Medicines used for gastrointestinal diseases

The mucous membrane of the gastrointestinal tract is constantly exposed to a variety of drugs that not only treat, but also damage the mucous membrane and disrupt the digestion of food in it. The topic of this article is drug-induced lesions of the stomach - those lesions caused by pharmacological agents, and the possible protection of the mucous membrane from damaging factors.

The most common mucosal lesions are associated with the use of non-steroidal anti-inflammatory drugs (NSAIDs), which are the most popular in the treatment of various cardiovascular diseases and musculoskeletal disorders, for the treatment of pain and inflammation.

The unique combination of analgesic, anti-inflammatory and antipyretic effects, ease of use and accessibility have determined the exceptional popularity of these drugs.

Their use is increasing due to the aging population, the peculiarities of human lifestyle in modern society - nutrition, low physical activity, prolonged work at the computer and the growth of various cardiovascular, inflammatory and dystrophic diseases of the musculoskeletal system, accompanied by acute and chronic pain. But, despite the frequency of use, NSAIDs are not safe drugs.

About 70% of people over 60 years of age take NSAIDs at least once a week. In 30% of patients suffering from coronary heart disease and taking acetylsalicylic acid (aspirin), gastric damage is detected. Taking small “cardiac” doses of aspirin increases the risk of gastrointestinal bleeding by 1.5 times and can lead to the formation of ulcers. In clinical practice, there are manifestations of side effects of aspirin in Russia: every third patient has dyspeptic complaints (gastropathy), gastric ulcers - in 9%, gastrointestinal bleeding in 1.5% of patients. It is believed that there is no dose of aspirin that would prevent blood clots in blood vessels and would not be toxic to the stomach.

According to the Scientific Center for Cardiovascular Surgery, 30% of patients suffering from coronary heart disease have gastric damage, of which gastric erosions in 76% and ulcers in 23% of cases. According to the Research Institute of Rheumatology, erosions and ulcers are detected in 33% of cases, with single erosions in 11%, multiple erosions in 6%, ulcers in 15% of cases.

Mechanism of action of NSAIDs

Since the advent of the first synthetic NSAIDs at the end of the 19th century, the most important problem limiting the use of these drugs has been the risk of developing damage to the gastrointestinal tract. The development of these complications is well known and is associated with the underlying mechanism of action of NSAIDs.

The main pharmacological “target” of NSAID action is the COX-2 enzyme, which is actively formed in the area of ​​organ tissue damage and increases the concentration of prostaglandins, which determine pain and inflammation. The use of NSAIDs leads to a decrease in the production of prostaglandins in the patient’s body and the occurrence of three positive effects - antipyretic, anti-inflammatory, analgesic, and aspirin, by reducing the concentration of thromboxane in platelets, in addition to the listed effects, has a pronounced antiplatelet (anti-clotting) effect.

However, in the human body there is another enzyme that is very similar to COX-2, but has a completely different purpose - COX-1. This enzyme is constantly working. And although it also forms prostaglandins, the physiological effect is completely different. In the absence of damage, prostaglandins are important regulators of body functions, “tissue hormones”, responsible, in particular, for maintaining the resistance of the gastrointestinal mucosa to the damaging effects of external aggressive factors.

Unfortunately, NSAIDs do not distinguish between these enzymes and block both. Thus, while providing an analgesic and anti-inflammatory effect, these drugs reduce the protection of the mucous membrane.

A decrease in prostaglandins (COX-1) negatively affects the gastric mucosa, leading to decreased blood flow, decreased production of protective mucus and alkalizing substances (bicarbonates), increased secretion of hydrochloric acid and enzymes, and changes in motility of the gastroduodenal zone (stomach and duodenum).

Drug-induced lesions of the stomach and duodenum

First, a little physiology. It should be recalled that in the stomach and duodenum there is a balance between “aggressive” and “protective” factors, called “neck scales”. In healthy individuals, protective factors always prevail over aggressive, damaging factors, which ensures the preservation of the structure of the mucous membranes of the gastrointestinal tract under changing environmental conditions under the influence of external and internal factors.

The following are the aggressive factors:

• hydrochloric acid of the stomach,
• pepsin enzyme,
• increased acid formation,
• rapid evacuation of acidic contents into the duodenum, accompanied by an “acid attack” on the mucous membrane of the small intestine,
• reflux of acid or bile into the esophagus, stomach,
• medications.

In the 60s of the last century, the concept of “protective mucus barrier of the stomach” was introduced - the first line of defense against aggressive factors. Protective factors include:

• slime,
• secretion of alkaline bicarbonate,
• epithelial cell membrane,
• state of blood flow (microcirculation),
• metabolic processes,
• synthesis of prostaglandins and nitric oxide.

Action of protective factors

Mucus is a barrier that protects the underlying mucosal cells. The impermeable membrane of epithelial cells that covers the stomach prevents acidic gastric juice from flowing back out of the stomach lumen.

The next line of defense for the mucosa is created by the microvasculature of the blood, which provides the epithelial cells of the gastrointestinal mucosa with water, oxygen, and nutrients.

Trophic processes in the mucosa determine the intensity of restoration (reparative) processes in the mucous membrane of the gastrointestinal tract.

Next are prostaglandins, which stimulate and promote the function of almost all protective mechanisms of the gastric and intestinal mucosa.

Let us dwell in more detail on the role of prostaglandins and nitric oxide, which are among the main factors of protection of the mucous membrane of the gastrointestinal tract exposed to various damaging drugs. The continuous formation of prostaglandins by the cells of the gastric mucosa is a necessary condition for ensuring the integrity and protection of the mucosa against damaging factors.

Prostaglandins are biological substances that improve blood flow in the mucous membrane and regulate gastrointestinal motility, reducing the secretion of gastric juice in the stomach, but stimulating the secretion of enzymes in the pancreas. PGs increase the formation of protective mucus and the secretion of bicarbonates, ensuring the resistance of mucosal cells to damaging factors, and reduce the release of inflammatory factors.

Nitric oxide (NO) is the second important component of protecting the gastrointestinal mucosa from damage by increasing mucus production, alkaline bicarbonate secretion, and blood flow.

Thus, PG and NO play a critical role in maintaining the integrity of the mucosa and jointly participate in its protection from various damaging factors (non-steroidal anti-inflammatory drugs (NSAIDs), aspirin, paracetamol, bile acids, oral antibiotics, potassium and iron preparations, theophylline, digitalis preparations , alcohol).

Toxic effect of NSAIDs

There is also a local toxic effect of NSAIDs during the very first days of taking the drug. Most NSAIDs are weak acids and can have a direct irritant effect on the mucous membrane of the stomach and duodenum. Under the influence of NSAIDs, the sensitivity of the mucous membrane decreases, the drug penetrates through the membrane into the cells of the mucous membrane, accumulates there and causes its damage, the sensitivity of pain receptors decreases and pain and dyspeptic syndromes occur. Taking NSAIDs after meals with plenty of water, especially when using capsule forms, significantly reduces the likelihood of contact irritation from these medications.

Studies have shown that in almost 100% of cases, taking NSAIDs leads to the development of acute gastritis a week after the start of treatment, and regular use of NSAIDs is associated with the occurrence of erosive and ulcerative lesions of the gastrointestinal tract (GIT) mucosa. The leader among the digestive organs is the stomach, damage to which occurs 6 times more often than damage to other organs.

Medicines used for gastrointestinal diseases

Medicines used for diseases of the gastrointestinal tract

• Antibiotics in Helicobacter pylori
• Antibiotics used to treat diarrhea
• Other antimicrobial agents

• Materials for doctors
• Video for medical university students
• Patient Materials

Antacids

Antacids are medications whose mechanism of action is based on the chemical neutralization of gastric acid.
Most modern antacid medications use a balanced combination of magnesium and aluminum compounds. Such antacid drugs are characterized by a slower onset of therapeutic effect compared to sodium and calcium compounds, but they have a longer effect time. They do not dissolve in water, are practically not absorbed into the blood, are characterized by antipeptic properties and partially adsorb toxins. Antacids are divided into absorbable and non-absorbable. Absorbed antacids are those that either themselves or the products of their reaction with gastric acid dissolve in the blood. A positive quality of absorbed antacids is the rapid decrease in acidity after taking the medicine. Negative - short duration of action, possible acid rebound (increased secretion of hydrochloric acid after the end of the drug), the formation of carbon dioxide during their reaction with hydrochloric acid, stretching the stomach and stimulating gastroesophageal reflux. Examples of antacids:

• absorbable antacids:
• sodium bicarbonate (baking soda)
• Rennie

• aluminum phosphate: Phosphalugel
• aluminum-magnesium combinations: Almagel, Gastratsid, Maalox
• aluminum-magnesium combination with the addition of benzocaine: Almagel A
• aluminum-magnesium preparations with the addition of simethicone (to prevent flatulence): Almagel Neo, Antareit, Relzer

For more information, see the article “Antacids.”

Alginates

When alginate salts enter the stomach, they react with its acidic contents, resulting in the formation of an alginate gel that has an almost neutral acidity value (gel pH is about 7).
The gel forms a protective barrier on the surface of the stomach contents, preventing the occurrence of gastroesophageal reflux. In case of regurgitation or reflux, the gel enters the esophagus, where it has a neutralizing effect on hydrochloric acid and pepsin that enter during reflux and additionally protects the mucous membrane of the esophagus. Drugs of this class form an alginate “barrier-raft” in the stomach, preventing gastric acid from entering the esophagus. The main components of alginates are not absorbed into the systemic circulation. The only alginate Gaviscon is registered in Russia (variants: Gaviscon, Gaviscon Forte and Gaviscon Double Action), which in its composition is an antacid drug with the addition of sodium alginate. For more information, see the Gaviscon article.

Antisecretory drugs

Antisecretory antiulcer drugs are used to reduce the production of hydrochloric acid by the parietal cells of the stomach through various effects on the cell, blocking the activation of secretion or the mechanism of acid secretion itself. In practical medicine, two groups of antisecretory drugs are used: H2-blockers of histimine receptors and proton pump inhibitors (see below).

pH-gram, effect of antisecretory drug (Storonova O.A., Trukhmanov A.S.)

H2-blockers of histamine receptors

The mechanism of action of H2-blockers of histamine receptors is based on blocking H2-receptors (also called histamine) of the parietal cells of the gastric mucosa and, for this reason, reducing the secretion and flow of hydrochloric acid into the lumen of the stomach.
They are historically the first antisecretory drugs and, compared to proton pump inhibitors, are less effective. Examples of H2 blockers: Tagamet and Histodil (active ingredient cimetidine), Zantac and Ranisan (ranitidine), Kvamatel, Kvamatel mini and Ulfamid (famotidine). For more information, see the article “H2-blockers of histamine receptors.”

Proton pump inhibitors

Proton pump inhibitors inhibit the secretion of hydrochloric acid by blocking the proton pump (H+/K+-ATPase) of the parietal cells of the gastric mucosa. They are the most effective drugs in the treatment of ulcerative lesions of the stomach, duodenum (including those associated with Helicobacter pylori
) and esophagus, reducing acidity and, as a consequence, aggressiveness of gastric juice. Examples of proton pump inhibitors:

• Gastrozol, Zerotsid, Losek, Losek MAPS, Omez, Omeprazole-AKOS, Omeprazole-acri, Omeprazole Sandoz, Omeprazole-Teva, Omitox, Ortanol, Romesec, Ultop, Helitsid, Helol, Cisagast (active ingredient omeprazole)
• Zypantola, Controloc, Nolpaza, Panum, Sanpraz (pantoprazole)
• Helicol, Lanzap, Lanzoptol, Lancid, Epicur (lansoprazole)
• Bereta, Zulbex, Noflux, Pariet, Rabiet, Razo, Rabeloc, Khairabezol (rabeprazole)
• Nexium, Neo-Zext, Emanera (esomeprazole)
• Dexilant (dexlansoprazole)

For more information, see the article “Proton pump inhibitors.”

Prokinetics

Prokinetics - drugs that stimulate gastrointestinal motility:
domperidone

Notes
*) Tegaserod and prucalopride, which are enterokinetics (prokinetics that selectively act on the intestines), were moved in ATC from section “A03 Drugs for the treatment of functional gastrointestinal disorders” to section “A06 Laxatives”. **) Sulpiride and levosulpiride are antipsychotics, substituted by benzamides, with pronounced prokinetic properties. According to ATC, they belong to the group “N05A Antipsychotic drugs”. For more information, see the article “Prokinetics”.

Antispasmodics

Antispasmodics are medications that reduce smooth muscle spasms. Antispasmodics are the first choice drugs for the treatment of mild to moderate abdominal pain. In gastroenterology, antispasmodics are used in the pharmacological treatment of patients with functional dyspepsia, patients with mild irritable bowel syndrome, biliary dyskinesias, as well as in the treatment of exacerbation of peptic ulcer before prescribing Helicobacter pylori
, exacerbation of cholelithiasis before cholecystectomy, etc. Examples of drugs with antispasmodic action used in gastroenterology are: papaverine, No-shpa (drotaverine), Duspatalin and Niaspam (mebeverine), Neobutin, Neobutin Retard, Trimedat, Trimedat Valenta and Trimedat Forte (trimebutine), Dicetel (pinaverium), Spasmomen (otilonium bromide ), nifedipine. A selective antispasmodic that acts exclusively on the sphincter of Oddi and bile ducts - Odeston (gymecromone). Antispasmodic for children of infancy and older - Plantex. Complex drug Meteospasmil (myotropic antispasmodic alverine + defoamer simethicone). Herbal medicine Iberogast.

The zones of distribution and severity of the antispasmodic effect are indicated in the table below (Minushkin O.N. et al.):

For more details, see the article “Anspasmodics (in gastroenterology).”

Enzyme digestive drugs

Digestive enzyme preparations are medicines that help improve the digestion process and include digestive enzymes. Examples of enzyme preparations:

• Creon, Mezim forte, Panzinorm, Gastenorm forte, Pangrol, Pancitrate, Penzital (active ingredient pancreatin)
• Festal (combined active ingredient hemicellulase + bile components + pancreatin)

For more details, see the article “Enzyme preparations”.

Laxatives

Laxatives are medications that make bowel movements easier and are used to treat constipation. There are no clear criteria for choosing any type of laxative. The following classes of laxatives are distinguished:

• Osmotic laxatives. By binding water in chyme, osmotic laxatives increase the weight of stool, soften the consistency and accelerate the movement of chyme through the colon. Examples: Duphalac, Normaze (active ingredient lactulose), Exportal (lactitol), Lavacol, Forlax, Fortrans (macrogol), Flit Phosphosoda, Sorbitol, Mannitol.
• Laxatives, which increase the volume of stool and dilute the contents of the intestines by releasing water. The increase in intraluminal pressure caused by an increase in the volume of fecal matter stimulates motility and accelerates the movement of chyme through the intestines. These laxatives include dietary fiber, in particular Metamucil (the active ingredient isphagul), Citrucel (methylcellulose).
• Soft laxatives (plasticizers) soften stool and prevent dehydration. Plasticizers are often recommended after childbirth or surgery, or in patients who should avoid straining during bowel movements. Examples of emollient laxatives are glycerol (glycerin), almond oil
• Contact laxatives that stimulate intestinal receptors upon contact with them and thereby enhance peristalsis. Examples: Bisacodyl, Castor oil and the very widely used in the past, but now prohibited Purgen (phenolphthalein) and cascara (buckthorn bark), excluded from the category of medicines.
• Secretogens, guanylate cyclase-C receptor agonists: linaclotide, plecanatide.
• Disposable enemas: Enema Klin (sodium phosphates), Microlax (sodium citrate + sodium lauryl sulfoacetate + sorbitol).
• Peripheral opioid receptor antagonists (for the treatment of opioid constipation): naloxegol, naloxone, naldemedine.

For more information, see the articles “Laxatives” and “Preparation of the colon for instrumental studies.”

Antimicrobial agents (antibiotics)

Antimicrobial agents (or antibiotics in the broad, non-classical sense of the term) are used for various diseases and conditions of the gastrointestinal tract. They are used, in particular, in the treatment of infectious diseases and diarrhea. Antibiotics are necessary components of regimens used for the eradication of Helicobacter pylori
, etc.

Antibiotics in Helicobacter pylori eradication regimens

The composition of eradication regimens, recommended antimicrobial agents, dosages and duration of therapy, see Standards for the diagnosis and treatment of acid-dependent and Helicobacter pylori-associated diseases (4th Moscow Agreement). Examples of antimicrobial drugs included in Helicobacter pylori
:

• macrolides: clarithromycin (trade names Klacid, Fromilid, Ecositrin), azithromycin (Sumamed), josamycin (Vilprafen), roxithromycin (Rulid)
• nitroimidazole derivatives: metronidazole (Trichopol, Flagyl), tinidazole
• semisynthetic penicillins: amoxicillin (Flemoxin Solutab, Hiconcil)
• nitrofuran derivatives: furazolidone, nifuratel (Macmiror), nifuroxazide (Ersefuril)
• fluoroquinolones: levofloxacin (Tavanic), ciprofloxacin, moxifloxacin
• semisynthetic derivatives of rifamycin: rifaximin (Alfa Normix), rifabutin
• tetracycline

Helicobacter pylori
eradication schemes, bismuth preparations are also used as an antimicrobial agent; in Russia, this is bismuth tripotassium dicitrate (De-Nol, Novobismol and others).

Antibiotics used to treat diarrhea

In the absence of access to medical care (for example, on a tourist trip), if the stool becomes very frequent, very loose or contains blood and continues for more than three days, WHO recommends a three-day course of ciprofloxacin. The use of other broad-spectrum antibacterial agents, for example, norfloxacin, is allowed. Strictly depending on the infectious agent, furazolidone, rifaximin and other antibiotics can be used.

Other antimicrobial agents

Mesalazine is used, in particular, as an intestinal anti-inflammatory and antimicrobial drug.
Vancomycin is prescribed for enterocolitis caused by Clostridium difficile.

Probiotics

Probiotics are bacteria or other microorganisms that are non-pathogenic for humans (or animals) and have antagonistic activity against pathogenic and conditionally pathogenic microorganisms and ensure the restoration of normal human microflora or perform other functions useful for humans (or animals).
Most often, certain strains of lactobacilli and bifidobacteria are used as probiotics, which are included in various foods, medications and nutritional supplements. Probiotic medications include: Acylact, Acipol, Bifiform, Bifidumbacterin, Lactobacterin, Linex, Enterol and others.

For more information, see the article “Probiotics.”

Oral rehydration salts

Oral rehydration salts are medications intended to replace the loss of fluid and electrolytes in the body during profuse diarrhea, repeated vomiting, exudation from extensive wounds and burns, discharge through drains and fistulas, and frequent use of laxatives.
Rehydration salts, in addition, are involved in the correction of the acid-base environment in the patient’s body. WHO and UNICEF recommend oral rehydration salts based on glucose, sodium and potassium chloride and sodium citrate with an osmolarity of 245 mOsm/L. Examples of oral rehydration salts: Hydrovit, Hydrovit forte, Regidron. For more information, see the article “Oral rehydration salts.”

Enterosorbents

Enterosorbents are medications taken orally that absorb and bind toxic substances and metabolites during the passage of the gastrointestinal tract.
The enterosorption method is based on the binding and removal of various microorganisms, toxins, antigens, chemicals, etc. from the digestive tract. Enterosorbents include: activated carbon, dioctahedral smectite (Smecta), Enterosgel, Polyphepan and others. Also considered enterosorbents are bile acid sequestrants (cholestyramine, etc.) - ion exchange resins that bind bile acids and cholesterol in the intestine. Currently, they are not approved for use in Russia.

Carminatives and defoamers

Carminative and antifoaming drugs are intended to reduce gas formation in the gastrointestinal tract and promote the absorption of gases by the intestinal walls.
The most common medications in this class are simethicone preparations (Espumizan, Bobotik and others), as well as fennel preparations, in particular, Plantex, intended for use in children, including very young children.

Ursodeoxycholic acid preparations

Preparations containing urosdeoxycholic (another spelling “ursodeoxycholic”) acid are intended to replace bile acids that are more toxic to humans in the pool of bile acids circulating in the body with a less toxic one - urosdeoxycholic.
They are used to dissolve cholesterol gallstones, reflux gastritis, bile reflux esophagitis, biliary cirrhosis, alcoholic liver disease, chronic hepatitis and others. Examples of ursodeoxycholic acid drugs are: Grinterol, Livodexa, Ursodez, Ursosan, Ursofalk. For more information, see the article “Urosdeoxycholic acid”.

Antiemetic drugs

Antiemetic effects are exerted by drugs that affect various parts of nervous regulation; drugs differ in their mechanism of action, in particular:

• blocking serotonin receptors (ondansetron, tropisetron and others)
• blocking dopamine receptors (domperidone, metoclopramide, sulpiride and others)
• blocking dopamine and cholinergic receptors

Anthelmintic and antiprotozoal agents

Listed here is a small portion of the drugs used in the treatment of infestations caused by parasitic worms and protozoa:

• for the treatment of nematodes caused by geohelminths: human roundworm, whipworm, hookworm, intestinal eel and others: albendazole and mebendazole (see article “Helminthic infections transmitted through soil”)
• for pinworm infection: pyrantel, albendazole and mebendazole
• for the treatment of trematoses caused by: opisthorchiasis, Chinese fluke, liver fluke, paragonimus and others: praziquantel and triclabendazole (see article “Trematode infections of food origin”)

Antidepressants, nootropics, sedatives

• tricyclic antidepressants: imipramine, amitriptyline (in small doses)
• selective serotonin reuptake inhibitor: sertraline
• nootropic: piracetam
• mild sedative: validol

Drugs not included in other sections

Broad-spectrum intestinal antiseptic, antiprotozoal drug Intetrix.
A preparation made from polysaccharides of potato sprouts, used for the treatment of gastric and duodenal ulcers during exacerbation - Ultsep.

Vitamin and mineral complexes: Bio-Max, Complivit, Selmevit.

Alfazox is a non-drug esophagoprotector.

For further reading and viewing. Resources for healthcare professionals and patients

Materials for doctors

For healthcare professionals, we recommend the subsection “Medicines, dietary supplements, mineral waters” available on the website GastroScan.ru in the “Literature” section, which also contains publications on the treatment of diseases of the gastrointestinal tract with various medications.

Video for medical university students

Lecture for 3rd year students of the Faculty of Medicine of PSPbSMU named after. acad. I.P. Pavlova Melnikov K.N. Drugs affecting the gastrointestinal tract (video)

On the website in the “Video” section there are subsections “For doctors” and “For medical students and residents”, containing video recordings of reports, lectures, webinars in various areas of gastroenterology for healthcare professionals and medical students.

Patient Materials

We recommend the article: V.V.
Vasilenko. Medicines and the digestive tract. In addition, the GastroScan.ru website contains materials for patients on various aspects of gastroenterology:

• “Advice from doctors” in the “Patients” section of the site
• “Popular gastroenterology” in the “Literature” section
• “Popular gastroenterology” in the “Video” section

All medications have contraindications, side effects and application features; consultation with a specialist is necessary.

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Risk factors for drug-induced gastrointestinal tract injuries

1. A history of peptic ulcer in the family or in the patient, increased gastric secretion of the stomach.
2. Age over 65 years, more often female, which may be associated with increased, but not always justified, use of NSAIDs for headaches.
3. The combined use of NSAIDs and drugs acting on the blood coagulation system (anticoagulants) or NSAIDs and hormonal drugs (glucocorticoids).
4. High doses of NSAIDs or a combination of several NSAIDs, including low doses of aspirin and duration of use, are at high risk in the first week and month of taking the drug,
5. Helicobacter pylori infection. Today it is believed that Helicobacter and NSAIDs are independent, but significantly mutually reinforcing risk factors for ulcer formation. Before taking NSAIDs, it is necessary to exclude helicobacteriosis of the stomach. The presence of Helicobacter pylori infection increases the risk of damage to the gastric mucosa by 1.5 times. The use of NSAIDs and aspirin increases the risk of ulcers in the stomach and duodenum in individuals infected with H. pylori, increases the risk of developing ulcer bleeding and increases it by more than 6 times.
6. Combination of diseases of the cardiovascular system and rheumatic diseases.
7. The incidence of severe gastric complications is especially high, reaching 9%, within 6 months of taking the drug in patients with several risk factors.
8. Since the risk of gastrointestinal bleeding is directly proportional to the dose of the drug, minimally sufficient doses of aspirin are used to prevent cardiovascular complications. It has been established that taking even 10 mg/day for a long time can cause the formation of ulcers in the stomach. It is believed that there is no dose of aspirin that would have an antithrombotic effect and would not be toxic to the gastric mucosa. According to a survey of patients taking aspirin, in Russia bleeding developed in 1.5% of cases, the formation of ulcers in 9%, and approximately every third patient had dyspeptic complaints.

Drug and food interactions

Pharmacotherapy is the most important and integral method of treating most acute and chronic diseases in people of all ages. Medicines, entering the internal environment of the body, primarily the gastrointestinal tract, undergo a natural transformation through contact with the biological fluids of the stomach and intestines, preparing for the processes of their absorption by the mucous membrane. Human food, to a certain extent, influences all the designated mechanisms for preparing drugs for absorption, and, of course, the absorption itself. Moreover, various components of the diet can influence the pharmacological properties of drugs in multiple ways, especially their pharmacodynamics and pharmacokinetics. The most difficult situation arises in cases of complex pharmacotherapy, which requires the simultaneous use of a number of drugs of the most diverse chemical composition to solve the most important problems of treating a specific disease. A particularly difficult task to solve, requiring to predetermine the characteristics of the interaction of drugs and food, is faced by the attending physician and nutritionist in geriatric practice.

Every year in old age, and especially in old age, the number of diseases associated with previous chronic diseases, as well as those caused by the aging process, is progressively increasing. Most older people are forced to take a lot of medications prescribed by doctors, but also often the desire for good health pushes them onto the path of self-medication, forcing them to purchase the medications they think they need from open pharmacies.

A natural feature observed in the process of managing and counseling patients both in outpatient and inpatient clinical practice is polypharmacy. The attending physician, as a rule, a therapist or a representative of a narrower therapeutic specialty (cardiologist, pulmonologist, nephrologist, endocrinologist, etc.), often prescribes the necessary pharmacotherapy program to the patient, but taking into account the presence of concomitant diseases, often pathogenetically little related to each other, and is forced to increase basic and symptomatic drugs in proportion to the number of identified diseases. Consultants are specialists in related and so-called narrow clinical profiles (ophthalmologist, gynecologist, allergist, neurologist, orthopedist, etc.), of course, if necessary, make their pharmacological contribution to the complex of treatment programs, usually showing little interest in the quantity and pharmacological essence of medications drugs already being treated.

Significant factor

The interaction of drugs and food is a very important factor influencing the complex treatment of patients of all age categories. In addition, medications may affect food intake by suppressing appetite, changing the sense of taste or smell, reducing salivation, irritating the stomach, or causing nausea. Both the diseases themselves and the medications taken to treat them can limit food choices and affect good nutrition.

Some medications directly contribute to nutritional deficiencies. For example, nonsteroidal anti-inflammatory drugs (NSAIDs) taken long-term by rheumatology patients can cause bleeding in the gastrointestinal tract, leading to iron deficiency. NSAIDs also, according to some authors, increase the amount of folic acid that is excreted in the urine.

Systematic and long-term use of a number of antacid drugs (Almagel, Gaviscon, Maalox, Talcid, Rennie, etc.) can also negatively affect the absorption of folic acid and calcium. Some laxative drugs (eg, mineral oil) may interfere with the absorption of fat-soluble vitamins D, A, K, and E. Drugs used for different pharmacological purposes may have additive effects. For example, some laxatives and many diuretics deplete potassium in the body, but taken together they can cause a particularly noticeable and clinically manifested potassium deficiency.

The problem of interaction between drugs and food has several aspects (Zupanets I.A. et al., 2003). Here are the main ones:

• the effect of drugs on the physiological processes of digestion;
• the influence of food components on the therapeutic effectiveness of drugs;
• influence of food components on drug toxicity;
• the influence of drugs on the occurrence of pathology of the digestive system;
• clinical and pharmaceutical aspects of the use of dietary supplements;
• compensation with medications for physiologically active elements missing in food (vitamins, proteins, microelements, etc.);
• drug treatment of diseases caused by food products.

In this article we will dwell separately on the most important of the above-mentioned problems of the relationship between food and medicines.

Appetite

First of all, it should be noted that a considerable number of medications have the most unfavorable effect on appetite and, accordingly, on food consumption - either causing dietary restrictions or leading to overeating. Eating disorders are a very significant, sometimes severe factor in the genesis of nutritional disorders in patients with a wide variety of diseases (see Tables 1, 2).

For example, chemotherapy agents used to treat cancer typically suppress appetite, either causing severe nausea or dulling or impairing the sense of taste. The extreme discomfort caused by chemotherapy can also create negative psychological connections with certain foods or foods that the patient consumes during the treatment period. Cancer itself can negatively affect your appetite.

In addition, there are many other drugs, ranging from antibiotics, anti-inflammatory drugs used for arthritis, antidiabetic, psychotropic and other drugs to such vital drugs as cardiac glycosides, diuretics, antihypertensives, etc., which can reduce appetite, causing nausea or bad taste from food. These side effects tend to be aggravated in very elderly people, many of whose body systems are usually quite significantly impaired in their function with submaximal dosages of drugs, long-term use, but especially with various compositional drug regimens. The gastrointestinal tract is one of the body’s most vulnerable life support systems in this regard.

To date, there is a lot of evidence indicating that the gradual decrease in appetite, up to anorexia, progressive weight loss and subsequent physical failure, which often accompany chronic diseases, may in fact be the result of treatment, not disease. A striking example in this regard is the well-known digitalis, used to treat heart failure. Nausea, vomiting and loss of appetite are common reactions to digitalis. It is important to emphasize that even small doses of digitalis preparations, especially in older people, only slightly exceeding the minimum therapeutic, not to mention the average therapeutic doses, can significantly enhance these effects, raising the question of the possibility of further use of these very important means of correcting cardiac activity. To prevent loss of appetite and associated metabolic disorders, treating physicians must carefully monitor the doses of cardiac glycosides and, of course, any other drugs that they use in their clinical practice, try to individualize the use of the minimum sufficient single and daily doses of drugs, in a timely manner change medications or adjust their dosage if problems arise.

In contrast, there are a number of other medications, including psychotropic drugs, that stimulate appetite as a side effect. Chlorpromazine (aminazine), perphenazine (etaperazine) and other antipsychotic drugs used for severe forms of cerebral pathology can even cause obesity with a long course of treatment. However, some researchers have noted that these substances may have the opposite effect in older people, apparently reducing their interest in food. Lithium, used to treat manic depression and other psychiatric conditions, may also increase appetite and weight gain, as may MAO inhibitors and tricyclic antidepressants. An irresistible craving for sweets was observed in patients using tricyclic antidepressants - amitriptyline, azaphene, etc.

The antihistamine drug cyproheptadine (Peritol), which has a pronounced sedative effect, is sometimes specifically prescribed to stimulate appetite in people recovering from a severe debilitating illness. Corticosteroids such as prednisolone and triamcinolone, which are used to treat severe allergies, asthma, and autoimmune diseases, also increase appetite and promote weight gain, although in such cases such effects are undesirable.

Sodium and fluid retention is another common side effect that, although it does not change appetite, can lead to weight gain due to excess fluid. Medicines that cause fluid retention include some antihypertensive drugs (clonidine, guanethidine, hydralazine and methyldopa) and anti-inflammatory drugs (glucocorticosteroids, non-steroidal anti-inflammatory drugs - butadione, indomethacin, ortofen, and some others). This problem is usually controlled by reducing dietary salt intake and taking diuretics to remove excess fluid and sodium. However, many diuretics not only reduce sodium levels, but also deplete potassium and magnesium in the body. As discussed above, combining low potassium levels with taking digitalis medications (such as digoxin) can increase the potency of the drug to the point of toxicity. Because both diuretics and digitalis are commonly prescribed for heart failure, clinicians must be careful to avoid a three-way food-drug interaction effect. One way to avoid this is to prescribe simultaneously natriuretics and potassium-sparing diuretics, such as spironolactone (aldactone), or amiloride (midamore), or triamterene (pterophen, triampur).

Peristalsis, gastric phase of digestion

Food components trigger many physiological mechanisms of the digestive organs, and above all the regulation of secretory and motor-evacuation activity of the gastrointestinal tract. Fats, for example, in addition to activating cholekinesis, reduce the secretion of juice in the stomach, reduce its peristalsis, and lengthen the gastric phase of digestion. These features have the most unfavorable effect on the pharmacokinetic properties of a number of drugs that require optimally rapid transit into the small intestine: furadonin (often and successfully prescribed to patients for diseases of the urinary and biliary systems, microbe-dependent intestinal pathology), sodium benzoate, phenyl salicylate, sulfonamides, antihelminthic drugs. Long-term exposure to an acidic environment partially inactivates antibiotics such as benzylpenicillin, amoxicillin, erythromycin, lincomycin, oleandomycin, cycloserine, and biseptol. Therefore, during treatment with the indicated medications, the daily fat quota of the diet should be reduced to 40–50 g.

Similar physiological effects accompany sugar and sweets in food. These products, as well as fats, slow down the evacuation of gastric contents into the duodenum, which leads to a delay in absorption and, accordingly, to a significant loss of the therapeutic dose of most 5-aminosalicylic acid preparations, but especially sulfadimethoxine and sulfapyridazine. But fat-rich foods, due to their property of activating the absorption capacity of the small intestine, can be used in clinical practice for better absorption, for example, of anticoagulants, many sedatives (especially seduxen), antioxidants and, of course, fat-soluble drugs - vitamins A, D, E, K.

Laxatives

Just as the presence of food or dietary supplements in the digestive tract can affect the absorption of a drug, the presence of a drug can also affect the absorption of nutrients. Excessive use of laxatives, which often occurs in cases of chronic (habitual) constipation in older people, is a classic example of this. Mineral (petrolatum) oil laxatives tend to retain fat-soluble nutrients (vitamins A, K, D, and E) and prevent their absorption. Over time and with continued use of laxatives, a clinically noticeable deficiency of these vitamins may develop. Stimulant laxatives, such as bisacodyl (dulcolax), guttalax and phenolphthalein (purgen), exert their effect by causing peristaltic contractions in the digestive tract; they can also contribute to deficiencies by speeding up the passage of nutrients through the digestive tract, leaving no time for normal absorption. To relieve constipation, laxatives that increase the volume of intestinal contents (wheat bran, seaweed - laminarid, flaxseed, psyllium seed, agar-agar, methylcellulose preparations - MCC "Ankir", mucofalk, etc.) may ultimately be safer and more effective. .). Dietary fiber absorbs water and forms feces, which causes their normal movement with contraction of the intestinal muscles, facilitating bowel movements. Moreover, dietary fiber is a prebiotic, creating the most favorable conditions for the viability and functional activity of intestinal microflora and the prevention of intestinal dysbiosis.

It should be noted that laxative drugs are prokinetic, as well as excessive infatuation with food stimulants of intestinal motor-evacuation activity (plum and jam, plum jam, prunes, figs, dried apricots, dates, concentrated fruit and vegetable juices, warm flour and dessert dishes, etc.), are poorly compatible with slowly absorbed drugs (for example, digoxin, some vitamin preparations, antianginal drugs, etc.).

Self-medication with antacids

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There are often cases when patients suffering from gastroesophageal reflux disease, gastric dyspepsia, accompanied by heartburn, belching, regurgitation, a feeling of heaviness in the epigastrium, to relieve unpleasant symptoms of gastroduodenal pathology, instead of treatment under the guidance of a gastroenterologist, tend to unreasonably rely on antacids that reduce (of course, for a short time time) these manifestations of the disease. Large quantities of antacids containing magnesium and aluminum, such as Maalox, Gaviscon, Almagel, Rennie, etc., can deplete the body's reserves of phosphorus, a mineral that plays an important role in the metabolism of bone and dental tissue. Since older adults, especially women, are already at risk of developing osteoporosis, antacid abuse and resulting phosphorus deficiency may be a serious problem in this age group.

"Home" medicines

Nonsteroidal anti-inflammatory drugs (NSAIDs) - aspirin, Nise, ibuprofen, diclofenac, piroxekam, naproxen, etc., as well as combination drugs with NSAIDs in their composition - arthrotek, citramon, alka-Seltzer, baralgin, etc. - are widely used in therapeutic practice, and thanks to television advertising and their free sale in pharmacy chains, they are considered by the population today as “homemade” medicines.

NSAIDs can cause nutritional deficiencies when taken regularly in large doses. High doses prescribed for arthritis, as well as used by patients independently as an antipyretic and, most importantly, analgesic for radiculitis, myositis, and other pain-causing processes, when taken orally, irritate the gastric mucosa and can cause so-called NSAID gastropathy, accompanied by gastritis, microscopic gastric bleeding (prolonged loss of iron causes in this case the iron deficiency form of posthemorrhagic anemia). To prevent stomach irritation, it is best to use coated aspirin (provided the coating dissolves in the stomach) or take the medication with or after meals, or with water as a buffer.

Long-term use of aspirin may also lead to folic acid and vitamin C deficiency. For patients, especially older adults, taking aspirin or other NSAIDs for a long time, a diet rich in iron (found in liver, meat, seafood, legumes, whole grains, fortified bread and grain products) and vitamin C (citrus fruits and juices, melon, potatoes, cauliflower and dark leafy vegetables).

Many other medications may affect the absorption of specific vitamins and minerals. It is important to note that a food package formulated based on nutritional principles contains sufficient amounts of most nutrients to overcome these subtle and often temporary effects. However, when certain medications are taken for an extended period of time, or when a person's nutritional status is already compromised by a chronic disease, potentially dangerous deficiencies can occur. For example, people with inflammatory bowel disease may be deficient in folic acid. Sulfasalazine, which is still often prescribed to patients for the treatment of ulcerative colitis and Crohn's disease, increases this deficiency by affecting the absorption of folic acid. Therefore, for people suffering from this disorder, it is important to include various folate-rich foods in their diet (liver, parsley, spinach, lettuce, beans, cereals, cottage cheese, egg yolks, etc.) or take special dietary supplements fortified with folate.

Hormone therapy

Women of different ages taking hormone replacement therapy, especially after resection of the uterus or ovaries, may also encounter nutritional problems. For example, these medications may have some effect on the absorption of vitamin B6 and folic acid in the small intestine. If you do not take into account the noted features of the effect of drugs on the absorption of vitamins in the intestines, hypovitaminosis may occur with long-term hormone replacement therapy. The diet of elderly women in the indicated clinical cases must certainly include food sources of vitamin B6 and folic acid. Foods high in vitamin B6 include meat, fish, nuts, carrots, bananas, poultry, avocados and leafy green vegetables.

Lipid-lowering drugs

With the current high incidence of atherosclerosis and widespread concern among the Russian population about high levels of cholesterol in the body, drugs that lower cholesterol levels are used much more than before.

Lipid-lowering drugs may affect the absorption of fat and some other nutrients. This is especially true for oral medications such as cholestyramine (questran) and metamucil, which have a high sorption capacity for dietary cholesterol. There is evidence that long-term use of these drugs can lead to a deficiency of fat-soluble vitamins (vitamins A, D and E), as well as a deficiency of vitamin K. However, another cholesterol-lowering drug, lovastatin (cardiostatin, medostatin), should used during meals to maximize its absorption properties and, thus, as an enterosorbent is more effective.

Long-term use of medications

Even in small dosages, long-term drug exposure, especially in older adults, can lead to various nutritional deficiencies.

Taking certain medications may interfere with the absorption of nutrients from the intestine. Thus, a group of laxatives reduces the absorption of all nutrients and at the same time disrupts the water-salt balance in the body. Levomycetin impairs the absorption of proteins; large doses of this antibiotic taken against the background of a semi-starvation diet can provoke the development of aplastic anemia. The antibiotic neomycin reduces the absorption of carotene, amino acids, fats, iron, fat-soluble vitamins, and glucose.

Drugs used in neurological and psychiatric practice

A big problem of pharmacotherapy in patients of various clinical profiles is the hepatotropic nature of some modern drugs. Thus, a number of drugs used in neurological and psychiatric practice can significantly affect complex enzymatic systems in the liver, which largely control many metabolic processes. For example, anticonvulsants such as diphenine and phenobarbital, prescribed to people with seizure disorders, including epilepsy, can alter the microsomal liver metabolizing system in such a way that the body may become deficient in vitamin D. Because vitamin D regulates the absorption of calcium in the bones, the deficiency may contribute to bone disorders such as osteomalacia and osteoporosis. There is evidence that these medications may alter folate metabolism, in part due to structural similarity to the folic acid molecule. The metabolism of folic acid can also be disrupted by the immunosuppressant methotrexate, which is used to treat a number of autoimmune diseases, such as severe rheumatoid arthritis, ulcerative colitis, Crohn's disease, etc., the antimalarial drug pyrimethamine (chloridine), and the potassium-sparing diuretic triamterene (pterophen). All three of these drugs have structural similarities to folic acid and therefore may affect folate metabolism.

Conducted research

In a study by B. Dedt et al. (2007), which included 153 people aged 65 to 93 years with various chronic diseases, found that 23% had signs of early negative balance in relation to vitamin B1, 19% in relation to pyridoxine (vitamin B6) and 11% - regarding riboflavin (vitamin B2). Another study of 348 older adults on various pharmacological treatment regimens found that nearly half of all subjects studied had early negative balances of vitamin C, folic acid, and vitamin A. Although the researchers had no clear evidence that drug-food interactions were directly responsible for this negative balance or that clinical deficiencies of these vitamins developed, they believed that it was drug-food interactions that played a significant negative role.

The results of numerous scientific studies devoted to the peculiarities of the influence of drugs on the functional state of the digestive system are summarized by B. Mehl (1990, 1999, 2008) and presented with changes in table. 12.

Table 1 . Examples of drugs that affect digestion. Part 1

Table 2 . Examples of drugs that affect digestion. Part 2

NSAID gastropathy and peptic ulcer

In 1986, the term “NSAID gastropathy” was proposed to distinguish damage to the gastric mucosa that occurs with long-term use of NSAIDs from classic gastric and duodenal ulcers.

Unlike peptic ulcers, NSAID gastropathy often affects the stomach rather than the duodenum and occurs more often in older people than in young people. In addition, damage to NSAID drugs can cause serious, sometimes fatal complications from the gastric mucosa - perforation of ulcers (rupture of the ulcer) and bleeding.

Studies in recent years have shown that erosive and ulcerative lesions of the stomach and duodenum are observed, according to various sources, in 20-40% of patients regularly taking NSAIDs. Complications of NSAID gastropathy (bleeding, perforation of ulcers and their combination), according to American researchers, amount to 70,000 cases per year, and approximately every tenth with developed complications dies. Even taking small prophylactic doses of aspirin (for coronary heart disease) significantly increases the number of ulcer bleedings. So, in the UK they amount to about 3,500 cases per year.

Numerous studies have proven that there are no significant differences in the toxic effect on the cells of the mucous membrane of the stomach, duodenum and intestines. It does not matter how the drug entered the human body - through the mouth, intramuscularly or in the form of suppositories through the rectum. The main ulcerogenic effect of NSAIDs is determined by their systemic effect, which manifests itself after absorption into the blood.

Features of clinical manifestations of drug-induced gastric damage

Before taking especially long-term NSAIDs, it is advisable to undergo examination:

• determine the acidity of gastric juice,
• do an endoscopy
• exclude infection with Helicobacter pylori infection,
• study anamnesis,
• analyze possible risk factors for damage to the stomach, as well as the cardiovascular system (when using modern selective NSAIDs).

Attention should be paid to the features of clinical manifestations of drug-induced damage to the gastric mucosa. In most cases, patients do not have any complaints, while at the same time, 40% experience dyspeptic symptoms - heaviness in the epigastric region, heartburn, belching, nausea, bloating. These clinical manifestations are not characteristic of drug-induced damage and cannot be considered as reliable criteria for erosive and ulcerative damage to the mucous membrane. Moreover, these manifestations do not coincide with the degree of damage to the stomach according to endoscopic examination.

Gastroduodenoscopy reveals changes in the gastric mucosa of varying severity from swelling and redness to the formation of hemorrhages (petechiae), erosions and ulcers, which are found in 30-50% of patients. A number of patients have a clinical set of all dyspeptic disorders, and GDS reveals minimal changes in the mucous membrane. On the contrary, with an asymptomatic course of drug-induced damage during HDS, multiple erosions and ulcers of the stomach and duodenal bulb are detected, and there is a risk of complications (bleeding).

Thus, according to GDS data, 40% of people receiving NSAIDs with erosive and ulcerative lesions of the upper gastrointestinal tract do not have stomach complaints and, conversely, up to 50% of patients with dyspeptic complaints have normal mucous membrane without signs of local inflammation and morphological criteria of gastritis .

Almost everyone has stomach problems

Not everyone has joint pain, headaches or high blood pressure, but almost everyone has encountered gastrointestinal problems. People eat more than once a day, and their well-being and performance depend on how much, what exactly, in what combination and in what situation this happens. Not only food affects the functioning of the digestive system, but also many other things, such as taking antibiotics or strong emotions when appetite disappears.

Why is this so - it is customary to eat for any occasion: weddings and funerals, happiness and sadness, meeting and farewell - it all comes down to eating food together. Not always everything you want to eat fits safely into your stomach. And if it fits, it turns out to be of poor quality or too spicy, greasy, sweet or gross. That's why people either take enzymes or antispasmodics.

It seems that nothing bad will happen if you take the medicine once, but, more often than not, they don’t limit themselves to a single dose and wait for it to go away on its own. It is difficult for a person to believe that something can happen to him; it seems that anything can happen, but only to other people.

Modern NSAIDs

Depending on the inhibition of the enzymes that form prostaglandins, a selective NSAID is distinguished - a COX-1 inhibitor - low doses of aspirin, a non-selective inhibitor that inhibits COX-1 and COX-2, the most commonly used drugs are diclofenac (Voltaren), indomethacin, ibuprofen, ketoprofen etc. and selective NSAIDs in relation to the enzyme COX-2, which synthesizes prostaglandins - celecoxib, rofecoxib, etc. The development of side effects of NSAIDs is associated with the simultaneous inhibition of the physiological enzyme COX-1.

The popularity of NSAID drugs is growing due to the increase in diseases accompanied by pain, the need for long-term or constant use of drugs and their over-the-counter availability in pharmacies. It is important to know the risk factors for side effects of NSAIDs when prescribing them.