OMCAPRAZ-R

Indications

• Cerebral edema
• Elevated intracranial pressure
• Acute kidney injury
• Oliguria
• Glaucoma
• Renal function diagnostic aid

Dosage

Adults: For cerebral edema, administer 0

Mechanism of action

Mannitol elevates blood plasma osmolality, resulting in enhanced flow of water from tissues, including the brain and cerebrospinal fluid, into interstitial fluid and plasma. This action reduces cerebral edema and intracranial pressure. As a diuretic, it increases the osmolality of glomerular filtrate, leading to increased urinary excretion of water and preventing sodium and chloride reabsorption in the renal tubules. Mannitol also facilitates the urinary excretion of toxic substances and can help in assessing renal function by measuring glomerular filtration rate (GFR).

Pharmacodynamics

Mannitol is classified as an osmotic diuretic. It is chemically similar to other sugar alcohols but has a unique ability to promote diuresis by remaining unabsorbed in the renal tubules. Its use is indicated for conditions associated with increased body fluids, such as cerebral edema and glaucoma. Mannitol may be combined with other diuretics to enhance diuretic efficacy. Inhaled formulations are used in cystic fibrosis, though they may cause bronchospasm and hemoptysis.

Pharmacokinetics

Mannitol is freely filtered by the glomeruli with less than 10% tubular reabsorption, which allows for its urinary excretion rate to serve as a measurement of GFR. It does not undergo significant metabolism and is eliminated primarily through the kidneys. The onset of action occurs within 30 to 60 minutes after intravenous administration, with effects lasting for several hours. Administration may require monitoring of renal function and fluid balance.

Contra-indications

• Anuria
• Severe dehydration
• Severe renal impairment
• Intracranial bleeding

Adverse effects

• Asthenia
• Gastrointestinal disturbances
• Dry mouth
• Confusion
• Visual impairment
• Hypotension
• Electrolyte imbalances
• Pulmonary edema
• Hemoptysis (with inhalation use)
• Bronchospasm (with inhalation use)

Interactions

• Potassium-sparing diuretics may increase the risk of hyperkalemia
• Other diuretics may have additive effects
• Caution with nephrotoxic agents

Precautions

• Caution in patients with diabetes mellitus
• Caution in the elderly
• Caution in patients with gout
• Caution in patients with hepatic impairment
• Monitor renal function and electrolytes regularly
• May cause blue fluorescence of urine

Pregnancy

Manufacturer advises avoid due to potential toxicity in animal studies.

Breast-feeding

Manufacturer advises avoid due to lack of information available.

Storage

Store in a cool, dry place, away from light. Do not freeze.

Formulations

• Solution for injection
• Inhalation powder
• Oral solution

Indications

• Gastric ulcer
• Duodenal ulcer
• Gastro-oesophageal reflux disease (GERD)
• Functional dyspepsia
• NSAID-associated peptic ulcer disease
• Zollinger-Ellison syndrome

Dosage

Adults: Initially 20 mg once daily for 4 to 8 weeks for GERD. For gastric and duodenal ulcers, the initial dose is 20 mg daily for 4 to 8 weeks. For NSAID-associated peptic ulcer disease, the recommended dose is 20 mg once daily for 4 to 8 weeks. Dose adjustments may be necessary in hepatic impairment, with a maximum dose of 20 mg daily

Mechanism of action

Rabeprazole sodium acts by irreversibly binding to and inhibiting the H+/K+ ATPase enzyme system (proton pump) in the gastric epithelium. This action leads to a decrease in gastric acid secretion, both basal and stimulated. The inhibition is dose-dependent and can last for 24 hours or longer, which helps in healing peptic ulcers and alleviating symptoms of acid-related disorders.

Pharmacodynamics

Rabeprazole sodium effectively suppresses gastric acid secretion, providing symptomatic relief and promoting mucosal healing in conditions associated with excessive gastric acidity. It demonstrates a rapid onset of action, with peak plasma concentrations occurring approximately 3-4 hours after administration. The drug's effects on gastric acid secretion can lead to increased gastric pH and improved healing of ulcerative lesions.

Pharmacokinetics

Rabeprazole sodium is rapidly absorbed after oral administration, with bioavailability of approximately 52% due to first-pass metabolism. The drug is extensively metabolized in the liver, primarily via the cytochrome P450 system. Its elimination half-life ranges from 1 to 2 hours, and it is excreted primarily through urine as metabolites. Food does not significantly affect its absorption.

Adverse effects

• Asthenia
• Angioedema
• Electrolyte imbalance
• Muscle spasms
• Hyperlipidaemia
• Weight change

Precautions

• Manufacturer advises caution in severe hepatic impairment, monitor liver function and discontinue if deterioration occurs.

Pregnancy

Manufacturer advises to avoid unless potential benefit outweighs risk-fetotoxic in animals.

Breast-feeding

Specialist sources indicate that the amount in milk is small and not known to be harmful.

Storage

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

Formulations

• Gastro-resistant tablet
• Powder for solution for injection

Mechanism of action

Carbonate ions participate in buffering reactions that help maintain pH homeostasis in biological systems. They can react with acids to form bicarbonate and carbon dioxide, thus neutralizing excess acidity in the body. This mechanism is crucial in processes such as respiration and metabolism.

Pharmacodynamics

As a buffer, carbonate helps to stabilize pH levels in different biological environments, preventing excessive acidity or alkalinity that could impair cellular functions. It is involved in the transport of carbon dioxide in the blood and plays a role in maintaining the acid-base equilibrium necessary for physiological processes.

Pharmacokinetics

Carbonate ions are readily absorbed in the gastrointestinal tract when ingested and can be found in various body fluids. They are involved in the bicarbonate buffering system, where they are converted to bicarbonate (HCO3-) and carbon dioxide (CO2) through reactions with acids. The kidneys regulate the levels of bicarbonate and carbonate in the body, excreting or reabsorbing them as needed to maintain homeostasis.

Pregnancy

There is no specific information available regarding the use of carbonate compounds during pregnancy. Consult a healthcare provider for advice.

Breast-feeding

There is no specific information available regarding the use of carbonate compounds while breastfeeding. Consult a healthcare provider for advice.

Storage

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

Dosage

Children: Refer to specific guidelines for pediatric dosing; consult the BNF for Children for accurate dosage information.

Adults: Refer to specific guidelines for use; dosage may vary based on the context of use.

Mechanism of action

Hydroxide ions act primarily as bases, neutralizing acids to form water and salts. They participate in various biochemical pathways, including selenium metabolism and the degradation of reactive oxygen species. Hydroxide can influence enzyme activity and stability by altering the pH of the environment, thereby affecting metabolic reactions.

Pharmacodynamics

Hydroxide ions can impact biological processes by changing the local pH, which influences enzyme activity, ion transport, and the solubility of other compounds. Their ability to neutralize acids can help regulate physiological pH, contributing to homeostasis in living organisms.

Pharmacokinetics

As an inorganic ion, hydroxide does not undergo traditional pharmacokinetic processes like absorption, distribution, metabolism, or excretion. Instead, it is rapidly equilibrated in biological fluids and participates in acid-base reactions, having immediate effects on the local environment.

Pregnancy

There is limited information regarding the use of hydroxide during pregnancy. Consult a healthcare professional for advice.

Breast-feeding

Limited data is available on the excretion of hydroxide in breast milk. Consult a healthcare professional before use.

Storage

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

Indications

• Gastroesophageal reflux disease (GERD)
• Peptic ulcers
• Zollinger-Ellison syndrome
• Prevention of gastric ulcers associated with NSAID use

Dosage

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

Mechanism of action

Rabeprazole inhibits gastric acid secretion by irreversibly binding to the hydrogen-potassium ATPase enzyme system (H+, K+-ATPase) located at the parietal cell surface. This action blocks the final step in the gastric acid secretion process, leading to a reduction in hydrogen ion transport into the gastric lumen. Rabeprazole is activated in the acidic environment of the stomach, transforming into an active sulfenamide which exerts its inhibitory effects.

Pharmacodynamics

By preventing the production of gastric acid, rabeprazole alleviates symptoms associated with excessive acid secretion, such as heartburn and esophagitis. It is particularly effective in treating gastroesophageal reflux disease (GERD) and peptic ulcers, as well as in combination with antibiotics for the eradication of Helicobacter pylori. Furthermore, rabeprazole is utilized in managing conditions like Zollinger-Ellison syndrome, where there is an overproduction of gastric acid.

Pharmacokinetics

Rabeprazole is rapidly absorbed following oral administration, with peak plasma concentrations occurring within 1 to 2 hours. It is extensively metabolized in the liver through the cytochrome P450 system, primarily via CYP2C19 and CYP3A4 isoenzymes. The elimination half-life of rabeprazole ranges from 1 to 2 hours. The drug is excreted mainly in the urine as metabolites, with minimal unchanged drug present. Food intake can affect the absorption but not the overall efficacy of the drug.

Adverse effects

• Headache
• Nausea
• Diarrhea
• Constipation
• Abdominal pain
• Rash
• Dizziness

Interactions

• apalutamide+rabeprazole: Unknown (decreases exposure)

Precautions

• Use with caution in patients with hepatic impairment
• Monitor for potential vitamin B12 deficiency with long-term use
• Consider risk of Clostridium difficile infection in patients with diarrhea

Pregnancy

Rabeprazole is classified as category B. Animal studies have shown no harm, but there are no well-controlled studies in pregnant women. Use only if clearly needed.

Breast-feeding

Rabeprazole is excreted in breast milk. Caution should be exercised when administered to a nursing mother.

Storage

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

Formulations

• Tablets: 20 mg

Mechanism of action

Mannitol is an osmotic diuretic that is metabolically inert in humans and occurs naturally, as a sugar or sugar alcohol, in fruits and vegetables. Mannitol elevates blood plasma osmolality, resulting in enhanced flow of water from tissues, including the brain and cerebrospinal fluid, into interstitial fluid and plasma. As a result, cerebral edema, elevated intracranial pressure, and cerebrospinal fluid volume and pressure may be reduced. As a diurectic mannitol induces diuresis because it is not reabsorbed in the renal tubule, thereby increasing the osmolality of the glomerular filtrate, facilitating excretion of water, and inhibiting the renal tubular reabsorption of sodium, chloride, and other solutes. Mannitol promotes the urinary excretion of toxic materials and protects against nephrotoxicity by preventing the concentration of toxic substances in the tubular fluid. As an Antiglaucoma agent mannitol levates blood plasma osmolarity, resulting in enhanced flow of water from the eye into plasma and a consequent reduction in intraocular pressure. As a renal function diagnostic aid mannitol is freely filtered by the glomeruli with less than 10% tubular reabsorption. Therefore, its urinary excretion rate may serve as a measurement of glomerular filtration rate (GFR). The exact mechanism of action of inhaled mannitol in the symptomatic maintenance treatment of cystic fibrosis remains unclear. It is hypothesized that mannitol produces an osmotic gradient across the airway epithelium that draws fluid into the extracellular space and alters the properties of the airway surface mucus layer, allowing easier mucociliary clearance. MANNITOL IS.../USED/ IN PROPHYLAXIS OF ACUTE RENAL FAILURE. IT IS USED FOR THIS PURPOSE IN CONDITIONS AS DIVERSE AS CARDIOVASCULAR OPERATIONS, SEVERE TRAUMATIC INJURY, OPERATIONS IN THE PRESENCE OF SEVERE JAUNDICE, AND MGMNT OF HEMOLYTIC TRANSFUSION REACTIONS. IN EACH OF THESE CONDITIONS, A PRECIPITOUS FALL IN THE FLOW OF URINE MAY BE ANTICIPATED EITHER AS THE RESULT OF AN ACUTELY REDUCED FILTRATION RATE OR FROM ACUTE CHANGES IN TUBULAR PERMEABILITY. THE LATTER MAY BE CONSEQUENCE OF THE PRESENCE OF NOXIOUS AGENT WITHIN THE TUBULAR FLUID IN EXCESSIVELY HIGH CONCN, IN SOME INSTANCES SUFFICIENT TO RESULT IN ACTUAL PRECIPITATION. IN THESE SITUATIONS, MANNITOL EXERTS OSMOTIC EFFECT WITHIN THE TUBULAR FLUID, INHIBITS WATER REABSORPTION, & MAINTAINS THE RATE OF URINE FLOW. ...CONCN OF TOXIC AGENT WITHIN TUBULAR FLUID DOES NOT REACH EXCESSIVELY HIGH LEVELS THAT OTHERWISE WOULD HAVE BEEN ACHIEVED BY MORE COMPLETE REABSORPTION OF WATER. ...EVEN THOUGH /GLOMERULAR/ FILTRATION RATE IS REDUCED, MANNITOL IS STILL FILTERED @ GLOMERULUS. THE TUBULAR IMPERMEABILITY TO MANNITOL IS NOT ALTERED BY ACUTE RENAL ISCHEMIA OF SHORT DURATION. HENCE, THE MANNITOL THAT IS FILTERED IS ALSO EXCRETED IN THE VOIDED URINE. UNREABSORBED SOLUTE LIMITS BACK DIFFUSION OF WATER. ...URINE VOL CAN BE MAINTAINED EVEN IN PRESENCE OF DECR GLOMERULAR FILTRATION.

Pharmacodynamics

Chemically, mannitol is an alcohol and a sugar, or a polyol; it is similar to xylitol or sorbitol. However, mannitol has a tendency to lose a hydrogen ion in aqueous solutions, which causes the solution to become acidic. For this reason, it is not uncommon to add a substance to adjust its pH, such as sodium bicarbonate. Mannitol is commonly used to increase urine production (diuretic). It is also used to treat or prevent medical conditions that are caused by an increase in body fluids/water (e.g., cerebral edema, glaucoma, kidney failure). Mannitol is frequently given along with other diuretics (e.g., furosemide, chlorothiazide) and/or IV fluid replacement. Inhaled mannitol has the possibility to cause bronchospasm and hemoptysis; the occurrence of either should lead to discontinuation of inhaled mannitol.

Mechanism of action

Rabeprazole belongs to a class of antisecretory compounds (substituted benzimidazole proton-pump inhibitors) that do not exhibit anticholinergic or histamine H2-receptor antagonist properties, but suppress gastric acid secretion by inhibiting the gastric H⁺/K⁺ATPase (hydrogen-potassium adenosine triphosphatase) at the secretory surface of the gastric parietal cell. Because this enzyme is regarded as the acid (proton) pump within the parietal cell, rabeprazole has been characterized as a gastric proton-pump inhibitor. Rabeprazole blocks the final step of gastric acid secretion. In gastric parietal cells, rabeprazole is protonated, accumulates, and is transformed to an active sulfenamide. When studied in vitro, rabeprazole is chemically activated at pH 1.2 with a half-life of 78 seconds. Rabeprazole is a selective and irreversible proton pump inhibitor. Rabeprazole suppresses gastric acid secretion by specific inhibition of the hydrogen-potassium adenosine triphosphatase (H+, K+-ATPase) enzyme system found at the secretory surface of parietal cells. It inhibits the final transport of hydrogen ions (via exchange with potassium ions) into the gastric lumen. Since the H+, K+-ATPase enzyme system is regarded as the acid (proton) pump of the gastric mucosa, rabeprazole is known as a gastric acid pump inhibitor. Rabeprazole does not have anticholinergic or histamine H2-receptor antagonist properties. Rabeprazole binds to hydrogen-potassium ATPase in gastric parietal cells; inactivation of this enzyme system (also known as the proton, hydrogen, or acid pump) blocks the final step in the secretion of hydrochloric acid secretion. The antisecretory effect is apparent within 1 hour following oral administration with the median inhibitory effect on 24-hour gastric acidity being 88% of maximal after the first dose.

Pharmacodynamics

Rabeprazole prevents the production of acid in the stomach. It reduces symptoms and prevents injury to the esophagus or stomach in patients with gastroesophageal reflux disease (GERD) or ulcers. Rabeprazole is also useful in conditions that produce too much stomach acid such as Zollinger-Ellison syndrome. Rabeprazole may also be used with antibiotics to get rid of bacteria that are associated with some ulcers. Rabeprazole is a selective and irreversible proton pump inhibitor, suppresses gastric acid secretion by specific inhibition of the H⁺, K⁺ -ATPase, which is found at the secretory surface of parietal cells. In doing so, it inhibits the final transport of hydrogen ions (via exchange with potassium ions) into the gastric lumen.