PLASENZYM

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

• Exocrine pancreatic insufficiency
• Cystic fibrosis
• Chronic pancreatitis
• Post-surgical states involving the pancreas

Dosage

Children: Children aged 1–11 months: 1–2 capsules mixed with feeds. Children aged 1–17 years: 2–6 capsules to be taken with each meal, either swallowed whole or sprinkled on food.

Adults: Initially 1–2 capsules taken with each meal, and 1 capsule taken with snacks. Capsules may be swallowed whole or the contents mixed with a slightly acidic liquid or soft food, then swallowed immediately without chewing.

Mechanism of action

Pancreatin consists of a mixture of digestive enzymes including amylase, lipase, and proteases. These enzymes work in the gastrointestinal tract to break down carbohydrates, fats, and proteins into smaller molecules that can be easily absorbed by the body. The action of these enzymes is crucial, as their absence due to pancreatic insufficiency leads to malabsorption and nutrient deficiencies.

Pharmacodynamics

The pharmacodynamic effects of pancreatin are primarily seen in the gastrointestinal tract where it enhances digestion and nutrient absorption. By providing the necessary enzymes that are lacking in patients with pancreatic insufficiency, pancreatin helps alleviate symptoms such as steatorrhea (fatty stools), abdominal discomfort, and weight loss. It helps improve the overall nutritional status of patients.

Pharmacokinetics

Pancreatin is administered orally and is inactivated by gastric acid, making it necessary to take it with food or immediately before or after meals for optimal effect. The enzymes are released in the duodenum where they exert their action. The absorption of the resulting products of digestion occurs in the small intestine. The exact pharmacokinetic profile, including half-life and metabolism of the individual enzymes, varies and is often not detailed due to the complex nature of enzyme activity and digestion.

Adverse effects

• Abdominal distension
• Constipation
• Nausea
• Vomiting
• Skin reactions
• Fibrosing colonopathy

Interactions

• Pancreatin may reduce the effects of acarbose

Precautions

• Can irritate the perioral skin and buccal mucosa if retained in the mouth
• Excessive doses can cause perianal irritation

Pregnancy

Not known to be harmful.

Breast-feeding

Not known to be harmful.

Storage

Store in a cool, dry place. Keep the container tightly closed.

Formulations

• CREON® 10000
• CREON® 25000
• CREON® 40000
• PANCREX® V CAPSULES
• PANCREX® V POWDER
• PANCREX® V TABLETS
• PANCREX® V TABLETS FORTE
• CREON® MICRO

Indications

• Osteoarthritis
• Sinusitis
• Postoperative inflammation
• Wound healing
• Digestive disorders

Dosage

Children: Refer to specific product guidelines for paediatric doses, as bromelain usage in children should be approached with caution and under medical supervision.

Adults: Refer to specific product guidelines for dosing, as bromelain is available in various formulations. Doses may range widely based on the indication and formulation.

Mechanism of action

Bromelain acts by breaking down proteins into smaller peptides and amino acids, which aids in digestion. It also has anti-inflammatory effects by inhibiting the activity of pro-inflammatory mediators, including bradykinin and prostaglandins. Additionally, bromelain may enhance the absorption of certain antibiotics and improve the bioavailability of other therapeutic agents.

Pharmacodynamics

Bromelain exhibits anti-inflammatory and analgesic properties, which are beneficial in reducing swelling, bruising, and pain. Its proteolytic activity can promote the degradation of fibrin, a protein involved in blood clotting, thereby assisting in the reduction of inflammation and promoting healing. Its effects on the immune system also contribute to its therapeutic potential.

Pharmacokinetics

Bromelain is absorbed in the gastrointestinal tract, with its bioavailability influenced by the presence of food. Its systemic effects may vary based on the formulation and dosage. The elimination of bromelain occurs primarily through the renal pathway, and its half-life is not well established due to variations in individual metabolism and formulation.

Adverse effects

• Gastrointestinal disturbances (nausea, diarrhea, abdominal pain)
• Allergic reactions (skin rash, itching, anaphylaxis in sensitive individuals)
• Increased bleeding risk (due to its fibrinolytic activity)

Interactions

• Anticoagulants (increased risk of bleeding)
• Antiplatelet drugs (may enhance effects)
• Antibiotics (may enhance absorption and effects)

Precautions

• Use with caution in individuals with a history of allergies to pineapples or other bromelain sources
• Caution in patients with bleeding disorders or those undergoing surgery

Pregnancy

There is insufficient reliable information regarding the safety of bromelain during pregnancy. It should be used with caution and only if clearly needed.

Breast-feeding

Limited information is available; consult a healthcare provider before use.

Storage

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

Formulations

• Oral tablets
• Capsules
• Powder

Indications

• Constipation
• Chronic liver disease
• Gallbladder disorders

Dosage

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

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

Mechanism of action

Dehydrocholate acts by stimulating the secretion of bile acids and other digestive fluids, which enhances fat digestion and absorption. It also promotes peristalsis in the intestines, facilitating the movement of stool through the gastrointestinal tract.

Pharmacodynamics

The pharmacodynamic effects of dehydrocholate are primarily related to its role in enhancing bile flow and increasing intestinal motility. By promoting the secretion of bile, it aids in emulsifying fats, improving their digestion and absorption. Additionally, it enhances the peristaltic movements of the intestines, leading to faster transit time and alleviating constipation.

Pharmacokinetics

Dehydrocholate is absorbed in the gastrointestinal tract after oral administration. Its absorption can be influenced by the presence of food and other substances in the digestive system. Once absorbed, it undergoes hepatic metabolism before being excreted mainly in the bile. The half-life and elimination pathways are not well-documented, but like other bile acids, it is likely to undergo enterohepatic circulation.

Pregnancy

The safety of dehydrocholate during pregnancy has not been established. Caution is advised when administering to pregnant women.

Breast-feeding

It is not known if dehydrocholate is excreted in human breast milk. Caution is advised when administering to breastfeeding mothers.

Storage

Store below 25 degrees Celsius. Protect from light and moisture.

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)

Indications

• Flatulence
• Bloating
• Gastroesophageal reflux disease
• Functional dyspepsia

Dosage

Children: For children, refer to the BNF for Children for specific dosing recommendations.

Adults: The usual adult dose is 40 to 125 mg taken after meals and at bedtime, as needed.

Mechanism of action

Simethicone is a surfactant that decreases the surface tension of gas bubbles in the gastrointestinal tract, facilitating their expulsion. It acts by forming a film of low surface tension that promotes the coalescence of mucus-surrounded gas bubbles, allowing for easier passage of gas.

Pharmacodynamics

Simethicone decreases the surface tension of gas bubbles in the gastrointestinal tract, facilitating their expulsion. Its effects are generally short-lived, as it is typically administered as needed. The therapeutic index is wide since it is not absorbed systemically, making it safe for use in various patient populations.

Pharmacokinetics

Simethicone is not systemically absorbed following oral administration, which contributes to its safety profile. Due to its lack of systemic absorption, specific pharmacokinetic parameters such as half-life, clearance, and volume of distribution are not applicable.

Pregnancy

Simethicone can be used during pregnancy as there are no known risks associated with its use.

Breast-feeding

Simethicone is considered safe to use during breastfeeding, as it is not absorbed systemically.

Storage

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

Formulations

• Oral suspension
• Chewable tablets
• Soft gels

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.

Mechanism of action

Simethicone is a surfactant that decreases the surface tension of gas bubbles in the gastrointestinal tract, more easily allowing gas to exit the body. The clinical use of simethicone is based on its antifoam properties. Silicone antifoams spread on the surface of aqueous liquids, forming a film of low surface tension and thus causing collapse of foam bubbles. Simethicone reportedly allows mucus-surrounded gas bubbles in the GI tract to coalesce and be expelled.

Pharmacodynamics

Simethicone decreases the surface tension of gas bubbles in the gastrointestinal tract, facilitating their expulsion. It has a short duration of action as it is generally given as needed, and a wide therapeutic index as it is not systemically absorbed.