Currently, a common reason for visiting a doctor is problems in the work of the gastrointestinal tract. Almost all of them are characterized by impaired motor function. However, they can manifest as symptoms of a disease not related to the digestive system. In any case, you cannot do without drugs of the prokinetic group. The list of drugs in this group is not limited. Therefore, each doctor selects their drug depending on the course of the disease. Next, let's take a closer look at what prokinetics are, a list of new generation drugs most often used for treatment.

Prokinetics: general characteristics

Medicines that change the motor activity of the intestinal tract, accelerate the process of food transit and emptying, just belong to this group.

As mentioned above, there is no single list of these drugs in the gastroenterological literature. Each doctor includes a list of medications here. These include medicines of other groups, such as: antiemetic, antidiarrheal, as well as some antibiotics of the macrolide group, hormonal peptides. To begin with, let's find out what the pharmacological action of this group of drugs is.

Action of prokinetics

First of all, they activate the motility of the digestive tract, and also have an antiemetic effect. Such drugs accelerate the emptying of the stomach and intestines, improve the muscle tone of the gastrointestinal tract, inhibit pyloric and esophageal reflux. Prokinetics are prescribed as monotherapy or in combination with other medications. They can be divided into several types according to the principle of action.

Types of prokinetics

The principle of action on different parts of the gastrointestinal tract is different for drugs such as prokinetics. The list of drugs should be divided into the following types:

1. Dopamine receptor blockers:

• Selective 1st and 2nd generation.
• Non-selective.

2. Antagonists of 5-HT3 receptors.

3. Agonists of 5-HT3 receptors.

And now more about these groups.

Dopamine receptor blockers

Drugs in this group are divided into selective and non-selective. Their action is that they stimulate the motor and have antiemetic properties. What are these prokinetics? The list of medicines is as follows:

• "Metoclopramide".
• "Bromoprid".
• Domperidone.
• "Dimetpramide".

The main active ingredient is metoclopramide, it has been used for a long time. The action is as follows:

• Increased activity of the lower esophageal sphincter.
• Acceleration of gastric emptying.
• An increase in the rate of movement of food through the small and large intestines.

However, non-selective drugs can initiate serious side effects.

There are widely known first-generation prokinetics. List of drugs:

• "Cerucal".

• "Raglan".
• "Perinorm".
• "Ceruglan".

One of the disadvantages is the ability to cause signs and symptoms of parkinsonism in adults and children, and menstrual irregularities in women.

Selective drugs of the second generation include drugs with the active ingredient domperidone. These medications do not cause severe adverse reactions, but others may occur:

• Drowsiness.
• Weakness.
• Anxiety.
• Headache.

It is for this reason that preparations with the active substance domperidone are the best prokinetics. List of drugs:

1. Motilium.
2. Domidon.
3. "Motinorm".
4. "Motorrix".
5. "Gastropom".

New generation prokinetics

Selective prokinetics of the second generation include drugs with the active substance itoprid hydrochloride. Such funds have won recognition due to their excellent therapeutic effect and the absence of side effects, even with prolonged use. Most often, doctors prescribe:

• Itomed.
• "Ganatom".
• Itoprid.

This can be explained by the positive properties of itopride hydrochloride:

1. Improving the motor and evacuation function of the stomach.
2. Increased activity of the gallbladder.
3. Increasing the dynamism and tone of the muscles of the large and small intestines.
4. Assistance in elimination

Intestinal prokinetics

This includes prokinetics - 5-HT3 receptor agonists. The active substance is tegaserod. It has a positive effect on the motor and evacuation function of the large and small intestines. Promotes stool normalization, reduces irritable bowel symptoms.

Does not cause an increase in pressure, does not affect the cardiovascular system. However, there are a fair number of side effects. The risk of developing a stroke, angina pectoris, and the development of an anginal attack increases several times. Currently, drugs with this active substance have been discontinued in our country and in a number of other countries for further research. This includes the following prokinetics (list of drugs):

• Tegaserod.
• "Zelmak".
• "Fractal".

5-NTZ receptor antagonists

Prokinetics of this group are suitable for the treatment and prevention of nausea and vomiting. When they are taken, the residence time of food in the stomach decreases, the rate of transit of food through the intestines increases, and the tone of the large intestine is normalized.

The release of acetylcholine is observed, and the motor function of the gastrointestinal tract is improved. Currently, modern prokinetics are in great demand among patients and doctors. List of new generation drugs:

• Tropisetron.
• "Sturgeon".
• Ondasetron.
• Silansetron.

It should be noted that 5-NTZ receptor antagonists have no therapeutic effect if vomiting is caused by apomorphine.

These drugs are well tolerated, although they have side effects:

• Headache.
• Constipation.
• Flushes of blood.
• Feelings of heat.

Another plus of these drugs is that they do not have a sedative effect, do not interact with other drugs, do not cause endocrine changes, and do not disrupt motor activity.

What diseases are prescribed

As mentioned above, prokinetics are used in monotherapy or in conjunction with antibiotics. Doctors know that there are diseases in which the appointment of prokinetics increases the effectiveness of treatment several times. This group includes:

1. Diseases of the digestive system with impaired motor activity.
2. Gastroesophageal reflux disease.
3. Stomach ulcer (duodenal ulcer).
4. Idiopathic gastroparesis.
5. Vomiting.
6. Constipation.
7. Diabetic gastroparesis.
8. Flatulence.
9. Nausea caused by drug and radiotherapy, infection, functional disorders, unhealthy diet.
10. Dyspepsia.
11. Dyskinesia of the biliary tract.

Who shouldn't be taken

There are contraindications for drugs of the prokinetic group:

• Hypersensitivity to the active substance.
• Gastric or intestinal bleeding.
• or intestines.
• Intestinal obstruction.
• Acute liver failure, renal dysfunction.

Pregnant and lactating mothers

I would like to say a few words about taking medications during pregnancy. Studies have shown that prokinetics tend to pass into breast milk, so breastfeeding should not be continued during treatment with such medications.

During the first trimester of pregnancy, women often experience vomiting and nausea. In this case, it is possible to prescribe drugs such as prokinetics. The list of drugs for pregnant women will include only those that do not pose a threat to the life of the pregnant woman and to the fetus.

The benefits from it should exceed all possible risks. Prokinetics with the active substance metoclopromide can be used from this group only as directed by a physician. In the subsequent trimesters of pregnancy, prokinetics are not prescribed.

Currently, drugs in this group are not prescribed during pregnancy due to the large number of side effects.

Prokinetics for children

The use of prokinetics with the active substance metoclopramide in children should be especially careful, as there is a risk of dyskinetic syndrome. It is prescribed depending on the weight of the child.

If a pediatrician prescribes prokinetics, Motilium is most often included in this list. It is well tolerated and has a lot of positive reviews. But other prokinetics can also be prescribed. The list of drugs for children may also contain the following names:

• Domperidone.
• "Metoclopromide".

It is worth noting that Motilium is recommended for use in suspension for children under 5 years of age. The medicine is prescribed depending on the weight of the child, at the rate of 2.5 ml for every 10 kg of weight. If necessary, the dose can be increased, but only for babies over a year old. Also, the drug is available in the form of lozenges.

Prokinetics are prescribed for children if the child has:

• Vomit.
• Nausea.
• Esophagitis.
• Delayed digestion of food.
• Dyspeptic symptoms.
• Frequent regurgitation.
• Gastroesophageal reflux
• Impaired motility of the gastrointestinal tract.

It should be noted that in the very first months of life, the child's body and all its functions are not very developed, therefore, all drugs should be taken under the strict supervision and supervision of a doctor. In case of overdose, prokinetics can cause neurological side effects in infants and young children.

A herbal preparation that improves digestion and reduces gas formation in the intestines is very popular with parents of babies. This is a concentrate based on the fruits of Plantex fennel.

It is worth saying a few words about plant prokinetics.

Natural helpers

The world is arranged in such a way that a cure for any ailment can be found in some plant, you only need to know in which one. So, plant prokinetics are known that stimulate the motor function of the gastrointestinal tract. Here are some of them:

• Fennel ordinary.
• Pharmaceutical camomile.
• Black elderberry.
• Dill.
• Oregano.
• Motherwort.
• Dandelion.
• Melissa.
• The marsh drier.
• The plantain is large.
• Buckthorn alder.

The list of plants that help improve gastrointestinal motility includes a large number of other representatives of the flora. It should also be borne in mind that some vegetables and fruits have a similar effect:

• Swede.
• Melon.
• Cabbage.
• Carrot.
• Beet.
• Pumpkin.
• Cowberry.
• Grape.

The properties of prokinetics in these vegetables are very well manifested if fresh juices prepared from them are taken.

It should be noted that one should not replace herbal medicines during periods of exacerbation of diseases and without consulting a doctor.

Side effects

It is very important that the new generation prokinetics have much fewer side effects than the first generation drugs with the active substance metoclopramide. However, even the newest drugs have side effects:

• Headache.
• Increased excitability.
• Dry mouth, thirst.
• Spasm of smooth muscles of the gastrointestinal tract.
• Hives, rash, itching.
• Hyperprolactinemia.
• Babies may have extrapyramidal symptoms.

After discontinuation of the drug, the side effects completely disappear.

If the doctor prescribes prokinetics, the list of drugs may include several drugs with different names, but with one active ingredient. In this case, the side effects will be the same.

Features of the use of prokinetics

Prokinetics should be prescribed very carefully for people with hepatic insufficiency and with poor kidney function. Such patients should be under strict medical supervision.

With prolonged use of prokinetics, patients should also visit their doctor more often. Use prokinetics with caution in young children, especially under one year of age.

Care should be taken to prescribe drugs from this group to elderly patients.

When treating with prokinetics, you should not engage in work that requires increased attention and quick reaction.

Before taking it, be sure to consult a doctor. Your health depends on it. You should not replace a medicinal product with its herbal counterpart without first consulting a doctor.

However, in some cases, they can appear as signs of any other disease that has nothing to do with problems of the digestive system. In any case, one cannot do without the medicines of the prokinetic group. The list of drugs included in this group has almost no restrictions on admission. That is why the doctor selects each remedy strictly individually.

What are prokinetics: general characteristics

Prokinetics include pharmacological drugs that, using various mechanisms, change the activity of the stomach and intestines and accelerate the passage of food.

These medications are indicated to be consumed in the presence of diseases of the digestive tract. Basically, problems arise due to a violation of the activity of the stomach. They have also been shown to be taken as medication to prevent bouts of vomiting.

Action of prokinetics

Medicines prokinetics help to activate the motility of the digestive tract, and are also characterized by a pronounced antiemetic effect. Such medications help accelerate metabolic processes, improve muscle tone, and reduce reflux. They are prescribed as a single medication or in combination with other medications. They are divided into several types according to the basic principle of their impact.

What are the types of prokinetics

According to the mechanism of their action, all existing prokinetics can be divided into several different groups, namely, such as:

• dopamine receptor blockers;
• receptor agonists;
• receptor antagonists.

The list of prokinetic drugs includes macrolide antibiotics, hormonal peptides. Some types of such drugs have been used for several decades, while others are just beginning to appear on the pharmaceutical market. There are also drugs, the pharmacological qualities of which are just beginning to be studied.

The most famous and well-studied drugs are selective prokinetics, dopamine receptor blockers that increase intestinal and gastric motility. Doctors recommend taking these funds three times a day, always before bedtime. Such drugs are presented in the form of tablets and injections.

Dopamine receptor blockers

The principle of action on various parts of the stomach and intestines may differ for drugs such as prokinetics. The list of drugs in this group is divided into selective and non-selective. Their principle of action is that they improve the functioning of the stomach and help get rid of bouts of nausea.

The most effective prokinetics for the intestines are considered to be:

Such drugs are used in the treatment of gastroesophageal reflux disease, dyspepsia, narrowing of the esophagus after surgery, injuries, adhesions, impaired outflow of bile, increased gas production.

In addition, you can take them for nausea, vomiting, provoked by poisoning or violation of the rules of food intake, viral or bacterial diseases, toxicosis during pregnancy in the first trimester.

They can be ineffective with vomiting of vestibular origin. They contain the active active ingredient metoclopramide, which has been used for a long time. The action of such drugs is:

• increased activity of the esophagus;
• improving metabolic processes;
• increasing the rate of movement of food through the stomach and intestines.

However, such drugs can provoke the occurrence of many side effects, which is why you initially need to undergo a comprehensive examination and consult a doctor.

There are also first generation prokinetics. The list of medicines is quite extensive, and they include:

One of the main disadvantages of such funds is their ability to provoke menstruation disorders in women, deterioration of bowel function. Medicines of the second generation contain the active ingredient domperidone. These drugs do not cause severe side effects, however, when using them, there may be:

That is why doctors prescribe drugs of this particular group to patients. These include "Motilium", "Motorix", "Domidon", "Gastropon".

New generation prokinetics

For the treatment of constipation and diseases of the stomach and intestines, second-generation medicines are widely used. Before taking medications, you need to study the list of new generation prokinetic drugs. "Ganaton" is considered one of the most effective remedies, as it helps to restore the normal functioning of the stomach. This drug is used to treat chronic gastritis and is approved for use by people over 16 years of age.

In addition, doctors prescribe Itomed and Itoprid, as they have proven themselves very well due to their pronounced therapeutic effect, as well as the absence of side effects even after prolonged use. They help to increase the tone of the intestinal muscles and the activity of the gallbladder. "Itoprid" is well absorbed in the digestive tract, and the maximum possible concentration of the active substance is reached within a minute after the first intake.

Intestinal prokinetics

The list of new generation prokinetic drugs also includes drugs that affect type 4 serotonin receptors and are their agonists. The active ingredient tegaserod has a good effect on the functioning of the intestines. Also contributes to the rapid normalization of the stool. The most famous drugs in this group include:

• Tegaserod;
• "Fractal";
• "Zelmak".

They do not provoke an increase in blood pressure and do not cause diseases of the cardiovascular system. However, there are various side effects. To date, drugs in this group have been discontinued for further research.

Antagonists

The list of prokinetic drugs includes drugs for the treatment of nausea and vomiting. When they are taken, the time for digestion of food in the stomach is significantly reduced, the speed of its movement through the intestines increases, the tone of the walls of the gastrointestinal tract is normalized.

The most popular among doctors and patients are modern prokinetics. The list of new generation drugs includes:

These medicines are very well tolerated by the body, despite the fact that they have some side effects. Another advantage of such drugs is that they do not interfere with motor activity, do not cause sedation and do not interact with other drugs.

What diseases are prescribed

Prokinetic drugs are indicated for violations such as:

These drugs are characterized by the fact that they do not violate the secretory function of the stomach at all, that is, they do not affect the production of gastric juice. During treatment, these drugs are prescribed for adults 3 times a day at a dosage of 5-10 mg before meals. The daily dosage should not exceed 60 mg of the drug.

Despite all the advantages of prokinetics, it is advisable to take them in combination with other drugs.

Natural prokinetics

Today, in the treatment of diseases of the stomach and intestines, as well as to improve their functioning, prokinetics of plant origin are widely used, divided into several groups, depending on the mechanism of action. In particular, they can be divided into:

• drugs that improve metabolic processes;
• laxatives that help soften the accumulated feces;
• osmotic laxatives;
• non-absorbable;
• contact.

The first group includes agents that absorb water, as a result of which the feces soften, intestinal peristalsis is activated, and the movement of feces through it becomes more active. Such herbal products include wheat bran, preparations made from plantain seeds, seaweed.

Laxatives help to soften the accumulated feces and quickly eliminate them from the body. These include various mineral and vegetable oils.

Non-absorbable drugs include drugs made on the basis of lactulose. They have laxative properties in combination with probiotics. These funds are safe and can be used for a long time even during pregnancy. Such funds include "Laktovit", "Duphalac", "Normase".

Contraindications

Despite all the positive qualities of prokinetics, there are still certain contraindications for the use of this group of drugs, which include such as:

• hypersensitivity to components;
• intestinal obstruction and gastric bleeding;
• severe dysfunctions of internal organs;
• pregnancy and breastfeeding.

It is not recommended to take these funds for those whose professional activity is associated with a high concentration of attention, as well as when driving a car. Prokinetics for the treatment of diseases of the stomach and intestines have been used for a long time, however, due to the likelihood of various kinds of complications, only the attending doctor should prescribe them, based on the results of the examination.

Prokinetics for children: application features

Treatment with prokinetics of children should be carried out very carefully, since there is a high risk of gastric obstruction. These medicines are prescribed based on the weight of the child. Basically, children are prescribed "Motilium", as it is characterized by good tolerance and has a lot of positive reviews.

It is recommended to use it in the form of a suspension for up to 5 years. The drug is prescribed depending on the weight of the child, at the rate of 2.5 ml per 10 kilograms. If necessary, the dosage can be increased, but only when treating children over 1 year old. For children over 5 years of age, this drug is prescribed in the form of lozenges.

Prokinetics are prescribed to a child if he has:

• nausea, vomiting;
• delayed digestion of food;
• frequent regurgitation;
• dyspeptic disorders;
• deterioration of the digestive system.

It is worth noting that the baby's body is not well developed, which is why it is necessary to take medications under the strict supervision of a doctor. In case of an overdose or if used incorrectly, prokinetics can provoke nervous system problems, especially in infants and young children.

Parents are in great demand for preparations made on a plant basis, which reduce gas formation and improve the digestion process. These include a medicine created on the basis of the extract of fennel fruits - "Plantex".

Side effects

Medicines prokinetics are often recommended to be taken once or in short courses, since they have a pronounced effect on many internal organs and the nervous system. They can provoke side effects such as:

• drowsiness;
• severe fatigue;
• headaches, dizziness;
• intestinal spasms;
• the appearance of constipation;
• diarrhea;
• bronchospasm;
• allergy;
• arrhythmia.

Most of the side effects are observed when taking the drug "Metoclopramide", which is why it is prescribed in extreme cases as an adjuvant.

Application features

With extreme caution, prokinetics are prescribed for people with renal and hepatic insufficiency, as well as for other disorders of the functioning of these organs. Such patients must take the medicine under the strict supervision of a doctor.

With prolonged use of prokinetics, it is imperative to periodically undergo an examination, since they can negatively affect the work of many internal organs. Especially carefully you need to take these funds to infants and the elderly.

Before carrying out treatment, it is imperative to consult a doctor, and you should also not select analogues on your own, as this can have a bad effect on health. In case of deterioration in health, you must immediately stop taking the drug and consult a doctor.

Pro-Gastro

Diseases of the digestive system ... We will tell you everything you want to know about them.

Prokinetics are drugs that stimulate the motility of the gastrointestinal tract. They accelerate the movement of the food bolus through the digestive system and promote regular bowel movements. Interestingly, there is no generally accepted classification of these drugs in medicine. Gastroenterologists note that many antidiarrheal, antiemetic and even antibacterial agents have prokinetic activity. The drugs that are traditionally prescribed in Russia to stimulate gastrointestinal motility are presented in the review below.

Classification

Depending on the active substance and the effect on the body, prokinetics are divided into:

1. Serotonin 5-HT 4 receptor agonists (also called intestinal prokinetics). Do not cause an increase in intra-abdominal pressure. Drugs from this group accelerate the evacuation of food from the stomach and reduce the time it takes for the contents to pass through the intestines. They quickly normalize stools and relieve irritable bowel symptoms. The leading representatives of this group are tegaserod (Fractal, Zelmak) and cisapride (Propulside, Coordinax). However, due to the considerable number of side effects (increased risk of progressive angina pectoris, stroke, life-threatening arrhythmias, and others), the question of the advisability of prescribing these drugs is currently being resolved.
2. Dopamine receptor blockers are agents that bind (block) D 2 -dopamine receptors and have prokinetic and antiemetic effects:
   • non-selective (non-selective) - Metoclopramide (Cerucal); it is a remedy that has long been known and has been successfully used to relieve nausea and stop vomiting; the disadvantages of the drug include the frequent development of side effects (drowsiness, lethargy) and the effect on the extrapyramidal nervous system;
   • selective I generation - domperidone (Motilium, Motinorm, Motorix);
   • selective II generations - Itoprid (Ganatom, Itomed).
3. Selective antagonists of 5-HT 3 -receptors. These drugs improve gastric and intestinal motor function by blocking receptors and releasing the neurotransmitter acetylcholine. They are gaining more and more popularity, as they have a minimum of side effects and do not affect the nervous system:
   • ondansetron (sturgeon):
   • silansetron.

Mechanism of action

The mechanism of action is determined by the type of medication.

Dopamine receptor blockers:

• stimulate the activity of the lower esophageal sphincter of the stomach;
• accelerate the evacuation of gastric contents into the duodenum;
• stimulate the motor work of the smooth muscles of the small and large intestines;
• contribute to the rapid advancement and elimination of feces from the body.

This is due to the binding of dopamine receptors in the intestine.

Selective drugs of the new generation have practically no side effects and are successfully used to treat chronic diseases of the gastrointestinal tract, including GERD. Means based on Cisapride and Itoprid improve the motor and evacuation functions of the stomach, increase the dynamism of the gallbladder and small intestine.

5-HT 4 agonists and 5-HT 3 antagonists have similar medicinal effects:

• reduce the residence time of food in the stomach;
• increase the speed of food transit;
• normalize the tone of the large intestine.

Indications for use

The main indication for the appointment of prokinetics is diseases of the digestive system, in which there is a violation of the motor function of the gastrointestinal tract. Such diseases include:

They can also be used as symptomatic treatment for:

• nausea caused by poor diet, infection, chronic diseases of the biliary system, radio and chemotherapy;
• vomiting;
• flatulence, including caused by pancreatitis;
• constipation;
• feeling of heaviness in the stomach.

Contraindications

• individual intolerance or hypersensitivity to one of the components of the product;
• bleeding from the gastrointestinal tract;
• perforated stomach or intestinal ulcer;
• intestinal obstruction;
• severe kidney disease, acute renal failure.

During pregnancy, prokinetics can be prescribed only in case of urgent need, for example, with indomitable vomiting in the first trimester, which threatens the health of the woman and the child. Since the drugs of the group are able to penetrate into breast milk, breastfeeding should be stopped during treatment.

The use of drugs that improve gastrointestinal motility in childhood is possible under the strict supervision of a physician. More often, pediatricians prescribe domperidone-based products to babies in a convenient suspension form.

Another important feature of these drugs is the ability to influence concentration. Therefore, they are not assigned to people whose work requires the utmost precision (drivers, control workers, and others).

Side effects

Side effects are rare when treated with new-generation drugs. In some cases, patients are faced with:

• headache;
• psychoemotional excitability or, on the contrary, drowsiness, lethargy;
• thirst, dry mouth;
• spasm of the muscles of the gastrointestinal tract, manifested by cramping pain in the abdomen.

Since prokinetics accelerate the movement of the food bolus along the gastrointestinal tract, they can reduce the effectiveness of drugs taken simultaneously, especially prolonged-release tablets. Therefore, it is desirable that the interval between taking these drugs is at least 3-4 hours.

Modern prokinetics are an effective way to treat functional disorders of the gastrointestinal tract and eliminate such unpleasant symptoms as nausea, a feeling of fullness in the stomach, and constipation. Before taking the drugs of the group, you should consult with a therapist or gastroenterologist to select the correct dose and determine the duration of the course of treatment.

Health-preserving channel, a specialist talks about prokinetics in GERD:

New generation prokinetics

All diseases of the digestive system are associated with deterioration of motility and evacuation functions of the small and large intestines, stomach and esophagus. This problem is especially relevant in functional dyspepsia, biliary dyskinesia and gastroesophageal reflux disease. In the treatment of such pathologies, new generation prokinetics are used - medicines that allow you to restore the normal functioning of the gastrointestinal tract.

Modern prokinetics

Many chemical compounds have prokinetic properties, including hormonal peptides, macrolide antibiotics, and opiate receptor antagonists. But you should prefer drugs that perform the following functions:

• increased tone of the lower esophageal sphincter;
• improved esophageal cleansing;
• increased gastric motility;
• a decrease in the number of esophageal refluxes and the time of contact of the esophageal mucosa with the contents of the stomach;
• elimination of delayed evacuation of gastric contents.

Today, a group of prokinetics is mainly used, which affects the work of the upper gastrointestinal tract:

Let's consider them in more detail.

Which prokinetics are better?

Itopride or Itopride hydrochloride is an active substance that produces two simultaneous effects:

• increased release of acetylcholine molecules;
• stimulation of muscarinic receptors.

The advantages of itopride are its positive effect on the esophageal sphincter, an increase in the tone of the gallbladder and the motor activity of the muscles of the large and small intestines. Thus, preparations based on the presented substance can be used for irritable bowel syndrome in combination with functional dyspepsia and constipation. Moreover, the compound significantly improves contractile movements in the antrum of the stomach, contributes to the disappearance of duodenogastric reflux and produces an antiemetic effect.

New generation prokinetics based on itopride:

They are available in tablets with the same dosage of the active substance of 50 mg.

The next line of drugs is metoclopramide. The group of drugs under consideration is very effective due to several prokinetic mechanisms performed, one of which is the direct intensification of contractions of the smooth muscles of the digestive tube.

It is worth noting that metoclopramides are prescribed only in cases where a short course of therapy is required with the need to achieve results as quickly as possible. This is due to the presence of a large number of adverse side effects. Among the representatives of this group, we note:

Cisaprides are considered one of the most effective medications of the type described. Their feature is the activation of a new type of serotonin receptors, which are localized in the plexuses of neurons in the stomach, esophagus and intestines. The drugs in this group include:

At the same time, cisapride prokinetics in tablets provoke the development of serious side effects from the cardiovascular system.

The most popular and affordable drug of the described group is domperidone (Motilium). Its therapeutic efficacy does not exceed the efficacy of metoclopramide, but it does not cause negative effects. The only drawback of Motilium is manifested with prolonged courses of administration in the form of an increase in the level of the hormone prolactin.

Best prokinetic

Considering all the properties of modern prokinetic drugs described above, it can be concluded that the most preferred drugs are drugs based on itopride.

Modern prokinetics (list of drugs)

Prokinetics, the list of drugs of which will be discussed below, refer to drugs that stimulate the motility of the gastrointestinal tract. Since gastroenterologists do not have a generalized list of these drugs, the list offered below is not something obligatory. It includes prokinetic drugs, which are currently sold in the pharmacy network.

Dopamine receptor antagonist therapies

The effect of this type of drugs is based on their rapid binding to D2-dopamine receptor structures, and a sharp decrease in their response to signals from other body systems. At the same time, the motility of the gastrointestinal tract is instantly activated, the stimulation of actions aimed at eliminating vomiting is enhanced. In the list of drugs that have such an effect on the stomach, you can enter the following drugs:

The last drug indicated in this list is most often used to eliminate diseases of the gastrointestinal tract, although it belongs to the second generation prokinetics. Its increased use is largely due to the fact that Domperidone does not have severe side effects.

Sometimes the drug Itopride is added to the group of antagonists, but many doctors are against this, since this drug has an inhibitory effect on acelincholine. Raglan and Cerucal on this list represent the first generation of D2 dopamine receptor antagonists. They include the main medicinal substance - metoclopramide, as well as in the means of a newer generation. Their disadvantage is that under some circumstances they cause such phenomena in patients as symptoms of tachycardia, tinnitus, severe dizziness, increased drowsiness.

These drugs are most often prescribed for the prevention of emetic processes before examination by endoscopy or when using contrast agents in radiology.

Antagonists are used in the following cases:

• ulcerative lesion of the duodenum or stomach;
• if the patient has flatulence or achalasia in the esophagus;
• the cuts of the intestinal structures that have arisen after the operation;
• they can be used to treat gastroesophageal reflux syndrome;
• antagonists are used for signs of functional dyspepsia;
• with the development of severe dyskinesia on the channels that conduct bile.

Very carefully and rarely, the above antagonists are used to treat patients with diseases of the liver and renal structures. They try not to use them for nausea and vomiting, which is caused by an infectious lesion. Antagonists are rarely used when patients are undergoing radiation therapy.

Remedies to stimulate intestinal peristalsis

The most popular prokinetics from this group are the medicines Mosaprid and Coordinax. They are connected by the similarity of the method of influencing the intestinal peristalsis. Their only difference is that, unlike Coordinax, Mosaprid does not have any effect on the work of the channels carrying potassium, which greatly reduces the possibility of arrhythmias in the work of the heart muscle.

This group includes the following drugs:

Motilin receptor antagonist group

Such medications - prokinetics include drugs that bind to the receptors of a hormone (motilin), which is responsible for increasing the pressure in the esophageal sphincter, which is located in the lower part of the organ, and empties it when opened.

This group includes the following drugs:

These medicines have a strong effect on the intestines, causing it to contract. In this case, the stomach is cleared of solid or liquid food fractions. During this process, the period of passage of the residues through the large intestine drops sharply. This happens even in cases where there is some pathology in the organ, for example, with progressive systemic scleroderma or diabetic gastroparesis.

Some caution should be exercised when using these drugs, since most of the prokinetics of this type have many side effects. Most often, many patients use Erythromycin, but they do not know that treatment with such a remedy for more than 30 days can significantly increase the risk of sudden death due to the occurrence of severe disorders and lesions that impair cardiac conduction.

List of prokinetics and features of their administration

Prokinetics are a group of drugs that regulate the motility of the digestive tract. Preparations with prokinetic action improve the movement of intestinal contents through the digestive tract, promote better functioning of the sphincter between the stomach and the esophagus, and prevent food from being thrown from the stomach into the esophagus.

In Russia, the pharmacy market is represented by three approved prokinetics: Metoclopramide, Domperidone, Itoprid. Other drugs are prohibited or under development.

Types of prokinetics and drug names

There are several pharmacological groups of prokinetics.

Dopaminergic D2 receptor blockers

They are the most studied and widely used group of prokinetics. The drugs of this group, by blocking dopamine D2 receptors, regulate the motor activity of the digestive tract by increasing the tone of smooth muscle cells in the intestine and stomach. They have an antiemetic and antiemetic effect.

• Metoclopramide (Gastrosil, Cerucal, Raglan). A feature of this drug is the effect on dopamine D2 receptors and serotonin H3 receptors at the same time. Stimulates the work of the upper digestive tract (stomach, esophagus, sphincter between these organs). Reduces the excitability of the vomiting center in the central nervous system, therefore it has proven itself as an antiemetic. Virtually no effect on intestinal motility. The use is limited by the appearance of specific adverse reactions (extrapyramidal disorders, hormonal disorders, dizziness), which is associated with penetration through the blood-brain barrier and the effect on the central structures of the brain, as well as the effect on the cardiovascular system (causes arrhythmias).
• Domperidone (Domperon, Motilak, Motilium). The drug belongs to the 1st generation of selective blockers of dopamine D2 receptors, which does not penetrate the blood-brain barrier and is devoid of side effects from the central nervous system. It has the main effect on the motility of the stomach and duodenum, since there is the largest number of peripheral D2 receptors. Does not affect the intestines. The antiemetic effect is moderate. Domperidone is one of the main prokinetic drugs used in medical practice. Adverse reactions from the cardiovascular system are less common than with metoclopramide.

Serotonin 5-HT4 receptor agonists

Drugs of this group, acting on serotonin H4 receptors in the submucous layer of the digestive tract, stimulate the release of acetylcholine. Acetylcholine increases the motor activity of the stomach and intestines. Studies have shown the ability of these drugs to reduce abdominal discomfort, normalize stool in irritable bowel syndrome. At this stage, active trials of drugs of this group are underway, as a promising direction in treatment.

• Tegaserod. The first synthesized agonist of serotonin H4 receptors, which has shown high efficiency in the treatment of intestinal neurosis with constipation. The disadvantages of the drug included a high percentage of side effects from the cardiovascular system. Banned for use now.
• Cisapride (Coordinax, Peristil). Has an effect on the entire gastrointestinal tract, stimulating motor skills. Improves the passage of food through the intestines, affects the work of the esophageal sphincter. During the use of Cisaprid, serious adverse reactions from the cardiovascular system were identified, so the drug was banned from production.
• Mosaprid. Has similar properties to Cisapride. Approved for use in a number of countries (Belarus, Kazakhstan). Not registered in Russia. The disadvantages of the drug include interaction with other drugs, so it is used with caution with non-steroidal anti-inflammatory drugs, cholinergic drugs, etc.
• Prucaloprid (Resolor). It has the highest affinity for serotonin receptors, therefore it has a pronounced effect on intestinal motility. It is used in the treatment of chronic constipation, when the main groups of laxatives have no effect. When used, the most common side effects were headache, nausea, and abdominal pain. Registered in Russia.

Serotonin H3 receptor antagonists

The study of this pharmaceutical group began after the discovery of the properties of metoclopramide to inhibit the work of serotonin H3 receptors and the advancement of the theory that part of its prokinetic properties are associated precisely with serotonin and its receptors. The synthesis of drugs that would selectively act only on H3 receptors began.

• (Latran, Zofran). The drug accelerates the movement of food from the stomach into the duodenum, normalizes the tone of the large intestine. It is used in the treatment of nausea and vomiting caused by chemotherapy in cancer patients or anesthesia. Not widely used in the treatment of gastroesophageal reflux disease and irritable bowel syndrome.
• Tropindol (Tropisetron, Navoban). The first drug from this group, which can normalize the work of the lower esophageal sphincter for a long time, preventing the reflux of gastric contents. Has a pronounced antiemetic effect. It is used in cancer patients after chemotherapy.

New generation prokinetics with double action

• Itoprid (Ganaton, Itomed). The drug simultaneously acts on dopamine D2 receptors and anticholinesterase receptors, which expands its scope. It has a positive effect on the tone of the lower esophageal sphincter, preventing the reflux of gastric contents into the esophagus. Simultaneously stimulates the peristalsis of all parts of the intestine, improving bowel movement in case of constipation. It has a mild antiemetic effect. Does not affect the secretory activity of the stomach. Does not affect the structure of the central nervous system. In the treatment of gastroesophageal reflux disease, it has proven itself better than Domperidone. The advantages of Itoprid include the lack of interaction with other drugs.

The choice of prokinetic is based on clinical efficacy in the treatment of different parts of the digestive tract, safety and contraindications.

Of all the listed drugs, only 2 drugs meet the efficacy / safety condition - Itoprid and Domperidone. In the treatment of disorders of the motor activity of the upper gastrointestinal tract (esophagus, stomach), the drug of choice is Itoprid.

Indications for use

• GERD (gastroesophageal reflux disease);
• functional dyspepsia;
• stomach ulcer;
• irritable bowel syndrome;
• nausea and vomiting;
• achalasia of the esophagus.

Contraindications

• gastrointestinal bleeding;
• perforation of the stomach;
• pregnancy;
• mechanical obstruction of the gastrointestinal tract;
• prolactinoma (for Domperidone).

Natural prokinetics

• Iberogast. Herbal preparation based on extracts of 9 plants. The mechanism of action is associated with the individual effect of each plant on the digestive tract. The main point of application is the stomach. Strengthens the passage of food from the stomach, normalizes motor skills. Reduces the production of hydrochloric acid and increases the production of mucus in the stomach.

Differs from "chemical prokinetics" in efficiency combined with a high safety profile. Used in the treatment of functional dyspepsia.

Prokinetics - a list of drugs and features of their use

In some diseases, the motor-evacuation function of our gastrointestinal tract is impaired. With this problem, drugs that belong to prokinetics help to cope. They affect antiperistaltic contractions of smooth muscles, thereby normalizing its activity.

Prokinetics can be divided according to their origin into plant and artificial. The well-known ginger is a herbal remedy. And by the type of action on selective (domperidone) and non-selective (metoclopramide). In this article, we will look at some prokinetics, a list of drugs, a mechanism of action and when to resort to their help. And also the possibility of using during pregnancy and treatment of children.

The main active ingredient of Motilium is domperidone, a new generation drug with an improved mechanism of action. Reduces vomiting, nausea, or completely prevents their occurrence. Sometimes the patient complains that the stomach is "standing". The process of food digestion and its timely evacuation into the duodenum does not take place in it. Food does not move further along the gastrointestinal tract. Domperidone-based prokienetics are able to help in this case as well. Motilium increases the duration of the contractions of the lower stomach, thereby speeding up its emptying. Domperidone improves the tone of the lower alimentary sphincter, which also has a beneficial effect on the motor activity of the digestive organs. Here is a list of violations when it is worth using Motilium:

It is important to distinguish whether nausea and vomiting are caused by overeating or poor motor-evacuation activity of the stomach or symptoms of poisoning. In the second case, a completely different treatment regimen is needed.

Use of Motilium during pregnancy and for children

Domperidone can be prescribed for toxicosis during pregnancy. However, in the instructions for the drug, pregnancy and lactation are on the list of restrictions for use. Motilium has no specific contraindications for pregnancy. But there is also no data on serious clinical studies of the effect of this drug on the processes occurring in the body of the expectant mother. Therefore, the aforementioned prokinetic cannot be included in the list of drugs that are clearly recommended for use. Taking the drug during lactation leads to the fact that a small concentration of domperidone is recorded in breast milk.

Motilium is used to treat even the smallest children. When diagnosing regurgitation syndrome in the first year of life, prokinetics are prescribed as part of complex therapy. The Belgian drug is one of the permissible ones.

Domperidone does not pass well through the blood-brain barrier. But in children under one year old, it is still poorly developed. And therefore, taking the drug can cause dystonic reactions. It is worth remembering this when using it in the treatment of children under one year old.

Babies are often sick in transport. Their vestibular apparatus is not yet as developed as in adults. Therefore, it is possible to use Motilium to reduce motion sickness in children.

It will also be useful to find out about contraindications:

• obstruction of the gastrointestinal tract;
• pituitary tumor;
• stomach bleeding;
• individual intolerance.

Motilium is capable of causing allergies as it contains Polysorbate 20. This agent is used in industry to emulsify fragrances or essential oils. Sorbitol (E420) is able to enhance the toxic effects of certain drugs on the body.

Metoclopramide

Metoclopramide belongs to the first generation prokinetic drugs. It has several prokinetic mechanisms of action. Blocks dopamine and serotonin receptors, reduces the motor activity of the esophagus and increases the tone of its lower sphincter. The medicine is available in the form of tablets and ampoules for injection.

Effects of metoclopramide on the gastrointestinal tract

Metoclopramide blocks nerve endings that transmit signals from the stomach and duodenum to the vomiting center, thus interrupting their connection. Dopamine inhibits the motor activity of the upper gastrointestinal tract. Blocking dopamine receptors leads to the normalization of the stomach. Acting on various types of serotonin receptors, the prokinetic, at the same time, prevents the relaxation of the smooth muscle tissues of the hollow organs and tones them up, increasing the contraction of muscle fibers. This helps move food from the stomach into the duodenum.

However, the prokinetic metoclopramide has a long list of side effects:

• spastic torticollis;
• weakness;
• violation of mental activity;
• spasm of the facial muscles;
• opisthotonus, etc.

Such a number of possible side reactions from the body is not observed in the new generation of prokinetics. The list of indications is quite common for drugs in this group: flatulence, nausea, vomiting, caused by very different reasons, from drugs to the effects of trauma.

With vomiting of vestibular genesis, it is useless. Although, metoclopramide has some interesting advantages:

• it has a positive effect on the healing of gastric ulcer;
• also, this remedy is able to help with migraines;
• its effectiveness is high in Tourette's syndrome;
• facilitates X-ray diagnostics of the stomach and small intestine.

But don't self-medicate. You can get an effect that you absolutely do not expect.

Metoclopramide for expectant mothers and babies

In Denmark, a large-scale study was carried out on the possibility of taking this prokinetic during pregnancy. The control group consisted of about 35 thousand women who received the drug in the first trimester. There was no increase in the level of congenital malformations, spontaneous miscarriages, stillbirths. The findings were published in the Journal of the American Medical Association on October 16, 2013. The presence of these data allows doctors to more consciously approach the appointment of metoclopramide during pregnancy. Due to the large number of side effects, they try not to use the drug in the treatment of children under 12 years of age.

Finally, I would like to provide a small list of prokinetics that you can find on the shelves in our pharmacies: Cerucal, Ganaton, Itomed, Passages, Motilak. Unfortunately, almost all drugs are either contraindicated during pregnancy or require careful use under medical supervision. Remember that you need to go to your doctor for advice on the use of any medication.

When to take prokinetic medications: stop bloating and nausea

Prokinetics are drugs for stimulating the motility of the digestive system. They have a prokinetic effect, that is, they promote the movement of a lump of food through the digestive tract.

A number of antiemetic, antidiarrheal and antibacterial drugs have prokinetic activity.

General classification

The list of prokinetic drugs can be submitted depending on the pharmacological effect on the body.

1. Serotonin receptor agonists, or intestinal prokinetics. They do not increase intra-abdominal pressure, accelerate the exit of food from the stomach. The most common medicines from this group are Tegaserod or Cisapride.
2. Non-selective dopamine blockers - Cerucal.
3. Selective - Domrid (Motilium), Itoprid.
4. Acetylcholine receptor blockers (promote the release of its neurotransmitter) - Ondansetron, Silansetron. They belong to the new generation of prokinetics.

Note! Now the drug Ondasetron and its analogues are gaining more and more popularity, because it has a minimal risk of side effects and is well tolerated by patients.

Mechanism of action

Dopamine-sensitive receptor blockers have the following effects:

• stimulating the activity of the lower gastric sphincter;
• acceleration of the movement of stomach contents into the duodenum of the intestine;
• increased peristalsis of smooth muscles;
• acceleration of excretion of feces from the large intestine.

Selective medicines of the latest generation gently activate the motor work of the stomach, increase the contractility of the bile.

Activators of 5 HT4 and inhibitors of 5 HT3 reduce the period of stay of food in the stomach, bring the tone of the intestinal muscles to a normal state.

When to take

Doctors have a choice in prescribing one of the prokinetics to the patient: the list of drugs is varied. The main indications of such remedies are pathologies of the digestive organs, in which gastric motility is impaired.

These include:

• reflux esophagitis;

• acute or chronic stomach ulcer;
• persistent bowel irritation syndrome;
• atony of the stomach, which develops as a result of diabetes mellitus.

As symptomatic therapy, prokinetics must be taken to relieve:

• nausea caused by eating poor quality food;
• vomiting;
• bloating caused by many diseases, including pancreatitis;
• constipation;
• feeling of heaviness in the abdominal cavity.

Note! Prokinetics affect the concentration of attention, so they should not be taken by drivers and persons servicing precision machinery.

Side effects

It is necessary to consider the following when prescribing prokinetics: the list of drugs is very extensive, and many of them have side effects.

1. Tegaserod, Cisapride may increase the risk of angina pectoris.
2. Metoclopramide may cause drowsiness.
3. Lethargy.
4. Negative effect on the central nervous system.
5. Thirst, dry mouth.

Important! Since prokinetics accelerate the movement of food through the gastrointestinal tract, they should not be taken simultaneously with drugs that have a prolonged effect. It is desirable that the interval between taking such drugs be at least 4 hours.

The use of prokinetics helps to normalize the digestive system in a relatively short time. In childhood and old age, treatment with these funds is possible only under the supervision of a specialist. Self-medication with prokinetics is strictly not allowed.

Prokinetics: a list of drugs

Many diseases of the digestive system are accompanied by a decrease in gastrointestinal motility. To activate peristalsis, drugs are prescribed - prokinetics. The list of such drugs includes medicines that in various ways enhance the tone of smooth muscles.

How prokinetics work

The motor function is activated by cholinergic nerve fibers. Serotonin and opioid receptors are located on the membrane of smooth muscle cells of the stomach and intestines. When exposed to the neurotransmitter serotonin, smooth muscles contract. Under the influence of enkephalins and endorphins, peristalsis is inhibited. Gastrointestinal motility activators enhance motor function in various ways. Acetylcholine drugs affect cholinergic nerve fibers, while others block or activate receptors responsible for the contraction and relaxation of smooth muscle fibers.

Increasing the tone of smooth muscles, prokinetics:

• accelerate the passage of food through the esophagus;
• prevent relaxation of the body of the stomach;
• increase the activity of the antrum of the stomach and the upper part of the small intestine;
• prevent duodenogastric reflux;
• normalize gallbladder motility;
• facilitate the passage of bile;
• eliminate constipation caused by intestinal hypokinesia.

Prokinetics not only stimulate peristalsis. They prevent:

Many drugs used to treat diseases of the gastrointestinal tract, biliary system enhance motor skills, but not all of them are recommended as prokinetics.

What drugs have a prokinetic effect

The activators of motor function include drugs of various groups. Strengthen the tone of smooth muscles of the gastrointestinal tract:

• laxatives;
• antiemetic;
• choleretic drugs;
• prostaglandins;
• some antibiotics (erythromycin, oleandomycin).

Antibiotics are not used as prokinetics. They have many side effects and cause intestinal dysbiosis.

Most often they are prescribed:

• metoclopramide (cerucal; raglan);
• domperidone (motilium, motilac);
• cisapride (peristil, co-ordinate);
• Mosaprid (Mozax, Mosid).

Metoclopramide belongs to the 1st generation prokinetics. It has many side effects, although it has a pronounced antiemetic effect, it is preferable to use more modern drugs instead. Prokinetics of the 4th generation are effective. They have less pronounced side effects, fewer contraindications. These include:

Each of these drugs affects the peristalsis of the gastrointestinal tract in its own way. Therefore, before using it is necessary to consult a doctor. The specialist will prescribe the necessary medicine, depending on the disease and the characteristics of the use of the drugs.

Features of the use of prokinetics

There are many drugs with prokinetic action. Depending on the underlying disease, the causes of hypokinesia and atony of the gastrointestinal tract are prescribed:

1. Metoclopramide and domperidone mainly affect the motor function of the esophagus, stomach, and duodenum. To eliminate dyspepsia, it is better to use the lingual form of motilium. The medicine begins to act 15 minutes after application and has significantly fewer side effects. And metoclopramide is prescribed with intense vomiting, but it is not advisable to take it for a long time.
2. Cisapride enhances the contractions of the stomach and intestines. It reduces the sensitivity of the baroreceptors of the rectal ampulla, facilitates the act of defecation. Take the medicine 15 minutes before meals. Cardiotoxic.
3. Mosaprid enhances the peristalsis of the stomach and duodenum, and practically does not affect the lower parts of the gastrointestinal tract. The drug is effective for eliminating vomiting and heartburn in patients with chronic gastritis.
4. Tegaserod (fractal) is prescribed to enhance the motility of the large intestine. They activate the production of intestinal secretions. It is contraindicated in case of intestinal obstruction, pathologies of the kidneys, liver, gastrointestinal bleeding.
5. Loxiglumide. Strengthens peristalsis, accelerates the evacuation function of the stomach and colon.
6. Itopride (ganaton, zirid, primer). The drug affects the peristalsis of the upper gastrointestinal tract, eliminates the manifestations of functional dyspepsia.

The choice of the most optimal one depends on the goals of treatment, the cause of the onset of symptoms. If the disease is accompanied by smooth muscle spasm, then motility activators are contraindicated. The dosage of drugs and the duration of administration depends on the severity of the disease, the patient's condition and is determined by the doctor.

Conclusion

Prokinetics, according to the international classification, are not separated into a separate group. There are drugs that activate the motility of the gastrointestinal tract. They belong to different types of medications affecting the tone of smooth muscles. They are recommended as monotherapy for esophagogastroduodenal reflux disease. More often they are prescribed as a component of complex therapy for other pathologies of the digestive system, when it is necessary to increase peristalsis for treatment. Which of the drugs will be more effective, the gastroenterologist will determine, after finding out the cause of hypokinesia of the gastrointestinal tract.

Prokinetics Is a group of drugs that regulates the motility of the digestive tract. Preparations with prokinetic action improve the movement of intestinal contents through the digestive tract, promote better functioning of the sphincter between the stomach and the esophagus, and prevent food from being thrown from the stomach into the esophagus.

In Russia, the pharmacy market is represented by three approved prokinetics: Metoclopramide, Domperidone, Itoprid. Other drugs are prohibited or under development.

There are several pharmacological groups of prokinetics.

Dopaminergic D2 receptor blockers

They are the most studied and widely used group of prokinetics. The drugs of this group, by blocking dopamine D2 receptors, regulate the motor activity of the digestive tract by increasing the tone of smooth muscle cells in the intestine and stomach. They have an antiemetic and antiemetic effect.

Serotonin 5-HT4 receptor agonists

Drugs of this group, acting on serotonin H4 receptors in the submucous layer of the digestive tract, stimulate the release of acetylcholine. Acetylcholine increases the motor activity of the stomach and intestines. Studies have shown the ability of these drugs to reduce abdominal discomfort, normalize stool in irritable bowel syndrome. At this stage, active trials of drugs of this group are underway, as a promising direction in treatment.

Serotonin H3 receptor antagonists

The study of this pharmaceutical group began after the discovery of the properties of metoclopramide to inhibit the work of serotonin H3 receptors and the advancement of the theory that part of its prokinetic properties are associated precisely with serotonin and its receptors. The synthesis of drugs that would selectively act only on H3 receptors began.

• (Latran, Zofran). The drug accelerates the movement of food from the stomach into the duodenum, normalizes the tone. It is used in the treatment of nausea and vomiting caused by chemotherapy in cancer patients or anesthesia. Not widely used in the treatment of gastroesophageal reflux disease and irritable bowel syndrome.
• Tropindol (Tropisetron, Navoban). The first drug from this group, which can normalize the work of the lower esophageal sphincter for a long time, preventing the reflux of gastric contents. Has a pronounced antiemetic effect. It is used in cancer patients after chemotherapy.

New generation prokinetics with double action

• Itoprid (Ganaton, Itomed). The drug simultaneously acts on dopamine D2 receptors and anticholinesterase receptors, which expands its scope. It has a positive effect on the tone of the lower esophageal sphincter, preventing the reflux of gastric contents into the esophagus. Simultaneously stimulates the peristalsis of all parts of the intestine, improving bowel movement in case of constipation. It has a mild antiemetic effect. Does not affect the secretory activity of the stomach. Does not affect the structure of the central nervous system. In the treatment of gastroesophageal reflux disease, it has proven itself better than Domperidone. The advantages of Itoprid include the lack of interaction with other drugs.

The choice of prokinetic is based on clinical efficacy in the treatment of different parts of the digestive tract, safety and contraindications.

Of all the listed drugs, only 2 drugs meet the efficacy / safety condition - Itoprid and Domperidone. In the treatment of disorders of the motor activity of the upper gastrointestinal tract (esophagus, stomach), the drug of choice is Itoprid.

Indications for use

Contraindications

• gastrointestinal bleeding;
• perforation of the stomach;
• pregnancy;
• mechanical obstruction of the gastrointestinal tract;
• prolactinoma (for Domperidone).

Natural prokinetics

• Iberogast. Herbal preparation based on extracts of 9 plants. The mechanism of action is associated with the individual effect of each plant on the digestive tract. The main point of application is the stomach. Strengthens the passage of food from the stomach, normalizes motor skills. Reduces the production of hydrochloric acid and increases the production of mucus in the stomach.

Differs from "chemical prokinetics" in efficiency combined with a high safety profile. Used in the treatment of functional dyspepsia.

Prokinetics, the list of drugs of which will be discussed below, refer to drugs that stimulate the motility of the gastrointestinal tract. Since gastroenterologists do not have a generalized list of these drugs, the list offered below is not something obligatory. It includes prokinetic drugs, which are currently sold in the pharmacy network.

The effect of this type of drugs is based on their rapid binding to D2-dopamine receptor structures, and a sharp decrease in their response to signals from other body systems. At the same time, the motility of the gastrointestinal tract is instantly activated, the stimulation of actions aimed at eliminating vomiting is enhanced. In the list of drugs that have such an effect on the stomach, you can enter the following drugs:

• Dimetpramide;
• Raglan;
• Bromopride;
• Metoclopramide;
• Cerutsal;
• Domperidone.

The last drug indicated in this list is most often used to eliminate diseases of the gastrointestinal tract, although it belongs to the second generation prokinetics. Its increased use is largely due to the fact that Domperidone does not have severe side effects.

Sometimes the drug Itopride is added to the group of antagonists, but many doctors are against this, since this drug has an inhibitory effect on acelincholine. Raglan and Cerucal on this list represent the first generation of D2 dopamine receptor antagonists. They include the main medicinal substance - metoclopramide, as well as in the means of a newer generation. Their disadvantage is that under some circumstances they cause such phenomena in patients as symptoms of tachycardia, tinnitus, severe dizziness, increased drowsiness.

These drugs are most often prescribed for the prevention of emetic processes before examination by endoscopy or when using contrast agents in radiology.

Antagonists are used in the following cases:

• ulcerative lesion of the duodenum or stomach;
• if the patient has flatulence or achalasia in the esophagus;
• the cuts of the intestinal structures that have arisen after the operation;
• they can be used to treat gastroesophageal reflux syndrome;
• antagonists are used for signs of functional dyspepsia;
• with the development of severe dyskinesia on the channels that conduct bile.

Very carefully and rarely, the above antagonists are used to treat patients with diseases of the liver and renal structures. They try not to use them for nausea and vomiting, which is caused by an infectious lesion. Antagonists are rarely used when patients are undergoing radiation therapy.

Remedies to stimulate intestinal peristalsis

The most popular prokinetics from this group are the medicines Mosaprid and Coordinax. They are connected by the similarity of the method of influencing the intestinal peristalsis. Their only difference is that, unlike Coordinax, Mosaprid does not have any effect on the work of the channels carrying potassium, which greatly reduces the possibility of arrhythmias in the work of the heart muscle.

This group includes the following drugs:

• Mosaprid;
• Ceruletide;
• Pyridostigmine bromide;
• Neostigmine monosulfate;
• Coordinax;
• Galantimin;
• Aceclidine;
• Physiostigmine.

Motilin receptor antagonist group

Such medicines - prokinetics include drugs that bind to receptors for a hormone (motilin), which is responsible for increasing pressure in the esophageal sphincter, which is located in the lower part of the organ, and empties it when opened.

This group includes the following drugs:

• Erythromycin;
• Azithromycin;
• Attilmotin;
• Clarithromycin.

These medicines have a strong effect on the intestines, causing it to contract. In this case, the stomach is cleared of solid or liquid food fractions. During this process, the period of passage of the residues through the large intestine drops sharply. This happens even in cases where there is some pathology in the organ, for example, with progressive systemic scleroderma or diabetic gastroparesis.

Some caution should be exercised when using these drugs, since most of the prokinetics of this type have many side effects. Most often, many patients use Erythromycin, but they do not know that treatment with such a remedy for more than 30 days can significantly increase the risk of sudden death due to the occurrence of severe disorders and lesions that impair cardiac conduction.

When using prokinetics from any of the groups described above, it is necessary to undergo an examination at a medical institution. The dose, method of administration and duration of treatment are determined by the attending physician. Unauthorized attempts to use these medicines are strictly prohibited.

Catad_tema Heartburn and GERD - Articles

Prospects for the use of a new prokinetics with a dual mechanism of action in the treatment of gastroesophageal reflux disease

I.V. Maev, A.A. Samsonov, A.N. Odintsova, E.V. Belyavtseva, M.G. Zadorova
GOU VPO RGMU Roszdrav, Moscow The problem of the development of gastroesophageal reflux disease (GERD) and the tactics of its treatment, taking into account the main pathogenetic mechanisms, are discussed. To date, the leading direction in the treatment of GERD is acid suppressive therapy, in particular, with the use of proton pump inhibitors (PPIs). However, given that even the most effective PPIs do not affect the root cause of the disease - impaired motor function of the digestive tract, in the treatment of patients with GERD, the use of drugs with a prokinetic effect on the upper gastrointestinal tract is additionally indicated. The drug of a new generation of prokinetics is itopride hydrochloride (Ganaton), an antagonist of dopamine D 2 receptors and an acetylcholinesterase blocker. The features of the pharmacodynamics and pharmacokinetics of Ganaton make it possible to use it in patients with GERD in the regimen of long-term anti-relapse therapy, both in combination with PPIs and as monotherapy.
Keywords: gastroesophageal reflux disease, lower esophageal sphincter, duodeno-gastric reflux, prokinetics, itopride hydrochloride, proton pump inhibitors

In the development of many common gastroenterological diseases, primarily gastroesophageal reflux disease (GERD), impairments of the motor function of the digestive tract play an important role. The development of GERD is based on a violation of the motor-evacuation function of the organs of the esophagogastroduodenal zone, leading to systematic, long-term reflux of gastric and duodenal contents into the esophagus, which is a damaging aggressive agent for the esophageal mucosa.

Pathogenetic mechanisms of GERD development

It is believed that GERD develops as a result of an imbalance between the aggressive effects of thrown components and a three-stage esophageal defense system, including anti-reflux barriers, acid clearance mechanisms, and tissue resistance. The components that determine the damaging properties of the injected substances are hydrochloric acid, pepsin, bile salts (bound and free) and pancreatic enzymes. Damage to the esophagus is determined by the pH of the gastric contents. If the pH is neutral or alkaline, as in patients after gastrectomy or with atrophic gastritis, the damaging agents are free bile salts and pancreatic enzymes. At the same time, hydrogen ions are the main damaging agent of refluctate, and their ability to have a damaging effect depends both on the exposure time and on the concentration, i.e., on pH.

Antireflux barriers, which represent the first stage of a three-step protection of the esophagus, include the lower esophageal sphincter (LES), intra-abdominal segment of the esophagus, phrenic legs, phrenoesophageal ligament, mucosal rosette, and acute angle of His. Great importance is attached to the decrease in basal pressure in the area of ​​the LPS. The LPS and the diaphragm are the main structures responsible for creating high pressure (from 10 to 30 mm Hg) in the gastroesophageal junction. This zone prevents reflux by separating two adjacent low pressure zones: in the stomach cavity (5 mm Hg above atmospheric pressure) and in the esophagus (5 mm Hg below atmospheric pressure). The tonic pressure created by the smooth circular muscle of the LPS increases with contraction of the legs of the diaphragm during inhalation and exhalation and at times when intragastric pressure increases, for example, when sneezing, coughing, bending the body. At rest, the tonic contraction of the LPS is maintained, in addition to the visceral tone of its muscle, by cholinergic excitatory neurons. Brief relaxation of the LPS when swallowing food is accompanied by a peristaltic wave that closes and clears the lumen of the esophagus.

In both healthy people and in GERD, there is such a phenomenon as a transient, transient relaxation of the LPS, which is most often caused by the stretching of the stomach walls when eating to reduce intragastric pressure by venting air from the gas bladder of the stomach (belching with air). At the same time, in addition to belching with air (often when the LPS relaxes), the occurrence of reflux of gastric contents is explained by the fact that transient LPS relaxations persist in the high pressure zone as long (about 20 seconds) as the LPS relaxations initiated by swallowing, but there is no cleansing the lumen of the esophagus of the peristaltic wave. In patients with GERD, the described phenomena are observed often, for a long time and are the cause of the onset of symptoms of the disease (heartburn, belching, regurgitation).

In general, in GERD, three main situations are described when pathological reflux occurs: with transient relaxation of the LPS, insufficient function of the LPS, and due to increased intra-abdominal pressure.

The reason for the frequent transient relaxation of the LPS in GERD remains unclear. At the same time, an increasing number of researchers are inclined to believe that the pathology of the obturator mechanism of LPS in GERD is associated with impaired motor activity of the stomach, its delayed emptying, leading to stretching of the walls of the organ, or with increased sensitivity to normal stretching of the stomach, including against the background inflammatory process in the stomach wall. According to A.S. Trukhmanov, from a pathophysiological point of view, GERD is an acid-dependent disease that develops against the background of a primary violation of the motor function of the upper digestive tract. Moreover, a number of authors argue that impaired gastric motor function may be an important, if not the main factor in the onset and development of GERD. Particular attention is paid to such disorders of gastric and duodenal motility as gastric dysrhythmias, accompanied by delayed evacuation from the proximal stomach, impaired antroduodenal coordination and duodeno-gastric reflux (GDR). It is noteworthy that for antroduodenal discoordination, the characteristic symptoms are heartburn, sour, bitter belching, regurgitation of food, that is, the characteristic symptoms of GERD.

When we studied the motor activity of the stomach and duodenum by the method of dynamic gastroscintigraphy in 204 patients with GERD, a significant prevalence (68.6%) of cases of delayed gastric evacuation was revealed (Fig. 1). Moreover, with grade III GERD according to the Savary – Miller classification, this type of dysmotility was observed in 100% of cases.

Rice. 1. The frequency of detecting violations of the evacuation
gastric function in patients with GERD
(data of dynamic gastroscintigraphy) (%)

Peripheral computed electrogastroenterography (PCEGEG) in 76% of cases revealed changes in the type of functional discoordination of gastric and duodenal motility. Moreover, before a meal, 23.2% of patients showed a reduced electrical activity of the stomach with normal motor activity in the duodenum, followed by normalization of gastric motility after a meal. In 45.8% of patients on an empty stomach, increased electrical activity of the duodenum was found with normalization of motor activity after food stimulation with unchanged indicators of gastric electrical activity, i.e., transient duodenal hyperkinesia. In 31% of cases, decreased indicators of the electrical activity of the duodenum on an empty stomach were revealed, which returned to normal after food stimulation with the simultaneous absence of any changes in electrical activity at the frequencies of the stomach. It is characteristic that in all three cases, but with different frequencies, GHR was observed, which was much more often (93%) recorded in patients with the second variant of dysmotility.

In general, the frequency of GDR detection in all patients with GERD by SCEGEG method was 82.4%, increasing in direct proportion to the severity of the disease (Fig. 2). This confirms the data that with an increase in the severity of GERD, the number of mixed refluxes (stomach contents + duodenal contents) also increases. This pattern cannot be ignored, since it is mixed refluxes in a large number of cases that lead to such a formidable complication of GERD as Barrett's esophagus (the appearance in the esophagus of columnar metaplasia of squamous epithelium with the threat of further development of adenocarcinoma).

Rice. 2. Frequency of GDR detection
in patients with GERD by SCEGEG method

Also, an important role in the pathogenesis of GERD is played by a violation of the motility of the esophagus itself, including a change in the strength and duration of peristaltic contractions, an increase or decrease in the tone of its sphincters. In the pathogenesis of GERD, weakening of the peristalsis of the esophagus is important, which leads to a slowdown in its emptying and a decrease in the contractility of the walls of the esophagus during reflux; decrease in pressure of the pumping station; excessive relaxation and destructuring of its antireflux function.

An important role in the occurrence of motor disorders of the esophagus and stomach, underlying the development of GERD, is assigned to the imbalance of the parasympathetic and sympathetic links of the nervous regulation of the gastrointestinal tract (GIT) and, as a consequence, to the violation of peristaltic activity. Autonomic regulation of the motor-evacuation activity of the organs of the esophagogastroduodenal zone is carried out with the participation of the main receptors (cholinergic, adrenergic, dopaminergic, serotonin, motilin, cholecystokinin) and the most important messengers, including gastrointestinal hormones that stimulate, and inhibiting, inhibiting motor activity (dopamine, secretin, cholecystokinin, nitric oxide, glucagon, somatostatin, enkephalins, vasoactive intestinal peptide). One of the most important messengers that has a depressing effect on the smooth muscle elements of the stomach is dopamine, which is secreted in certain parts of the gastric wall and acts through specialized dopamine receptors located here. An imbalance in the coordinating action of stimulants and inhibitors of the motility of the digestive tract, expressed, for example, in excessive dopamine activity, leads to hypomotor dyskinesia of the esophagus, stomach, duodenum up to the appearance of uncoordinated contractions, antorduodenal discoordination, functional gastro- and duodenostasis. In this case, a parallel decrease in pressure in the LPS is often observed, cardia insufficiency and pathological gastroesophageal reflux develop.

Of certain importance in the development of motor disorders that underlie the pathogenesis of GERD, have an effect on the motility of some food components (fats, chocolate, citrus fruits, tomatoes, coffee, alcohol, etc.), as well as the use of medications (anticholinergics, β-blockers, antagonists calcium and nitric oxide donors) and smoking.

The organic reasons leading to the development of GERD include reflux with a hernia of the esophageal opening of the diaphragm, associated with the disappearance of the His angle - an important anatomical element of the obturator mechanism of the cardia.

All of the above indicates that impaired motor activity of the upper gastrointestinal tract in the pathogenesis of GERD is a determining factor that creates conditions for the contact of aggressive stomach contents with the esophageal mucosa, the occurrence of morphological changes and clinical manifestations of the disease.

GERD treatment tactics

At the same time, today the leading direction in the treatment of GERD is the elimination of acidification in the esophagus by blocking acid production carried out by the gastric parietal glands using proton pump inhibitors (PPIs); binding of aggressive components of gastric contents; creating an obstacle to the contact of the latter with the mucous membrane of the esophagus (by using antacids, alginates).

It should be said that this approach to the treatment of GERD is dictated, on the one hand, by real successes in stopping not only clinical, but also morphological manifestations of the disease, preventing complications, and with long-term maintenance acid-suppressive therapy - and stabilizing the state at normal rates of esophageal acidification. On the other hand, until recently, in the arsenal of the therapist, gastroenterologist, there were no effective and safe means for correcting motor disorders in patients with GERD, which would allow for a sufficiently long-term control of motor activity without causing side effects typical of prokinetics available on the pharmacological market.

In this regard, today the drugs of choice in the treatment of GERD, which effectively suppress acid secretion in the stomach, are PPIs, especially the latest generation (pantoprazole, rabeprazole). With erosive forms of the disease, they become an indispensable component.

However, it should be borne in mind that even the most effective PPIs today do not affect the root cause of the disease - impaired function of the obturator mechanism of the cardia, gastric and duodenal motility, therefore, after stopping their intake, most patients relapse relatively quickly. In some cases, PPIs do not eliminate some of the symptoms most often associated with impaired motility of the esophagus and stomach, hypersensitivity of the stomach to stretching. In such cases, in the treatment of patients with GERD, the use of prokinetics is additionally indicated.

Analyzing the features of drugs that have a prokinetic effect on the upper gastrointestinal tract, it is necessary to dwell separately on the following drugs:

• Betanechol is a cholinergic agonist, significantly increases the basal pressure of the LPS, enhances the contractions of the esophagus, the secretion of saliva, reduces the phenomena of gastroesophageal reflux, but does not accelerate the delayed gastric evacuation. At the same time, the clinical use of this drug is sharply limited due to pronounced side effects, primarily an increase in the secretion of hydrochloric acid, dysuric disorders, the appearance of spastic abdominal pain, the development of bronchospasm, etc.
• Metoclopramide (Cerucal) is a non-selective dopamine receptor blocker; the site of action is the chemoreceptor trigger zone of the brain and the upper gastrointestinal tract. The drug has a normalizing effect on the motor activity of the stomach, increases the amplitude of antral contractions, coordinates gastroduodenal motility, accelerates gastric evacuation, relaxes the duodenum, reduces the severity of GHD. However, penetrating the blood-brain barrier, the drug often causes pronounced side effects in the form of extrapyramidal reactions, drowsiness, lethargy, etc., especially with prolonged use.
• Domperidone (Motilium) - according to the mechanism of action, it is also an antagonist of peripheral and central dopamine receptors. The site of action is the chemoreceptor trigger zone of the brain and the upper gastrointestinal tract. The drug enhances gastric motility, normalizes its emptying, increases the duration of peristaltic contractions of the antrum and duodenum 12, eliminates discoordination of the pylorobulbar zone, reduces GHR, and also increases the tone of the lower esophageal sphincter. The drug weakly penetrates the blood-brain barrier and practically does not cause extrapyramidal disorders, but with prolonged use, an increase in the level of prolactin in the blood plasma and corresponding side effects are observed.
• Cisapride (Coordinax) is a serotonin agonist, one of the most effective drugs in the prokinetic group. Its mechanism of action is associated with the release of acetylcholine from the myoenteric plexus, activation of serotonin receptors. In addition, cisapride has a direct contractile effect on the smooth muscles of the gastrointestinal tract and, unlike other prokinetic agents, is able to stimulate the motility of all parts of the gastrointestinal tract. However, due to serious side effects - lengthening of the Q-T interval and the appearance of ventricular arrhythmias - the use of cisapride is sharply limited.
• Macrolides (erythromycin and its derivatives) interact with motilin receptors, mimicking the action of the physiological regulator of the gastroduodenal migrating motor complex. Erythromycin is able to induce powerful peristaltic contractions, similar to those of the migrating motor complex, accelerating gastric emptying from liquid and solid food, but erythromycin has not found wide application in the treatment of patients with GERD, since its effect on esophageal motility is practically absent. In addition, a significant decrease in the effectiveness of erythromycin against the background of gastric atony was found with prolonged use, which creates obstacles for the use of this drug in GERD.

The experience of using the listed prokinetics for GERD, especially drugs such as metoclopramide, domperidone and cisapride, both in our country and abroad, is quite large, however, due to the large range of side effects caused by drugs of previous generations, and the short duration of their action, the expediency of using the latter were often questioned.

Ganaton in the treatment of GERD

The drug of a new generation of prokinetics, which has proven itself (according to several meta-analyzes) in the treatment of GERD and functional dyspepsia, registered abroad, and since 2007 in Russia, is itopride hydrochloride - Ganaton (from “gastric natural tone” - restoring normal stomach tone). This is a new drug with a combined mechanism of action that is an antagonist of dopamine D 2 receptors and an acetylcholinesterase blocker. Itopride hydrochloride activates the release of acetylcholine, while preventing its degradation. It has a minimal ability to penetrate the blood-brain barrier, does not affect the duration of the Q-T interval and does not interact with drugs metabolized by enzymes of the cytochrome P450 system, including PPIs, which are often used in the treatment of GERD and functional dyspepsia. Itoprid hydrochloride has a pronounced antiemetic effect, enhances the propulsive motility of the stomach and accelerates its emptying.

Open clinical studies of itopride hydrochloride in the USA, Japan, Germany, India and other countries have shown high clinical efficacy of the drug in patients with functional dyspepsia, chronic gastritis, diabetic gastroparesis and GERD. The drug is well tolerated and has no significant side effects. In patients with functional dyspepsia and diabetic gastroparesis, itopride effectively stimulates the contractility of the stomach, accelerates its emptying, and eliminates antroduodenal discoordination.

When using itopride hydrochloride as part of combination therapy with PPIs in patients with GERD, it was found that this prokinetic significantly enhances the contractile activity of the NPS, which is confirmed by an increase in pressure in its area, and also enhances the motor activity of the stomach, accelerates gastric evacuation and normalizes impaired gastroduodenal coordination. An important positive side of using itopride for GERD is not only a fast and stable clinical effect, but also the possibility of its long-term use without the development of any significant side effects. Thus, Inoue K. et al. (1999), using itopride 50 mg 3 times a day for 7 weeks in patients with chronic gastritis with symptoms of reflux esophagitis, received a good clinical effect: the disappearance of complaints in 67% of patients with heartburn in the absence of side effects.

There is also a domestic positive experience of using Ganaton for the treatment of patients with GERD. So, Minushkin O.N. and Loshchinina Yu.N. (2008) treated patients with GERD stage 0 – I of recurrent course with Ganaton (in monotherapy mode) in a standard dose (50 mg 3 times a day) for 25 days. Against the background of Ganaton's monotherapy, heartburn was completely stopped by the end of the first week in 90% of patients, and epithelialization of esophageal erosions after a full course of treatment was recorded in all patients with erosive GERD. There was also a positive dynamics of the vegetative status and indicators of the quality of life of patients according to the SF-36 (Short-Form Health Survey) scale.

Thus, with the emergence of an effective and safe prokinetics of itopride hydrochloride (Ganaton) on the domestic market, new opportunities open up for a full-fledged pathogenetic therapy for GERD, including the correction of motor disorders of the esophagus, stomach and duodenum, restoration of their normal myoelectric activity and mutual coordination.

The use of Ganaton in patients with GERD is possible both as monotherapy for mild forms of the disease, and as part of a combined treatment with PPIs.

Apparently, taking into account the characteristics of the pharmacodynamics and pharmacokinetics of the drug Ganaton, it is possible to use it in patients with GERD in the regimen of long-term anti-relapse therapy and in combination with PPIs, and in the monotherapy regimen. At the same time, the correction of the standard doses of both components downward is not excluded.

Literature

1. Kalinin A.V. Gastroesophageal reflux disease: diagnosis, therapy, prevention // Farmateka. 2003. No. 7. P. 1–9.
2. Kalinin A.V. Gastroesophageal reflux disease: guidelines. M., 2004.S. 40.
3. Orlando RC. Reflux esophagitis. In: Yamada T., Alpers D. H., Owyang C., et al. Textbook of gastroenterology. Philadelphia: JB Lippincott 1991: 1123.
4. Dubois A. Role of gastric factors in the pathogenesis of gastroesophageal reflux. In: Castell D.O., Wu W.C., Ott D.J., eds. Gastroesophageal reflux disease: pathogenesis, diagnosis, therapy. Mount Kisco, N.Y .: Futura 1985: 81.
5. Heine KJ, Mittal RK. Crural diaphragm and lower esophageal sphincter as antireflux barriers. Viewpoints in Digestive Diseases 1991; 23: 1.
6. Vasiliev Yu.V. Gastroesophageal reflux disease: pathogenesis, diagnosis, drug treatment // Consilium medicum. Application. 2002. No. 3. P. 3–11.
7. Dent J, Dodds WJ, Friedman RH, et al. Mechanism of gastroesophageal reflux in recumbent asymptomatic human subjects. J Clin Invest 1980; 65: 256.
8. Usik S.F., Yurchenko I.N., Osadchuk M.A. Gastroesophageal reflux disease in young people: clinical and endoscopic, functional and morphological criteria / Materials of the Eighth Russian Gastroenterological Week, November 2002, Moscow // Russian Journal of Gastroenterology, Hepatology, Coloproctology. 2002. No. 5.P. 14.
9. Mittal RK, Holloway RH, Penagini R, et al. Transient lower esophageal sphincter relaxation. Gastroenterology 1995; 109: 601.
10. Williams NS, Grossman MI, Meyer JH. Gastric emptying of liquids in normal subjects and patients with healed duodenal ulcer disease. Dig Dis Sci 1986; 31: 943.
11. Trukhmanov A.S. Gastroesophageal reflux disease: clinical picture, diagnosis, treatment // BC. 2001. T. 3. No. 1. P. 19–24.
12. Pasechnikov V.D. The effectiveness of complex therapy with lansoprazole and cisapride in the treatment of gastroesophageal reflux disease // Gastroenterology of St. Petersburg. 2002. No. 1. P. 10–12.
13. Vyskrebentseva S.A., Alferov V.V., Kovaleva N.A. and other Disorders of gastric motility in gastroesophageal reflux disease // Russian journal of gastroenterology, hepatology, coloproctology. 2005. No. 6. P. 35–39.
14. Holloway RH, Hongo M, Berger K, et al. Gastric distention: a mechanism for postprandial gastroesophageal reflux. Gastroenterology 1985; 89: 779.
15. Pimanov S.I., Mikhailova N.A., Stoyakov A.M. and other Violations of the motor-evacuation function of the stomach // Medical news. 2000. No. 4. P. 39–43.
16. Vasiliev Yu.V. Clinical and pharmacoeconomic aspects of therapy for gastroesophageal reflux disease // Experimental and Clinical Gastroenterology. 2002. No. 1. P. 24–27.
17. Chernyakevich S.A., Dolgushkin A.N., Zelinsky B.I. et al. Motor function of the stomach and duodenum in gastroesophageal reflux disease / Materials of the Seventh Russian Gastroenterological Week, October 2001, Moscow // Russian Journal of Gastroenterology, Hepatology, Coloproctology. 2001. No. 5.P. 14.
18. Trukhmanov A.S. Clinical prospects for the diagnosis and treatment of gastroesophageal reflux disease // Russian Journal of Gastroenterology, Hepatology, Coloproctology. 1999. No. 1. P. 59–61.
19. Starostin B.D. The effectiveness of combined therapy with parietus and motilium of gastroesophageal reflux disease // Russian Journal of Gastroenterology, Hepatology, Coloproctology. 2001. No. 6. P. 44–47.
20. Ostapenko V.A., Akhmedov V.A., Bunova S.S. et al. Modern views on the mechanisms of formation and diagnosis of gastroesophageal reflux disease // Experimental and clinical gastroenterology. 2002. No. 1. P. 19–23.
21. Vyskrebentseva S.A., Alferov V.V., Kovaleva N.A. and other Electrical activity of the stomach in patients with gastroesophageal reflux disease // Proceedings of the 3rd scientific-practical conference “Geller's readings”. Supplement to the journal Healthcare of the Far East. 2002. No. 1. P. 76–83.
22. McCallum RW, Fink SM, Lerner E, et al. Effects of metoclopramide and bethanechol on delayed gastric emptying present in gastroesophageal reflux patients. Gastroenterology 1983; 84: 1573.
23. Hasler WL. Disorders of gastric emptying. Textbook of gastroenterology 2002: 1341–69.
24. Richards RD, Davenport K, McCallum RW. The treatment of idiopathic and diabetic gastroparesis with acute intravenous and chronic oral erythromycin. Am J Gastroenterol 1993; 88: 203.
25. Kahrilas PJ, Pandolfino JE. Gastroesophageal reflux disease and its complications, including Barrett's metaplasia. In: Feldman M. et al: (editors). Slelsenger and Fordtran s Gastromtestmal and Liver Disease, Pathophysiology / Diagnosis / Management, 7th Edition, Saunders, Philadelphia 2002; 1: 599-622.
26. Katz PO. Optimizing Medical Therapy for gastroesophageal reflux disease, State of the art: Reviews in Gastroenterological disorders: 2003; 3L2: 59–69.
27. Holtman G, Talley NJ, Libgrets T, at al. A placebo-controlled trial of itopride in functional dyspepsia. N Engl J Med 2006; 354: 832-40.
28. Masayuki N, et al. Effect of itopride hydrochloride on diabetic gastroparesis. Kiso to Rinsho 1997; 31: 2785–91.
29. Savant P, Das HS, Desai N, at al. Comparativ evaluation of the effiacacy and tolerability of itoprid hydrochloride and domperidone in patients with non-ulcer dyspepsia. JAPI 2004; 52: 626-28.
30. Babu S. Drug Therapy of Gastroesophageal Reflux Disease (GERD): Focus on Itopride Hydrochloride. Indian Practitioner 2003; 56 (12): 827-830. 2003; 56 (12): 827-30.
31. Inoue K, Sanada Y, Fujimura J, et al. Clinical effect of itopride hydrochloride on the digestive symptoms of chronic gastritis with reflux esophagitis. Clinical Medicine 1999; 15 (11): 1803-08.