5 aminosalicylic acid. Medicinal reference book geotar. Characteristics of the substance Aminosalicylic acid

Gross formula

Pharmacological group of the substance Aminosalicylic acid

Nosological classification (ICD-10)

CAS code

Characteristics of the substance Aminosalicylic acid

White or white with a slightly yellowish or slightly pinkish tint, fine crystalline powder, slightly soluble in water, quickly destroyed when heated, as well as when exposed to sunlight. The sodium salt is readily soluble in water, difficult in alcohol, relatively stable at room temperature.

Pharmacology

It competes with PABA for the active center of the enzyme that converts PABA to dihydrofolic acid and inhibits the synthesis of folic acid in the microbial cell. In terms of tuberculostatic activity, it is inferior to isoniazid and streptomycin. Effective against actively breeding Mycobacterium tuberculosis(IPC in vitro 1-5 µg/ml). Practically does not affect mycobacteria in the resting stage and located intracellularly. Does not affect other mycobacteria. Primary resistance is rare, secondary develops slowly. It is used only in combination with other anti-tuberculosis drugs, which slows down the development of resistance to them. It inhibits the emergence of resistance to isoniazid and streptomycin. In high doses, it has an antithyroid effect. With prolonged use, a goiter effect may be observed. May contribute to the development of anemia by interfering with the absorption of vitamin B 12.

Quickly and well absorbed from the gastrointestinal tract , has an irritating effect on the mucosa of the gastrointestinal tract . C max after administration at a dose of 4 g is 75 mcg / ml, with a / in the introduction - above. Plasma protein binding is low (15%). Easily distributed in tissues and body fluids, kidneys, lungs, liver. Reaches high concentrations in the pleural effusion and caseous tissue, in the cerebrospinal fluid is determined in low concentrations. Metabolized in the liver (more than 50% acetylated to inactive metabolites) and partly in the stomach. T 1/2 with normal kidney function is 30-60 minutes, with impaired - up to 23 hours. It is excreted by glomerular filtration and tubular secretion, reaching very high concentrations in the urine (alkalinization is necessary to prevent crystalluria). 85% of the dose is excreted within 7-10 hours, 14-33% - unchanged, 50% - in the form of metabolites.

Application of the substance Aminosalicylic acid

Drug-resistant tuberculosis (various forms and localization) in combination with other reserve anti-tuberculosis drugs.

Contraindications

Hypersensitivity, incl. to other salicylates, severe kidney and liver diseases (renal and / or liver failure, nephritis of non-tuberculous etiology, hepatitis, liver cirrhosis), amyloidosis, peptic ulcer of the stomach and duodenum, enterocolitis (exacerbation), myxedema (uncompensated), decompensated heart failure ( including on the background of heart disease), epilepsy.

In / in the introduction (optional): thrombophlebitis, bleeding disorders, severe atherosclerosis.

Application restrictions

Moderately severe pathology of the gastrointestinal tract, deficiency of glucose-6-phosphate dehydrogenase.

Use during pregnancy and lactation

Should not be used during pregnancy and breastfeeding (adequate and well-controlled studies in humans have not been conducted). In one study, children whose mothers took aminosalicylates during pregnancy simultaneously with other anti-tuberculosis drugs noted an increase in the frequency of malformations of the ears and limbs, the occurrence of hypospadias. However, in other studies, the teratogenic effect of aminosalicylates has not been identified.

Penetrates into breast milk, complications in humans are not registered.

Side effects of the substance Aminosalicylic acid

From the side of the cardiovascular system and blood (hematopoiesis, hemostasis): violation of the synthesis of prothrombin, granulocytopenia or agranulocytosis, hemolytic anemia (with a deficiency of glucose-6-phosphate dehydrogenase); rarely - thrombocytopenia, leukopenia (up to agranulocytosis), drug-induced hepatitis, B 12 deficiency megaloblastic anemia.

From the digestive tract: anorexia, nausea, vomiting, flatulence, diarrhea or constipation, gastric ulcer, gastric bleeding, abdominal pain, increased liver transaminase activity, hyperbilirubinemia, hepatomegaly, hepatitis.

From the genitourinary system: crystalluria, proteinuria, hematuria.

Allergic reactions: urticaria, purpura, enanthema, drug fever, asthmatic phenomena, bronchospasm, arthralgia, eosinophilia.

Others: goiter with or without hypothyroidism, myxedema (with prolonged use at high doses), mononucleosis-like syndrome (fever, headache, skin rash, sore throat), diabetes mellitus, hypokalemia, metabolic acidosis; with a / in the introduction - a feeling of heat, weakness, toxic-allergic reactions up to the development of shock.

Interaction

Violates the absorption of rifampicin, erythromycin, lincomycin and vitamin B 12 (risk of anemia). Simultaneous administration with aminobenzoates prevents the bacteriostatic effect (competition according to the mechanism of action). May weaken the antibacterial effects of aminoglycosides. When combined with capreomycin, it is possible to increase electrolyte disturbances, decrease in potassium concentration and pH. Increases the concentration of isoniazid in the blood, reducing its acetylation. Enhances the effect of coumarin and indandione derivatives by reducing the synthesis of blood coagulation factors in the liver (adjustment of the dose of anticoagulants is required). Do not use with pyrazinamide and ammonium chloride. Probenecid and sulfinpyrazone reduce tubular secretion, increasing the concentration of aminosalicylic acid in the blood and the risk of toxic effects. The risk of developing hypothyroidism is increased when taken concomitantly with ethionamide and prothionamide.

Substance precautions Aminosalicylic acid

Possible cross-sensitivity to compounds containing a para-aminophenyl group (some sulfonamides and dyes). For patients in whom acetylsalicylic acid in the form of uncoated tablets causes gastrointestinal disturbances, the drug should be administered in the form of granules, coated tablets or enteric tablets; possible temporary dose reduction or temporary cancellation of aminosalicylic acid, with a gradual increase in dose to therapeutic. During treatment, it is recommended to regularly monitor the activity of liver enzymes, analyze urine and blood. With the development of hematuria and proteinuria, temporary drug withdrawal is required. When used in patients with diabetes, it should be borne in mind that the granules contain 1 part of aminosalicylic acid and 2 parts of sugar (1 teaspoon contains 6 g of granules, which corresponds to 2 g of aminosalicylic acid and 4 g of sugar). Do not take aminosalicylic acid within 6 hours before and after taking rifampicin.

special instructions

A solution that has lost its transparency or changed color is unsuitable for use. May cause a false positive result in the study of glucosuria, interfere with the determination of urobilinogen in the urine (interaction with Ehrlich's reagent).

Interactions with other active substances

Trade names

These drugs include sulfasalazine, salazopyridazine, as well as 5-ASA in the form of salofalk, mesalazine, mesacol, etc.

The mechanism of action of these agents is described in detail in Chap. "Treatment of nonspecific ulcerative colitis". The most important aspect is the inhibition of the lipoxygenase pathway for the conversion of arachidonic acid, the metabolic products of which serve as mediators of the inflammatory process in the intestine, as well as the immunomodulatory effect (these effects are due to 5-ASA).

Treatment sulfasalazine A. R. Zlatkina (1994) recommends starting with a dose of 0.5 g 4 times a day, after 2-3 days the dose is increased by 2 times, and after a week it is increased to 2 g 4 times a day, in severe cases - up to 2 g 5 times a day. day for 2-3 weeks. The daily dose of sulfasalazine in some cases can be 4-6 g. The duration of treatment with sulfasalazine is not strictly regulated, it is determined by the dynamics of the disease and can be from 3-4 weeks to 3-4 months or more.

There are data in the literature on treatment with drugs containing 5-ASA for a year or even longer (Fiasse R., 1980). The effectiveness of treatment with sulfasalazine in terminal glue is lower than in Crohn's disease of the colon. This is due to the fact that the splitting of sulfasalazine into 5-ASA and sulfapyridine occurs under the influence of the colon microflora.

A drug salazopyridazine apply 2 g per day for 4 weeks, and the next 3-4 weeks - 1.5 g per day.

5-Aminosalicylic acid(salofalk, mesalazine) is prescribed 3 g per day. The effectiveness of the drug is higher, and tolerability is better than sulfasalazine and salazopyrndazine.

Side effects of drugs containing 5-ASA are manifested by dyspeptic disorders, skin rashes, leukopenia, agranulocytosis (sulfasalazine, salazopyridazine), so it is necessary to check the blood test once every 10 days.

Pharmacotherapy

Place and purpose of the use of aminosalicylates in ulcerative colitis

Summary

Various aspects of the use of 5-aminosalicylic acid (5-ASA) preparations in ulcerative colitis are considered. The mechanisms of action of this group and their points of application in the inflammatory cascade in this disease are analyzed in detail. The general characteristics of various 5-ASA preparations, the features of their pharmacodynamics, which determine the expediency of their prescription in different clinical situations, are given. The indications for use are listed, indicating treatment regimens and the duration of their use in exacerbation and remission of ulcerative colitis. The treatment of distal forms of the disease using different dosage forms of 5-ASA is considered in detail. Emphasis is placed on the duration of maintenance therapy, depending on the goal - prevention of recurrence of the disease or colon cancer. The mechanisms of the anticarcinogenic action of aminosalicylates and the feasibility of their use as a means for cancer prevention in ulcerative colitis are described with reference to controlled studies.

Keywords: 5-ASA, sulfasalazine, mesalazine, ulcerative colitis, colon cancer

Since 1946, 5-aminosalicylic acid (5-ASA) preparations have firmly entered the arsenal of therapeutic agents for ulcerative colitis (UC). Aminosalicylates (sulfasalazine and mesalazine) are traditionally used as first-line drugs for mild and moderate forms of the disease to stop an attack and induce remission, to maintain remission.

The mechanism of action of aminosalicylates

The mechanism of action of 5-ASA is due to the inhibition of inflammatory mediators (arachidonic acid derivatives and pro-inflammatory cytokines) involved in the implementation of intercellular interactions and the development of inflammation in inflammatory bowel diseases (IBD). Unlike derivatives of salicylic acid (aspirin, non-steroidal anti-inflammatory drugs [NSAIDs]), which block the cyclooxygenase pathway of the arachidonic cascade and selectively inhibit the synthesis of prostaglandins, aminosalicylates have a multidirectional effect on the synthesis of arachidonic acid metabolites (Fig. 1). Thus, high doses of 5-ASA and sulfasalazine suppress the production of prostaglandins, while low doses can stimulate it. This is a fundamentally important point, since prostaglandins in IBD play the same protective role for the intestinal mucosa as they do for the gastric mucosa in peptic ulcer disease. Their deficiency reduces the protective functions of the mucous membrane. The main point of application of 5-ASA in the arachidonic cascade is the enzyme 5-lipoxygenase, which results in the formation of eicosanoids peroxides and hydroperoxides of fatty acids and leukotrienes. The latter, primarily leukotriene B4, play a major role in the development of inflammation (Fig. 1). 5-ASA also inhibits the synthesis of pro-inflammatory cytokines of macrophage origin: interleukins (IL) - IL-1, IL-6, IL-8, IL-18 and tumor necrosis factor (TNF-α), the production of antibodies by B-lymphocytes, neutralizes free oxygen radicals (Fig. 2). In addition, it has been shown that 5-ASA is able to suppress the nuclear factor NFkb, which is responsible for the synthesis of pro-inflammatory cytokines.

Characteristics of 5-ASA preparations

Sulfasalazine, synthesized in 1946, is a 5-ASA connected by a nitrogenous bond with sulfanilamide (sulfapyridine). Sulfapyridine is an inert part of the molecule, prevents the absorption of the drug in the jejunum and serves, in fact, as a carrier of 5-ASA in the colon. The bond between 5-ASA and sulfapyridine is cleaved in the ileum and colon under the influence of bacterial enzymes (azoreductases) and the released 5-ASA exerts its anti-inflammatory effect by blocking the synthesis of mediators in the colonic mucosa (COMC). Free 5-ASA is only 20-30% absorbed from the colon, so its systemic effect is very small. The main part of the drug remains in the intestinal lumen and in the intestinal epithelium in a partially acetylated form. Thus, the 5-ASA released from sulfasalazine has mainly a local effect. A therapeutic dose of sulfasalazine is prescribed until clinical and endoscopic remission is achieved (within 4-8 weeks), after which a maintenance dose is recommended to prevent relapse for an average of 1.5 years after the attack of UC has subsided. However, the duration of anti-relapse therapy may vary over a wider range (from 6 months to 2 years) depending on the individual nature of the course of the disease and the frequency of recurrence.

Despite its more than 50-year history, sulfasalazine has not lost its clinical significance, although it has significant drawbacks that limit the possibility of increasing doses and duration of administration. Sulfasalazine is toxic and has a wide range of adverse reactions, including: leukopenia with agranulocytosis, toxic-allergic skin manifestations, impaired renal function, pancreatitis, infertility in men, etc. These reactions occur in 15-20% of patients. The development of side effects is associated with the sulfanilamide part of the drug, since sulfapyridine is almost completely absorbed from the colon and metabolized in the liver.

Mesalazine. The problem of toxicity was solved by creating 5-ASA preparations without sulfopyridine in the molecule (mesalazine, olsalazine, balsalazide). These drugs are not inferior to sulfasalazine in effectiveness, and possibly even surpass it, but are devoid of its side effects. The most widespread both abroad and in Russia received mesalazine (mesalamine). Tableted mesalazine preparations produced in different countries are similar in action and efficacy and are 5-ASA in a protective coating. They differ in the nature of the enteric coating (eudragit, acrylic or ethylcellulose) and, accordingly, in the site and rate of release of 5-ASA in the intestine. There is a clear correlation between the intraluminal concentration of 5-ASA and clinical efficacy, so the localization of the lesion must be taken into account when prescribing 5-ASA preparations. The dissolution of the enteric eudragit coating of most mesalazine preparations (salofalk, azacol, samezil claversal, mesacol, etc.) and the release of 5-ASA depends on pH in the intestinal lumen and is destroyed at certain values ​​(pH> 6-7) in the terminal ileum and in the colon, where the maximum therapeutic concentration of 5-ASA is reached. It follows that mesalazine is optimal for the treatment of UC and terminal ileitis in Crohn's disease. Long-term studies testify to its high efficiency in the indicated localization of the pathological process. In Russia, many years of experience in the use of mesalazine was acquired on the basis of work with the drug Salofalk , which is used for the treatment and prevention of relapses of IBD and has a minimum of side effects associated with individual intolerance to the drug.

Indications for the appointment of aminosalicylates

The goals of treatment in UC include suppression of the activity of the inflammatory process and induction of remission, maintenance of remission, prevention of complications and improvement of the quality of life of patients. The use of 5-ASA in UC is fully consistent with these goals, but this applies only to mild and moderate forms of the disease. In severe cases, these drugs are not effective.

Ulcerative colitis with widespread lesion in the acute stage

Aminosalicylates are used as basic agents for oral administration during an attack of UC. When taken orally, the maximum concentration of 5-ASA is achieved mainly in the ileum and caecum and in the ascending, to a lesser extent transverse, sections of the colon. In the left half of the colon, the concentration of 5-ASA is significantly lower, and in the sigmoid and rectum it is minimal, here the drug is practically absent. Therefore, oral administration of aminosalicylates is effective in widespread UC (total, subtotal, and, to a lesser extent, left-sided). In mild UC, it is usually sufficient to prescribe 5-ASA preparations - sulfasalazine at a dose of 3-4 g / day or mesalazine 3 g / day. The need for the use of hormonal agents, as a rule, does not arise, except in rare cases refractory to 5-ASA. For moderate UC, sulfasalazine 4–6 g/day or mesalazine 4–4.8 g/day are used. If there is no effect, corticosteroids are prescribed after 2-3 weeks.

Ulcerative colitis in remission

In UC, long-term anti-relapse therapy is a mandatory rule in the absence of contraindications. Refusal of maintenance treatment in most cases quickly leads to an exacerbation. In the case of induction and achievement of remission by aminosalicylates, these same drugs, of course, are the main means for maintenance treatment. In advanced forms of UC, mesalazine is the drug of choice for long-term therapy. Sulfasalazine, due to its high toxicity, is not desirable for long-term use. Prevention of UC recurrence requires prolonged therapy for 1.5-2 years after the attack subsides and remission is achieved. The dose of mesalazine is 1.5 g per day, sulfasalazine 2 g per day.

5-ASA preparations are not effective for maintenance therapy of UC in cases of steroid-dependent or steroid-resistant course of the disease. In these cases, azathioprine is used.

Distal ulcerative colitis

With distal forms of UC (proctitis, proctosigmoiditis), and, in some cases, with left-sided colitis, local treatment is recommended. To do this, there are dosage forms of mesalazine in the form of enemas, foams, gels and suppositories.

Rectal forms of 5-ASA are considered first-line drugs for effectiveness (have priority over steroids) to achieve both clinical and endoscopic remission. In the treatment of proctosigmoiditis, enemas with mesalazine (salofalk) are used at 2 and 4 g per day, depending on the degree of activity. Some studies indicate that the use of 1, 2 or 4 g of mesalazine rectally has the same efficacy, however, the clinical experience of most gastroenterologists around the world shows that the daily dose of drugs for rectal administration in active inflammatory process is the same as when taken orally 3-4 g / day. This dose allows you to quickly achieve remission with a favorable course of the disease, however, if necessary, the reception continues up to 30 weeks without dose reduction. For the treatment of ulcerative proctitis, mesalazine is prescribed in suppositories. The daily dose is 1-2 g per day once or in 2 divided doses. In children, lower dosages are used in suppositories of 250 mg 2 to 3 times a day.

Doses, schedule and duration of treatment of distal UC with aminosalicylates are similar to those in common forms of the disease. Patients need mandatory prolonged anti-relapse treatment with locally acting drugs for a long time. The maintenance dose can be 1 g/day of mesalazine rectally daily, every other day, or at least 2 times a week. Economic analysis showed that even with the high cost of topical mesalazine preparations, prolonged therapy is more beneficial for the patient, and the total cost of treatment per year is lower, since the cost of long-term maintenance doses is less than the cost of high doses of drugs for relapses.

The question of the advisability of combined treatment with oral and rectal aminosalicylates is being discussed. The effectiveness of such combinations for ulcerative proctitis is doubtful, for proctosigmoiditis has not been proven, but for left-sided colitis it may be optimal.

Recently created new rectal foam preparations for the treatment of active UC with distal or left-sided lesions have a more pronounced effect and better tolerance due to uniform spraying and prolonged contact with the mucous membrane compared to the same enemas and suppositories, especially in those patients who due to active inflammation, they are not able to keep even minimal volumes of fluid in the rectum. If there is no response to treatment with aminosalicylates for 2-4 weeks, it is recommended to switch to local administration of hormonal agents (budesonide, hydrocortisone, etc.). In case of further ineffectiveness, a combination of topical treatment with 5-ASA or steroids with oral mesalazine or sulfasalazine is possible.

Usually, the clinical effect of local treatment develops quickly, however, in some cases, distal forms of UC are more persistent and refractory to treatment. In accordance with the provisions developed at the international workshop (1991), distal UC is considered resistant to treatment if remission is not achieved within 6-8 weeks with rectal use of aminosalicylates and corticosteroids or with a combination of topical treatment and oral mesalazine.

With the established resistance and the absence of the effect of local treatment, they resort to the systemic administration of prednisolone in medium doses - pomg / day until improvement is achieved, then again it is necessary to switch to rectal administration of 5-ASA drugs (Table 1). These recommendations are purely empirical and are not supported by controlled studies.

Ulcerative colitis and colon cancer

It is well known that UC is associated with an increased risk of colon cancer (CC). It is believed that this risk is 7-8 times higher in patients with UC than in the general population. A meta-analysis based on the results of 194 studies showed that the incidence of RTC among patients with UC ranged from 3-6/1000 per year. In Russia, the frequency of RTK in UC is, according to different authors, from 1.6 to 6.1%. In this regard, the issue of RTC prevention in this category of patients is acute. Numerous studies have shown that aminosalicylates, used as basic drugs for the treatment of UC, also have an anticarcinogenic effect. The possibility of tumor growth inhibition has already been discussed for aspirin and NSAIDs. The similarity of the structure and mechanisms of action of salicylates and aminosalicylates made it possible to assume that the latter may have anticarcinogenic effects. This was confirmed in a retrospective study in which RTK was found in 3% of UC patients who regularly took 5-ASA preparations, while in patients who did not take these drugs, cancer developed in 31% of cases. A large population-based study conducted in Sweden, which included more than 3,000 patients with UC followed up for 10 years, showed a significant reduction in the relative risk of developing RTC for patients taking aminosalicylates systematically compared with those who took drugs episodically. In particular, in patients treated with sulfasalazine, the risk was reduced to 0.38 when compared with patients of the same age and sex with the same duration and severity of the disease, but not receiving maintenance therapy. It has also been demonstrated that long-term regular use of 5-ASA reduces the risk of RTC by 75-81% compared with the control group, with mesalazine showing significantly higher efficacy than sulfasalazine. The mechanism of action of aminosalicylates on tumors is due to their ability to inhibit proliferation and enhance apoptosis of colonic epithelial cells. The use of mesalazine (salofalk) in therapeutic doses for 4 weeks in patients with UC is accompanied by a decrease in the proliferation index of epithelial cells in the colon mucosa by 2-6 times compared with baseline.

Since long-term use of sulfasalazine is limited by its side effects, mesalazine is the drug of choice not only for the prevention of relapse, but also for the prevention of RTC in UC. It should be assumed that the use of mesalazine as an anticarcinogenic drug should be longer than its use for the prevention of relapse, possibly for life. Such a prolonged intake helps to reduce the proliferative activity of the epithelium and reduces the likelihood of developing RTC in risk groups. The general recommendation is to maintain a maintenance dose of 2 g for both mesalazine and sulfasalazine, regardless of the underlying problem. At the same time, the advisability of using higher doses for maintenance therapy, almost equal to the therapeutic one (3-4 g of mesalazine), is being discussed. This is due to the fact that it is not yet known which dose has the optimal anticarcinogenic effect and is indicated for cancer prevention.

Thus, there are clinical and experimental evidence of the anticarcinogenic effect of 5-ASA preparations. However, extended clinical studies are required to determine the minimum required dose of drugs and the optimal timing of its administration.

Literature

Crohn's disease and ulcerative colitis. Moscow: Geotar-Med, 2001. Belousov's colitis and Crohn's disease. M.: Triada, 2002. Sandborn W. J. Medical management of ulcerative colitis. In: Targan S., Shanahan S., Karp L., editors. Inflammatory dowel disease-from bench to bedside. 2nd ed. London: Kluwer Academic publishers, 2002. pp. 605-630 Egan L. J., Sandborn W. J. Clinical pharmacology in inflammatory bowel disease: optimizing current medical therapy. In: Targan S., Shanahan S., Karp L., editors. Inflammatory bowel disease-from bench to bedside. 2nd ed. London: Kluwer Academic publishers, 2002. pp. 495-522. Donovitz M. Arahidinic acid metabolites and there role in inflammatory bowel disease. An update requiring addition in a pathway. Gastroenterology 1985;88:580-7. Zimmerman M., Jewel D. Cytokins and mechanism of action of glucocorticoids and aminosalicylates in the treatment of ulcerative colitis and Crohn’s disease. Aliment Pharmacol Ther 1996;10(Suppl. 2):93-8. Hanauer S. B. Review article: aminosalicylates in inflammatory bowel disease. Aliment Pharmacol Ther 2004;20(Suppl. 4):60-5. Frieri G., Pimpo M. T., Palumbo G. C., Onori L., et al. Rectal and colonic mesalazine concentration in ulcerative colitis oral vs oral plus topical treatment. Aliment Pharmacol Ther 1999;13:1413-1417. Sandborn W. J. Marion J. F. Medical management of ulcerative colitis. In: Targan S., Shanahan S., Karp L., editors. Inflammatory dowel disease-from bench to bedside. 2nd ed. London: Kluwer Academic publishers, 2002. pp. 605-629. Cohen R. D., Woseth D. M., Thisted R. A., Hanauer S. B. A meta-analysis and overview of the literature on treatment options for left-side ulcerative colitis and ulcerative proctitis. Am J Gastroenterol 2000;95:1263-76. Marshall J. K., Irvine E. J. Rectal corticosteroids versus alternative treatment in ulcerative colitis: a meta analysis. Gut 1997;40:775-81. Ardizzone S., Doldo P., Ranzi T., Sturniolo G. C., et al. Mesalasine foam (Salofalk foam) in the treatment of active distal ulcerative colitis. A comparative trial vs. Salofalk enema. The SAF-3 study group. Ital J Gastroenterol Hepatol 1999;31:677-684. Pokrotnieks J., Marlicz K., Paradowski L., Margus B., et al. Efficacy and tolerability of mesalazine foam enema (Salofalk foam) for distal ulcerative colitis: a double-blind, randomized, placebo-controlled study. Aliment Pharmacol Ther 2000;14:1191-1198. Rufle W., Fruhmorgen P., Huber W., Kimmig J. M. Budesonide foam as a new therapeutic concept in the therapy of distal ulcerative colitis in comparision to mesalazine enemas. An open, controlled, randomized and prospective multicenter pilot study. Z Gastroenterol 2000;38:287-93. Jarnerot G., Lennard-Jones J., Brynskov J. Working team report: Medical treatment of refractory distal ulcerative colitis. Gastroenterol Int 1991;4:93-8. Bernstein C. N., Blanchard J. F., Kliever E., Wajda A. Cancer risk in patients with inflammatory bowel disease: a population-based study. Cancer 2001;91:854-62. Eaden J., Abrams K., Mayberry J. F. The risk of colorectal cancer in ulcerative colitis: a meta-analysis. Gut 2001;48:526-35. Ekbom A., Helmick C., Zack M., Adami H. O. Ulcerative colitis and colorectal cancer. A population-based study. N Engl J Med 1990;323:1228-33. , Belousova colitis and colon cancer. Formation of risk groups, screening and prevention. Farmateka 2004;(13):39-44. , etc. Colon cancer in patients with nonspecific ulcerative colitis. Wedge honey 1988;(9):108-13. Hixson L. J., Alberts D. S., Krutzsch M., et al. Antiproliferative effect of nonsteroidal antiinflammatory drugs against human colon cancer cells. Cancer Epidemiol Biomarkers Prev 1994;3:433-8. Moody G. A., Jayanthi V., Probert C. S. J., Mac Kay H., Mayberry J. F. Long-term therapy with sulphasalazine protects against colorectal cancer risk and compliance with treatment in Leicestershire. Eur J Gastroenterol Hepatol 1996;8(12):1179-83. Brown W. A., Farmer K. S., Skinner S. A., et al. 5-aminosalicylic acid and olsalazine inhibit tumor growth in a rodent model of colorectal cancer. Dig Dis Sci 2000;45:1578-84. Bus P. J., Nagtegaal I. D., Verspaget H. W., Lamers C. B., et al. Mesalazine-induced apoptosis of colorectal cancer: on the verge of a new chemopreventive era? Aliment Pharmacol Ther 1999;13:1397-402. Ekbom A., Kornfeld lphasalazine use as a preventive factor for colorectal cancer in ulcerative colitis patients - a review (Clinical review). Inflammatory Bowel Disease 1996;2(4):276-8. Eaden J., Abrams K., Ekbom A., et al. Colorectal cancer in prevention of ulcerative colitis: a case-control study. Aliment Pharmacol Ther 2000;14:145-53. Reinacher–Schick A., Seidensticker F., Petrasch S., et al. Mesalazine changes apoptosis and proliferation in normal mucosa of patients with sporadic polyps of the large bowel. Endoscopy 2000;32(3):245-54. , Isakov activity of the colonic epithelium in ulcerative colitis. Materials of the scientific session of TsNIIG. M, 1998. Velayos F. S., Loftus E. V., Jess T. et al. Predictive and protective factors associated with colorectal cancer in ulcerative colitis: a case-control study. Gastroenterology 2006;130:1941-9. Munkholm P., Loftus EV., Reinacher-Schick A. et al. Prevention of colorectal cancer in inflammatory bowel disease: value of screening and 5-aminosalicylates. Digestion 2006;73:11-9. , Nikitina of colorectal cancer: molecular mechanisms of the anticarcinogenic action of aminosalicylates of non-steroidal anti-inflammatory drugs. Farmateka 2005;(14):37-43.

Table 1 Treatment of distal and left-sided ulcerative colitis

_____________________________________________________________________________________________

proctitis mesalazine suppositories 500 mg x 4 r, 4-8 weeks before

1 g x 2 r achieve remission

500 mg x 2 r, 1.5 years

1 g x 1 p n/night, anti-relapse

minimal therapy

500 mg h/day

proctosigmoiditis mesalazine enemas 2 g x 2 r, 4 g x 1 r 4-8 weeks before

hydrocortisone rectally 125 mg x2 r, achieving remission

drip or enemas 250 mg x 1 r n / night

mesalazine enemas 2 g daily or q/d 1.5 years

anti-relapse

left-sided colitis mesalazine enemas 2-4 g/day 4-8 weeks to

hydrocortisone rectally 125-250 mg achieve remission

budesonide enemas 2-4 mg n/night

mesalazine per os 2 g/day

or sulfasalazine 3-4 g/day

mesalazine per os 1.5-2 g/day anti-relapse

or sulfasalazine 2 g/day therapy

refractory prednisolone per os 40-60 mg

distal colitis +

mesalazine or until remission is achieved

steroids rectally

mesalazine enemas

or anti-relapse suppositories

_____________________________________________________________________________________________

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Rice. 2. Scheme of intercellular interactions in the lesion and points of application of drugs in IBD

T-lymphocytes, Tx1 - type 1 helpers, Tcyt - cytotoxic cells, APC - antigen-presenting cell, IF-interferon

» Drugs for ulcerative colitis - an overview

Attention: the information is not intended for self-treatment. We do not guarantee its accuracy, reliability and relevance in your case (although we strive to do so). Treatment should be prescribed by a specialist doctor.

There are no magic drugs that can completely get rid of non-specific ulcerative colitis, but the choice of drugs that can achieve a stable remission in IBD is quite wide.

Let's consider some features of drug therapy for this disease (other methods of dealing with NUC - surgical intervention, a sparing diet - are described).

What is the treatment for UC?

As noted by S.R. Abdulkhakov and R.A. Abdulkhakov in the article "NUC: modern approaches to diagnosis and treatment", there are two basic groups of drugs used in the fight against ulcerative colitis:

• 5-ASA (aminosalicylates);
• GCS (glucocorticosteroids).

Treatment of non-specific ulcerative colitis: drugs 5-ASA

Means of 5-aminosalicylic acid increase the local concentration of prostaglandins that have a cytoprotective effect (i.e., increase the protective capabilities of the intestinal mucosa).

The group includes, first of all, such well-known drugs as sulfasalazine and mesalazine.

Sulfasalazine- an old drug, it has been used for more than half a century. Its drawback is a variety of side effects, from nausea to headache. Side effects appear in about a quarter of cases. The negative effect is due to the effect of sulfapyridine, which is formed during the breakdown of the drug and does not give its own anti-inflammatory effect.

Mesalazine(preparations with 5-ASA in a purer form) - a more modern development. The list of medicines based on mesalazine includes salofalk, mesacol, pentasa, tidocol. So far, these are the best remedies for NIBD. They give relatively few side effects, they are sometimes recommended even for children, as well as for pregnant and lactating women.

The drugs of the group are produced in various dosage forms - not only in tablets, but also in rectal suppositories, in microclysters. Suppositories and microenemas are used in the treatment of UC very widely, since with this type of IBD, the distal (lower) sections of the large intestine are primarily affected.

The term of application of aminosalicylates is quite long - months, or even years. Proper and timely discontinuation of therapy can prevent recurrence of the disease.

Glucocorticosteroids for ulcerative colitis

Known corticosteroids that are prescribed for nonspecific ulcerative colitis are:

• budesonide;
• hydrocortisone;
• prednisolone and its analogues.

Glucocorticosteroids are administered orally, rectally, and intravenously.

They have anti-inflammatory, desensitizing, immunosuppressive and antitoxic effects.

Possible negative effects with long-term use of GCS drugs are increased pressure, excessive growth of terminal hair, acne. In the worst cases, the development of steroid osteoporosis and neurological pathologies is not excluded.

If UC is mild, glucocorticosteroids are optional; treatment is often limited to a course of aminosalicylates.

Other medicines

What drugs are used in the fight against ulcerative colitis in addition to GCS and 5-ASA?

With resistance to steroids (it is detected in approximately 16% of patients) or, on the contrary, steroid dependence, immunosuppressive agents - cyclosporine, azathioprine - are included in the treatment regimen.

In situations where UC is detected simultaneously with an intestinal infection, it is necessary to turn to broad-spectrum antibiotics (gentamicin, kanamycin, etc.). Antibacterial drugs are also required if there is a threat of sepsis or toxic megacolon.

J.04.A.A.01 Aminosalicylic acid