VERIFIED CONTENTAuthor: Dominika Wilk

Prokinetic drugs are used in gastrointestinal motility disorders, where there is a slow intestinal transit or too slow gastric emptying. Thanks to their action, they reduce the number of flatulence, minimize the feeling of overflow in the stomach and make the functioning of the digestive system more efficient.

ProkineticsThese are both pharmacological drugs and herbal substances which, by acting on various mechanisms related to neurotransmitters, are able to affect the muscular membrane of the digestive system. They stimulate the peristalsis in the esophagus, empty the stomach faster, and shorten the passage of the intestinal contents.

This has nothing to do with the laxative effects that are usually found in constipation remedies. They also do not loosen the fecal masses. They only restore the proper functioning of, for example, MMC (a wandering myoelectric complex that is responsible for cleansing the intestines of food debris). In turn, by facilitating pyloric relaxation, as well as increasing the amplitude of gastric contractions, they allow food to pass from the stomach to the duodenum faster.

In which diseases are prokinetics used?

Prokinetics are most often prescribed by doctors in the case of diseases accompanied by impaired digestive system function and in cases where the patient reports a tendency to constipation or retention of food in the stomach.

The most common reasons for using procient drugs are:

  • gastroesophageal reflux disease,
  • esophageal motility disorders,
  • dyspepsia,
  • gastroparesis,
  • and the necessity to perform endoscopy in the presence of upper gastrointestinal bleeding or selectively in the case of pseudo-obstruction or impaired tolerance of enteral nutrition.

Prokinetics in gastro-esophageal reflux disease

Gastro-oesophageal reflux disease (GERD) is one of the more popular diseases with which patients visit a gastroenterologist. It is based on the acid reflux into the esophagus, which results in:

  • burning sensation in the throat as well as behind the breastbone,
  • bitter taste in the mouth,
  • pain inepigastric,
  • acid reflux cough,
  • chest pain.

This condition can also lead to damage to the enamel of the tooth and the formation of erosions, which increases the risk of caries.

There may be various reasons for the appearance of acid reflux disease:

  • may be due to a malfunction of the lower esophageal sphincter,
  • malfunctioning esophageal motor,
  • too slow gastric emptying,
  • as well as excessive pressure increase both in the stomach and abdominal cavity.

In addition, GERD may be associated with inappropriate eating habits, e.g. eating too large meals at once, eating just before going to bed or resulting from inappropriate lifestyle habits: e.g. sitting too long and not being physically active or experiencing too much stressful situation.

Treatment of gastro-oesophageal reflux disease consists primarily of administering PPIs (proton pump inhibitors) to reduce gastric acid secretion. Another, no less important drug are prokinetics, which increase pressure in the lower gastric sphincter as well as accelerate gastric emptying.

Thanks to this, they reduce the number of reflux episodes, as the gastric contents do not return to the esophagus as often. The most common prokinetics used in this disease are:

  • metoclopramide,
  • cisapride
  • and itoprid.

However, the first two cannot be used in a long-term manner as they cause many side effects.

Itopride is the safest, but the time of its use is also limited. It is usually given for 8 weeks, but if your individual circumstances require it, your doctor may prescribe it for a longer period of time. Research shows that prokinetic drugs can be helpful not only in the treatment of gastroesophageal reflux disease, but also its version beyond the esophagus, which affects the larynx and is subject to ENT treatment.

Prokinetics in functional dyspepsia

Functional dyspepsia is a functional disorder of the digestive tract not associated with organic changes. Some patients who have this condition experience epigastric pain, others - too slow emptying of the stomach, others - nausea or excessive belching after eating. Due to the frequent feeling of overflow, patients experience anorexia.

The specific causes of this condition have not yet been established. It is suspected that both genetic andenvironmental, psychosomatic, and those related to visceral hypersensitivity, disorders of the nervous system, and gastrointestinal motility disorders.

To be able to talk about functional dyspepsia, the existence of: other organic diseases that may disturb the digestive tract, metabolic and electrolyte disorders, or other functional digestive system disorders, e.g. gall bladder disorders, should be excluded.

The doctor must also make sure that it is not the result of regular consumption of ethyl alcohol or taking medications that may disturb the gastrointestinal motility.

Treatment of functional dyspepsia depends on the symptoms reported by the patient. If the patient is accompanied by epigastric pain, then the more important drugs are antacids - PPIs. On the other hand, when the symptoms are related to the feeling of being overcrowded after meals, getting satiety too quickly, then the most important drugs will be prokinetics.

Prokinetics in gastroparesis

Gastroparesis is delayed gastric emptying caused by an anatomical neuropathy that can have a variety of causes. It may result from complications after surgery, when the vagus nerve is damaged, it may also be the result of diabetes mellitus, as well as a consequence of connective tissue diseases, e.g. scleroderma.

The most common symptoms of this condition are:

  • nausea,
  • fast saturation after a meal,
  • abdominal pain and bloating,
  • weight loss,
  • vomiting.

An important element in the treatment of gastroparesis is changing eating habits, e.g. eating smaller meals. It is also important to limit the amount of fat and fiber in them and eat the last meal at least 2 hours before bedtime. It is equally important to stop drinking carbonated drinks and to balance your blood glucose levels.

In the treatment of this disease, prokinetics are helpful, which stimulate gastric motility, and thus facilitate its emptying.

The safest drug that can be used for a long time in gstroparesis is itopride, and for short-term use, cisapride, erythromycin or domperidone are suitable.

Characteristics of the most popular prokinetics

Itopryd

Itopride hydrochloride is a drug whose action is based on blocking dopamine receptors - D2, thanks to which it is possible to increase the release of acetylcholine. Acetylcholine causes greater contractility of the gastrointestinal tract and stimulation of the motility of both the upper and lower gastrointestinal tract, which affects, for example,faster gastric emptying.

It is important that the action of itopride on dopamine D2 receptors is limited only to peripheral receptors, not those that act on the central nervous system.

This avoids many undesirable effects, such as extrapyramidal symptoms or hyperprolactinemia. Another advantage of itopride is its selective action. This means that it has no affinity for other receptors, which reduces the risk of drug interactions.

The main indication for the use of itopride is:

  • indigestion,
  • abdominal gas,
  • feeling that your stomach is full after eating a small meal,
  • epigastric pain,
  • lack of appetite,
  • nausea,
  • vomiting,
  • heartburn
  • and gastrointestinal complaints in general, not accompanied by ulcers, and resulting from functional disorders of the digestive tract.

Treatment with itopride usually lasts 2 months. It is administered at a dose of 50 mg 3 times a day before meals. A contraindication to the use of itopride is hypersensitivity to it or to other substances that are part of the prokinetic.

Itopride use may or may not cause side effects. With this drug uncommonly (i.e. ≥ 1/1000 to<1/100), może pojawić się:

  • leukopenia,
  • hyperprolactinemia,
  • irritability,
  • headaches,
  • dizziness,
  • sleep disorders,
  • stomach ache,
  • constipation,
  • diarrhea,
  • salivation,
  • chest pain,
  • fatigue,
  • back pain.

In addition, they can rarely appear:

  • pruritus,
  • erythema,
  • or rash.

In a few cases (unknown frequency) it can be:

  • jaundice,
  • increasing the concentration of urea nitrogen and creatinine,
  • increased activity of: bilirubin, AST, ALT, alkaline phosphatase, GGTP,
  • nausea,
  • trembling,
  • gynecomastia,
  • Anaphylactoid reactions.

Metoclopramide

Metoclopramide is an antagonist of dopamine D2 receptors, it also stimulates the cholinergic system to release acetylcholine. In addition, it affects the activity of 5-HT4 serotonin receptors. All this causes that it stimulates the peripheral motor activity of the upper digestive system, positively influences gastric emptying and improves the functioning of esophageal peristalsis, as it increases the tone of the LES (lower esophageal sphincter).

In addition to the prokinetic action,metoplocramide is also used as an antiemetic. For this reason, it is used not only in gastroparesis, but also in nausea and vomiting that accompany migraines or radiotherapy. Due to a number of side effects, it can only be used for a short time.

Side effects associated with the use of metoclopramide include:

  • excessive motor agitation,
  • uncontrolled movements,
  • tiki,
  • muscle spasms,
  • lowering blood pressure,
  • anxiety,
  • weariness,
  • depression,
  • diarrhea,
  • Is general weakness.

The above-mentioned symptoms are common. Less often, after using this drug, we deal with:

  • allergic,
  • acute dystonia,
  • visual impairment,
  • uncoordinated body movements independent of our will,
  • increasing the level of prolactin,
  • irregular periods.

Under the influence of this drug, rarely but still possible, it may lead to:

  • seizures,
  • visual impairment,
  • insomnia,
  • dizziness,
  • swelling of the tongue or larynx.

However, it very rarely happens:

  • lowering the number of white blood cells,
  • rashes,
  • hives
  • or bronchospasm.

Although metaclopramide brings improvement in diseases associated with gastrointestinal motility disorders, not everyone can use it. It cannot be used by people who are allergic to metoclopramide or another active substance that is part of the prokinetic.

In addition, it cannot be used for gastric or intestinal perforation, obstruction or bleeding.

Not recommended for people with epilepsy and Parkinson's, as well as those taking levodopa or dopamine agonists.

Also, it is not possible to use it when someone is prone to involuntary muscle contractions after taking medications (if there have been such cases in the past).

Cisapride

Cisapride is a 5-HT3 and 5HT1 receptor antagonist and a non-selective 5-HT4 receptor agonist. Due to the fact that it stimulates the motor activity of the upper gastrointestinal tract, it can be used in gastroparesis. However, due to its numerous side effects, its use has been limited only to exacerbations of idiopathic gastroparesis and that associated with diabetes.

The commencement of its use should be initiated in a hospital setting and be associated with close medical observation. Contraindication to taking cisapride is:

  • hypokalemia and hypomagnesaemia,
  • clinical bradycardia,
  • significant arrhythmias,
  • decompensated heart failure,
  • fructose intolerance,
  • glucose and galactose malabsorption.

In addition, it should not be used by people who take (orally or parenterally) drugs that are strong inhibitors of cytochrome P 450 3A4, e.g. nefazodone or drugs that induce ventricular tachycardia or drugs that prolong the QT interval.

Erythromycin

Although it is a macrolide antibiotic used in the treatment of bacterial infections, it is also used as a prokinetic, because it affects the amplitude of stomach contraction and facilitates its emptying. Used as a prokinetic, it is used in ¼ of the daily dose compared to its antibiotic effect.

Erythromycin acts on motilin receptors, which is a tissue hormone that stimulates, among others, contraction of smooth muscles of the small intestine, positively influencing the stimulation of the MMC (a traveling myoelectric complex that cleans the body of food residues in the intervals between meals).

Currently, this drug is used for short-term therapies, mainly in cases of gastroparesis and in hospitalized patients with difficulties in enteral nutrition.

Not every person for whom there are indications can use erythromycin. It cannot be taken by patients with hypersensitivity to this substance or other excipients contained in the drug containing erythromycin.

Besides, it cannot be taken by people using:

  • terphenadine,
  • cisapride,
  • domperidon,
  • astemizol,
  • ergotamine,
  • dihydroergotamine,
  • pimozide.

Also people with a tendency to ventricular tachycardia or prolonged QT interval, with arrhythmias, with disturbed electrolyte balance, cannot use this drug.

People who have no contraindications to take erythromycin, however, must remember that its use may have side effects, e.g. it may lead to:

  • anaphylaxis,
  • hives,
  • erythema multiforme,
  • hearing impairment,
  • arrhythmia,
  • ventricular fibrillation,
  • cardiac arrest,
  • pseudomembranous colitis,
  • liver failure
  • or cholestatic hepatitis,
  • interstitial nephritis.

Iberogast

Iberogast is a herbal medicine, but its prokinetic effect is highly appreciated. It consists of a mixture of 9 herbs, namely:

  • chamomile,
  • lemon balm,
  • mint,
  • caraway,
  • licorice,
  • thistle,
  • bitter dress,
  • celandine,
  • angelica.

Studies with Iberogast as well as with placebo show that herbal medicine is more effective in minimizing symptoms associated with functional dyspepsia and irritable bowel syndrome than placebo. In addition, the results of the meta-analysis of 12 clinical trials proved that it has as good a prokinetic effect as cisapride.

It is important that the use of Iberogast is not associated with the risk of side effects. The only side effects may result from hypersensitivity or allergy to any of the herbs in the mixture.

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