Metoclopramide Overview

Drug Classification

Metoclopramide is classified as a dopamine antagonist. It is also known as a prokinetic agent due to its effects on gastrointestinal motility.

Indications for Use

Primarily indicated for the treatment of gastroesophageal reflux disease (GERD) and diabetic gastroparesis. It is also used to prevent nausea and vomiting associated with certain medical treatments and conditions.

Mechanism of Action

It works by blocking dopamine receptors in the brain and the gut. This, in turn, enhances the movements of the stomach and intestines, promoting gastric emptying.

Medication Guidelines

Administration Methods

Oral tablets and liquid formulations are common. Injectable forms are used in hospital settings. The mode of administration depends on the condition being treated and the patient’s medical needs.

Dosage Information

Typical dosing for GERD is 10 to 15 mg up to four times daily, 30 minutes before meals and at bedtime. For diabetic gastroparesis, the dose is generally 10 mg taken 30 minutes before each meal and at bedtime for two to eight weeks.

Special Population Considerations

In the elderly, the dose should be reduced due to increased sensitivity to the drug. Pediatric dosing requires careful adjustment based on weight and clinical response.

Physiological Effects

Central Nervous System

In the CNS, metoclopramide affects the chemoreceptor trigger zone (CTZ) to alleviate nausea. It also crosses the blood-brain barrier, acting on dopamine receptors to exert its therapeutic effects.

Gastrointestinal Tract

Increases the tone and amplitude of gastric contractions. Facilitates the transit of gastrointestinal contents and enhances gastric emptying without affecting gastric secretions.

Endocrine System

Can increase the release of prolactin due to its dopamine antagonist properties. This effect may lead to galactorrhea, gynecomastia, or menstrual disturbances.

Potential Side Effects

Extrapyramidal Symptoms

These include acute dystonia, akathisia, and parkinsonism. Symptoms may occur within a few days of initiating therapy.

Gastrointestinal Reactions

Common gastrointestinal side effects include cramps, diarrhea, and constipation. Reduced bowel transit time is often reported during treatment.

Psychiatric Effects

May cause symptoms such as anxiety, restlessness, and depression. Monitor patients for changes in mood and behavior.

Drug Interactions

Concomitant Medications

Anticholinergic drugs may reverse the effects of metoclopramide on gastrointestinal motility. Combining with other CNS depressants like alcohol and sedatives can enhance central nervous system depression.

Impact on Metabolism

Inhibits the metabolism of drugs metabolized by cytochrome P450 enzymes. It may enhance the levels and effects of certain drugs, requiring dosage adjustments.

Sympathomimetic Interactions

Can increase catecholamine activity, caution advised when used with sympathomimetics, which can increase the risk of hypertensive crisis.

Pharmacokinetics Profile

Absorption and Distribution

Well-absorbed from the gastrointestinal tract. Peak plasma concentrations are achieved within one to two hours after oral administration. Distributed widely in body tissues and crosses the blood-brain barrier.

Metabolism Pathways

Undergoes first-pass metabolism in the liver, metabolized primarily by cytochrome P450 enzymes. The majority of the drug is metabolized to inactive compounds.

Elimination Half-life

The elimination half-life ranges from 5 to 6 hours. Excreted predominantly by the kidneys, about 25% is excreted unchanged in the urine.

Overdose Management

Immediate Measures

Administration of activated charcoal to reduce gastrointestinal absorption. Gastric lavage may be appropriate if performed soon after ingestion.

Symptomatic Treatment

Extrapyramidal symptoms can be treated with anticholinergic agents such as diphenhydramine. Severe cases may require intensive supportive measures and monitoring.