Metoclopramide

Metoclopramide is a drug that is used to treat a variety of gastrointestinal disorders and a number of other conditions.

The drug has several pharmacological properties:

1. Procinetic action: Metoclopramide stimulates the movement of food through the gastrointestinal tract, improving gastric and intestinal motility. This may be useful for treating symptoms of vomiting, nausea, heartburn, and other gastrointestinal disorders.
2. Anti-emetic action: Metoclopramide helps reduce nausea and vomiting by blocking the action of dopamine in the vomiting center of the brain.
3. Reducing reflux: The drug may be effective in reducing acid reflux from the stomach into the esophagus, which helps reduce heartburn and other symptoms of gastroesophageal reflux disease (GERD).

Metoclopramide is usually taken orally in tablet or syrup form. It may also be used in injectable form in hospitals for urgent relief of nausea and vomiting.

It is important to note that metoclopramide can have side effects including drowsiness, dizziness, movement disorders and others. Therefore, the use of this drug should be under the supervision of a doctor and adhere to the recommended dosages. You should not take metoclopramide without consulting your doctor, especially if you have any other medical conditions or are taking other medications.

Indications Metoclopramide

1. Nausea and Vomiting: Metoclopramide is used for the symptomatic treatment of nausea and vomiting due to various causes such as surgery, drug therapy, radiation therapy, or gastrointestinal diseases.
2. Gastroesophageal reflux (GERD): Metoclopramide can be used to treat GERD symptoms such as heartburn, vomiting, dysphagia (difficulty swallowing), etc.
3. Hyperemesis gravidarum: In cases of severe nausea and vomiting, including hyperemesis gravidarum, metoclopramide may be prescribed to relieve symptoms.
4. Gastrointestinal motility support: Metoclopramide may be used to stimulate gastric and intestinal motility in patients with gastroparesis or other gastrointestinal motility disorders.
5. Chemotherapy treatment support: Metoclopramide is sometimes used as part of an antiemetic protocol when administering chemotherapy.

Release form

1. Tablets: The most commonly used form, intended for oral administration. Metoclopramide tablets may be standard-acting or modified-release for prolonged effect.
2. Oral solution (syrup): This form is suitable for patients who have difficulty swallowing tablets, including children and the elderly. The solution makes it easier to dose and take the medicine.
3. Injections: Metoclopramide in the form of injections is used for rapid relief of symptoms when oral administration is not possible or desirable. Injections can be given intramuscularly (IM) or intravenously (IV).
4. Rectal suppositories: Although less common, suppositories may be used to relieve nausea and vomiting when other routes of administration are inappropriate or ineffective.

Pharmacodynamics

1. Anti-emetic action:

   • Metoclopramide is an effective antiemetic due to its effect on dopamine D2 receptors in the area of the permanent vomiting center in the cerebellum. It reduces the gag reflex and stimulates gastric motor activity, which helps to accelerate digestion and movement of food through the gastrointestinal tract.

2. Prokinetic action:

   • Metoclopramide stimulates upper gastrointestinal motor activity by increasing acetylcholine release and suppressing dopamine inhibition. This may be useful in the treatment of functional and organic digestive motility disorders such as gastroparesis and reflux esophagitis.

3. Decreased prolactin secretion:

   • Metoclopramide exerts prolactinsecretory effects by blocking dopamine D2 receptors in the anterior lobe of the pituitary gland. This may be useful in the treatment of hyperprolactinemia and its associated symptoms such as hyperprolactinemic amenorrhea and galactorrhea.

4. Central Action:

   • Metoclopramide may have central sedative and anxiolytic effects associated with its effects on dopamine and serotonin receptors in the central nervous system.

5. Additional effects:

   • In some cases, metoclopramide may have antidepressant, anti-inflammatory, and antioxidant effects, although the mechanisms of these effects require further investigation.

Pharmacokinetics

1. Absorption: Metoclopramide can be efficiently absorbed from the gastrointestinal tract after oral administration. Food may slow the rate of absorption but usually does not affect total absorption.
2. Distribution: It is well distributed in the body and can penetrate the blood-brain barrier, allowing it to affect the central nervous system and reduce nausea and vomiting.
3. Metabolism: Metoclopramide is metabolized in the liver, mainly through hydroxylation and conjugation. The major metabolite is metoclopramide sulfoxide.
4. Excretion: Excretion of metoclopramide from the body occurs mainly through the kidneys. About 85-95% of the dose is excreted unchanged within the first 24 hours after administration.
5. Half-life: The half-life of metoclopramide is about 5-6 hours in adults and up to 15 hours in neonates.
6. Mechanism of Action: Metoclopramide is an antagonist of dopamine D2 receptors in the central nervous system. It also has a stimulatory effect on gastrointestinal motility by increasing the release of acetylcholine.

Dosing and administration

Adults

• Oral (ingestion): The standard dose is 10 mg 30 minutes before meals and before bedtime, up to 4 times daily, depending on symptoms and response to treatment. The maximum daily dose should not exceed 40 mg.
• Intravenousand intramuscular administration: The dosage for injection is usually 10 mg up to 4 times a day. Intravenous administration should be done slowly, for at least 1-2 minutes, to avoid side effects.

Children

The dosage of metoclopramide for children is calculated individually, based on body weight, and should be determined by a doctor. In general, it is 0.1-0.15 mg per kilogram of body weight 30 minutes before meals and before bedtime, up to 3-4 times a day.

Special Instructions

• The duration of treatment with metoclopramide should usually not exceed 12 weeks because of the risk of side effects, including movement disorders.
• Carefully follow your doctor's instructions regarding the length of the course of treatment and do not stop taking it suddenly without consulting a specialist, especially for long-term use.
• When metoclopramide is administered intravenously, it should be administered slowly to minimize the risk of side effects such as orthostatic hypotension.

Use Metoclopramide during pregnancy

When metoclopramide is used during pregnancy, the potential risks and benefits to the mother and fetus must be considered. There are insufficient data to state its safety during pregnancy, especially in the early stages. Therefore, it is generally recommended to avoid the use of metoclopramide during pregnancy, especially without consulting a doctor.

However, in some cases, when the potential benefits to the mother outweigh the possible risks to the fetus, the doctor may decide to prescribe metoclopramide during pregnancy. This may be necessary in cases of severe nausea and vomiting associated with pregnancy (called hyperemesis gravidarum).

Contraindications

1. Hypersensitivity: People with known hypersensitivity to metoclopramide or any other components of the drug should not use it, as it may cause allergic reactions.
2. Pituitary tumors: Metoclopramide may stimulate prolactin production and may be contraindicated in patients with pituitary tumors such as prolactinomas.
3. Mechanical or perforated bowel obstruction: The use of metoclopramide may be contraindicated in the presence of mechanical or perforated bowel obstruction as it may exacerbate symptoms and complicate the condition.
4. Pheochromocytoma: Metoclopramide may exacerbate symptoms of pheochromocytoma, including high blood pressure, and is therefore contraindicated in patients with this condition.
5. Epilepsy: Metoclopramide may worsen the seizure threshold, therefore its use may be contraindicated in patients with epilepsy or other disorders associated with the occurrence of seizures.
6. Pregnancy and breastfeeding: Data on the safety of metoclopramide during pregnancy and breastfeeding are limited and its use should be evaluated and recommended by a physician.
7. Children: The use of metoclopramide in children should be cautious and should only be prescribed by a doctor, especially in children with certain medical conditions.

Side effects Metoclopramide

1. Drowsiness and fatigue: Metoclopramide may cause drowsiness or fatigue, especially at the beginning of treatment or with increasing dosage.
2. Insomnia: Metoclopramide may cause insomnia or sleep disturbances in some people.
3. Dizziness: Some patients may experience dizziness or a feeling of unsteadiness.
4. Heart palpitations or changes in heart rhythm: Rarely, metoclopramide may cause changes in heart rhythm such as palpitations or arrhythmias.
5. Dry mouth: Metoclopramide may cause dry mouth in some people.
6. Digestive disorders: This may include diarrhea, constipation, nausea or vomiting.
7. Masking the symptoms of tardive dyskinesia: This is a rare but serious side effect in which metoclopramide can mask the symptoms of tardive dyskinesia, a condition characterized by involuntary movements that may become irreversible.
8. Elevation of prolactin: Metoclopramide may increase prolactin levels in the blood, which may lead to undesirable effects in men (e.g. Gynecomastia) and in women (e.g. Hyperprolactinemic amenorrhea).

Overdose

1. Extrapyramidal symptoms: Includes dyskinesias, dystonia, psychomotor agitation, muscle spasms and tremors. These symptoms are associated with blockage of dopamine receptors in the central nervous system.
2. Sedation and drowsiness: Excess metoclopramide may cause drowsiness, lethargy, general weakness and even loss of consciousness.
3. Cardiotoxicity: In some cases, overdose may lead to heart rhythm disturbances, including arrhythmias and prolongation of the QT interval.
4. Anticholinergic symptoms: Include dry mouth, constipation, blurred vision, urinary disturbances, etc.
5. Neuroleptic syndrome: In rare cases,neuroleptic syndrome may develop, manifested as hyperthermia, convulsions, decreased consciousness and other symptoms.
6. Other symptoms: Nausea, vomiting, diarrhea, hypertension, hypotension and other undesirable effects may also occur.

Interactions with other drugs

1. Antiemetics: Metoclopramide may enhance the effects of other antiemetics such as centrally acting antiemetics (e.g. Dimenhydrinate), which may result in increased sedation.
2. Drugs affecting the cardiovascular system: Metoclopramide may increase the effect of antihypertensive agents, such as antihypertensive drugs or drugs that reduce heart rhythm (e.g. Beta-adrenoblockers), which may lead to a significant decrease in blood pressure.
3. Drugs affecting the central nervous system: Metoclopramide may increase the sedative and anticholinergic effects of other drugs such as benzodiazepines or antidepressants, which may result in increased drowsiness and decreased responsiveness.
4. Drugs that cause QT-interval prolongation: Metoclopramide may increase the risk of arrhythmias when used concomitantly with other drugs that cause QT-interval prolongation, such as antiarrhythmic drugs or antibiotics from the macrolide group.
5. Drugs that increasemediator secretion: Drugs that increase mediator secretion (e.g. Antihistamines) may reduce the efficacy of metoclopramide.
6. Drugs that cause extrapyramidal symptoms: Use of metoclopramide with other drugs that may cause extrapyramidal symptoms (e.g. Neuroleptics) may increase this side effect.