Bismuth preparations instructions for use. Analogues of bismuth tripotassium dicitrate: a review of substitutes for action and active substance. Vitridinol during pregnancy and lactation

Among preparations containing organic and inorganic bismuth compounds, there are agents (basic bismuth nitrate, dermatol, xeroform), which are traditionally used in practice as astringents, adsorbents, antiseptics and drying agents. Newer organic compounds (especially subsalicylate, bismuth subcitrate) have a number of important properties that have become the basis for their successful use in antiulcer therapy, in particular colloidal and "film-forming" properties when interacting with the proteins of the affected mucosa, as well as the ability to stimulate natural protective functions mucous and resist Helicobacter pylori.

Pharmacodynamic properties of bismuth preparations

Note. Bismuth subnitrate is part of the complex preparations vikalin, vikair, and also in combination with bismuth subgallate - in bismofalk.

Basic bismuth nitrate has been used for many years in gastroduodenal ulcers, usually in combined preparations(vikalin, vikair). However, a more specific antiulcer effect is currently attributed to bismuth colloid preparations.

Colloidal bismuth compounds and their preparations are complex salts of bismuth with citrate, salicylic or gallic acids. Bismuth subcitrate is soluble in water, but forms a precipitate (bismuth and oxychloride and citrate) at pH less than 5. The optimum pH value for the formation of precipitate in gastric juice is 3.5. In pharmacodynamics, colloidal bismuth compounds play a role in the following main mechanisms of action:

1. Colloidal bismuth compounds form a glycoprotein-bismuth complex in an acidic environment with proteins of the gastric mucosa. main feature This complex consists in the fact that it settles only in small quantities on the normal mucosa, concentrating mainly in the area of ​​eroded and ulcerated areas. As a result, a kind of protective barrier is formed that prevents the reverse diffusion of H + and promotes the fastest healing. Colloidal compounds of bismuth (subcitrate, as well as subsalicylate, subgallate) possess this property to the greatest extent.

Colloidal bismuth compounds have a relatively weak effect on the aggressive factors of ulcerogenesis. So, basal and stimulated acid production does not change significantly, there is practically no interaction with bile salts, but the peptic activity of the juice decreases by an average of 20-30%.

2. Colloidal bismuth compounds have their own gastroprotective effect, which is revealed in the experiment, for example, the ability to prevent mucosal damage caused by chemical irritants (ethanol, acetic acid, etc.). Apparently, this effect depends on the prostaglandin mechanism, since the blockade of the synthesis of these autocoids eliminates the protective effect of colloidal bismuth compounds. It was found that under the influence of colloidal bismuth compounds, local synthesis of prostaglandin E2 is enhanced (by 50% on average) in the antral mucosa and duodenum, and alkaline secretion associated with the action of prostaglandins increases. It is noted that morphologically, the mucosa after healing of an ulcer during therapy with colloidal bismuth compounds is closer to the normal microstructure than during treatment with other means.

3. Colloidal bismuth compounds are able to exert a bactericidal effect on Helicobacter pylori, which is considered as an important pathogenic factor in ulcer formation.

H. pylori is a gram-negative spiral bacterium that lives in the epithelium and mucous layer of the stomach. The microorganism has a high urease activity, which allows it to function in an acidic environment, and also provides the ability to damage intercellular epithelial contacts. It is believed that antral gastritis (type B) is associated with H. pylori. In duodenal ulcers, due to acidification of the medium, metaplasia of the gastric epithelium occurs with infection with H. pylori and subsequent duodenitis. Thus, the pathogen plays the role of a permissive (triggering) factor of ulcerogenesis.

There is evidence that under the influence of colloidal bismuth compounds, the disappearance of H.pylon on the preparations of the gastric mucosa is observed within 30-90 minutes. Against the background of the action of colloidal bismuth compounds, vacuolization occurs, fragmentation of the pathogen cell wall, condensation of cellular contents, and the ability of the bacterium to bind to the epithelium is impaired. . After a 3-week course of therapy with colloidal bismuth compounds, the mucosa is freed from H. pylori, but monotherapy does not lead to a long-term trace effect: after drug withdrawal, rapid recolonization occurs. For this reason, the combination of bismuth preparations with chemotherapeutic agents, in particular antibiotics (ampicillin, erythromycin), nitrofuran derivatives and metronidazole, is considered more rational. Effective and persistent decolonization of H. pylori leads to a 3-5-fold decrease in the frequency of relapses at a one-year follow-up period. (This aspect of pharmacodynamics will be discussed in more detail in the "Anti-Helicobacter Therapy" section.)

A feature of the pharmacokinetics of preparations of colloidal bismuth compounds is their low bioavailability. With course treatment, stationary plasma concentration is reached after about 1 month and does not exceed 50 μg / l (at standard dosages, it is usually 5-8 μg / l). At the same time, the concentration in gastric juice reaches 100 mg / l. The absorbed part of the substance is concentrated mainly in the kidneys. The absorbed fraction of colloidal bismuth compounds is excreted in the urine. Stationary concentration in the urine is established on average after 2 weeks of course treatment and varies over a wide range (17-170 mcg / l). The unabsorbed part of the colloidal bismuth compounds is excreted in the feces in the form of sulfide. The drug is excreted from the body rather slowly (the half-life of bismuth during intoxication is 4-5 days). It is believed that approximately 8 weeks after the completion of the course of therapy with colloidal bismuth compounds is required for its complete removal from the body. Therefore, a second course cannot be started earlier than the specified period.

The main indications for the use of colloidal bismuth compounds are gastroduodenal ulcers, as well as chronic antral gastritis and non-ulcerative dyspepsia, in the pathogenesis of which H. pylori colonization is believed to play an important role. Bismuth subsalicylate is also recommended as an effective antidiarrheal agent.

Colloidal bismuth compounds are available as tablets (chewable or coated), solutions, gels and suspensions. Since for the manifestation of a specific pharmacological action preparations of colloidal bismuth compounds require an acidic environment in the stomach, a certain time regimen for their administration is necessary. In addition, it should be noted that antacids or milk should not be taken within 30 minutes before and after taking colloidal bismuth compounds. Recommend the following options for taking a daily (480 mg) dose of drugs (using bismuth subcitrate as an example): 1) 120 mg 3 times 30 minutes before meals and 1 time (120 mg tablet) 2 hours after dinner or at night; 2) 2 times a day, 240 mg 30 minutes before breakfast and before dinner or 2 hours after eating.

Preparations of colloidal bismuth compounds are well tolerated, because they have a predominantly local effect. Due to the formation of bismuth sulfide in the intestine, the stool may darken; the tongue may also darken. Occasionally noted headache, dizziness, diarrhea. The resorptive effects of bismuth are possible with long-term treatment in high doses. Characteristic bismuth encephalopathies (threshold toxic concentration in plasma -100 μg/l) are described. At kidney failure risk of unwanted side effects increases. not excluded and drug interactions. So, when taken simultaneously with tetracycline, iron and calcium preparations, colloidal bismuth compounds can worsen their absorption. There is a possibility of chelation with antacids. Bismuth subsalicylate should be used with caution in patients receiving anticoagulants, anti-gout agents, and oral antidiabetic drugs.

pharmachologic effect

Indications for use

Mode of application

Side effects

Contraindications

Release form

Storage conditions

Active substance:

The authors

Links

• The official instructions for the drug Bismuth subcitrate.
• Modern medications: a complete practical guide. Moscow, 2000. S. A. Kryzhanovsky, M. B. Vititnova.

Dosage form

Composition

Description

Pharmacotherapeutic group

The code

ATX

Pharmacological properties

Pharmacodynamics

Pharmacokinetics

Side effect

Overdose

Overdose

Interaction with other drugs

special instructions

Release form

Storage conditions

Best before date

Terms of dispensing from pharmacies

Structural formula

Russian name

Latin name for Bismuth tripotassium dicitrate

chemical name

Bismuth (III) potassium 2-hydroxy-1,2,3-propane tricarboxylate (salt 1:3:2)

Gross formula

Pharmacological group of substance Bismuth tripotassium dicitrate

Nosological classification (ICD-10)

CAS code

Pharmacology

At pH 4 and below (gastric juice), insoluble oxychloride and bismuth citrate precipitate, chelate compounds with a protein substrate are formed; they cover the ulcer surface, protect it (this polymer glycoprotein complex is more effective than normally excreted mucus) from the effects of acid, pepsin and bile. Coagulates proteins and causes death Helicobacter pylori. When administered orally, it is practically not absorbed and is excreted in the faeces. Only a small amount of bismuth is cleaved from the colloidal complex, enters the bloodstream, and then is excreted in the urine. It promotes the healing of peptic ulcers, restores the protective function and preserves the integrity of the barrier of the gastric mucosa, reduces the frequency of recurrence of duodenal ulcers. Stimulates the synthesis of PGE 2, which increases the formation of mucus and bicarbonate secretion, improves the quantitative and qualitative characteristics of gastric mucus and mucin production. Leads to the accumulation of epidermal growth factor in the area of ​​the defect. Reduces the activity of pepsin and pepsinogen. Covers the ulcerative surface with a white foamy coating that persists for several hours; in patients who took the drug 3 hours before surgery, a thin white layer is present only on the ulcer craters. With monotherapy Helicobacter pylori disappears in 30% of cases, when combined with metronidazole or amoxicillin - in 90%. With prolonged use of high doses, especially in patients with impaired renal function, reversible encephalopathy may develop.

Application of the substance Bismuth tripotassium dicitrate

Peptic ulcer of the stomach and duodenum in the acute phase, incl. associated with Helicobacter pylori; chronic gastritis and gastroduodenitis in the acute phase, incl. associated with Helicobacter pylori; irritable bowel syndrome, which occurs mainly with symptoms of diarrhea; functional dyspepsia, unrelated to organic diseases GI tract.

Contraindications

Hypersensitivity, pronounced impaired renal function, pregnancy, breastfeeding period.

Use during pregnancy and lactation

Contraindicated in pregnancy.

Stop during treatment breast-feeding.

Side effects of the substance Bismuth tripotassium dicitrate

From the digestive tract: nausea, vomiting, frequent stools, constipation.

Allergic reactions: skin rash, itching.

Others: with prolonged use in high doses - encephalopathy associated with the accumulation of bismuth in the central nervous system.

Interaction

Reduces the absorption of tetracycline. Preparations containing bismuth (including Vikalin, Vikair) increase the risk of systemic side effects (the concentration of bismuth in the blood increases).

Overdose

Symptoms: with frequent use of large doses, the development of renal failure is possible.

Treatment: gastric lavage, appointment activated carbon and saline laxatives, symptomatic therapy. Patients with impaired renal function, accompanied by a high level of bismuth in plasma, are administered complexing agents containing SH groups - dimercaptosuccinic and dimercaptopropanesulfonic acids. In case of severe renal failure, hemodialysis is performed.

Routes of administration

inside.

Substance precautions Bismuth tripotassium dicitrate

Long-term use of high doses is not recommended. Within 30 minutes before and after taking it is necessary to refrain from drinks (including milk, fruits and fruit juices), solid food, antacids. During therapy, you should not drink alcohol.

special instructions

Colors feces black.

Interactions with other active substances

Trade names