When you need to take prokinetic medications: we relieve bloating and nausea. Metoclopramide or domperidone, which is better?

And intestines. Almost every disease is characterized by a violation of motor function. However, in some cases they may appear as signs of any other disease that is in no way related to problems of the digestive system. In any case, you cannot do without prokinetic medications. The list of drugs included in this group has almost no restrictions on its use. That is why the doctor selects each remedy strictly individually.

What are prokinetics: general characteristics

Prokinetics include pharmacological drugs that, through various mechanisms, change the activity of the stomach and intestines and speed up the process of food passage.

These medications are indicated for use in the presence of diseases of the digestive tract. Mostly problems arise due to disturbances in the activity of the stomach. In addition, they are indicated to be taken as a medicine to prevent attacks of vomiting.

Action of prokinetics

Prokinetic drugs help to activate the motility of the digestive tract and are also characterized by a pronounced antiemetic effect. Such medications help speed up metabolic processes, improve muscle tone, and reduce reflux. They are prescribed as a separate medicine or in combination with other drugs. They are divided into several types according to the basic principle of their effect.

What types of prokinetics are there?

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

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

The list of prokinetic drugs includes macrolide antibiotics and 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 medicines whose pharmacological properties are just beginning to be studied.

The most famous and well-studied drugs are selective prokinetics, dopamine receptor blockers, which enhance intestinal and gastric motility. Doctors recommend taking these medications three times a day for 10-14 days, always before bed. Such medications are presented in the form of tablets and injections.

Dopamine receptor blockers

The principle of action on different 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. The principle of their action is that they improve the functioning of the stomach and help get rid of attacks of nausea.

The most effective prokinetics for the intestines are:

• "Metoclopramide";
• "Domperidone";
• "Bromopride";
• "Dimetpramide".

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

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

They may be ineffective in case of vomiting of vestibular origin. They contain the active ingredient metoclopramide, which has been used for a long time. The effect of such drugs is to:

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

However, such drugs can cause many side effects, which is why you should initially undergo a comprehensive examination and consult a doctor.

There are also first generation prokinetics. The list of medications is quite extensive, and includes:

• "Cerucal";
• "Perinorm";
• "Raglan".

One of the main disadvantages of such drugs is their ability to provoke menstruation disorders in women and deterioration of intestinal function. Second generation drugs contain the active ingredient domperidone. These drugs do not cause severe side effects, but their use may cause:

• weakness;
• drowsiness;
• headache;
• anxiety.

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

New generation prokinetics

Second generation medications are widely used to treat constipation and diseases of the stomach and intestines. 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 restore normal functioning of the stomach. This drug is used for the treatment of chronic gastritis and is approved for use by people over 16 years of age.

In addition, doctors prescribe Itomed and Itopride, as they have proven themselves very well due to their pronounced therapeutic effect, as well as the absence of side effects even after long-term use. They help increase intestinal muscle tone and gallbladder activity. "Itopride" is well absorbed in the digestive tract, and the maximum possible concentration of the active substance is achieved within 30-45 minutes after the first dose.

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. It also helps to quickly normalize stool. The most well-known 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 also includes drugs for the treatment of nausea and vomiting. When taken, the time for digestion of food in the stomach is significantly reduced, the speed of its movement through the intestines increases, and the tone of the walls of the gastrointestinal tract is normalized.

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

• "Sturgeon";
• "Tropisetron";
• "Silancetron".

These medications 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 a sedative effect and do not interact with other medications.

For what diseases is it prescribed?

Prokinetic drugs are indicated for disorders such as:

• nausea and vomiting;
• hiccups;
• impaired intestinal motor function;
• stomach and intestinal disorders;
• migraine;
• nausea and vomiting.

These drugs are characterized by the fact that they do not at all disrupt the secretory function of the stomach, that is, they do not affect the production of gastric juice. During treatment, these drugs are prescribed to 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 medications.

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 accumulated stool;
• osmotic laxatives;
• non-absorbable;
• contact.

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

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

Non-absorbable drugs include drugs based on lactulose. They have laxative properties in combination with probiotics. These products are safe and can be used for a long time, even during pregnancy. These products include “Laktovit”, “Duphalak”, “Normaze”.

Contraindications

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

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

It is not recommended to take these drugs for those whose professional activities involve high concentration of attention, as well as when driving a car. Prokinetics have been used for the treatment of diseases of the stomach and intestines for quite a long time, however, due to the likelihood of various kinds of complications, they should only be prescribed by the attending physician, based on the results of the examination.

Prokinetics for children: application features

Treatment of children with prokinetics should be carried out very carefully, as there is a high risk of gastric obstruction. These medications are prescribed depending on the child's weight. Most children are prescribed Motilium, as it is well tolerated and has a lot of positive reviews.

Up to 5 years it is recommended to use it in the form of a suspension. The drug is prescribed depending on the child’s weight, 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 of age. 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;
• slow 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 overdose or if used incorrectly, prokinetics can cause problems with the nervous system, especially in infants and young children.

Plant-based preparations that reduce gas formation and improve the digestion process are in great demand among parents. These include a medicine created on the basis of an extract of fennel fruits - “Plantex”.

Side effects

Prokinetic drugs are often recommended to be taken once or in short courses, as 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;
• bronchospasms;
• allergy;
• arrhythmia.

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

Features of application

Prokinetics are prescribed with special caution to people with renal and liver failure, as well as other disorders of the functioning of these organs. Such patients should take the medicine under the strict supervision of a doctor.

With prolonged use of prokinetics, it is necessary to undergo periodic examinations, as they can negatively affect the functioning of many internal organs. Infants and older people should take these medications especially carefully.

Before carrying out treatment, you should definitely consult a doctor, and you should not select analogues on your own, as this can have a bad effect on your health. If you feel worse, you should immediately stop taking the medicine and consult a doctor.

... currently, practicing doctors have a sufficient arsenal of modern prokinetic drugs for the rational treatment of dyskinesias in various parts of the gastrointestinal tract.

Prokinetics- pharmacological drugs that, at different levels and using different mechanisms, change the propulsive activity of the gastrointestinal tract and accelerate the transit of a food bolus through it.

Indications for which evidence of the effectiveness of prokinetics has been obtained:

1. diseases of the digestive tract, in the development of which a significant role is played by disturbances in the motor activity of the digestive tract (gastroesophageal reflux disease, postprandial distress syndrome as a variant of functional dyspepsia, peptic ulcer with impaired antroduodenal coordination, idiopathic gastroparesis, functional nausea, functional constipation, as well as irritable bowel - variant with constipation);

2. the use of prokinetics as antiemetics (for example, for nausea and vomiting associated with taking cytostatics);

3. diabetic gastroparesis, in which delayed gastric emptying affects the variability of glucose absorption, which causes difficulties in glycemic control and can lead to chronic symptoms of gastroparesis and low glycemic control; This also includes the prescription of prokinetics for gastroparesis of other etiologies.

According to the mechanism of action, existing prokinetics can be divided into the following groups:

1. dopamine receptor blockers:
1.1. non-selective (metoclopramide);
1.2. selective 1st generation (domperidone);
1.3. selective 2nd generation (itopride [Primer]);

2. 5-HT4 receptor agonists (tegaserod);

3. 5-HT3 receptor antagonists (ondansetron, tropisetron, alosetron, silansetron);

Macrolide antibiotics, hormonal peptides (sandostatin, octreotide), and opiate receptor antagonists also have prokinetic properties.

Some of these drugs have been used for several decades, others have just appeared on the pharmaceutical market. There are a number of drugs whose pharmacological capabilities are only being studied. The most studied and currently widely used prokinetics are non-selective and selective blockers of dopamine receptors, which can, to varying degrees, enhance motility of the entire gastrointestinal tract. The macrolide antibiotic erythromycin has prokinetic activity as a motilin receptor agonist. However, as a prokinetic agent, erythromycin is unlikely to find its therapeutic niche, and this is not only due to the antibacterial effect of the drug. Erythromycin, when taken for a long time (a month or more), doubles the risk of mortality associated with cardiac conduction disorders. Motilin receptor agonists. The polypeptide hormone motilin is produced in the distal stomach and duodenum, increases the pressure of the lower esophageal sphincter and increases the amplitude of peristaltic contractions of the antrum, stimulating gastric emptying. The study of the effectiveness and safety of long-term use of atilmotin, as well as research on the creation of new motilin agonists, continues. Thus, as one of the promising agents of this subgroup of prokinetics, the effects of ghrelin, a neurohumoral neurotransmitter secreted by the gastric mucosa, are being studied. Ghrelin is a physiological stimulant of gastrointestinal motility and is structurally related to motilin; it has a prokinetic effect with normalization of gastric emptying in patients with both diabetic and idiopathic gastroparesis.

Metoclopramide- according to its chemical structure, it belongs to the benzamide subtype with several prokinetic mechanisms: agonism of 5-hydroxytryptamine (HT) 4 receptors, antagonism towards central and peripheral dopamine (D) type 2 receptors, as well as direct stimulation of contractions of digestive smooth muscles tubes. Metoclopramide has been used in gastroenterology for quite a long time. Experience with its use has shown that the prokinetic properties of metoclopramide (increased tone of the lower esophageal sphincter, increased motor activity, accelerated gastric emptying and transit of contents through the small and large intestines), unfortunately, are combined with its unfavorable central side effects. This is due to the fact that metoclopramide penetrates the blood-brain barrier and causes serious side effects such as extrapyramidal disorders, dizziness, drowsiness and lethargy, as well as galactorrhea, hyperprolactinemia, gynecomastia, and menstrual irregularities. Typically, metoclopramide is prescribed for adults orally at 5–10 mg 3 times a day before meals; IM or IV - 10 mg; the maximum single dose is 20 mg, the maximum daily dose is 60 mg (for all routes of administration). It is in connection with the above disadvantages that drugs have been developed that belong to a new generation of drugs that block dopamine receptors - selective dopamine receptor blockers.

Domperidone- selective drug of the 1st generation. It is a peripherally acting selective dopamine antagonist that blocks D2 receptors in the central and peripheral nervous system. However, unlike metoclopramide, it hardly penetrates the blood-brain barrier and thus does not cause unwanted side effects on the central nervous system. The pharmacodynamic effect of domperidone is associated with its blocking effect on peripheral dopamine receptors localized in the wall of the stomach and duodenum. Domperidone increases the spontaneous activity of the stomach, increases the pressure of the lower esophageal sphincter and activates peristalsis of the esophagus and antrum of the stomach. The drug also increases the frequency, amplitude and duration of contractions of the duodenum and reduces the time of passage of food masses through the small intestine. The drug has no effect on other parts of the gastrointestinal tract due to the lack of specific receptors in them. In addition, the drug can be used to treat patients with secondary gastroparesis that occurs due to diabetes mellitus, systemic scleroderma, and also after gastric surgery. Typically, domperidone is prescribed in a dose of 10 mg 3-4 times a day 20 minutes before meals. Side effects with its use (usually headache, general weakness) are rare, and extrapyramidal disorders and endocrine effects occur only in isolated cases, which allows its use for a fairly long time (28–48 days). Domperidone is widely used in clinical practice as an effective and safe prokinetic agent. Even in countries with strict OTC regulations, this drug is usually sold without a prescription.

Itopride hydrochloride is both a dopamine receptor antagonist and an acetylcholinesterase blocker. Due to the dual mechanism of action, itopride has a positive effect on the tone of the lower esophageal sphincter, enhances the motor-evacuation function of the stomach, helps eliminate duodenogastric reflux, and increases the tone of the gallbladder. In addition, the drug increases motor activity and muscle tone of the small and large intestine, which makes its use potentially possible in irritable bowel syndrome (IBS) with a predominance of constipation, especially when IBS is combined with functional dyspepsia. Itopride has been shown to be effective in dyspepsia and IBS in clinical trials. The dual mechanism of action explains the positive effect of itopride (Primer) on the tone of the lower esophageal sphincter. Thus, along with antisecretory drugs, itopride, unlike domperidone, can be prescribed for GERD as a means that directly affects esophageal motility. Compared with domperidone, itopride has a more pronounced effect on the motor-evacuation function of the stomach in relation to both solid and liquid foods, improves the contractile function of the antrum of the stomach and, thus, more actively contributes to the elimination of duodenogastric reflux. In addition, the drug has an antiemetic effect, which is realized through interaction with D2-dopamine chemoreceptors of the trigger zone. In the case of IBS with a predominance of constipation, itopride can be used along with laxatives, as it increases intestinal tone and accelerates small and large intestinal transit. For adults and children over 12 years of age, itopride (Primer) is prescribed 1 tablet (50 mg) 3 times a day 15–30 minutes before meals. The average daily dose is 150 mg. The maximum daily dose should not exceed 1200 mg. The recommended course of treatment is 2–3 weeks.

Tegaserod- a partial 5-HT4 agonist, which in experimental studies has shown its ability to enhance gastrointestinal motility and reduce visceral sensitivity. In controlled studies in patients with constipation-predominant IBS, tegaserod showed significant clinical benefit compared with placebo. In patients with IBS with predominant constipation, tegaserod enhances small intestinal and proximal colonic motility, reduces abdominal discomfort, and normalizes stool frequency and consistency. Use 2–6 mg 2 times a day. Tegaserod does not have any cardiotoxicity or effect on blood pressure, pulse, or QT interval even when the dose is increased to 100 mg. Tegaserod is currently considered one of the most effective drugs for the treatment of IBS with constipation.

5-HT3 receptor antagonists. Since metoclopramide (and cisapride) were found to inhibit 5 HT3 receptors and stimulate 5 HT4 receptors, it has been suggested that at least part of their prokinetic effects are due to these effects. This concept was developed, and large-scale studies soon began to study other 5-HT3 receptor antagonists that would not be dopamine receptor antagonists and at the same time have prokinetic activity. The biological effects of serotonin (5-hydroxytryptamine, 5-HT) are due to its interaction with specific receptors: 5-HT, 5-HT2, 5-HT3, 5-HT4. One of the first serotonin receptor modulators is the drug tropisetron, which increases the pressure of the lower esophageal sphincter for a long period. 5-HT3 receptor antagonists (ondasetron, granisetron, tropisetron, alosetron, silansetron) accelerate the evacuation of food from the stomach. In the colon, 5-HT3 receptor antagonists increase the transit time of contents, reduce the tonic component of the gastrocolytic response to food administration, and normalize colon tone in patients with carcinoid diarrhea. Clinically, 5-HT3 receptor antagonists are effective in the treatment of patients with irritable bowel syndrome with dominant diarrhea. 5-HT4 receptors are localized in the nerve endings of cholinergic interneurons and motor neurons. Their stimulation is also accompanied by an increase in acetylcholine release and a prokinetic effect. Thus, possible mechanisms of action of drugs that interact with 5-HT receptors include blockade of 5-HT3 receptors or a combined effect. An example of a combined effect is cisapride (coordinax), which, on the one hand, is an agonist of 5-HT4 receptors, and on the other, an antagonist of 5HT3 receptors.

In the domestic gastroenterological literature there is no single generally accepted list of prokinetics. Different gastroenterologists define the range of prokinetic drugs differently. Many of the prokinetics can also be included in other groups (antiemetics, antidiarrheals and even antibiotics). In the “theoretical” (scientific) plan of analysis of the group of prokinetics, it is important that only a minority of the prokinetics existing in the world are present on the Russian market. However, for practical medicine this does not matter. Prokinetics that are not registered in Russia today are either prohibited (for example, by the FDA in the USA) or do not have any advantages over the approved ones. For the Russian patient, only two types of prokinetics are of interest: with the active substance domperidone(motilium, motilak, etc.) and with active ingredient itopride ().

Previously common prokinetic agents (cerucal, raglan, etc.) are considered obsolete due to the large number of side effects. For the same reasons, bromopride (bimaral), which is similar in pharmaceutical properties to metoclopramide, has not been sold in the Russian Federation for several years (it is prohibited in the USA). Cisapride (Coordinax, etc.), which was previously considered promising, was banned in 2000 in both the USA and the Russian Federation.

Trade names of prokinetic agents

• Domperidone (ATC code A03FA03): Damelium, Domet, Domperidone, Domperidone Hexal, Domstal, Motilak, Motilium, Motinorm, Motonium, Passazhix

• medicine with the active ingredient itopride hydrochloride: (primer on the Ukrainian pharmaceutical market)

• medications with active substance (ATC code A03FA01): apo-metoclop, metamol, metoclopramide, metoclopramide 0.01 g, metoclopramide-acri, metoclopramide-promed, metoclopramide hydrochloride, metoclopramide tablets 0.01 g, perinorm, raglan, ceruglan, cerucal

• medications with the active ingredient cisapride (ATC code A03FA02): coordinax, peristil, prepulsid, cisap

• medicine with the active ingredient bromopride (ATC code A03FA04): bimaral

• medications with the active ingredient bethanechol sold in the USA: Duvoid and Urecholine

Prokinetics - dopamine receptor antagonists

Dopamine receptor antagonists block D 2 -dopamine receptors and, thereby, have a stimulating motor function of the stomach and antiemetic effects.

D2-dopamine receptor antagonists include: metoclopramide, bromopride, domperidone, dimethpramide. Itopride is also an antagonist of D2-dopamine receptors, but it is also an inhibitor of acelinecholine and, therefore, is often not considered in the group of dopamine receptor antagonists.

The widely known prokinetics cerucal and raglan (active substance metoclopramide), the less well-known bimaral (bromopride) belong to the first generation prokinetics.
Domperidone is a second-generation prokinetic agent and, unlike metoclopramide (and bromopride), does not penetrate the blood-brain barrier and does not cause extrapyramidal disorders characteristic of metoclopramide: spasm of the facial muscles, trismus, rhythmic protrusion of the tongue, bulbar type of speech, spasm of extraocular muscles, spastic torticollis, opisthotonus, muscle hypertonicity, etc. Also, unlike metoclopramide, domperidone does not cause parkinsonism: hyperkinesis, muscle rigidity. When taking domperidone, side effects of metoclopramide such as drowsiness, fatigue, tiredness, weakness, headaches, increased anxiety, confusion, and tinnitus are less common and less pronounced. That's why Domperidone is a better prokinetic agent than metoclopramide .

Prokinetics - dopamine receptor antagonists are used in the treatment of GERD, gastric and duodenal ulcers, functional dyspepsia, achalasia of the esophagus, diabetic gastroparesis, postoperative intestinal paresis, biliary dyskinesia and flatulence.

Prokinetics from this group are also used for nausea and vomiting due to diet disorders, infectious diseases, early toxicosis of pregnancy, kidney and liver diseases, myocardial infarction, traumatic brain injury, anesthesia, radiation therapy, as a prophylaxis for vomiting before endoscopy and X-ray contrast studies. Dopamine receptor antagonists have no effect on vomiting for vestibular reasons.

According to the pharmacological index, prokinetic dopamine receptor antagonists belong to the group “Gastrointestinal motility stimulants, including emetics.” For ATC - to group A03FA “Gastrointestinal motility stimulants”.

Acetylcholine agonists — stimulants of intestinal motility

Drugs in this group are most often only partially classified as prokinetics, although all of them have prokinetic properties. In Russia, the most famous of the drugs in this group is coordinax. However, its active substance, cisapride, being a cholinomimetic, can cause the development of long QT interval syndrome and, as a consequence, life-threatening heart rhythm disturbances. Therefore, although it has the best prokinetic properties among drugs in its group, cisapride is not currently recommended for use and existing permissions for its use have been revoked.

This group also includes: the domestically developed M-cholinomimetic aceclidine (approved for use in the USSR), reversible cholinesterase inhibitors (physiostigmine, distigmine bromide, galantamine, neostigmine monosulfate, pyridostigmine bromide), as well as ceruletide and tegaserod.

Prokinetics - motilin receptor agonists

The hormone motilin is produced in the stomach and duodenum, increases the pressure of the lower esophageal sphincter and increases the amplitude of peristalsis in the antrum of the stomach, stimulating its emptying. Erythromycin (as well as other macrolides: azithromycin, clarithromycin, atilmotin, the latter is not approved for sale in the USA or Russia), interact with motilin receptors, imitating the action of the physiological regulator of the gastroduodenal migratory motor complex. Erythromycin can cause powerful peristaltic contractions, similar to those of the migratory motor complex, accelerating gastric emptying of liquid and solid food, erythromycin increases the rate of gastric emptying in a number of pathological conditions, in particular gastroparesis in diabetics and patients with progressive systemic scleroderma, reduces intestinal transit time contents in the proximal colon. However, it has virtually no effect on the motility of the esophagus and, therefore, is not used in the treatment of GERD (Maev I.V. et al.). However, erythromycin, when taken for a month or more, doubles the risk of mortality associated with impaired cardiac conduction and, therefore, is not considered as a promising prokinetic agent.

The table below summarizes the characteristics of the main prokinetics

Active substance	Trade marks	Mechanism of action	Prokinetic action	Antiemetic effect	QT interval prolongation	Extrapyramidal effects	Note
	tserukal, raglan, etc.	D 2 - antagonist, 5-HT 4 -agonist	expressed	expressed	does not cause	often	outdated product (not prohibited)
bromopride	bimaral	D 2 - antagonist, 5-HT 4 -agonist	expressed	expressed	does not cause	often	not allowed in the Russian Federation and the USA
domperidone	motilium, motilak, etc.	D 2 -antagonist	expressed	moderate	does not cause	rarely	most commonly used prokinetic agent
itopride		D 2 -antagonist, acetylcholine inhibitor	expressed	moderate	does not cause	rarely	new, promising prokinetic agent
cisapride	coordinatex, etc.	5-HT 4 -agonist	expressed	moderate	causes	infrequently	banned* in the USA and Russia
tegaserod	fractal, zelnorm	partial 5-HT 4 agonist	used to treat irritable bowel syndrome with constipation				banned in the USA (not sold in Russia)

*) the wording “prohibited” means that the regulatory authority initially approved the drug for use, and then, during the period of approval, issued a directive to withdraw the drug from circulation.

Currently, a common reason for visiting doctors is problems in the gastrointestinal tract. Almost each of them is characterized by impaired motor function. However, they can appear as symptoms of a disease not related to the digestive system. In any case, there is no way to do without prokinetic drugs. The list of drugs in this group has no limiting framework. Therefore, each doctor selects a 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, speed up the process of food transit and emptying, belong to this group.

As mentioned above, there is no single list of these drugs in the gastroenterological literature. Each doctor includes his own list of medications here. These include medications of other groups, such as: antiemetics, antidiarrheals, as well as some antibiotics of the macrolide group, hormonal peptides. First, 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 muscle tone of the gastrointestinal tract, and 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 differs 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. 5-HT3 receptor agonists.

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 motor function and have antiemetic properties. What are these prokinetics? The list of medications is as follows:

• "Metoclopramide."
• "Bromopride."
• "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 stomach emptying.
• Increasing the speed of food movement through the small and large intestines.

However, non-selective drugs can cause 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.

Second-generation selective drugs include drugs with the active ingredient domperidone. These medications do not cause severe side effects, but others may occur:

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

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

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

New generation prokinetics

Second-generation selective prokinetics include drugs with the active substance itopride hydrochloride. Such products have gained recognition due to their excellent therapeutic effect and the absence of side effects even with long-term use. Most often doctors prescribe:

• "Itomed."
• "Ganatom".
• "Itopride."

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

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

Intestinal prokinetics

These include 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. Helps normalize stool and reduce symptoms of irritable bowel.

Does not cause an increase in blood pressure and has no effect on the cardiovascular system. However, there are a fair number of side effects. The risk of stroke, angina pectoris, and 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-NT3 receptor antagonists

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

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

• "Tropisetron".
• "Sturgeon".
• "Ondasetron".
• "Silancetron".

I would like to note that 5-HT3 receptor antagonists do not have a 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 advantage of these drugs is that they do not have a sedative effect, do not interact with other medications, do not cause endocrine changes, and do not interfere with motor activity.

For what diseases is it prescribed?

As mentioned above, prokinetics are used in monotherapy or together with antibiotics. Doctors know that there are diseases for which the administration 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. Peptic ulcer of the stomach (duodenum).
4. Idiopathic gastroparesis.
5. Vomiting.
6. Constipation.
7. Diabetic gastroparesis.
8. Flatulence.
9. Nausea caused by drug and radiotherapy, infection, functional disorders, poor nutrition.
10. Dyspepsia.
11. Biliary dyskinesia.

Who should not take it

There are contraindications for prokinetic drugs:

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

Pregnant and nursing 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 medications 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 the fetus.

The benefits from it must exceed all possible risks. Prokinetics with the active substance metoclopromide can be used from this group only as prescribed by a doctor. Prokinetics are not prescribed in subsequent trimesters of pregnancy.

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

Prokinetics for children

Prokinetics with the active substance metoclopramide should be used with particular caution in children, as there is a risk of dyskinetic syndrome. It is prescribed depending on the child's weight.

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

• "Domperidone".
• "Metoclopromide."

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

Prokinetics are prescribed to children if the child has:

• Vomit.
• Nausea.
• Esophagitis.
• Slow 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, so all medications should be taken under the strict supervision and control 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 among parents of infants. This is a concentrate based on Plantex fennel fruits.

It is worth saying a few words about plant prokinetics.

Natural Helpers

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

• Common fennel.
• Pharmaceutical camomile.
• Black elderberry.
• Dill.
• Oregano.
• Motherwort.
• Dandelion.
• Melissa.
• Swamp dry grass.
• The plantain is big.
• Alder buckthorn.

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

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

The prokinetic properties of these vegetables manifest themselves very well if you take fresh juices prepared from them.

It is worth noting that you should not replace herbal medications during periods of exacerbation of diseases and without consulting a doctor.

Side effects

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

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

After discontinuation of the drug, side effects completely disappear.

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

Features of the use of prokinetics

Prokinetics should be prescribed very carefully to people with liver failure and poor kidney function. Such patients should be under strict medical supervision.

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

Caution should be exercised when prescribing drugs from this group to elderly patients.

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

Before taking, you should definitely consult your doctor. Your health depends on it. You should not replace a medicine with its herbal counterpart without first consulting a doctor.

What is better to take, Metoclopramide or Cerucal

As much as we might like it, digestive disorders, nausea and vomiting often occur in our lives at different ages. Whether it is a child suffering from banal functional digestive disorders, or a pregnant woman who cannot tolerate a pungent smell, a girl who cannot find a place for herself due to a migraine attack, or a person with cancer after radiation therapy. Cerucal and Metoclopramide are indispensable in these cases. These drugs belong to the pharmacological properties of central dopamine antagonists and have the same active ingredient - metoclopramide hydrochloride. Many people have questions: what is better to take Metoclopramide or Cerucal? Why does the latter cost so much more, since Metoclopramide and Cerucal are the same thing?

Are Cerucal and Metoclopramide the same thing or not?

According to its pharmacological properties, metoclopramide is classified as a blocker. dopamine (D 2) And serotonin (5-HT 3) receptors. It increases the tone of the stomach and intestines, thereby accelerating its emptying, eliminates food stagnation, prevents reflux, and stimulates intestinal motility. Has an antiemetic effect against vomiting of various origins. Normalizes the secretion of bile, reduces spasm of the sphincter of Oddi, which makes it possible to use metoclopramide for GIVP (functional disorders). Takes part in stimulating the secretion of prolactin.

De Jure Cerucal and Metoclopramide are the same drugs. In their composition, as mentioned above, they have the same active ingredient, belong to the same pharmacological group, and have the same indications and contraindications.

De facto, Cerucal and Metoclopramide are not the same thing. Cerucal is an original drug with the active substance - metoclopramide hydrochloride, on the basis of which, after the expiration of the patent period, all other drugs with the same active substance were synthesized. They are called generics (Metoclopramide-Acri, Melomide hydrochloride, etc.). Based on patient reviews and my personal experience, I will say that there are differences, but they cannot be called significant. Cerucal has less pronounced side effects than generic metoclopramides, and compared to some domestically produced metoclopramides, it even has a stronger therapeutic effect. It depends on what substance is used to produce the medicine, where it is taken and where it is produced. In some countries, they do not pay special attention to quality and production standards. This results in a cheaper price for lower quality.

Indications for use of Cerucal and Metoclopromide

1. Nausea and vomiting caused by:
   • chemotherapy and radiotherapy for oncology;
   • liver and kidney diseases;
   • traumatic brain injury (TBI);
   • migraine and migraine conditions;
   • the use of various drugs (digitalis, antibiotics, morphine and its derivatives);
2. Disorders of the motor-evacuation function of the stomach (conditions after surgery).
3. Inflammatory diseases of the stomach and duodenum (gastritis, reflux esophagitis, uncomplicated peptic ulcer).
4. Functional dyspepsia with:
   • liver cirrhosis;
   • chronic cholecystopancreatitis; (Read the article Dietary table No. 5 for diseases of the liver and gall bladder)
   • uremia.
5. Prolonged hiccups and belching.
6. For diagnostic purposes during fibrogastroduodenoscopy (FGDS, gastroscopy), X-ray diagnosis of diseases of the stomach and duodenum.

Contraindications to the use of Cerucal and Metoclopramide

• Allergic reactions (intolerance to metoclopraimd or excipients included in the composition);
• Acute, emergency conditions (“Acute abdomen”): gastrointestinal bleeding, perforation, obstruction;
• Confirmed or suspected pheochromocytoma (due to the risk of severe attacks of arterial hypertension);
• History of tardive dyskinesia caused by antipsychotics or metoclopramide;
• History of epileptic seizures: (grand and minor epileptic seizures, convulsive readiness);
• Various extrapyramidal disorders, including Parkinson's disease (cannot be taken with levodopa);
• Do not take together with drugs that stimulate dopamine receptors (Bromocriptine, Pergolide, etc.) and drugs that increase dopamine levels (Levodopa);
• Established methemoglobinemia with the use of metoclopramide or a history of NADH-cytochrome b5 reductase deficiency;
• Prolactin-dependent tumors;
• The drug should not be taken by children under one year of age.

Cerucal in ampoules of 2 ml (5 mg/ml) is represented by a sufficient number of analogues. The package contains in most cases 10 ampoules, but there are also 5, it all depends on the manufacturer. Cerucal and its analogues in injections can be used both intramuscularly and intravenously. For intramuscular administration, it is necessary to inject the contents of the ampoule into the muscle tissue. When administered intravenously, the ampoule will need to be diluted in physiological solution (0.9% NaCl solution) or in 5% glucose solution.

The injection form is of greater importance, since the tablet taken during severe nausea or vomiting, in almost 100% of cases, does not reach its destination and comes out along with the vomit.

• Metoclopramide Hydrochloride;
• Metoclopramide-Health, -ESKOM, -Promed, -Vial;
• Metukal-Health;
• Raglan.

Analog of Cerucal in tablets

• Perinorm;
• Apo-Metoclop;
• Melomide hydrochloride;
• Metamol;
• Metoclopramide-Acri, - Hydrochloride, -Health;
• Raglan.

Reglan is also available in the form of a flavored drinking solution in bottles of 200 ml of 0.1% (1 bottle contains 200 mg of metoclopramide).

Interestingly, Cerucal tablets and injections have the same potency. After injection, the medicine acts faster, but to take the pill you do not need a stranger to give the injection.

Analogs of Cerucal (Metoclopramide) with other active ingredients

The most common analogue of Cerucal (metoclopramide) is a drug with the active ingredient domperidone. Domperidone is very similar in pharmacological properties; it also blocks dopamine receptors and, accordingly, has almost the same indications for use.

• Domrid Sr;
• Domperidone - Hexal, - Sandoz, etc.;
• Motilium;
• Motinorm;
• Motorix;
• Nausilium;
• Peridon;
• Motilak.

Haloperidol is in most cases used in psychiatric practice for the treatment of mental disorders and acute psychoses, and is classified as an antipsychotic. Haloperidol also blocks dopamine receptors and, accordingly, has a pronounced antiemetic effect. The drug is available with a prescription and is therefore not available for sale.

Preparations with the active substance - haloperidol.

• Halopril
• Senorm
• Apo-Haloperidol
• Haloper Haloperidol decanoate
• Haloperidol-Acri, (-PAR -ratiopharm, -Richter, etc.)