ROTAVAC

Indications

• Bowel sterilization before surgery
• Hepatic coma
• Topical infections caused by susceptible organisms

Dosage

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

Adults: By mouth: 1 g every 1 hour for 4 hours, then 1 g every 4 hours for 2–3 days. For hepatic coma: Up to 4 g daily in divided doses usually for 5–7 days.

Mechanism of action

Neomycin sulfate binds to the 30S ribosomal subunit of bacteria, leading to the misreading of mRNA and the inhibition of protein synthesis. This disrupts the production of essential proteins needed for bacterial growth and function, ultimately resulting in cell death.

Pharmacodynamics

Neomycin demonstrates bactericidal activity against susceptible bacteria. Its efficacy is enhanced in alkaline environments, which is why it is often used in combination with other agents for surgical prophylaxis. The drug is primarily effective against a range of gram-negative organisms, including Escherichia coli and Klebsiella species, but also has some activity against gram-positive organisms.

Pharmacokinetics

Neomycin is poorly absorbed from the gastrointestinal tract, and its systemic absorption is minimal when administered orally. In cases of systemic use, such as intramuscular or intravenous administration, neomycin is distributed widely in the body but is primarily excreted unchanged in the urine. The elimination half-life varies but is generally around 2 to 3 hours in individuals with normal renal function. Monitoring of serum concentrations is essential to prevent toxicity, especially in patients with renal impairment.

Adverse effects

• neurotoxicity
• ototoxicity
• nephrotoxicity
• allergic reactions
• skin rashes
• hearing loss

Interactions

• other nephrotoxic drugs
• loop diuretics
• neuromuscular blocking agents

Precautions

• monitor renal function
• use cautiously in patients with hearing impairment
• avoid concurrent use with other ototoxic medications
• ensure adequate hydration

Pregnancy

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

Breast-feeding

Use caution; neomycin can be absorbed systemically and may affect the nursing infant.

Storage

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

Formulations

• oral tablets
• topical ointments
• injectable solutions

Indications

• Constipation
• Irritable bowel syndrome
• Diverticular disease
• Prevention of straining during defecation post-surgery
• Management of stool consistency in patients with fecal incontinence

Dosage

Children: Refer to specific product guidelines for dosing information, as doses may vary depending on the formulation and the child's age and condition.

Adults: Refer to specific product guidelines for dosing information, as doses may vary depending on the formulation and the patient's condition.

Mechanism of action

Bulk-forming agents function by absorbing water in the intestinal lumen, which increases the stool volume. This mechanical effect stretches the intestinal walls, stimulating peristalsis and facilitating bowel movement. Additionally, the hydrated bulk can help to improve stool consistency and reduce the incidence of straining during defecation.

Pharmacodynamics

The pharmacodynamic effects of bulk-forming agents are primarily localized to the gastrointestinal tract. They increase stool bulk and moisture content, which can help to alleviate constipation. The onset of action typically occurs within 12 to 72 hours after ingestion, depending on the specific agent and individual patient factors.

Pharmacokinetics

Bulk-forming agents are not absorbed into the bloodstream and remain within the gastrointestinal tract. They exert their effects locally and are eliminated in the feces. The hydration of the bulk-forming agent occurs within the intestinal lumen, which helps to form a gel-like substance that enhances stool passage without systemic absorption.

Adverse effects

• Gastrointestinal discomfort
• Bloating
• Flatulence
• Diarrhea
• Nausea

Precautions

• Ensure adequate fluid intake to prevent gastrointestinal obstruction.
• Monitor for signs of allergic reactions in sensitive individuals.
• Use cautiously in patients with gastrointestinal disorders.

Pregnancy

Generally considered safe, but consult a healthcare provider for individual assessment.

Breast-feeding

Considered safe, but consult a healthcare provider for individual assessment.

Storage

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

Formulations

• Powder
• Capsules
• Tablets
• Granules

Indications

• Vascular health
• Oxidative stress-related conditions
• Anti-aging applications
• Inflammatory disorders

Dosage

Children: Refer to the BNF for Children for pediatric dosing information regarding hydrogen-rich water.

Adults: Refer to the BNF for specific dosages and administration guidelines for hydrogen-rich water.

Mechanism of action

Molecular hydrogen exerts its effects primarily through its antioxidant properties, which involve the activation of the Nrf2 pathway. This pathway regulates the expression of various antioxidant enzymes, thereby reducing oxidative stress and inflammation. In endothelial cells, H2 has been shown to prevent TCDD-induced senescence and promote cellular longevity by maintaining cellular homeostasis and modulating redox status.

Pharmacodynamics

The pharmacodynamics of dihydrogen are characterized by its ability to scavenge free radicals and reduce oxidative stress. It also influences cellular signaling pathways related to inflammation and aging. Specifically, H2 aids in maintaining the balance of NAD+/NADH, which is crucial for cellular metabolism and energy production. The modulation of the Nrf2 pathway leads to enhanced production of endogenous antioxidants, contributing to its protective effects on vascular endothelial cells.

Pharmacokinetics

Dihydrogen is rapidly absorbed and distributed in the body. When administered as hydrogen-rich water, it is absorbed through the gastrointestinal tract. Its concentration decreases over time, becoming nearly undetectable after 12 hours in aqueous solutions. The pharmacokinetic profile indicates that the effects of hydrogen may persist even after the gas has been eliminated, likely due to the activation of protective cellular mechanisms.

Pregnancy

There is insufficient data on the use of dihydrogen during pregnancy. Consult a healthcare provider for guidance.

Breast-feeding

Limited information is available regarding the safety of dihydrogen during breastfeeding. Consult a healthcare provider before use.

Storage

Store in a cool, dry place away from direct sunlight. Keep container tightly closed.

Formulations

• Hydrogen-rich water

Indications

• Hypokalemia
• Electrolyte imbalance
• Nutritional supplementation

Dosage

Children: Refer to the BNF for Children for specific dosing recommendations based on the child's age and condition.

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

Mechanism of action

Dipotassium phosphate dissociates in solution to release potassium and phosphate ions. Potassium is essential for numerous physiological functions, including nerve impulse transmission, muscle contraction, and maintenance of normal cellular function. Phosphate plays a critical role in energy production, cellular signaling, and bone mineralization.

Pharmacodynamics

Dipotassium phosphate affects the body by replenishing potassium levels, which can be depleted in conditions causing hypokalemia. The phosphate component supports various biochemical processes, including ATP synthesis and cellular metabolism. The balance of electrolytes is crucial for normal physiological function, and dipotassium phosphate helps maintain this balance.

Pharmacokinetics

Dipotassium phosphate is rapidly absorbed in the gastrointestinal tract after oral administration. The potassium is distributed to various tissues, and excess is excreted primarily through the kidneys. The phosphate component is also regulated by renal excretion. The biological half-life of potassium varies depending on the individual's renal function and overall health.

Pregnancy

Consult relevant guidelines, as data on safety in pregnancy may be limited.

Breast-feeding

Consult relevant guidelines, as data on safety during breastfeeding may be limited.

Storage

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

Indications

• Clinical term 1
• Common term 1
• Clinical term 2
• Common term 2

Dosage

Children: Refer to the BNF for Children for specific paediatric dosing guidelines.

Adults: Refer to the BNF for specific adult dosing guidelines.

Mechanism of action

Dose acts by modulating the activity of specific neurotransmitter receptors and ion channels, influencing various physiological pathways. Its precise mechanism may involve interactions with G-protein coupled receptors, leading to downstream signaling effects that impact cellular responses.

Pharmacodynamics

Dose exhibits a range of effects depending on the dosage and target tissues. It is known to alter neurotransmitter release, affect ion conductance, and influence metabolic pathways, thereby contributing to its therapeutic efficacy and potential side effects.

Pharmacokinetics

Dose is generally absorbed following administration, with peak plasma concentrations occurring within a specified timeframe. Its distribution is influenced by tissue binding and permeability across cell membranes. The drug is metabolized primarily in the liver, with metabolites being excreted via renal and biliary routes. The half-life can vary based on individual patient factors, including age, liver function, and other concurrent medications.

Indications

• Oxidative stress-related conditions
• Inflammatory conditions
• Potential anti-aging applications
• Vascular health enhancement

Dosage

Children: Refer to specific product formulations and guidelines, as dosing can vary based on the concentration of hydrogen in the product used.

Adults: Refer to specific product formulations and guidelines, as dosing can vary based on the concentration of hydrogen in the product used.

Mechanism of action

Molecular hydrogen acts primarily as an antioxidant and anti-inflammatory agent. It is believed to exert its beneficial effects through the activation of the Nrf2 pathway, which enhances the expression of antioxidant enzymes and protects cells from oxidative stress. Hydrogen-rich environments have been shown to mitigate the harmful effects of various toxins on human umbilical vein endothelial cells, thereby promoting vascular health and longevity.

Pharmacodynamics

Hydrogen's pharmacodynamic properties are linked to its role as a potent antioxidant, which reduces reactive oxygen species (ROS) and modulates inflammation. It has been documented to counteract cellular senescence in endothelial cells, thereby maintaining vascular integrity and promoting overall health. The long-lasting effects of hydrogen exposure can be observed even after its concentration in the medium has decreased, suggesting a sustained activation of protective cellular pathways.

Pharmacokinetics

Hydrogen is a gaseous molecule that diffuses rapidly across biological membranes. Its absorption and distribution in the body are influenced by the method of administration, with hydrogen-rich water being a common delivery form. Once in the bloodstream, hydrogen is quickly utilized by tissues, and its concentration diminishes rapidly, with a half-life that can vary based on conditions. The elimination of hydrogen primarily occurs via exhalation, making it a non-toxic molecule with a favorable safety profile.

Pregnancy

Hydrogen is generally considered safe during pregnancy, but it is advisable to consult a healthcare provider for specific recommendations.

Breast-feeding

Hydrogen is considered safe during breastfeeding, but as with any substance, it is recommended to discuss with a healthcare provider.

Storage

Hydrogen should be stored in a cool, dry place away from direct sunlight and heat sources, in appropriate gas cylinders designed for compressed gases.

Formulations

• Hydrogen gas (H2)
• Hydrogen-rich water

Mechanism of action

Hydrogenphosphate acts as a substrate for various enzymatic reactions where phosphate groups are transferred or incorporated into organic molecules. It is involved in metabolic pathways such as nicotine biosynthesis and NAD/NADH cycling, facilitating biochemical reactions that are vital for cellular function.

Pharmacodynamics

Hydrogenphosphate is crucial for maintaining cellular homeostasis. It regulates acid-base balance and is involved in energy metabolism. The phosphate groups it provides are integral to the structure and function of ATP, which is the primary energy currency of the cell. Additionally, hydrogenphosphate influences signal transduction pathways through phosphorylation and dephosphorylation processes.

Pharmacokinetics

Hydrogenphosphate is readily absorbed in the gastrointestinal tract and distributed throughout the body. Its elimination primarily occurs through renal excretion, where it is filtered and reabsorbed by the kidneys. The balance of hydrogenphosphate levels is tightly regulated by various physiological mechanisms to ensure proper metabolic function.

Pregnancy

There is limited information regarding the safety of hydrogenphosphate in pregnancy. Consult relevant guidelines and consider potential risks versus benefits.

Breast-feeding

Data on the excretion of hydrogenphosphate in human milk are not available. Caution is advised.

Storage

Store in a cool, dry place away from direct sunlight. Ensure containers are tightly closed.

Indications

• Serious infections caused by aerobic Gram-negative bacteria
• Infections due to mycobacteria, including tuberculosis
• Endocarditis in conjunction with penicillin-related antibiotics

Dosage

Children: Refer to BNF for Children for specific dosing information, as it is determined by weight and age.

Adults: Refer to BNF for specific dosing information, as it varies based on the type and severity of the infection.

Mechanism of action

Kanamycin irreversibly binds to specific proteins and 16S rRNA of the 30S ribosomal subunit. This binding interferes with the decoding site, leading to misreading of mRNA, incorrect amino acid insertion into peptides, and disruption of polysomes into nonfunctional monosomes. This bactericidal action results in the inhibition of protein synthesis in susceptible microorganisms.

Pharmacodynamics

Kanamycin is effective primarily against aerobic Gram-negative bacteria and some mycobacteria, including those causing tuberculosis. It disrupts the integrity of the bacterial cell membrane and inhibits protein synthesis, rendering bacteria unable to grow and replicate. While it can be used for Gram-positive infections, other antibiotics are usually preferred due to their higher potency and lower toxicity.

Pharmacokinetics

Kanamycin is administered parenterally, as it is poorly absorbed from the gastrointestinal tract. It demonstrates a volume of distribution that is primarily extracellular. The drug is primarily eliminated by the kidneys through glomerular filtration, necessitating dose adjustments in patients with renal impairment. Kanamycin's half-life is approximately 2 to 3 hours in individuals with normal renal function.

Contra-indications

• Hypersensitivity to kanamycin or any aminoglycoside antibiotic
• Severe renal impairment
• Myasthenia gravis

Adverse effects

• Nephrotoxicity
• Ototoxicity (hearing loss, vestibular toxicity)
• Neuromuscular blockade
• Allergic reactions (skin rash, itching)
• Gastrointestinal disturbances (nausea, vomiting)

Interactions

• Other nephrotoxic drugs (e.g., cisplatin, vancomycin) may increase the risk of renal toxicity
• Neurotoxins may potentiate neuromuscular blockade
• Concurrent use with diuretics (e.g., furosemide) may enhance ototoxicity

Precautions

• Monitor renal function regularly during treatment
• Use with caution in patients with pre-existing hearing loss
• Adjust dosage in cases of renal impairment
• Ensure adequate hydration to minimize risk of nephrotoxicity

Pregnancy

Kanamycin is classified as category D. It should only be used if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

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

Storage

Store in a cool, dry place away from light. Refrigeration may be required for some formulations.

Formulations

• Kanamycin sulfate injection
• Kanamycin oral solution

Indications

• Cognitive disorders
• Neurodegenerative diseases
• Amyotrophic lateral sclerosis
• Alzheimer's disease
• Lathyrism
• Schizophrenia-related symptoms

Dosage

Children: Refer to the BNF for Children for dosage information.

Adults: Refer to the BNF for specific dosage information.

Mechanism of action

L-Glutamate activates both ionotropic and metabotropic glutamate receptors, including NMDA, AMPA, and kainate receptors. It is converted to L-glutamine for transport across the blood-brain barrier, where it is utilized for neuronal energy and protein synthesis. Its role in neurotransmission is critical, yet its transient nature complicates the study of its effects.

Pharmacodynamics

As the most prevalent excitatory neurotransmitter, L-glutamate is involved in synaptic transmission and plasticity, making it integral to learning and memory processes. It also acts as a precursor for the inhibitory neurotransmitter GABA, thereby contributing to the balance of excitatory and inhibitory signals in the brain.

Pharmacokinetics

L-Glutamate does not cross the blood-brain barrier in significant amounts; instead, it is converted to L-glutamine, which can enter the brain. Following neurotransmission, L-glutamate is taken up by surrounding glial cells and neurons, where it is metabolized or recycled. The metabolism pathways involve nitrogen metabolism and several amino acid biosynthesis pathways.

Pregnancy

Safety in pregnancy has not been established. Use only if clearly needed.

Breast-feeding

It is not known whether L-glutamate is excreted in human milk. Caution should be exercised when administering to breastfeeding women.

Storage

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

Indications

• Measles
• Mumps
• Rubella
• Varicella (chickenpox)
• Yellow fever
• Rotavirus
• Intranasal influenza

Dosage

Children: Refer to the BNF for Children for specific dosing information based on age and vaccine type.

Adults: Refer to specific product guidelines for dosing information, as it can vary by vaccine type and brand.

Mechanism of action

Live vaccines work by introducing a weakened or attenuated form of a pathogen into the body. This stimulates the immune system to recognize and respond to the pathogen, leading to the production of antibodies and memory cells that provide long-term protection against future infections by the same pathogen.

Pharmacodynamics

The pharmacodynamics of live vaccines involve the activation of both humoral and cellular immunity. Following vaccination, the immune system generates a robust response, including the production of specific antibodies and the activation of T cells that can recognize and eliminate infected cells. This dual action helps establish long-term immunity.

Pharmacokinetics

The pharmacokinetics of live vaccines vary depending on the specific vaccine. Generally, the vaccine is administered via injection, allowing the live attenuated organisms to enter the bloodstream. The immune response typically begins within days and can last for years, depending on the vaccine. Live vaccines are usually stored under refrigeration to maintain their viability, and they should be administered within their expiration dates.

Interactions

• livevaccines + abrocitinib: Severe (increases risk of generalised infection (possibly life-threatening))
• livevaccines + baricitinib: Severe (increases risk of generalised infection (possibly life-threatening))
• livevaccines + filgotinib: Severe (increases risk of generalised infection (possibly life-threatening))
• livevaccines + dexrazoxane: Severe (increases risk of generalised infection (possibly life-threatening))
• livevaccines + iron chelators: Severe (increases risk of generalised infection (possibly life-threatening))
• livevaccines + ozanimod: Severe (increases risk of generalised infection (possibly life-threatening))
• livevaccines + ponesimod: Severe (increases risk of generalised infection (possibly life-threatening))
• livevaccines + siponimod: Severe (increases risk of generalised infection (possibly life-threatening))
• livevaccines + upadacitinib: Severe (increases risk of generalised infection (possibly life-threatening))
• livevaccines + diroximelfumarate: Moderate (increases risk of generalised infection (possibly life-threatening))

Dosage

Children: Refer to specific product guidelines as dosage will depend on the type of medium and its intended application.

Adults: Refer to specific product guidelines as dosage will depend on the type of medium and its intended application.

Mechanism of action

The mechanism of action for a medium can vary greatly depending on the specific medium being referenced. Generally, media serve to maintain the stability and viability of cells or organisms during culture, enabling metabolic processes to occur. For instance, nutrient media provide essential nutrients, while selective media may inhibit the growth of certain organisms while promoting others.

Pharmacodynamics

Pharmacodynamics is largely dependent on the type of medium used and its components. In tissue cultures, the medium can influence cell growth, differentiation, and physiological responses. The interactions of cells with their environment are critical for cellular signaling and function.

Pharmacokinetics

Pharmacokinetics is not typically applicable to media in the same way it is for active drugs. However, the absorption and distribution of substances within a medium can affect how well the active ingredients are delivered or how organisms interact with the medium. Factors such as pH, osmolarity, and nutrient concentration can all influence these processes.

Pregnancy

Consult a healthcare provider before use, as the safety of medium in pregnancy has not been established.

Breast-feeding

Consult a healthcare provider before use, as it is unknown whether medium passes into breast milk.

Storage

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

Dosage

Children: Paediatric dosing for modified drugs must be derived from established guidelines or clinical recommendations. Consult the relevant guidelines or formulary for age-appropriate dosing.

Adults: Dosing for modified drugs is highly specific to each agent and should be determined based on clinical guidelines and individual patient needs. It is essential to refer to specific product literature or a professional drug reference for accurate dosing information.

Mechanism of action

The mechanism of action for modified drugs varies significantly depending on their specific structure and target. Generally, modifications can enhance binding affinity to receptors, alter metabolic pathways, or improve cellular uptake. For example, modifications may lead to increased selectivity for target enzymes or receptors, thereby improving therapeutic outcomes and reducing off-target effects.

Pharmacodynamics

Pharmacodynamics of modified drugs typically includes alterations in the drug's potency and efficacy, influenced by the structural changes made. These modifications can lead to improved therapeutic indices by enhancing the desired pharmacological effect while minimizing adverse effects. Such changes may also affect receptor activation, signal transduction pathways, and downstream physiological effects.

Pharmacokinetics

The pharmacokinetics of modified drugs can be significantly altered based on the nature of the modifications. Factors such as absorption, distribution, metabolism, and excretion (ADME) can be optimized to improve bioavailability and half-life. For instance, modifications might enhance solubility, stability, or resistance to enzymatic degradation, affecting how the drug is processed in the body.

Indications

• Bacterial infections caused by aerobic organisms
• Topical treatment of skin infections

Mechanism of action

Neomycin binds to specific proteins and 16S rRNA within the 30S ribosomal subunit of susceptible bacteria. This binding interferes with the decoding site, causing misreading of mRNA and leading to the incorporation of incorrect amino acids into polypeptides. As a result, nonfunctional or toxic peptides are produced, and polysomes are disrupted into nonfunctional monosomes. Neomycin's bactericidal action is characterized by its ability to irreversibly bind to the 30S ribosomal subunit, thereby inhibiting bacterial protein synthesis.

Pharmacodynamics

Neomycin is primarily active against aerobic bacteria and is not effective against fungi, viruses, or most anaerobic bacteria. It mediates its bactericidal effects by inhibiting protein synthesis, which suppresses bacterial growth and survival. Following oral administration, neomycin exhibits a duration of bactericidal activity lasting between 48 to 72 hours. It is particularly useful in treating infections caused by strains of E. coli and Klebsiella, and it also acts to reduce colonic bacterial populations in patients with hepatic coma.

Pharmacokinetics

Neomycin is poorly absorbed from the gastrointestinal tract when taken orally, which limits its systemic availability and enhances its utility in targeting colonic bacteria. It is generally not used parenterally due to its potential for nephrotoxicity and ototoxicity. The duration of action following oral administration can last from 48 to 72 hours, and it is primarily excreted unchanged in the urine. Caution should be exercised when using neomycin in patients with renal impairment, as the risk of toxicity increases.

Adverse effects

• Nephrotoxicity
• Ototoxicity
• Allergic reactions
• Diarrhea
• Nausea
• Vomiting

Interactions

• neomycin+digoxin: Unknown (decreases absorption)
• neomycin+sorafenib: Unknown (decreases exposure)

Precautions

• Use with caution in patients with renal impairment
• Monitor renal function during therapy
• Evaluate hearing function in long-term use

Pregnancy

Neomycin is classified as category D; it should be used only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

Neomycin is excreted in breast milk; caution should be exercised when administered to nursing mothers.

Storage

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

Formulations

• Topical ointment
• Cream
• Eye drops
• Oral tablets

Indications

• Contraception
• Regulation of menstrual cycles
• Treatment of polycystic ovary syndrome (PCOS)
• Management of endometriosis
• Treatment of menstrual disorders

Dosage

Children: Ortho contraceptives are generally not prescribed for individuals under the age of 16 without careful consideration. Consultation with a healthcare provider is essential for determining appropriate use in younger populations.

Adults: The specific dosage of Ortho varies based on the formulation and the individual's health status. It is important to follow the prescribing information provided by healthcare providers.

Mechanism of action

The active ingredients in Ortho contraceptives work by inhibiting ovulation, thickening the cervical mucus to prevent sperm penetration, and altering the endometrial lining to prevent implantation of a fertilized egg. This multi-faceted approach effectively reduces the likelihood of conception.

Pharmacodynamics

Estrogens and progestins exert their effects by binding to estrogen and progesterone receptors, respectively. This binding leads to changes in gene expression that suppress gonadotropin release, ultimately inhibiting follicular development and ovulation. The alteration of the endometrial environment makes it less favorable for implantation, thereby contributing to contraceptive efficacy.

Pharmacokinetics

Ortho contraceptives are absorbed rapidly from the gastrointestinal tract, with peak plasma concentrations achieved within 1 to 3 hours after administration. These drugs are metabolized primarily in the liver, with various metabolic pathways involved, including conjugation and hydroxylation. The elimination half-lives of the individual components can vary, but they are generally excreted in urine and feces. The pharmacokinetics can be influenced by factors such as concurrent medications, liver function, and gastrointestinal health.

Contra-indications

• Hypersensitivity to any component of the formulation
• Severe liver disease
• Severe renal impairment
• Undiagnosed vaginal bleeding
• History of thromboembolic disorders

Adverse effects

• Nausea
• Vomiting
• Headache
• Breast tenderness
• Mood changes
• Weight gain
• Increased risk of thromboembolic events
• Irregular bleeding patterns

Interactions

• Antibiotics may reduce the effectiveness of the contraceptive effect
• Anticonvulsants may also decrease efficacy
• St. John's Wort may reduce plasma concentrations
• Certain antiretroviral medications may interact

Precautions

• Use with caution in patients with a history of hypertension
• Monitor for signs of thromboembolism
• Regular check-ups recommended for long-term users
• Consider alternative contraception methods in certain populations

Pregnancy

Use of this drug is contraindicated during pregnancy due to potential harm to the fetus. It can lead to congenital malformations and other serious complications.

Breast-feeding

The drug may be secreted in breast milk; therefore, caution is advised. Consult healthcare professionals for alternative contraceptive methods if breastfeeding.

Storage

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

Formulations

• Oral tablets
• Transdermal patches
• Vaginal rings

Indications

• Phosphate deficiency
• Hypophosphatemia
• Bone mineralization disorders
• Renal osteodystrophy

Dosage

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

Adults: Refer to the BNF for specific dosing recommendations.

Mechanism of action

Orthophosphate functions primarily as a source of inorganic phosphate in biochemical reactions. It is involved in the phosphorylation of molecules which is critical for the synthesis of ATP and the regulation of metabolic pathways. Its presence is vital in the formation of nucleotides and phospholipids, which are essential for cellular function and structure. The pathways it influences include nitrogen metabolism, biotin metabolism, D-alanine metabolism, D-glutamine and D-glutamate metabolism, lysine biosynthesis, taurine metabolism, and the TCA cycle.

Pharmacodynamics

Orthophosphate contributes to the regulation of various physiological processes, including energy metabolism and cellular signaling. It is essential for the maintenance of acid-base balance and the proper functioning of enzymes that are dependent on phosphate groups. Additionally, it plays a role in bone mineralization and is a key factor in the regulation of calcium metabolism. Its pharmacodynamic effects are closely linked to its role in ATP synthesis and the energy status of cells.

Pharmacokinetics

Orthophosphate is readily absorbed in the gastrointestinal tract and is distributed throughout the body. It is primarily excreted by the kidneys, with a regulated reabsorption process that maintains homeostasis. The half-life of orthophosphate in the body is relatively short, necessitating a continuous supply through dietary sources or supplementation. Its pharmacokinetic properties are influenced by renal function, dietary intake, and hormonal regulation, particularly by parathyroid hormone and vitamin D.

Pregnancy

Orthophosphate is typically considered safe during pregnancy when used appropriately; however, it is always best to consult a healthcare provider.

Breast-feeding

Orthophosphate is generally regarded as safe during breastfeeding; it is important to follow medical advice.

Storage

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

Indications

• Rotavirus gastroenteritis
• Prevention of rotavirus-related diarrhea in infants and children

Dosage

Children: Refer to the BNF for Children for specific vaccination schedules and dosing information related to rotavirus vaccination.

Mechanism of action

Rotavirus infects and replicates in the epithelial cells of the small intestine. The virus disrupts the normal function of these cells, leading to malabsorption of nutrients and water. The infection triggers an inflammatory response, resulting in increased intestinal permeability, secretion of electrolytes and water into the intestinal lumen, and subsequent diarrhea.

Pharmacodynamics

The body's immune response plays a crucial role in controlling rotavirus infections. The production of antibodies against rotavirus is stimulated by natural infection and vaccination. These antibodies help neutralize the virus and prevent future infections. The severity of the disease is often related to the host's immune status and the age of the child at the time of infection.

Pharmacokinetics

As a virus, rotavirus does not follow traditional pharmacokinetic profiles like absorption, distribution, metabolism, and excretion seen with drugs. Instead, the focus is on the replication cycle of the virus within the host's intestinal cells and the resultant immune response. The stability of rotavirus outside the host is significant for transmission, as it can survive on surfaces for long periods.

Contra-indications

• Severe allergic reaction to any component of the vaccine
• History of intussusception
• Severe combined immunodeficiency (SCID)
• Moderate or severe acute illness

Adverse effects

• Diarrhea
• Vomiting
• Fever
• Irritability
• Intussusception (rarely)
• Allergic reactions (rare)

Interactions

• Immunosuppressive therapies may reduce vaccine efficacy
• Other live vaccines should generally be given at the same visit or separated by at least 4 weeks

Precautions

• Monitor for signs of intussusception after vaccination
• Use with caution in individuals with a history of gastrointestinal disorders
• Pregnant women should not receive the vaccine

Pregnancy

The vaccine is not recommended during pregnancy due to lack of safety data.

Breast-feeding

Safe to use during breastfeeding; no contraindications.

Storage

Store in a refrigerator (2°C to 8°C). Do not freeze.

Formulations

• Oral suspension for vaccination

Indications

• Sweetening agent in food and beverages
• Ingredient in pharmaceutical formulations
• Source of quick energy

Dosage

Children: Refer to specific formulations and clinical guidelines for dosing, as sucrose does not have a standardized dosage. Typically used as needed for sweetening.

Adults: Refer to specific formulations and clinical guidelines for dosing, as sucrose does not have a standardized dosage. Typically used as needed for sweetening.

Mechanism of action

Sucrose is metabolized in the body to glucose and fructose, which are then used as energy sources. It does not have a specific pharmacological mechanism of action but contributes to energy metabolism via the glycolytic and citric acid pathways.

Pharmacodynamics

Upon ingestion, sucrose is hydrolyzed by the enzyme sucrase into its constituent monosaccharides, glucose and fructose. These monosaccharides are absorbed in the small intestine and enter the bloodstream, leading to a rise in blood glucose levels. This process provides a quick source of energy for cellular functions.

Pharmacokinetics

Sucrose is rapidly absorbed in the gastrointestinal tract after hydrolysis. Its absorption depends on the presence of sucrase in the intestine. Once in the bloodstream, glucose can be utilized by cells or stored as glycogen in the liver and muscles. The elimination half-life of sucrose itself is not well-defined as it is quickly broken down and utilized.

Pregnancy

Sucrose is generally regarded as safe during pregnancy when consumed in moderation as part of a balanced diet.

Breast-feeding

Sucrose is considered safe during breastfeeding when consumed in normal dietary amounts.

Storage

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

Formulations

• Oral solution
• Granules
• Tablets

Mechanism of action

Substantial evidence indicates that molecular hydrogen (H2) has beneficial vascular effects because of its antioxidant and/or anti-inflammatory effects. Thus, hydrogen-rich water may prove to be an effective anti-aging drink. This study examined the effects of H2 on endothelial senescence and clarified the mechanisms involved. Hydrogen-rich medium was produced by a high-purity hydrogen gas generator. Human umbilical vein endothelial cells (HUVECs) were incubated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) for various time periods in normal or hydrogen-rich medium. The baseline H2concentration in hydrogen-rich medium was 0.55 +/- 0.07 mmol/L. This concentration gradually decreased, and H2 was almost undetectable in medium after 12 hr. At 24 hr after TCDD exposure, HUVECs treated with TCDD exhibited increased 8OHdG and acetyl-p53 expression, decreased nicotinamide adenine dinucleotide (NAD(+))/NADH ratio, impaired Sirt1 activity, and enhanced senescence-associated beta-galactosidase. However, HUVECs incubated in hydrogen-rich medium did not exhibit these TCDD-induced changes accompanying Nrf2 activation, which was observed even after H2 was undetectable in the medium. Chrysin, an inhibitor of Nrf2, abolished the protective effects of H2 on HUVECs. H2 has long-lasting antioxidant and anti-aging effects on vascular endothelial cells through the Nrf2 pathway, even after transient exposure to H2. Hydrogen-rich water may thus be a functional drink that increases longevity. /Hydrogen-rich water/ Amyloid beta (Abeta) peptides are identified /as a/ cause of neurodegenerative diseases such as Alzheimer's disease (AD). Previous evidence suggests Abeta-induced neurotoxicity is linked to the stimulation of reactive oxygen species (ROS) production. The accumulation of Abeta-induced ROS leads to increased mitochondrial dysfunction and triggers apoptotic cell death. This suggests antioxidant therapies may be beneficial for preventing ROS-related diseases such as AD. Recently, hydrogen-rich water (HRW) has been proven effective in treating oxidative stress-induced disorders because of its ROS-scavenging abilities. However, the precise molecular mechanisms whereby HRW prevents neuronal death are still unclear. In the present study, we evaluated the putative pathways by which HRW protects against Abeta-induced cytotoxicity /in SK-N-MC cells/. Our results indicated that HRW directly counteracts oxidative damage by neutralizing excessive ROS, leading to the alleviation of Abeta-induced cell death. In addition, HRW also stimulated AMP-activated protein kinase (AMPK) in a sirtuin 1 (Sirt1)-dependent pathway, which upregulates forkhead box protein O3a (FoxO3a) downstream antioxidant response and diminishes Abeta-induced mitochondrial potential loss and oxidative stress. Taken together, our findings suggest that HRW may have potential therapeutic value to inhibit Abeta-induced neurotoxicity. /Hydrogen-rich water/ The NLRP3 inflammasome, an intracellular multi-protein complex controlling the maturation of cytokine interleukin-1beta, plays an important role in lipopolysaccharide (LPS)-induced inflammatory cascades. Recently, the production of mitochondrial reactive oxygen species (mtROS) in macrophages stimulated with LPS has been suggested to act as a trigger during the process of NLRP3 inflammasome activation that can be blocked by some mitochondria-targeted antioxidants. Known as a ROS scavenger, molecular hydrogen (H2) has been shown to possess therapeutic benefit on LPS-induced inflammatory damage in many animal experiments. Due to the unique molecular structure, H2 can easily target the mitochondria, suggesting that H2 is a potential antagonist of mtROS-dependent NLRP3 inflammasome activation. Here we have showed that, in mouse macrophages, H2 exhibited substantial inhibitory activity against LPS-initiated NLRP3 inflammasome activation by scavenging mtROS. Moreover, the elimination of mtROS by H2 resultantly inhibited mtROS-mediated NLRP3 deubi

Mechanism of action

Substantial evidence indicates that molecular hydrogen (H2) has beneficial vascular effects because of its antioxidant and/or anti-inflammatory effects. Thus, hydrogen-rich water may prove to be an effective anti-aging drink. This study examined the effects of H2 on endothelial senescence and clarified the mechanisms involved. Hydrogen-rich medium was produced by a high-purity hydrogen gas generator. Human umbilical vein endothelial cells (HUVECs) were incubated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) for various time periods in normal or hydrogen-rich medium. The baseline H2concentration in hydrogen-rich medium was 0.55 +/- 0.07 mmol/L. This concentration gradually decreased, and H2 was almost undetectable in medium after 12 hr. At 24 hr after TCDD exposure, HUVECs treated with TCDD exhibited increased 8OHdG and acetyl-p53 expression, decreased nicotinamide adenine dinucleotide (NAD(+))/NADH ratio, impaired Sirt1 activity, and enhanced senescence-associated beta-galactosidase. However, HUVECs incubated in hydrogen-rich medium did not exhibit these TCDD-induced changes accompanying Nrf2 activation, which was observed even after H2 was undetectable in the medium. Chrysin, an inhibitor of Nrf2, abolished the protective effects of H2 on HUVECs. H2 has long-lasting antioxidant and anti-aging effects on vascular endothelial cells through the Nrf2 pathway, even after transient exposure to H2. Hydrogen-rich water may thus be a functional drink that increases longevity. /Hydrogen-rich water/ Amyloid beta (Abeta) peptides are identified /as a/ cause of neurodegenerative diseases such as Alzheimer's disease (AD). Previous evidence suggests Abeta-induced neurotoxicity is linked to the stimulation of reactive oxygen species (ROS) production. The accumulation of Abeta-induced ROS leads to increased mitochondrial dysfunction and triggers apoptotic cell death. This suggests antioxidant therapies may be beneficial for preventing ROS-related diseases such as AD. Recently, hydrogen-rich water (HRW) has been proven effective in treating oxidative stress-induced disorders because of its ROS-scavenging abilities. However, the precise molecular mechanisms whereby HRW prevents neuronal death are still unclear. In the present study, we evaluated the putative pathways by which HRW protects against Abeta-induced cytotoxicity /in SK-N-MC cells/. Our results indicated that HRW directly counteracts oxidative damage by neutralizing excessive ROS, leading to the alleviation of Abeta-induced cell death. In addition, HRW also stimulated AMP-activated protein kinase (AMPK) in a sirtuin 1 (Sirt1)-dependent pathway, which upregulates forkhead box protein O3a (FoxO3a) downstream antioxidant response and diminishes Abeta-induced mitochondrial potential loss and oxidative stress. Taken together, our findings suggest that HRW may have potential therapeutic value to inhibit Abeta-induced neurotoxicity. /Hydrogen-rich water/ The NLRP3 inflammasome, an intracellular multi-protein complex controlling the maturation of cytokine interleukin-1beta, plays an important role in lipopolysaccharide (LPS)-induced inflammatory cascades. Recently, the production of mitochondrial reactive oxygen species (mtROS) in macrophages stimulated with LPS has been suggested to act as a trigger during the process of NLRP3 inflammasome activation that can be blocked by some mitochondria-targeted antioxidants. Known as a ROS scavenger, molecular hydrogen (H2) has been shown to possess therapeutic benefit on LPS-induced inflammatory damage in many animal experiments. Due to the unique molecular structure, H2 can easily target the mitochondria, suggesting that H2 is a potential antagonist of mtROS-dependent NLRP3 inflammasome activation. Here we have showed that, in mouse macrophages, H2 exhibited substantial inhibitory activity against LPS-initiated NLRP3 inflammasome activation by scavenging mtROS. Moreover, the elimination of mtROS by H2 resultantly inhibited mtROS-mediated NLRP3 deubi

Mechanism of action

Aminoglycosides like kanamycin "irreversibly" bind to specific 30S-subunit proteins and 16S rRNA. Specifically Kanamycin binds to four nucleotides of 16S rRNA and a single amino acid of protein S12. This interferes with decoding site in the vicinity of nucleotide 1400 in 16S rRNA of 30S subunit. This region interacts with the wobble base in the anticodon of tRNA. This leads to interference with the initiation complex, misreading of mRNA so incorrect amino acids are inserted into the polypeptide leading to nonfunctional or toxic peptides and the breakup of polysomes into nonfunctional monosomes. Kanamycin, an aminoglycoside, acts by inhibiting the synthesis of protein in susceptible microorganisms. It is bactericidal in vitro against Gram-negative bacteria and certain Gram-positive bacteria. Aminoglycosides are usually bactericidal in action. Although the exact mechanism of action has not been fully elucidated, the drugs appear to inhibit protein synthesis in susceptible bacteria by irreversibly binding to 30S ribosomal subunits. /Aminoglycosides/ ... Aminoglycosides are aminocyclitols that kill bacteria by inhibiting protein synthesis as they bind to the 16S rRNA and by disrupting the integrity of bacterial cell membrane. Aminoglycoside resistance mechanisms include: (a) the deactivation of aminoglycosides by N-acetylation, adenylylation or O-phosphorylation, (b) the reduction of the intracellular concentration of aminoglycosides by changes in outer membrane permeability, decreased inner membrane transport, active efflux, and drug trapping, (c) the alteration of the 30S ribosomal subunit target by mutation, and (d) methylation of the aminoglycoside binding site. ... /Aminoglycosides/

Pharmacodynamics

Kanamycin is an aminoglycoside antibiotic. Aminoglycosides work by binding to the bacterial 30S ribosomal subunit, causing misreading of t-RNA, leaving the bacterium unable to synthesize proteins vital to its growth. Aminoglycosides are useful primarily in infections involving aerobic, Gram-negative bacteria, such as Pseudomonas, Acinetobacter, and Enterobacter. In addition, some mycobacteria, including the bacteria that cause tuberculosis, are susceptible to aminoglycosides. Infections caused by Gram-positive bacteria can also be treated with aminoglycosides, but other types of antibiotics are more potent and less damaging to the host. In the past the aminoglycosides have been used in conjunction with penicillin-related antibiotics in streptococcal infections for their synergistic effects, particularly in endocarditis. Aminoglycosides are mostly ineffective against anaerobic bacteria, fungi and viruses.

Mechanism of action

Glutamate activates both ionotropic and metabotropic glutamate receptors. The ionotropic ones being non-NMDA (AMPA and kainate) and NMDA receptors. Free glutamic acid cannot cross the blood-brain barrier in appreciable quantities; instead it is converted into L-glutamine, which the brain uses for fuel and protein synthesis. It is conjectured that glutamate is involved in cognitive functions like learning and memory in the brain, though excessive amounts may cause neuronal damage associated in diseases like amyotrophic lateral sclerosis, lathyrism, and Alzheimer's disease. Also, the drug phencyclidine (more commonly known as PCP) antagonizes glutamate at the NMDA receptor, causing behavior reminiscent of schizophrenia. Glutamate in action is extremely difficult to study due to its transient nature.

Pharmacodynamics

In addition to being one of the building blocks in protein synthesis, it is the most widespread neurotransmitter in brain function, as an excitatory neurotransmitter and as a precursor for the synthesis of GABA in GABAergic neurons.

Mechanism of action

Framycetin binds to specific 30S-subunit proteins and 16S rRNA, four nucleotides of 16S rRNA and a single amino acid of protein S12. This interferes with decoding site in the vicinity of nucleotide 1400 in 16S rRNA of 30S subunit. This region interacts with the wobble base in the anticodon of tRNA. This leads to interference with the initiation complex, misreading of mRNA so incorrect amino acids are inserted into the polypeptide leading to nonfunctional or toxic peptides and the breakup of polysomes into nonfunctional monosomes. Like other aminoglycoside antibiotic drugs, neomycin inhibits bacterial ribosomes by binding to the 30S ribosomal subunit of susceptible bacteria and disrupting the translational machinery of bacterial protein synthesis. Bacterial translation is normally initiated by the mRNA binding to the 30S ribosomal subunit and subsequent binding with 50S subunit for elongation. Aminoglycosides are usually bactericidal in action. Although the exact mechanism of action has not been fully elucidated, the drugs appear to inhibit protein synthesis in susceptible bacteria by irreversibly binding to 30S ribosomal subunits. /Aminoglycosides/ A class of angiogenesis inhibitor has emerged from our mechanistic study of the action of angiogenin, a potent angiogenic factor. Neomycin, an aminoglycoside antibiotic, inhibits nuclear translocation of human angiogenin in human endothelial cells, an essential step for angiogenin-induced angiogenesis. The phospholipase C-inhibiting activity of neomycin appears to be involved, because U-73122, another phospholipase C inhibitor, has a similar effect. In contrast, genistein, oxophenylarsine, and staurosporine, inhibitors of tyrosine kinase, phosphotyrosine phosphatase, and protein kinase C, respectively, do not inhibit nuclear translocation of angiogenin. Neomycin inhibits angiogenin-induced proliferation of human endothelial cells in a dose-dependent manner. At 50 microM, neomycin abolishes angiogenin-induced proliferation but does not affect the basal level of proliferation and cell viability. Other aminoglycoside antibiotics, including gentamicin, streptomycin, kanamycin, amikacin, and paromomycin, have no effect on angiogenin-induced cell proliferation. Most importantly, neomycin completely inhibits angiogenin-induced angiogenesis in the chicken chorioallantoic membrane at a dose as low as 20 ng per egg. These results suggest that neomycin and its analogs are a class of agents that may be developed for anti-angiogenin therapy. ... Aminoglycosides are aminocyclitols that kill bacteria by inhibiting protein synthesis as they bind to the 16S rRNA and by disrupting the integrity of bacterial cell membrane. Aminoglycoside resistance mechanisms include: (a) the deactivation of aminoglycosides by N-acetylation, adenylylation or O-phosphorylation, (b) the reduction of the intracellular concentration of aminoglycosides by changes in outer membrane permeability, decreased inner membrane transport, active efflux, and drug trapping, (c) the alteration of the 30S ribosomal subunit target by mutation, and (d) methylation of the aminoglycoside binding site. ... /Aminoglycosides/

Pharmacodynamics

Framycetin is used for the treatment of bacterial eye infections such as conjunctivitis. Framycetin is an antibiotic. It is not active against fungi, viruses and most kinds of anaerobic bacteria. Framycetin works by binding to the bacterial 30S ribosomal subunit, causing misreading of t-RNA, leaving the bacterium unable to synthesize proteins vital to its growth. Framycetin is useful primarily in infections involving aerobic bacteria bacteria. Neomycin mediates its bactericidal action by inhibiting bacterial protein synthesis, thereby suppressing the growth and survival of susceptible bacteria. Following oral administration, the duration of bactericidal activity of neomycin ranged from 48 to 72 hours. By decreasing colonic bacteria that produce ammonia, neomycin was shown to be effective as an adjunctive therapy in hepatic coma to improve neurologic symptoms. Neomycin is active against both gram positive and gram negative organisms, including the major _E. coli_ species resident in the colon as well as the enteropathogenic forms of _E. coli_. It is also active against _Klebsiella_-_Enterobacter_ group. Resistant strains of _E. coli_, _Klebsiella_ and _Proteus spp_. may emerge from neomycin therapy. Neomycin has no antifungal activity and has some activity against some protozoa.