxicam, metamizole sodium, mefenamic acid, nabumetone, naproxen, nimesulide, paracetamol, piroxicam, propyphenazone, sulindac, tenoxicam, tiaprofenic acid, phenacetin, phenylbutazone, fenoprofen, flurbiprofen, celecoxib, etodolac, etoricoxib, etofena mat, etc. ... [1–3].

There are over thirty NSAIDs in total; some are used only topically. In pediatric practice, the most widely used are ibuprofen, paracetamol and acetylsalicylic acid. The use of the latter in a number of cases is associated with serious adverse events (internal bleeding, Reye's syndrome, etc.), which significantly limits the use of acetylsalicylic acid in pediatrics (officially prescribed from the age of 16 years). There is a certain caution regarding the use of nimesulide, since cases of severe adverse reactions (hepatotoxicity, etc.) are known with its use, which does not allow this NSAID to be considered safe. The pyrazolone NSAID metamizole (sodium), extremely popular in the Russian Federation in the treatment of various pain and hyperthermic conditions in adults, can lead to agranulocytosis. For this reason, metamizole is prohibited for use in many countries around the world [4].

In this regard, the World Health Organization (WHO) officially recognizes only ibuprofen and paracetamol as NSAIDs that fully meet the safety and effectiveness criteria in pediatric practice and recommends their use in children [4]. In some cases, their joint or intermittent use is provided.

ER Southey et al. (2009) presented data from a systematic review and meta-analysis of the clinical safety and tolerability of ibuprofen compared with paracetamol in the treatment of pain and fever in pediatric practice, which was subsequently published in the Russian version in the Ukrainian journal Clinical Research [5, 6]. In this paper, authors from the UK, who analyzed data from Medline, EMBASE, the Cochrane Library and other electronic literature sources, emphasize the safety of ibuprofen (the tolerability of this NSAID was comparable to that of placebo) [5, 6].

Lokshina E. E. et al. (2010, 2011) consider ibuprofen to be the antipyretic drug of choice for acute respiratory diseases in children [7, 8]. We and other pediatric neurologists have repeatedly reported on the use of ibuprofen for febrile seizures (FS), in the correction of influenza-like syndrome associated with the use of interferon-beta (IFN-beta) drugs in the treatment of multiple sclerosis (MS); in the treatment of acute attacks of migraine and other types of headaches (primary and secondary), with thermopathological syndromes accompanying various types of food intolerance, etc. [9–16].

Ibuprofen, synthesized in 1961, has been used in medicine since 1969. If initially this representative of propionic acid derivatives was used primarily in the treatment of rheumatoid arthritis, then later this drug became one of the main NSAIDs, which is explained by the antipyretic and analgesic effects of ibuprofen. In addition to them, ibuprofen (gross formula C13H18O2) has anti-inflammatory and antiplatelet effects [4].

Ibuprofen is a non-selective blocker of both known forms of cyclooxygenase (COX-1 and COX-2), has the property of stimulating the production of endogenous interferon in the body and has a moderate immunomodulatory effect [4]. A recent work by Al-Janabi AA (2010) also demonstrated the antibacterial activity of ibuprofen against some pathogenic microorganisms, in particular Staphylococcus aureus, which indicates the role of this NSAID in increasing the nonspecific resistance of the body [17].

As mentioned above, the indications for the use of ibuprofen are extremely numerous: rheumatoid arthritis, juvenile rheumatoid arthritis, osteochondrosis, arthritis: psoriatic, lupus, gout, etc.; other inflammatory and degenerative diseases of the musculoskeletal system, pain syndrome in various diseases and pathological conditions (myalgia, arthralgia, ossalgia, bursitis, tendonitis, tendovaginitis, headache or toothache, post-traumatic and postoperative pain syndrome, neuralgia, neuralgic amyotrophy, etc. .); hyperthermia of infectious and non-infectious origin, post-immunization fever, etc. [1–3]. The most common indications for the use of ibuprofen in pediatrics are hyperthermic and pain conditions (including teething reactions) [4].

Ibuprofen can be used from 3 months of age. Since many infants and young children may have difficulty taking oral forms of NSAIDs (regurgitation, refusal of medications given by mouth, etc.), in such cases, the use of ibuprofen in the form of rectal suppositories is provided (Nurofen for children). It is important that the rate of absorption of ibuprofen from this dosage form is similar to that when using an oral suspension.

In childhood, ibuprofen is prescribed at a rate of 5–10 mg/kg body weight 3–4 times a day. The following dosing regimen of ibuprofen in the form of suppositories of 60 mg is proposed (depending on the age of the patients): 3–9 months - 1 suppository 3 times a day (body weight 5.5–8.0 kg), 9–24 months - 1 suppository 4 times a day (body weight 8.0–12.5 kg). The maximum dose of the drug should not exceed 30 mg/kg/day.

Lokshina E. E. et al. (2011) conclude that “due to its high effectiveness and safety, Nurofen for children (ibuprofen) rectal suppositories can be recommended for the treatment of fever and moderate pain in young children, both in hospital and emergency settings, and on an outpatient basis, in home conditions" [8]. In Russia and abroad, among NSAIDs for pediatrics (treatment of pain and fever), ibuprofen deservedly occupies one of the leading places [18]. There is evidence that the effectiveness of ibuprofen as an analgesic and antipyretic exceeds that of paracetamol. In typical pediatric situations, for example, reactions to teething in infancy and early childhood, Nurofen for children is absolutely indispensable and can effectively solve this problem.

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V. M. Studenikin, Doctor of Medical Sciences, Professor S. Sh. Tursunkhuzhaeva V. I. Shelkovsky, Candidate of Medical Sciences L. A. Pak, Candidate of Medical Sciences

SCCD RAMS, Moscow

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