How metoclopramide works
The active ingredient metoclopramide (MCP) has a stimulating effect on gastric emptying and small intestinal passage (prokinetic) and an emetic (antiemetic) effect.
The human body sometimes protects itself from the absorption of toxic substances via the digestive tract by vomiting. As soon as certain substances enter the blood via the stomach or intestinal mucosa, they are transported via the bloodstream to the so-called medulla oblongata.
This is where the vomiting center is located. It has a special area: the so-called chemoreceptor trigger zone with numerous docking sites (receptors) for a wide variety of messenger substances. Harmful substances can be registered here directly by the vomiting center (there is no blood-brain barrier in this area). The body reacts with nausea and vomiting to prevent further absorption of the harmful substance.
Certain drugs can be used to inhibit receptors in this chemoreceptor trigger zone and thus suppress nausea and vomiting. These agents include metoclopramide:
MCP inhibits dopamine D2 receptors and, at higher doses, certain serotonin receptors. Dopamine and serotonin are important nerve messengers.
Absorption, degradation and excretion
After ingestion, MCP is rapidly absorbed into the blood through the intestinal wall and reaches peak blood levels after about one hour. The active ingredient is largely broken down by the liver and excreted in the urine.
In this way, about 80 percent of the active ingredient is eliminated from the body. However, this process is slowed down in cases of kidney dysfunction.
When is metoclopramide used?
MCP is used to:
- prevention and treatment of nausea and vomiting
- Therapy of disorders of gastrointestinal movement (motility disorders)
The duration of treatment should be kept as short as possible. It should not exceed five days.
How metoclopramide is used
Preparations containing metoclopramide come in many dosage forms. On the one hand, there are oral preparations (drops, tablets, capsules). Adults usually take ten milligrams three times a day before meals with a glass of water.
Secondly, the active ingredient can also be administered in the form of injections and suppositories. This is particularly advantageous in cases of severe vomiting – oral preparations would then not remain in the body long enough for the active substance to be absorbed into the blood.
What are the side effects of metoclopramide?
In addition, one in ten to one hundred people treated experience side effects such as diarrhea, weakness, depression, low blood pressure and – especially in children – extrapyramidal movement disorders (dyskinesias). These are movement disorders, especially in the facial region, which in rare cases are delayed and may be irreversible.
Occasionally, a drop in blood pressure or an excess of prolactin in the blood (hyperprolactinemia) is observed as a result of MCP intake.
What should be considered when taking metoclopramide?
Contraindications
Metoclopramide must not be used in:
- Gastrointestinal bleeding
- pheochromocytoma (rare tumor of the adrenal medulla)
- known extrapyramidal movement disorders
- Parkinson’s disease
- Methemoglobinemia (increased blood level of methemoglobin = derivative of hemoglobin, which unlike hemoglobin cannot bind oxygen)
Drug interactions
Metoclopramide must not be used together with agents for the treatment of dopamine deficiency diseases (such as Parkinson’s disease), which are supposed to lead to higher dopamine levels in the brain. This is because MCP would weaken their effect.
Centrally depressant drugs such as strong painkillers, anti-allergic agents, sedatives and sleeping pills as well as alcohol may increase the depressant effect of metoclopramide.
If MCP is combined with other active ingredients that lead to increased serotonin levels in the brain, life-threateningly high serotonin levels and the so-called serotonin syndrome can occur (acute life-threatening condition with palpitations, fever, nausea, vomiting, etc.). This applies, for example, to antidepressants (especially SSRIs), some painkillers, migraine medications and tryptophan (a mild sleep-inducing agent).
Metoclopramide increases the availability of ciclosporin (immunosuppressant) and decreases the availability of digoxin (heart failure medication) and oral contraceptives (“the pill”).
MCP is broken down in the liver with the involvement of the enzyme CYP2D6. CYP2D6 inhibitors (e.g., fluoxetine, paroxetine) may therefore potentiate the effects and side effects of metoclopramide. Conversely, CYP2D6 inducers (including dexamethasone, rifampicin) may attenuate the effect of MCP.
Age Limitation
Metoclopramide tablets are approved for ages nine years and older. Drops and suppositories are available for children one year of age and older.
Pregnancy and lactation
MCP may be used for a short time during breastfeeding. If therapy is prolonged, there is a possibility that the active ingredient may pass into breast milk and cause side effects in the infant (e.g., flatulence, slightly elevated prolactin levels).
How to obtain medication with metoclopramide
All preparations containing the active ingredient metoclopramide require a prescription in Germany, Austria, and Switzerland. Since 2014, high-dose MCP drops (4mg/ml) are no longer approved. Lower-dose drops (1mg/ml) are still available.
The suppositories and sustained-release capsules (delayed-release capsules) available in Germany are not on the market in Switzerland and Austria.
How long has metoclopramide been known?
Metoclopramide was first manufactured in 1964. The preparations that have been on the German pharmaceutical market for the longest time received their initial approval in 1979. In the meantime, there are numerous generics containing the active ingredient.
