METOCLOPRAMIDE USP TABLETS (Each tablet contains Metoclopramide 5mg )

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

• Skin disinfection
• Preparation of skin before injections
• Cleansing minor wounds

Dosage

Children: Apply to the skin as required; consult product literature for specific guidance.

Adults: Apply to the skin as required for disinfection.

Mechanism of action

Alcohol exerts its antiseptic effect by denaturing proteins, disrupting cell membranes, and dehydrating microbial cells, leading to cell lysis and death.

Pharmacodynamics

Alcohol has broad-spectrum antimicrobial activity, effective against bacteria, fungi, and viruses. Its efficacy is influenced by concentration, with higher concentrations generally being more effective.

Pharmacokinetics

Alcohol is rapidly absorbed through the skin and mucous membranes. It is metabolized primarily in the liver, with a half-life that varies based on the individual's metabolic rate and the amount consumed.

Contra-indications

• Concomitant use with lithium
• Regular use in neonates
• Patients with severe burns when diathermy has been preceded by application of alcoholic skin disinfectants

Adverse effects

• Eye erythema
• Punctate keratitis
• Cytotoxicity
• Eye discolouration

Interactions

• Increases risk of visual disturbances with antiepileptics
• Increases concentration with methylphenidate
• Increases risk of facial flushing and skin irritation with topical pimecrolimus
• Increases concentration with retinoids
• Increases concentration with acitretin
• Increases risk of facial flushing and skin irritation with topical tacrolimus
• Decreases antidiuretic effect with vasopressin

Precautions

• Avoid regular application to inflamed or broken skin or mucosa
• Avoid broken skin
• Flammable

Pregnancy

Sufficient iodine may be absorbed to affect the fetal thyroid in the second and third trimester.

Breast-feeding

Avoid regular or excessive use.

Storage

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

Formulations

• Betadine 2.5% dry powder spray
• Industrial methylated spirit
• Povidone-Iodine 25 mg per 1 gram

Indications

• Bacterial infections
• Pneumonia
• Meningitis
• Syphilis
• Endocarditis
• Skin and soft tissue infections

Dosage

Children: Paediatric dosing for benzylpenicillin is determined by the child's weight and the severity of the infection. Refer to the BNF for Children for specific dosing guidelines.

Adults: The usual adult dose for benzylpenicillin varies based on the type and severity of the infection. It is generally administered via intramuscular or intravenous routes. For severe infections, doses may range from 1 to 4 million units every 4 to 6 hours.

Mechanism of action

Benzylpenicillin exerts its antibacterial effects by inhibiting the synthesis of bacterial cell walls. It binds to penicillin-binding proteins (PBPs) located inside the bacterial cell wall, disrupting the transpeptidation process, which is crucial for cross-linking peptidoglycan layers. This inhibition leads to cell lysis and death of the bacteria.

Pharmacodynamics

Benzylpenicillin demonstrates time-dependent bactericidal activity, meaning its effectiveness is related to the duration of time the drug concentration remains above the minimum inhibitory concentration (MIC) for the target bacteria. It has a narrow spectrum of activity, primarily targeting Gram-positive cocci and some Gram-negative rods.

Pharmacokinetics

Benzylpenicillin is typically administered parenterally due to poor oral absorption. It is rapidly distributed throughout the body and can penetrate various tissues, including the central nervous system during inflammation. The drug is primarily eliminated by renal excretion, with a half-life of approximately 30 minutes to 1 hour in healthy individuals. Dosage adjustments may be necessary in patients with renal impairment.

Interactions

• leflunomide+benzylpenicillin: Unknown (increases exposure)
• nitisinone+benzylpenicillin: Unknown (increases exposure)
• teriflunomide+benzylpenicillin: Unknown (increases exposure)

Pregnancy

Benzylpenicillin is generally considered safe to use during pregnancy, as it is a penicillin antibiotic and has a long history of use.

Breast-feeding

Benzylpenicillin is excreted in breast milk in small amounts, but it is not expected to have adverse effects on a nursing infant.

Storage

Store in a cool, dry place, protected from light. Reconstituted solutions should be used promptly or stored in a refrigerator and used within a limited time frame.

Formulations

• Benzylpenicillin injection

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

Ethanol affects the brain’s neurons in several ways. It alters their membranes as well as their ion channels, enzymes, and receptors. Alcohol also binds directly to the receptors for acetylcholine, serotonin, GABA, and the NMDA receptors for glutamate. The sedative effects of ethanol are mediated through binding to GABA receptors and glycine receptors (alpha 1 and alpha 2 subunits). It also inhibits NMDA receptor functioning. In its role as an anti-infective, ethanol acts as an osmolyte or dehydrating agent that disrupts the osmotic balance across cell membranes. ... Ethanol is known to affect a large number of membrane proteins that participate in signaling pathways such as neurotransmitter receptors, enzymes, and ion channels, and there is extensive evidence that ethanol interacts with a variety of neurotransmitters. The major actions of ethanol involve enhancing the inhibitory effects of gamma-aminobutyric acid (GABA) at GABAa receptors and blockade of the N-methyl-D-aspartate (NMDA) subtype of glutamate, an excitatory amine acid (EAA) receptor. Animal studies indicate that the acute effects of ethanol result from competitive inhibition of glycine binding to NMDA receptor and disruption of glutamatergic neurotransmission by inhibiting the response of the NMDA receptor. Persistent glycine antagonism and attenuation of glutamatergic neurotransmission by chronic ethanol exposure results in tolerance to ethanol by enhancing EAA neurotransmission and NMDA receptor upregulation. The latter appears to involve selective increases in NMDA R2B subunit concentrations and other molecular changes in specific brain loci. The abrupt withdrawal of ethanol thus produces a hyperexcitable state that leads to the ethanol withdrawal syndrome and excitotoxic neuronal death. GABA-mediated inhibition, which normally acts to limit excitation, is eliminated during ethanol withdrawal syndrome and further intensifies this excitation. In addition, NMDA receptors function to inhibit the release of dopamine in the nucleus accumbens and mesolimbic structures, which modulate the reinforcing action of addictive xenobiotics such as ethanol. By inhibiting NMDA receptor activity, ethanol could increase dopamine release from the nucleus accumbens and ventral tegmental area and could thus create dependence. Chronic ethanol administration also results in tolerance, dependence, and an ethanol withdrawal syndrome, mediated, in part, by desensitization and or downregulation of GABAa receptors. The development of alcoholic ketoacidosis (AKA) requires that a combination of physical and physiologic events occur. The normal response to starvation and depletion of hepatic glycogen stores is for amino acids to be converted to pyruvate. Pyruvate can serve as a substrate for gluconeogenesis, be converted to acetyl-CoA, which can enter the Krebs cycle or can be utilized in various biosynthetic pathways (eg, fatty acid, ketone bodies, cholesterol, and acetylcholine) ... Ethanol metabolism generates NADH, resulting in an excess of reducing potential. This high redox state favors the conversion of pyruvate to lactate, diverting pyruvate from being a substrate for gluconeogenesis. To compensate for the lack of normal metabolic substrates, the body mobilizes fat from adipose tissue and increased fatty acid metabolism as an alternative source of energy. This response is mediated by a decrease in insulin and an increased secretion of glucagon, catecholamines, growth hormone, and cortisol. Fatty acid metabolism results in the formation of acetyl-CoA and it combines with the excess acetate that is generated from ethanol metabolism to form acetoacetate. Most of the acetoacetate is reduced to beta-hydroxybutyrate due to the excess reducing potential or high redox state of the cell. Volume depletion interferes with the renal elimination of acetoacetate and beta-hydroxybutyrate, and contributes to the acidosis. An elevated lactate concentration may result from shunting from pyruvate or

Pharmacodynamics

Alcohol produces injury to cells by dehydration and precipitation of the cytoplasm or protoplasm. This accounts for its bacteriocidal and antifungal action. When alcohol is injected in close proximity to nerve tissues, it produces neuritis and nerve degeneration (neurolysis). Ninety to 98% of ethanol that enters the body is completely oxidized. Ethanol is also used as a cosolvent to dissolve many insoluble drugs and to serve as a mild sedative in some medicinal formulations. Ethanol also binds to GABA, glycine, NMDA receptors and modulates their effects. Ethanol is also metabolised by the hepatic enzyme alcohol dehydrogenase.

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.