Metoclopramide: Pharm effects
Numerous systems in the body produce signals to induce vomiting. Some of these systems include the cerebral cortex, vestibular system, and GI tract. Additionally, the Chemoreceptor Trigger Zone (CTZ), located in the area postrema on the floor of the fourth ventricle, is not protected by a true blood-brain barrier and is therefore exposed to toxins and neurotransmitters in the blood. The signals that these systems send are organized into the action of emesis by the nucleus tractus solitarius (NTS) in the medulla.
Metoclopramide is a D2 receptor antagonist as well as 5-HT3 antagonist and 5-HT4 agonist. Through its anti-dopaminergic and anti-serotonergic effects, it blocks the communication between the CTZ and NTS and thereby acts as an potent antiemetic. Additionally, its antagonist effect on dopamine receptors combined with its agonistic effects on 5-HT4 receptors yield increased GI motility and contractility. Given these pharmacologic effects, metoclopramide can be used as both an antiemetic and a promotility agent.
Adverse effects from metoclopramide primarily extend from its antidopaminergic actions. Similar to antipsychotics with antidopaminergic action, metoclopramide can cause extrapyramidal symptoms including acute dystonia, parkinsonism, and akathisia, as well as Neuroleptic Malignant Syndrome . Additionally, metoclopramide has been associated with the development of tardive dyskinesia, particularly with long-term use. The FDA has recommended that the drug not be given for longer than 12 weeks. Like other antidopaminergic antiemetic medications, metoclopramide has been associated with arrhythmias and cardiac arrest due to QTc prolongation.
Whelan, R. & Apfel, C.C. (2013). Pharmacology of Postoperative Nausea and Vomiting. In H.C. Hemmings, Jr. & T.D. Egan (Eds.), Pharmacology and Physiology for Anesthesia: Foundations and Clinical Application (503-522). Philadelphia: Elsevier Inc.