In recent years, drugs with sorption and detoxification properties of enterosorbents have become increasingly recognized in clinical practice. Enterosorption is a method based on the binding and removal naturally from the gastrointestinal tract (GIT) for therapeutic or prophylactic purposes of endogenous (toxic metabolites, heavy metals, bacterial toxins, etc.) and exogenous substances, supramolecular structures and cells (bacteria , viruses, etc.). Enterosorbents are substances that have a sorption capacity, do not degrade in the gastrointestinal tract, effectively bind and remove endogenous and exogenous toxic compounds, supramolecular structures and cells from the body, used for the treatment and prevention of diseases [1–3].
The therapeutic effect of enterosorbents is achieved as a result of their direct and indirect effects on pathogenetic mechanisms. The direct action of enterosorbents is aimed at binding and eliminating from the gastrointestinal tract toxic products of metabolism and the inflammatory process, pathogenic bacteria and their toxins, viruses, biologically active substances (neuropeptides, prostaglandin, serotonin, histamine), binding gases formed in excess during the fermentation or putrefactive process. The indirect effect is due to the prevention or weakening of clinical manifestations of endotoxicosis, toxic-allergic reactions, diarrhea syndrome, as well as restoration of the integrity and permeability of the mucous membranes, improvement of blood supply, stimulation of intestinal motility. Enterosorbents reduce the metabolic load on the liver and kidneys, help normalize the motor, evacuation and digestive functions of the gastrointestinal tract, and have a positive effect on the functional state of the immune system and intestinal microbiocenosis [2, 4–7].
The enterosorption method was known to our ancestors, who used wood ash, charcoal, and a number of clay aluminosilicates to treat various poisonings and toxic conditions. Of these, by 70–80. In our century, the well-known activated carbon came as an officially registered drug, and then other carbon enterosorbents (Carbolong, Microsorb, the drug SKN-1, etc.). Carbon sorbents increase the amount of dense components in the intestinal contents, having a positive effect on intestinal motility, and adsorb gases, alkaloids, and toxins. However, they do not have pronounced binding selectivity and with prolonged use, side effects are possible (constipation, decreased levels of vitamins, hormones, fats, proteins, and some microelements in the body), which can lead to serious metabolic disorders.
Since the late 1980s - mid-1990s. enterosorbents from fibrous forms of pyrolyzed cellulose - lignin (Polyphepan, Filtrum-STI, Laktofiltrum, Lignosorb, etc.), chemical ones (Enterodez, Enterosgel, etc.) were introduced into medical practice.
As well as enterosorbents based on highly dispersed silicon oxide (Polysorb-MP), obtained using a special technology from sea brown algae or alginates (Algisorb), preparations based on aluminosilicates and aluminas (Smecta, Neosmectin, Kaopectate). Among the listed enterosorbents, the most worthy of attention are drugs that can absorb or adsorb in the gastrointestinal tract and excrete not only toxic metabolites, but also pathogenic bacteria and viruses. It has been proven that Smecta has this property [43]. Enterosorbents are widely used in clinical practice as pathogenetic agents, and in recent years as an alternative to etiotropic antibiotic and chemotherapy for intestinal infections of both bacterial and viral etiology [8–11].
When choosing an enterosorbent for inclusion in the complex therapy of acute intestinal infection (AIE), it is necessary to take into account not only their ability to adsorb and eliminate pathogenic bacteria and viruses, but also the presence of side effects. For example, with long-term use of carbon sorbents (activated carbon, Microsorb P), constipation, diarrhea, and a decrease in the level of vitamins, hormones, fats, proteins and microelements in the body are possible; drugs based on hydrolytic lignin (Polifepan, Entegnin, Filtrum) may interfere with the absorption of vitamins and calcium in the gastrointestinal tract, Enterosgel - increased nausea and flatulence. An important criterion for choosing a sorbent is also its sorption capacity and the rate of absorption of endo- and exotoxins of pathogenic bacteria. As studies have shown [15], the highest rate of absorption of endotoxin by Salmonella abortus th. has dioctahedral smectite (Smecta), maintaining a leading position during the first hour of sorption. The second and third places in terms of absorption rate are shared by Enterosgel, Polysorb and Filtrum (see figure).
When analyzing the average daily sorption capacity of enterosorbents, which was determined as the ratio of the toxin concentration after sorption to the volume of the sorbent, it was shown that Smecta also occupies a leading position in this group, with Filtrum, Polysorb and Enterosgel in second place. At the same time, Polyphepan and activated carbon, widely used in clinical practice, did not show satisfactory results and occupy the penultimate and last places, respectively, both in terms of the rate of endotoxin absorption and sorption capacity.
Due to the multifaceted and multifactorial nature of the action, a widely used enterosorbent in clinical practice is Smecta - a dioctahedral smectite, which is one of the sorbents highly standardized for the raw materials from which it is obtained, has a durable polymeric organosilicon base containing aluminum and magnesium as heteroatoms, and has a high sorption activity. The introduction of the enterosorption method into clinical practice for various pathological conditions has significantly increased the clinical effectiveness of traditional basic therapy, incl. and for intestinal infections in children [12–14].
With its appearance on the domestic market in the mid-1990s. of the new enterosorbent Smecta (Ipsen, France), we studied its clinical effectiveness in the complex therapy of intestinal infections of bacterial etiology in 30 patients with moderate and severe forms of the disease [16]. It was found that in the majority (80%) of patients who received antibiotics and Smecta as part of complex therapy, already on the 1st day from the start of treatment, the severity of symptoms of intoxication and exicosis significantly decreased. At the same time, the frequency and volume of bowel movements decrease, on the 3rd day - in 32%, and on the 5th - in 64% of patients, clinical recovery occurs with persistent normalization of stool, while in the group of patients who did not receive Smecta, clinical recovery occurred in these terms occurred only in 20 and 45% of cases. When Smecta enterosorbent was included in the basic therapy for acute intestinal infections in children, the average duration of the acute period of the disease was reduced from 5.6±0.8 to 4.8±0.6 days (p<0.05). The second stage of our research was to study the clinical effectiveness and possibility of using Smecta as the only means of etiotropic “starter” therapy for mild and moderate forms of acute intestinal infections in children [17].
Material and methods
We observed 66 patients with acute intestinal infections aged from 6 months to 14 years with mild (18.2%) and moderate (81.8%) forms of the disease. The main group (63.6%) consisted of children of early (24.3%) and preschool (39.3%) age. The etiological diagnosis of AEI, taking into account the results of laboratory tests (bacteriological, serological, diagnosis using polymerase chain reaction) was established in 27 (40.9%) patients, incl. salmonellosis (3), shigellosis (2), klebsiellosis (6), enterobacteriosis (4) and rotavirus-bacterial co-infection (12 patients). The majority (81.8%) of patients had an “invasive” and only 18.2% of cases a mixed “invasive-osmotic” type of diarrhea; 48.5% were intestinal infections that occurred with clinical manifestations of enteritis or gastroenteritis and 51.5% were colitis or enterocolitis.
Depending on the etiotropic therapy performed, the patients were divided into three groups: 1st (main) - 22 children, received Smecta in a 3-5-day course, other drugs with etiotropic effects were not prescribed to these patients; 2nd (comparison group) – 20 patients, received furazolidone in a 5-day course and 3rd group (24 patients) – furazolidone and Smecta.
Research results
It was established that with etiotropic monotherapy with Smecta enterosorbent, in contrast to treatment with furazolidone alone, the average duration of intoxication symptoms (from 3.80±0.18 to 3.01±0.16 days), fever (from 2.51±0.29 to 1.95±0.15 days) and abdominal pain (from 2.58±0.16 to 1.70±0.11 days). The average duration of the acute period of the disease with normalization of stool is reduced from 5.30±0.36 to 4.22±0.18 days (p<0.05).
In the group of patients with acute intestinal infections who received combination etiotropic therapy (furazolidone + Smecta), the clinical effectiveness was significantly higher than furazolidone monotherapy. Clinical recovery at the end of a 3-5-day course of treatment with Smecta enterosorbent occurred in 72.7%, with furazolidone alone in 60%, and in combination with Smecta in 83.3% of cases. Analysis of the results of a study of stool for intestinal dysbiosis in 25 children showed that in the group of patients receiving only furazolidone, dysbiotic changes in the intestinal microflora progressed over the course of the disease, and when combined with Smecta, they remained virtually unchanged. While with monotherapy with Smecta, there was a clear tendency towards an increase in the Ig-concentration of bifidobacteria and lactobacilli, complete sanitation or a decrease in the titer of representatives of opportunistic microflora to 102–3 CFU/g.
Thus, the results of the study indicate that etiotropic “starter” monotherapy for mild and moderate forms of acute intestinal infections of bacterial and viral-bacterial etiology in children with Smecta enterosorbent is effective and additional prescription of antibacterial drugs is, as a rule, not required. However, as our further studies have shown, in moderate and severe forms of acute intestinal infections of bacterial etiology, the use of antibiotics in combination with enterosorbents significantly increases the clinical and sanitizing effectiveness of therapy and prevents further progression of intestinal dysbiosis.
Discussion
Clinical studies have established that enterosorbents are capable of exerting not only pathogenetic, but also etiotropic effects due to the sorption and elimination of pathogenic bacteria and viruses from the intestine. Experimental studies confirmed the adsorbing properties of Smecta against gram-negative microorganisms and their toxins (Echerichii coli, Vibrio cholerae, Campylobacter jejuni, Clostridium difficile), as well as rotavirus [18].
In vitro studies revealed the effect of this drug on the replication mechanism of rotaviruses. In in vivo experiments, it was found that Smecta effectively limits the penetration of rotaviruses through the protective mucous barrier of the intestines of animals, and also has a high binding ability against rotaviruses - up to 90% of viral particles are removed with a minimum sorbent concentration in the first minutes after their contact [19, 20 ]. In animal experiments, not only the intestinal absorption of rotavirus, cholera toxin and campylobacter was established, but also the regulating effect of smectite on the amplitude of peristaltic contractions of intestinal smooth muscles [21–23]. The results of these studies indicate that Smecta in combination with rehydration and diet can be used not only as a means of pathogenetic, but also etiotropic therapy for viral diarrhea [24, 25]. According to a prospective randomized controlled trial, which included 804 children, it was proven that Smecta contributed to a significant increase in the effectiveness of rehydration and quality of life in case of enteritis and gastroenteritis [26, 27].
Data from other active pharmacological studies have also shown that the clinical effectiveness of Smecta is based on its ability to bind and remove bile acids (due to which physiological enterohepatic circulation is restored), as well as intestinal gases [28]. No less important are the unique properties of the drug - the ability to fix and remove undigested carbohydrates from the intestine, which play a key role in the pathogenesis of rotavirus diarrhea, increasing the enzymatic activity of the glycocalyx and reducing the loss of water and electrolytes with feces [29].
In 2008, a joint working group of ESPGHAN and ESPID published evidence-based recommendations on the use of antidiarrheal drugs that are appropriate for use as adjunctive therapy for diarrheal syndrome in children. Among enterosorbents, dioctahedral smectite (Smecta®) was recommended with a high level of evidence (II, B) in combination with oral rehydration [30]. Dioctahedral smectite has fluidity and enveloping properties, protects the intestinal mucosa from the effects of aggressive and toxic factors. Dioctahedral smectite penetrates the mucin layer and changes the physical properties of mucus, increasing the enzymatic activity of the glycocalyx, thereby reducing the loss of electrolytes and water in the feces [31]. Being a selective sorbent, smectite removes bacteria, viruses, toxins, bile acids, excess carbohydrates from the body and reduces the amount of gas [32].
In the studies of M.S. Grigorovich [33] found that in a group of children with prolonged diarrhea due to rotavirus infection who received Smecta in the convalescent period, normalization of stool frequency occurred on the 3rd day of rehabilitation therapy, while in patients in the comparison group, diarrhea resolved on the 5th–6th day of treatment. The pathological nature of stool in the convalescent period persisted for an average of 4.9±0.4 days in children taking Smecta and 6.3±0.6 days in children in the control group. In general, the total duration of intestinal dysfunction in children receiving Smecta was 2.8 ± 0.2 days shorter than in children in the comparison group.
In recent years, Smecta has been successfully used in the treatment of not only acute, but also chronic gastroenterological pathologies, which is due to the protective and adsorbing properties of this drug.
Indications for prescribing Smecta are patients who have had infectious colitis and have a tendency to have unstable stools with a predominance of diarrhea; for inflammatory bowel diseases (nonspecific ulcerative colitis and the colonic form of Crohn's disease during a period of unstable remission); for antibiotic-associated diarrhea and pseudomembranous colitis as part of complex therapy. According to G.A. Grigorieva et al. [34], the use of Smecta by patients with infectious colitis already in the 1st week of treatment (1 powder 3 times a day 30 minutes before meals) normalizes stool, reduces flatulence and improves the psycho-emotional state. However, the duration of the course should be determined individually and vary from 3 to 5–6 weeks to consolidate the results obtained.
From the point of view of evidence-based medicine, an important quality of Smecta is also the ability of the drug to neutralize enterotoxins A and B of Clostridium difficile, which allows its use in the prevention and treatment of antibiotic-associated diarrhea in children [35–38].
Conducted scientific studies indicate that Smecta is a mucoactive drug, the preferred target for which is destructured mucins. Having a high affinity for them, the drug inhibits destruction and thereby leads to the restoration of the physical and rheological properties of mucus [39]. Due to the ability to potentiate the protective functions of the intestinal mucous barrier, Smecta is considered a surface-type cytoprotector. Prospective randomized studies have shown that, due to its membrane-stabilizing properties, Smecta prevents the destructive effects of inflammatory cytokines, including tumor necrosis factor, which is important for patients with ulcerative colitis and Crohn's disease.
Literature data confirm the effectiveness of using Smecta as a prophylactic agent, as part of complex therapy and for other gastroenterological pathologies. Thus, in one of the studies by K.V. Arifullina [40] included Smecta in eradication treatment regimens for children with chronic Helicobacter-associated gastroduodenitis. It was found that additional use of Smecta eliminates side effects associated with antibiotic therapy. At the same time, Smecta inhibits the rapid growth of pathogenic microflora and prevents the development of clinical symptoms of clostridial and staphylococcal dysbiosis. In another study by G.A. Grigorieva et al. [41] obtained good results when adding Smecta to the complex therapy of pseudomembranous colitis.
In the studies of A.A. Korsunsky et al. [42] studied the effectiveness of Smecta on 19 children with Helicobacter pylori-positive and 11 negative gastritis and gastroduodenitis. Smecta was prescribed for a course of 21 days at an age-appropriate dosage 3 times a day 60 minutes after meals. The clinical effectiveness of the drug was expressed in the reduction of pain and other dyspeptic symptoms (nausea, heartburn, belching and flatulence), which were present to varying degrees before treatment in all patients. A week after the start of treatment, positive dynamics were noted in 78% of patients, pain disappeared in 56% of patients. The maximum effect of treatment was achieved by the end of the 2nd week. Objective confirmation of the effectiveness of Smecta was the improvement in the endoscopic picture of the gastric mucosa. Positive dynamics in the prevalence of the inflammatory process were also noted - after therapy, pangastritis and/or erosions were not detected in any of the children. The frequency of the presence of bile in the stomach (a sign of impaired motility) after treatment decreased by 4 times, signs of gastroesophageal and duodenogastric reflux were observed less frequently by 2.5 times. Dynamic studies showed a significant increase in the viscosity of gastric mucus (p<0.01).
Conclusion
Thus, dioctahedral smectite (Smecta) is one of the enterosorbents with proven clinical effectiveness. The inclusion of Smecta in a complex of therapeutic measures for various diseases and pathological conditions, primarily accompanied by diarrhea, has rapid and pronounced detoxification, hypothermic and antidiarrheal effects. Reducing the frequency and volume of bowel movements quickly leads to relief of exsicosis and, accordingly, symptoms of intoxication. In addition, Smecta has not only pathogenetic, but also etiotropic effects against both pathogenic bacteria and viruses. It prevents the progression of intestinal dysbiosis during antibiotic therapy and thereby contributes to a more rapid relief of functional disorders of the gastrointestinal tract. The cytomucoprotective and trophic effects of Smecta contribute to the restoration of morphological disorders in the gastrointestinal tract and relief of the inflammatory process. Smecta should be recommended as initial therapy for diarrhea of any etiology and type (secretory, osmotic, invasive, etc.).
Smectite E pore.d/preg.susp.d/ext. approx. 3000 mg in pack No. 30
Name
Smectite E.
Description
Powder from almost white to light beige. The suspension is almost white to light beige in color with a slight orange odor.
Main active ingredient
Dioctahedral smectite.
Release form
Powder.
Dosage
3000 mg.
Indications for use
For children from 2 years old:
- Symptomatic treatment of acute diarrhea in combination therapy with oral rehydration solution.
For adults:
- Symptomatic treatment of acute diarrhea in adults in combination therapy with oral rehydration solution.
- Symptomatic treatment of chronic diarrhea.
— Symptomatic treatment of abdominal pain, which is associated with esophagogastroduodenal and intestinal diseases.
Directions for use and doses
Before use, dissolve the contents of the package in water to obtain a suspension. It is preferable to use the drug:
- after eating with esophagitis;
- in between meals for other indications.
For children:
- Dissolve the contents of the package in 50 ml of water and distribute into several doses throughout the day or mix thoroughly with some semi-liquid product: broth, compote, puree, baby food.
For adults:
- Dissolve the contents of the package in half a glass (100 ml) of water.
Treatment of acute diarrhea. For children:
- 2 years and older: 4 packets per day for 3 days, then 2 packets per day for 4 days.
For adults:
- on average 3 packets per day.
At the beginning of treatment, the daily dose can be doubled. Other indications. For adults:
- on average 3 packets per day.
The recommended course of treatment is 3-7 days. If one or more doses are missed, the drug should be resumed as usual without doubling the dose.
Use during pregnancy and lactation
Use during pregnancy and breastfeeding is not recommended.
Precautionary measures
The drug Smectite E should be prescribed with caution to patients with a history of chronic constipation. In the treatment of acute diarrhea in children over 2 years of age, the drug is used in combination with early rehydration therapy to prevent the development of dehydration. In adults, rehydration is prescribed if necessary. The duration of rehydration and the method of its administration (oral or intravenous) should be determined by the attending physician depending on the age and clinical picture of the disease. The patient must be informed that:
- it is necessary to rehydrate with salty or sweet solutions to replenish fluid loss due to diarrhea (the daily fluid intake for an adult is up to 2 liters);
- Monitor your diet during diarrhea: exclude raw fruits and vegetables, spicy and fried foods, canned foods and drinks.
The medicine contains glucose. The use of the drug is not recommended in patients with impaired glucose absorption or sucrase-isomaltase deficiency (a rare hereditary disease).
Interaction with other drugs
Given the significant absorption properties of the drug, which may affect the rate and/or extent of absorption of another drug, it is recommended to take another drug some time before or after taking Smectite E.
Contraindications
- Hypersensitivity to dioctahedral smectite or one of the components of the drug.
- Intestinal obstruction.
- Children under 2 years of age.
Compound
Each package contains: active substance: dioctahedral smectite – 3000.0 mg; excipients: glucose monohydrate, sodium saccharin (E954), orange flavoring, vanillin. Composition of the Orange flavor: dextrose, flavoring component (contains natural flavoring substances and preparations), anti-caking agent: silicon dioxide E551 (5%), sodium chloride.
Overdose
Possible increased side effects. Currently, there is no information on cases of overdose with drugs containing dioctahedral smectite.
Side effect
Cases of adverse reactions have been reported when taking the drug in children and adults. These side effects were generally minor, short-lived, and mostly related to the digestive system. The frequency of adverse reactions is determined according to the following classification: often (? 1/100, but
Storage conditions
Store at a temperature not exceeding 25 °C. Keep out of the reach of children.
Buy Smectite E po.d/prig.susp.d/in.p.m. 3000 mg in pack No. 30 in a pharmacy
Price for Smectite E por.d/preg.susp.d/internal approx.3000 mg in pack No. 30
Instructions for use for Smectite E po.d/adj.susp.d/internal approx.3000 mg in pack No. 30
