| Indication |
For the treatment of gastroesophageal reflux disease (GERD). It is
also used in treating nausea and vomiting, and to increase gastric
emptying. |
| Pharmacodynamics |
Metoclopramide, although chemically related to procainamide,
does not possess local anesthetic or antiarrhythmic properties.
Metoclopramide is used to enhance GI motility, to treat diabetic
gastroparesis, as an antinauseant, and to facilitate intubation of the
small bowel during radiologic examination. Metoclopramide may be used to
treat chemotherapy-induced emesis and as a radiosensitizing agents in
the treatment of non-small cell lung carcinoma and glioblastomas in the
future. |
| Mechanism of action |
Metoclopramide inhibits gastric smooth muscle relaxation produced
by dopamine, therefore increasing cholinergic response of the
gastrointestinal smooth muscle. It accelerates intestinal transit and
gastric emptying by preventing relaxation of gastric body and increasing
the phasic activity of antrum. Simultaneously, this action is
accompanied by relaxation of the upper small intestine, resulting in an
improved coordination between the body and antrum of the stomach and the
upper small intestine. Metoclopramide also decreases reflux into the
esophagus by increasing the resting pressure of the lower esophageal
sphincter and improves acid clearance from the esophagus by increasing
amplitude of esophageal peristaltic contractions. Metoclopramide's
dopamine antagonist action raises the threshold of activity in the
chemoreceptor trigger zone and decreases the input from afferent
visceral nerves. Studies have also shown that high doses of
metoclopramide can antagonize 5-hydroxytryptamine (5-HT) receptors in
the peripheral nervous system in animals. |
| Absorption |
Rapidly and well absorbed (oral bioavailability 80±15.5%). |
| Volume of distribution |
|
| Protein binding |
30% |
| Metabolism |
Hepatic |
| Route of elimination |
Approximately 85% of the radioactivity of an orally administered dose appears in the urine within 72 hours. |
| Half life |
5-6 hr |
| Clearance |
- 0.67 +/- 0.14 L/hr/kg [infants (0.9-5.4 months) with gastroesophageal reflux (GER)]
|
| Toxicity |
Oral, mouse LD50: 280 mg/kg. Signs of overdose include drowsiness, disorientation, and extrapyramidal reactions. |
