Metogen

Indications

• Symptomatic treatment of nausea and vomiting
• Postoperative nausea and vomiting
• Chemotherapy-induced nausea and vomiting
• Nausea associated with migraine

Dosage

Children: In children, the recommended dose is 100–150 micrograms/kg up to 3 times a day, with

Adults: For adults weighing up to 60 kg, the recommended dose is up to 500 micrograms/kg daily in 3 divided doses, administered by slow intravenous injection over at least 3 minutes. For adults weighing 60 kg and above, the standard dose is 10 mg up to 3 times daily.

Mechanism of action

Metoclopramide exerts its antiemetic effects by antagonizing dopamine D2 receptors in the chemoreceptor trigger zone of the central nervous system. Additionally, it enhances the release of acetylcholine in the gastrointestinal tract, promoting gastric emptying and increasing lower esophageal sphincter tone. This dual mechanism addresses both central and peripheral pathways related to nausea and vomiting.

Pharmacodynamics

The pharmacodynamic profile of metoclopramide includes its ability to decrease nausea and vomiting by acting on the central nervous system and enhancing gastrointestinal motility. It also has a peripheral effect by increasing peristalsis and reducing gastric stasis. The onset of action is typically rapid, with effects seen within 30 minutes when administered intravenously.

Pharmacokinetics

Metoclopramide is well-absorbed after oral administration, with peak plasma concentrations reached within 1 to 2 hours. It undergoes significant first-pass metabolism in the liver, and its bioavailability is approximately 80% when taken orally. The drug is primarily eliminated via renal excretion, with a half-life of about 5 to 6 hours. Dose adjustments may be necessary in patients with hepatic or renal impairment to avoid accumulation and increased risk of adverse effects.

Contra-indications

• 3-4 days after gastrointestinal surgery
• epilepsy
• gastrointestinal hemorrhage
• gastrointestinal obstruction
• gastrointestinal perforation
• Parkinson's disease
• uncorrected electrolyte imbalance

Adverse effects

• acute dystonic reactions
• anxiety
• dizziness
• dyspnoea
• oedema
• skin reactions
• visual impairment
• asthenia
• depression
• diarrhoea
• tremor
• prolongation of QT interval
• shock
• syncope

Interactions

• may mask underlying disorders such as cerebral irritation
• antimuscarinic drugs may abort dystonic attacks
• caution with drugs that prolong QT interval

Precautions

• use with caution in patients with asthma
• atopic allergy
• bradycardia
• cardiac conduction disturbances
• elderly patients due to increased risk of adverse effects

Pregnancy

Not known to be harmful; benefits and risks should be evaluated.

Breast-feeding

Small amount present in milk; avoid if possible.

Storage

Store below 25°C. Protect from light.

Formulations

• oral tablets
• oral solution
• intramuscular injection
• intravenous injection

Indications

• Metabolic disorders
• Energy supplementation
• Fatty acid synthesis disorders

Dosage

Children: Refer to specific product guidelines for dosing information.

Adults: Refer to specific product guidelines for dosing information.

Mechanism of action

Acetate is primarily involved in the metabolic processing of carbohydrates and fats. It is converted to acetyl-CoA, which enters the citric acid cycle to produce energy in the form of ATP. Acetate also serves as a substrate for the synthesis of lipids and may influence various signaling pathways related to metabolism.

Pharmacodynamics

Acetate contributes to energy balance by participating in lipid metabolism and the regulation of glucose homeostasis. It can modulate the activity of various enzymes involved in metabolic pathways, thus affecting the overall metabolic rate and energy utilization. Additionally, acetate may have effects on appetite regulation and insulin sensitivity.

Pharmacokinetics

Acetate is rapidly absorbed and distributed throughout the body. It is metabolized primarily in the liver, where it is converted to acetyl-CoA. The elimination half-life of acetate is relatively short, with metabolites being excreted primarily in the urine. The pharmacokinetics can vary based on the formulation and route of administration.

Pregnancy

Safety in pregnancy has not been established. Use only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

The effects on breastfed infants are unknown. Caution is advised when administering to nursing mothers.

Storage

Store in a cool, dry place away from direct sunlight. Keep out of reach of children.

Mechanism of action

Bisulfite functions primarily as a reducing agent in biochemical reactions. It can donate electrons, which is essential in various metabolic processes, including the degradation of cysteine and homocysteine. The compound is involved in pathways related to amino acid metabolism, specifically influencing sulfur amino acid metabolism, which is critical in maintaining cellular redox homeostasis.

Pharmacodynamics

The pharmacodynamic properties of bisulfite include its role in reducing oxidative stress by participating in redox reactions. It helps maintain the balance of thiol groups within proteins, which is vital for their structural integrity and function. Additionally, bisulfite may influence the activity of certain enzymes involved in the metabolism of amino acids.

Pharmacokinetics

Information on the pharmacokinetics of bisulfite is limited. However, it is known to be rapidly absorbed and metabolized in the body. Its primary metabolic pathways involve the degradation of sulfur-containing amino acids. Excretion typically occurs through urine, reflecting its metabolic products.

Pregnancy

Bisulfite is not recommended during pregnancy due to potential risks, consult healthcare professionals for alternatives.

Breast-feeding

Caution is advised when using bisulfite while breastfeeding, consult with healthcare professionals before use.

Storage

Store in a cool, dry place away from direct sunlight.

Indications

• Nausea and vomiting associated with chemotherapy
• Postoperative nausea and vomiting
• Gastroparesis
• Gastroesophageal reflux disease (GERD)
• Facilitation of small bowel intubation

Dosage

Children: Refer to the BNF for Children for appropriate paediatric dosing information.

Adults: Refer to the BNF for specific dosing guidelines based on the condition being treated.

Mechanism of action

Metoclopramide causes antiemetic effects by inhibiting dopamine D2 and serotonin 5-HT3 receptors in the chemoreceptor trigger zone (CTZ) of the brain. It enhances gastric motility by acting on presynaptic and postsynaptic D2 receptors, agonizing serotonin 5-HT4 receptors, and antagonizing muscarinic receptors, which ultimately increases acetylcholine release. This results in increased lower esophageal sphincter tone and gastric contractions, facilitating gastric emptying and intestinal transit.

Pharmacodynamics

Metoclopramide increases gastric emptying by decreasing lower esophageal sphincter (LES) pressure, while preventing and relieving nausea and vomiting. It enhances gastrointestinal motility without increasing biliary, gastric, or pancreatic secretions. However, due to its antidopaminergic effects, it may cause adverse reactions such as tardive dyskinesia, dystonia, and akathisia, warranting limited use to a maximum of 12 weeks.

Pharmacokinetics

Metoclopramide is rapidly absorbed, with peak plasma concentrations typically occurring within 1 to 2 hours after oral administration. It has a half-life of approximately 5 to 6 hours and is primarily excreted in urine, mostly as metabolites. The drug undergoes hepatic metabolism, and its pharmacokinetics may be affected in patients with renal impairment.

Contra-indications

• Hypersensitivity to metoclopramide or any of its components
• Pheochromocytoma
• Gastrointestinal obstruction
• History of tardive dyskinesia or other extrapyramidal symptoms
• Severe renal impairment

Adverse effects

• Drowsiness
• Fatigue
• Dizziness
• Diarrhea
• Nausea
• Extrapyramidal symptoms such as akathisia, dystonia, and tardive dyskinesia
• Headache
• Restlessness

Interactions

• Severe interaction with levodopa (decreases effects)
• Severe interaction with topical anesthetics and prilocaine (increases risk of methaemoglobinaemia)
• Severe interaction with antimalarials (decreases concentration)
• Unknown interaction with posaconazole oral suspension (decreases absorption)
• Unknown interaction with atovaquone (decreases concentration)
• Unknown interaction with dopamine receptor agonists (decreases effects)
• Unknown interaction with apomorphine (decreases effects)
• Unknown interaction with bromocriptine (decreases effects)

Precautions

• Use with caution in patients with a history of depression
• Monitor for signs of tardive dyskinesia, especially with prolonged use
• Caution in patients with renal impairment, dosage adjustment may be necessary
• Avoid use in patients with a history of seizures

Pregnancy

Use during pregnancy only if clearly needed. Animal studies have shown adverse effects. The potential benefits should be weighed against the risks.

Breast-feeding

Metoclopramide is excreted in breast milk. Caution is advised when administering to nursing mothers.

Storage

Store at room temperature, away from light and moisture. Keep out of reach of children.

Formulations

• Tablets (5 mg, 10 mg)
• Oral solution (1 mg/mL)
• Injection (10 mg/2 mL)

Mechanism of action

Metoclopramide causes antiemetic effects by inhibiting dopamine D2 and serotonin 5-HT3 receptors in the chemoreceptor trigger zone (CTZ) located in the area postrema of the brain. Administration of this drug leads to prokinetic effects via inhibitory actions on presynaptic and postsynaptic D2 receptors, agonism of serotonin 5-HT4 receptors, and antagonism of muscarinic receptor inhibition. This action enhances the release of acetylcholine, causing increased lower esophageal sphincter (LES) and gastric tone, accelerating gastric emptying and transit through the gut. Metoclopramide antagonizes the dopamine D2 receptors. Dopamine exerts relaxant effect on the gastrointestinal tract through binding to muscular D2 receptors. Metoclopramide accelerates gastric emptying and intestinal transit from the duodenum to the ileocecal valve by increasing the amplitude and duration of esophageal contractions, the resting tone of the lower esophageal sphincter, and the amplitude and tone of gastric (especially antral) contractions and by relaxing the pyloric sphincter and the duodenal bulb, while increasing peristalsis of the duodenum and jejunum. Unlike nonspecific cholinergic-like stimulation of upper GI smooth muscle, the stimulant effects of metoclopramide on GI smooth muscle coordinate gastric, pyloric, and duodenal motor activity. The pharmacologic actions of metoclopramide on the upper GI tract are similar to those of cholinergic drugs (e.g., bethanechol); however, unlike cholinergic drugs, metoclopramide does not stimulate gastric, biliary, or pancreatic secretions and does not affect serum gastrin concentration. Although the exact mechanism of action of metoclopramide is unclear, the effects of metoclopramide on GI motility may be mediated via enhancement of cholinergic excitatory processes at the postganglionic neuromuscular junction; antagonism of nonadrenergic, noncholinergic inhibitory motor nerves (i.e., dopaminergic); and/or a direct effect on smooth muscle. The effects of metoclopramide on GI motility do not depend on intact vagal innervations but are reduced or abolished by anticholinergic drugs (e.g., atropine) and potentiated by cholinergic drugs (e.g., carbachol, methacholine). These findings suggest that metoclopramide's effects on GI motility may depend in part on intramural cholinergic neurons of smooth muscle that are intact after vagal denervation. Unlike cholinergic drugs, metoclopramide requires intrinsic neuronal storage sites of acetylcholine to exert its pharmacologic effects. Postsynaptic activity results from metoclopramide's ability to enhance release of acetylcholine from postganglionic cholinergic neurons in the GI tract and to sensitize muscarinic receptors of GI smooth muscle to the actions of acetylcholine. Metoclopramide is a potent dopamine-receptor antagonist, and some of the actions of metoclopramide on GI smooth muscle may be mediated via antagonism of dopaminergic neurotransmission, Specific dopamine receptors in the esophagus and stomach have been identified; however, it is not known if there is a dopaminergic control system for smooth muscle function in the upper GI tract. In the GI tract, dopamine is principally an inhibitory neurotransmitter. Dopamine decreases the intensity of esophageal contractions, relaxes the proximal stomach, and reduces gastric secretion. Although metoclopramide blocks these inhibitory effects of dopamine, the actual role of dopamine in the peripheral control of GI motility has not been fully elucidated. Since cholinergic mechanisms are responsible for most excitatory motor activity in the GI tract, it appears that metoclopramide's therapeutic effects are principally caused by the drug's cholinergic-like activity; however, antagonism of GI dopaminergic activity may augment metoclopramide's cholinergic-like activity. For more Mechanism of Action (Complete) data for Metoclopramide (10 total), please visit the HSDB record page.

Pharmacodynamics

Metoclopramide increases gastric emptying by decreasing lower esophageal sphincter (LES) pressure. It also exerts effects on the area postrema of the brain, preventing and relieving the symptoms of nausea and vomiting. In addition, this drug increases gastrointestinal motility without increasing biliary, gastric, or pancreatic secretions. Because of its antidopaminergic activity, metoclopramide can cause symptoms of tardive dyskinesia (TD), dystonia, and akathisia, and should therefore not be administered for longer than 12 weeks.