Reglan

REGLAN Info

Metoclopramide Info __Katsung__ (pg356 CH16) METOCLOPRAMIDE & DOMPERIDONE Metoclopramide and domperidone are dopamine D2 receptor antagonists. Within the gastrointestinal tract activation of dopamine receptors inhibits cholinergic smooth muscle stimulation; blockade of this effect is believed to be the primary prokinetic mechanism of action of these agents. These agents increase esophageal peristaltic amplitude, increase lower esophageal sphincter pressure, and enhance gastric emptying but have no effect on small intestine or colonic motility. Metoclopramide and domperidone also block dopamine D2 receptors in the chemoreceptor trigger zone of the medulla (area postrema), resulting in potent antinausea and antiemetic action. Clinical Uses GASTROESOPHAGEAL REFLUX DISEASE Metoclopramide is available for clinical use in the USA; domperidone is available in many other countries. These agents are sometimes used in the treatment of symptomatic GERD but are not effective in patients with erosive esophagitis. Because of the superior efficacy and safety of antisecretory agents in the treatment of heartburn, prokinetic agents are used mainly in combination with antisecretory agents in patients with regurgitation or refractory heartburn. IMPAIRED GASTRIC EMPTYING These agents are widely used in the treatment of patients with delayed gastric emptying due to postsurgical disorders (vagotomy, antrectomy) and diabetic gastroparesis. Metoclopramide is sometimes administered in hospitalized patients to promote advancement of nasoenteric feeding tubes from the stomach into the duodenum. NONULCER DYSPEPSIA These agents lead to symptomatic improvement in a small number of patients with chronic dyspepsia. PREVENTION OF VOMITING Because of their potent antiemetic action, metoclopramide and domperidone are used for the prevention and treatment of emesis. POSTPARTUM LACTATION STIMULATION Domperidone is sometimes recommended to promote postpartum lactation (see also Adverse Effects). Adverse Effects The most common adverse effects of metoclopramide involve the central nervous system. Restlessness, drowsiness, insomnia, anxiety, and agitation occur in 10–20% of patients, especially the elderly. Extrapyramidal effects (dystonias, akathisia, parkinsonian features) due to central dopamine receptor blockade occur acutely in 25% of patients given high doses and in 5% of patients receiving long-term therapy. Tardivedyskinesia, sometimes irreversible, has developed in patients treated for a prolonged period with metoclopramide. For this reason, long-term use should be avoided unless absolutely necessary, especially in the elderly. Elevated prolactin levels (caused by both metoclopramide and domperidone) can cause galactorrhea, gynecomastia, impotence, and menstrual disorders. Domperidone is extremely well tolerated. Because it does not cross the blood-brain barrier to a significant degree, neuropsychiatric and extrapyramidal effects are rare. (pg1316 CH62) (pg1330 CH62) Metoclopramide (generic, Reglan, others) Oral: 5, 10 mg tablets; 5 mg/5 mL syrup, 10 mg/mL concentrated solution Parenteral: 5 mg/mL for injection (pg1333 CH62)

__Lippincott’s Illustrated Review of Pharmacology__
 * Substituted benzamides:** One of several substituted benzamides with antiemetic activity, //metoclopramide// [met-oh-kloe-PRAH-mide], is highly effective at high doses against the highly emetogenic //cisplatin,// preventing emesis in 30 to 40 percent of patients and reducing emesis in the majority. Antidopaminergic side effects, including sedation, diarrhea, and extrapyramidal symptoms, limit its high-dose use. (pg613 CH28)

__Stoeling & Hiller__ Prolonged QTc Interval Droperidol, like many drugs administered during anesthesia (thiopental, propofol, isoflurane, sevoflurane, succinylcholine, neostigmine, atropine, glycopyrrolate, metoclopramide, SSRIs, 5HT3 receptor antagonists) produces dose-dependent prolongation of the QTc (pg350) Metoclopramide (methoxychloroprocainamide) is a dopamine antagonist that is structurally similar to procainamide but lacks local anesthetic activity. This drug acts as a gastrointestinal prokinetic (accelerated gastric clearance and shortened transit time through the small intestine) that increases lower esophageal sphincter tone. Metoclopramide produces selective cholinergic stimulation of the gastrointestinal tract, which is largely restricted to smooth muscles of the proximal gastrointestinal tract. This may be offset by the concomitant administration of atropine in the preoperative medication. Dopamineinduced inhibition of gastrointestinal motility is not considered to be clinically significant. In the central nervous system (CNS), metoclopramide blocks dopamine receptors (may produce extrapyramidal effects). Extensive first-pass hepatic metabolism limits the bioavailability of metoclopramide. Recent ingestion of solid food Diabetes mellitus and gastroparesis Trauma Obese Parturients Antiemetic (antagonism of dopamine at the chemoreceptor trigger zone, reverses gastric stasis produced by morphine) Treatment of gastroparesis Treatment of gastroesophageal reflux Abdominal cramping Hypotension, tachycardia, cardiac dysrhythmias (following IV administration) Sedation Dysphoria Breast enlargement (galactorrhea) Dystonic extrapyramidal reactions (oculogyric crises, opisthotonus, trismus, torticollis) Akathisia Inhibition of plasma cholinesterase activity (prolonged responses to succinylcholine and mivacurium, slowed metabolism of ester local anesthetics) Drug interactions (monoamine oxidase inhibitors, tricyclic antidepressants) (pg430)
 * GASTROINTESTINAL PROKINETICS **
 * // Mechanism of Action //**
 * // Pharmacokinetics //**
 * // Clinical Uses (Table 26-3) //**
 * TABLE 26-3. CLINICAL USES OF METOCLOPRAMIDE **
 * // Side Effects (Table 26-4) //**
 * TABLE 26-4. SIDE EFFECTS OF METOCLOPRAMIDE **