LIVOLUK FIBRE

Indications

• Chronic constipation
• Portal-systemic encephalopathy

Dosage

Children: Child 1-11 months: 2.5 mL twice daily, adjusted according to response. Child 1-4 years: 5 mL twice daily, adjusted according to response. Child 5-10 years: 10 mL twice daily, adjusted according to response. Child 5-17 years: 5-20 mL twice daily, adjusted according

Adults: Initially 15 mL twice daily, adjusted according to response. For hepatic encephalopathy, doses can be 30-50 mL three times a day, adjusted to produce 2-3 soft stools per day.

Mechanism of action

Lactulose is broken down by saccharolytic bacteria in the large intestine into organic acids, such as lactic acid, which increases intraluminal gas formation and enhances peristaltic gut motility. This osmotic effect increases water content in stool, facilitating bowel movements. Additionally, it acidifies the colonic contents, helping to treat portal-systemic encephalopathy by promoting the conversion of ammonia to ammonium ions, which are less absorbable.

Pharmacodynamics

Lactulose has minimal systemic absorption, exerting its effects predominantly within the gastrointestinal tract. It enhances stool volume and softens stool, which may lead to increased bowel sounds, feelings of bloating, belching, flatus, and diarrhea. These effects contribute to its laxative properties and its role in treating hepatic encephalopathy.

Pharmacokinetics

Lactulose is poorly absorbed from the gastrointestinal tract and exerts its action locally. It typically takes 24 to 48 hours to manifest its laxative effect. The substance is not metabolized before reaching the colon, where it is fermented by gut bacteria, resulting in the production of short-chain fatty acids and gases.

Contra-indications

• Galactosaemia
• Gastrointestinal obstruction
• Gastrointestinal perforation
• Risk of gastrointestinal perforation
• Lactose intolerance

Adverse effects

• Diarrhoea
• Gastrointestinal discomfort
• Nausea
• Abdominal pain
• Flatulence
• Vomiting
• Electrolyte imbalance

Precautions

• Caution in patients with a history of gastrointestinal disorders
• Monitor for electrolyte imbalance in prolonged use

Pregnancy

Not known to be harmful, but manufacturer advises to avoid.

Breast-feeding

Manufacturer advises to avoid.

Storage

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

Formulations

• Lactulose 10g/15ml oral solution
• Lactulose 680 mg per 1 ml
• Lactulose granules

Pregnancy

There is limited data on the safety of color additives during pregnancy. Use only if clearly needed and after consultation with a healthcare provider.

Breast-feeding

The safety of color additives during breastfeeding is not well studied. Use with caution and consult a healthcare provider.

Storage

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

Indications

• Acute pain
• Chronic pain
• Osteoarthritis
• Rheumatoid arthritis
• Musculoskeletal disorders
• Postoperative pain
• Fever

Dosage

Children: Refer to the BNF for Children for appropriate dosing information based on age and weight.

Adults: Refer to specific guidelines or the local formulary for recommendations, as dosing may vary depending on the specific formulation and individual patient factors.

Mechanism of action

The active ingredients in durarome exert their effects by inhibiting the cyclooxygenase (COX) enzymes, which play a crucial role in the conversion of arachidonic acid to prostaglandins. By reducing the production of prostaglandins, the drug decreases inflammation, pain, and fever. This mechanism of action is common among non-steroidal anti-inflammatory drugs (NSAIDs).

Pharmacodynamics

Durarome demonstrates dose-dependent analgesic, antipyretic, and anti-inflammatory effects. Its efficacy in pain relief is associated with its ability to modulate pain signaling pathways in the central nervous system as well as peripheral tissues. The onset of analgesia typically occurs within a few hours of administration, depending on the route of administration and the specific formulation used.

Pharmacokinetics

Durarome is absorbed rapidly after oral administration, with peak plasma concentrations occurring within 1 to 3 hours. The drug is metabolized primarily in the liver, and its metabolites are excreted mainly via urine. The half-life of the active ingredients varies but is generally in the range of 2 to 4 hours, necessitating multiple doses for sustained therapeutic effect. Factors such as age, liver function, and concurrent medications can affect the pharmacokinetics of durarome.

Pregnancy

Consult a healthcare professional before use. The safety of durarome during pregnancy has not been well established.

Breast-feeding

Consult a healthcare professional before use. The safety of durarome during breastfeeding has not been well established.

Storage

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

Indications

• To enhance the palatability of oral medications
• To improve compliance in pediatric patients
• To mask unpleasant tastes of active pharmaceutical ingredients

Dosage

Children: Refer to specific formulations for guidance, as flavoring agents are typically used in very small quantities and are not dosed independently.

Adults: Refer to specific formulations for guidance, as flavoring agents are typically used in very small quantities and are not dosed independently.

Mechanism of action

Flavor compounds act primarily by stimulating taste receptors on the tongue, which can enhance the overall sensory experience of ingesting a product. Certain flavor compounds may also interact with olfactory receptors, contributing to the perception of flavor through smell. The stimulation of these receptors can lead to increased salivation and improved swallowing.

Pharmacodynamics

The use of flavoring agents in pharmaceuticals can influence compliance, particularly in children and individuals who may have difficulty swallowing pills. By enhancing the taste of a medication, these agents can reduce gag reflex and aversion, potentially improving therapeutic outcomes. However, the pharmacodynamic effects are largely dependent on the individual's taste preferences and sensitivities.

Pharmacokinetics

The pharmacokinetics of flavoring agents vary widely depending on the specific compounds used. Generally, these compounds are rapidly absorbed through the gastrointestinal tract upon ingestion, with their effects occurring within minutes. Some flavoring agents may undergo metabolism in the liver, while others may be excreted unchanged. The specific absorption, distribution, metabolism, and excretion (ADME) profiles depend on the chemical structure of each flavor compound.

Pregnancy

Generally considered safe, but specific flavoring agents may need to be evaluated individually.

Breast-feeding

Generally considered safe, but specific flavoring agents may need to be evaluated individually.

Storage

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

Indications

• Severe infections caused by gram-negative bacteria
• Complicated urinary tract infections
• Bacterial sepsis
• Endocarditis caused by susceptible organisms

Dosage

Children: Dosing in children is also weight-based and varies by indication. Refer to the BNF for Children for specific dosing recommendations.

Adults: Dosage varies significantly based on the infection severity and type, renal function, and the specific bacterial susceptibility. Refer to clinical guidelines or the BNF for precise dosing.

Mechanism of action

Gram works by inhibiting bacterial protein synthesis. It binds to the 30S ribosomal subunit of the bacteria, causing misreading of the mRNA and ultimately preventing the synthesis of essential proteins necessary for bacterial growth and replication.

Pharmacodynamics

The pharmacodynamics of Gram include its bactericidal activity against susceptible bacteria. The drug shows concentration-dependent killing, meaning that higher drug concentrations correlate with greater bactericidal effects. The post-antibiotic effect is noted, where bacterial growth is inhibited even after the drug concentration falls below the minimum inhibitory concentration (MIC).

Pharmacokinetics

Gram is usually administered parenterally (intravenously or intramuscularly), and its absorption can vary based on the route of administration. It is distributed widely in body fluids and tissues, although it does not penetrate well into the central nervous system. The drug is primarily eliminated through the kidneys, and its half-life may be prolonged in patients with renal impairment. Monitoring of drug levels may be necessary to avoid toxicity.

Adverse effects

• Nausea
• Vomiting
• Diarrhea
• Abdominal pain
• Allergic reactions
• Rash
• Renal dysfunction

Precautions

• Use with caution in patients with renal impairment
• Monitor renal function during therapy
• Assess for potential allergic reactions

Pregnancy

Use only if the potential benefit justifies the potential risk to the fetus. Consult with a healthcare provider.

Breast-feeding

Use with caution, as it may be excreted in breast milk. Consult with a healthcare provider.

Storage

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

Indications

• Constipation
• Irritable bowel syndrome (IBS)
• Diverticular disease
• Cholesterol management
• Blood sugar control in diabetes

Dosage

Children: For children, it is recommended to consult a healthcare provider for appropriate dosing based on age and weight, as specific pediatric dosing

Adults: For adults, the typical dosage is 1 to 2 teaspoons (5 to 10 grams) of psyllium husk taken 1 to 3 times daily, mixed with at least 8 ounces of water or other liquid.

Mechanism of action

Psyllium husk acts as a bulk-forming laxative. It is not digested by the body, but when mixed with water, it expands and forms a viscous gel. This gel increases the bulk of the stool and triggers peristalsis, enhancing bowel movements. Additionally, it may slow down the absorption of carbohydrates and fats, contributing to its cholesterol-lowering and blood sugar-regulating effects.

Pharmacodynamics

The primary pharmacodynamic effect of husk is its ability to increase stool bulk and water content, which facilitates easier passage of stool through the intestines. This leads to improved bowel regularity and relief from constipation. Furthermore, psyllium husk has been shown to have a mild effect on lowering serum cholesterol levels, particularly low-density lipoprotein (LDL) cholesterol, and may improve glycemic control in patients with type 2 diabetes.

Pharmacokinetics

Psyllium husk is not absorbed systemically; it remains in the gastrointestinal tract, where it exerts its effects. The onset of action for bowel regulation typically occurs within 12 to 72 hours after ingestion, depending on the individual's digestive transit time and fluid intake. Adequate hydration is essential to maximize its efficacy and prevent potential gastrointestinal obstruction.

Adverse effects

• Bloating
• Abdominal cramping
• Diarrhea
• Nausea

Precautions

• Ensure adequate fluid intake when using husk to prevent gastrointestinal obstruction
• Monitor for allergic reactions in sensitive individuals

Pregnancy

Generally considered safe to use during pregnancy, but always consult a healthcare provider.

Breast-feeding

Considered safe while breastfeeding, but consult a healthcare provider for personalized advice.

Storage

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

Formulations

• Psyllium husk powder
• Psyllium husk capsules
• Psyllium husk granules

Indications

• Constipation
• Irritable bowel syndrome
• Diverticular disease
• Hyperlipidemia

Dosage

Children: Refer to the BNF for Children for appropriate dosing guidelines in children.

Adults: Refer to the BNF for specific dosing recommendations, typically starting with a standard dose that can be adjusted based on individual response.

Mechanism of action

Ispaghula acts as a soluble fiber that increases the water content and bulk of the stool. This action stimulates peristalsis (the wave-like muscle contractions of the intestines) and facilitates easier passage of stool through the gastrointestinal tract. It may also contribute to the modulation of intestinal microbiota and has prebiotic effects, promoting the growth of beneficial gut bacteria.

Pharmacodynamics

Ispaghula exhibits its pharmacodynamic effects through its ability to absorb water and swell in the gastrointestinal tract, which increases stool mass and triggers bowel movements. This bulk-forming property helps alleviate constipation and maintains bowel health. Additionally, the gel-like substance formed can slow down the absorption of glucose and cholesterol, providing further metabolic benefits.

Pharmacokinetics

Ispaghula is not absorbed in the gastrointestinal tract, which means it does not have systemic effects. It passes through the digestive system and is excreted unchanged. The onset of action typically occurs within 12 to 72 hours after ingestion, depending on the individual and the volume of fluid consumed with the fiber. Adequate hydration is necessary for optimal efficacy.

Contra-indications

• Intestinal obstruction
• Severe dehydration
• Dysphagia

Adverse effects

• Abdominal bloating
• Flatulence
• Diarrhea
• Constipation
• Esophageal obstruction

Interactions

• May reduce the absorption of concomitantly administered oral medications due to its bulk-forming properties
• Caution should be exercised when taken with anticoagulants as it may affect their absorption

Precautions

• Adequate fluid intake should be ensured to prevent esophageal obstruction
• Caution in patients with a history of gastrointestinal disorders

Pregnancy

Generally considered safe for use during pregnancy, but it is advisable to consult a healthcare provider.

Breast-feeding

Considered safe during breastfeeding; however, maternal hydration should be maintained.

Storage

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

Formulations

• Powder for oral suspension
• Granules for oral intake
• Tablets

Indications

• Scurvy prevention
• Digestive aid
• Immune system support
• Skin health
• Antimicrobial applications

Dosage

Children: There is no specific paediatric dosage for lemon; it can be given to children in moderate amounts as part of a balanced diet.

Adults: There is no specific adult dosage for lemon; it can be consumed in various forms such as fresh fruit, juice, or as part of food and beverages.

Mechanism of action

Lemon contains compounds such as citric acid, flavonoids, and essential oils. Citric acid may enhance the absorption of minerals and has a role in the Krebs cycle, promoting energy metabolism. Flavonoids possess antioxidant properties, which help combat oxidative stress and inflammation, while essential oils can exhibit antimicrobial and anti-inflammatory effects.

Pharmacodynamics

The pharmacodynamic effects of lemon are primarily attributed to its antioxidant properties, which help neutralize free radicals, reduce oxidative stress, and support overall health. The citric acid in lemon may also aid in alkalizing the body, improving metabolic processes, and supporting digestion.

Pharmacokinetics

The bioavailability of lemon compounds can vary based on the form of consumption (whole fruit, juice, or extract). Vitamin C is rapidly absorbed in the gastrointestinal tract and distributed throughout the body. The metabolism of flavonoids occurs primarily in the liver, and they may have a variable half-life depending on individual metabolism.

Adverse effects

• Allergic reactions in sensitive individuals
• Gastrointestinal discomfort
• Tooth enamel erosion with excessive use

Precautions

• Caution in individuals with citrus allergies
• May cause skin irritation if applied topically in concentrated forms

Pregnancy

Lemon is generally considered safe during pregnancy, but excessive intake should be avoided.

Breast-feeding

Lemon is safe during breastfeeding when consumed in normal dietary amounts.

Storage

Store in a cool, dry place. Fresh lemons should be kept in the refrigerator to maintain freshness.

Formulations

• Fresh lemon
• Lemon juice
• Lemon essential oil
• Lemon zest

Indications

• Malignancies
• Lung Fibrosis
• Bronchitis
• Cancer Chemotherapy

Dosage

Children: Refer to the BNF for Children for appropriate dosing guidelines in pediatric patients.

Adults: Refer to the BNF for specific dosage recommendations based on the condition being treated, as it varies by cancer type and patient response.

Mechanism of action

Low-dose exposure to alkylating agents like melphalan induces long-term respiratory complications characterized by bronchitis and lung fibrosis. It stimulates an early release of pro-inflammatory cytokines, such as IL-1beta, IL-6, and IL-23, resulting in neutrophil infiltration in lung tissue within 24 hours. A sustained lymphocytic response follows, lasting at least 14 days, ultimately leading to lung fibrosis, with T lymphocytes, particularly the gamma delta T cell subset, playing a significant role in both the acute and chronic inflammatory responses.

Pharmacodynamics

As an alkylating agent, Lost acts by forming covalent bonds with DNA, resulting in cross-linking that prevents replication and transcription. This mechanism is crucial in its efficacy against rapidly dividing cancer cells, although it also contributes to its toxicity, particularly in normal tissues. The inflammatory response induced can lead to complications, such as lung fibrosis, due to the prolonged recruitment of immune cells.

Pharmacokinetics

The pharmacokinetics of Lost are characterized by its absorption, distribution, metabolism, and excretion, which can vary based on the route of administration. Typically, it is rapidly distributed in tissues, including the lungs. Metabolism occurs primarily via hepatic pathways, leading to active and inactive metabolites. Excretion is mainly renal, and the drug's half-life is influenced by the individual's overall health and organ function.

Pregnancy

There is limited information on the safety of this drug during pregnancy. Use only if the benefits outweigh the risks.

Breast-feeding

Caution is advised as it is not known whether this drug is excreted in human milk.

Storage

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

Dosage

Children: Refer to specific drug formulations and guidelines for dosing.

Adults: Refer to specific drug formulations and guidelines for dosing.

Pregnancy

Consult healthcare providers for risk assessment; data may be limited.

Breast-feeding

Consult healthcare providers as the effects on the infant may vary.

Storage

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

Dosage

Children: Refer to specific drug formulations and product labels as purified substances can vary widely in their use and dosing.

Adults: Refer to specific drug formulations and product labels as purified substances can vary widely in their use and dosing.

Mechanism of action

The mechanism of action for purified compounds varies widely depending on the specific substance. Generally, purified drugs exert their effects by interacting with specific biological targets, such as receptors, enzymes, or ion channels, leading to a desired therapeutic effect. This interaction can involve binding to receptors to activate or inhibit signaling pathways, modulating enzymatic activity, or altering physiological processes.

Pharmacodynamics

Pharmacodynamics describes the effects of a drug on the body and the relationship between drug concentration and effect. For purified drugs, this can involve dose-response relationships and the time course of their action. The purified form often enhances potency and reduces variability in response among patients, which can lead to more predictable therapeutic outcomes. The overall effect is determined by the drug's affinity for its target, the efficacy of the drug-receptor interaction, and the downstream signaling pathways activated as a result of this interaction.

Pharmacokinetics

Pharmacokinetics involves the absorption, distribution, metabolism, and excretion (ADME) of a drug. For purified substances, absorption can be more efficient due to the absence of impurities that may affect solubility or stability. Distribution may also be enhanced, leading to higher bioavailability. Metabolism can be influenced by the structure of the purified compound, as it may be metabolized more readily by liver enzymes. Excretion typically occurs through the kidneys or liver, depending on the molecular characteristics of the purified drug.

Pregnancy

Consult with a healthcare professional, as the safety of purified forms of medications during pregnancy may vary depending on the specific substance.

Breast-feeding

Consult with a healthcare professional, as the safety of purified forms of medications during breastfeeding may vary depending on the specific substance.

Storage

Store in a cool, dry place, away from light and moisture, and keep out of reach of children.

Indications

• Urinary tract infections
• Respiratory tract infections
• Gastrointestinal infections
• Bone and joint infections
• Skin and soft tissue infections

Dosage

Children: Refer to BNF for Children for specific dosage instructions.

Adults: Refer to BNF for specific dosage instructions.

Mechanism of action

Quinolones exert their antibacterial action primarily by inhibiting DNA gyrase and topoisomerase IV. This inhibition prevents the supercoiling of DNA, which is crucial for DNA replication and transcription, ultimately leading to cell death.

Pharmacodynamics

Quinolones exhibit concentration-dependent killing, meaning that higher drug concentrations lead to a more significant antibacterial effect. They display a post-antibiotic effect, where bacterial growth remains suppressed even after the drug concentration drops below the minimum inhibitory concentration (MIC). Quinolones have a relatively long half-life, allowing for once or twice daily dosing in most cases.

Pharmacokinetics

Quinolones are well-absorbed orally, with bioavailability typically exceeding 70%. They are widely distributed in body tissues and fluids, including the lungs, liver, kidneys, and bones. Metabolism primarily occurs in the liver, with renal excretion being the primary route for elimination. The half-life varies among different quinolones but generally ranges from 3 to 10 hours, allowing for convenient dosing schedules.

Interactions

• strontium+quinolones: Severe (decreases absorption)
• lanthanum+quinolones: Unknown (decreases exposure)
• leflunomide+quinolones: Unknown (increases exposure)
• sucralfate+quinolones: Unknown (decreases exposure)
• zinc+quinolones: Unknown (decreases exposure)
• teriflunomide+quinolones: Unknown (increases exposure)

Indications

• Adjunct in weight management
• Sugar substitute for diabetics
• Flavoring agent in various food products

Dosage

Children: Refer to the BNF for Children for specific pediatric dosing guidance. Saccharin is often used in pediatric populations as a sugar substitute but should be administered with caution and within recommended limits.

Adults: As saccharin is used as a sweetener rather than a medication, specific dosing guidelines are not typically established. The acceptable daily intake (ADI) is generally considered to be safe within the limits set by health authorities.

Mechanism of action

Saccharin activates specific T2R bitter taste receptors, which are involved in the perception of taste. Additionally, it has been shown to stimulate transient receptor potential vanilloid-1 (TRPV1) receptors, which are present in taste receptor cells and nerve terminals throughout the oral cavity. This activation may contribute to the bitter aftertaste and metallic taste sensations associated with saccharin and similar sweeteners.

Pharmacodynamics

Saccharin's primary pharmacodynamic effect is its intense sweetness, which is mediated through the activation of taste receptors. The stimulation of T2R receptors and TRPV1 channels can lead to varying taste sensations, including sweetness and bitterness. The sweet taste perception occurs through the activation of taste receptor cells that signal through gustatory pathways to the brain, allowing for the recognition of sweet flavors.

Pharmacokinetics

Saccharin is rapidly absorbed from the gastrointestinal tract and is excreted unchanged in urine. It does not undergo significant metabolism, which contributes to its safety profile as a non-caloric sweetener. The elimination half-life and pharmacokinetic parameters are not typically documented due to its minimal systemic effects in the context of sweetening agents.

Adverse effects

• Gastrointestinal disturbances
• Allergic reactions
• Headaches
• Metallic taste

Precautions

• Use with caution in patients with a history of hypersensitivity to sweeteners
• Consider potential for allergic reactions

Pregnancy

Safety during pregnancy has not been established. Use with caution and consult healthcare professionals.

Breast-feeding

Safety during breastfeeding has not been established. Consult healthcare professionals before use.

Storage

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

Formulations

• Tablets
• Powder

Indications

• Constipation
• Diagnostic aid in colonoscopy preparation
• Management of hyperosmolality in various conditions

Dosage

Children: For children, the dosage should be determined based on age and condition, and it is advised to refer to the BNF for Children for specific dosing guidelines.

Adults: The typical dose for adults is 30 to 150 mL of sorbitol solution (70%) taken orally, as needed, usually before bedtime.

Mechanism of action

Sorbitol exerts its laxative effect by drawing water into the large intestine, thereby stimulating bowel movements. It acts as a hygroscopic agent, pulling water from tissues into the feces, which reflexively stimulates evacuation. In metabolic pathways, sorbitol is produced from glucose via aldose reductase and is converted to fructose by sorbitol dehydrogenase, with implications in diabetic complications such as retinopathy.

Pharmacodynamics

Sorbitol's laxative effect results from its osmotic properties, which increase the water content of the stool and soften it, facilitating easier passage. Additionally, sorbitol can induce apoptosis in certain cancer cell lines, indicating potential therapeutic implications beyond its laxative use. The modulation of intracellular signaling pathways through the regulation of proteins such as Bax and Bcl-2 suggests a complex role in cellular health and disease.

Pharmacokinetics

Sorbitol is poorly absorbed in the gastrointestinal tract, which contributes to its efficacy as a laxative. It is metabolized in the liver, primarily through the polyol pathway. The absorption and distribution of sorbitol are affected by its osmotic properties, leading to increased intestinal water retention. Its elimination is primarily via renal excretion, with minimal systemic absorption, thus reducing the risk of systemic side effects.

Adverse effects

• Diarrhea
• Abdominal cramps
• Nausea
• Vomiting
• Electrolyte imbalances

Precautions

• Use with caution in patients with renal impairment
• May exacerbate gastrointestinal conditions

Pregnancy

Sorbitol is generally considered safe during pregnancy, but should be used under medical supervision.

Breast-feeding

Sorbitol is excreted in breast milk in small amounts; consult a healthcare provider before use.

Storage

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

Formulations

• Oral solution
• Syrup

Indications

• Magnetic resonance imaging (MRI) contrast enhancement
• Drug delivery systems
• Potential therapeutic applications in oncology

Dosage

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

Adults: Refer to the specific guidelines for dosage as per BNF and clinical protocols.

Mechanism of action

The principal uptake mechanism for superparamagnetic iron oxide nanoparticles involves clathrin-mediated endocytosis that is dependent on scavenger receptor A. This process allows phagocytic cells, particularly macrophages, to internalize the nanoparticles effectively. The interaction of these nanoparticles with macrophages is critical for their application in imaging and potential therapeutic interventions.

Pharmacodynamics

Superparamagnetic iron oxide nanoparticles exhibit properties that enhance the visibility of tissues during imaging procedures. Their magnetic properties allow for a significant increase in contrast during MRI scans. Additionally, they may have implications in therapeutic contexts, such as in the targeting of cancer cells, where their uptake by macrophages could facilitate localized drug delivery.

Pharmacokinetics

The pharmacokinetics of superparamagnetic iron oxide nanoparticles are characterized by rapid uptake by phagocytic cells, particularly in the liver and spleen. Following systemic administration, these nanoparticles are primarily cleared by macrophages through endocytosis. The particles tend to accumulate in the reticuloendothelial system, which can influence their distribution and elimination from the body.

Pregnancy

There is limited data on the safety of iron oxide nanoparticles during pregnancy. Caution is advised.

Breast-feeding

Limited data is available regarding the excretion of iron oxide nanoparticles in breast milk. Caution is advised.

Storage

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

Formulations

• Carboxydextran-coated superparamagnetic iron oxide nanoparticles

Pregnancy

No specific data available, consult a healthcare professional.

Breast-feeding

No specific data available, consult a healthcare professional.

Storage

Store in a cool, dry place away from light.

Mechanism of action

Lactulose is a synthetic disaccharide derivative of lactose that consists of one molecule of galactose and one molecule of fructose. Saccharolytic bacteria present in the large intestine subsequently break the substance down into organic acids like lactic acid and small amounts of formic and acetic acids. Such resultant volatile fatty acid metabolites, in combination with hydrogen and methane that is also generated consequently enhance intraluminal gas formation, peristaltic gut motility, and elicit an osmotic effect that facilitates an increase in the water content of stool as well as associated stool softening. All of these actions ultimately assist in facilitating and increasing the frequency of bowel movements in patients experiencing constipation, although it may take 24 to 48 hours after using the medication for this laxative effect to become evident. At the same time, the formation of such acids via the metabolism of lactulose by colonic bacteria also acidifies the contents of the colon, thereby contributing to the treatment of portal-systemic encephalopathy (PSE). As one of the principal features of PSE involves the accumulation of nitrogenous waste products like ammonia in the systemic circulation, a state in which the colonic contents become more acidic than blood allows ammonia in the circulation to diffuse into the colon.. Furthermore, ammonia that diffuses into the acidic colon is ionized to ammonium ions that are incapable of being absorbed back into the blood. These effects, combined with the laxative action of lactulose facilitates the excretion of excess ammonia. And finally, it is also believed that an acidic colonic environment results in the elimination of urease-producing bacteria that contribute to the formation of ammonia while surviving colonic bacteria use up any trapped ammonia in the colon as a source of nitrogen for protein synthesis.

Pharmacodynamics

Lactulose formulations are most commonly administered via the oral route or the rectal route. Consequently, because the substance experiences minimal absorption by the gut it typically remains localized in the gastrointestinal tract environment and ultimately demonstrates almost all of its pharmacologic effects within the gut. In particular, as lactulose elicits its laxative effects in enhancing stool amounts and softening stool, such biochemical and physiologic activities can cause increased bowel sounds (borborygmi), a feeling of bloatedness, belching, frequent flatus, and diarrhea.

Mechanism of action

Low-dose exposure of alkylating mustard gas causes long-term respiratory complications characterized by bronchitis and lung fibrosis. In this study, we utilized a mouse model for lung exposure of the nitrogen mustard melphalan, in order to define early and late events in the pathogenesis such as expression of pro-inflammatory cytokines, recruitment of inflammatory cells to airways and late-phase fibrosis. /The authors/ investigated the roles of different T lymphocyte subsets on the inflammatory response by using knockout mice lacking either the genes expressing T cell receptor (TCR)-alpha beta or TCR-gamma delta, and compared the responsiveness with that of wild type mice and double knockout mice completely deficient in T cells. Exposure to melphalan induced an early burst of the pro-inflammatory cytokines interleukin (IL)-1beta, IL-6 and IL-23 in airways, followed by extensive infiltration of neutrophils in the lung tissue and airways within 24hr. The acute phase was followed by a sustained lymphocytic response that persisted for at least 14 days with resulting lung fibrosis. Engagement of T lymphocytes, particularly the gamma delta T cell subset, was crucial both for the acute cytokine and neutrophil response and for the late-phase lung fibrosis as indicated by the lack of response in gamma delta T cell deficient mice. /The/ data demonstrate that T lymphocytes play a prominent role in the pathogenesis of long-term lung injuries caused by strong alkylating agents. Sulphur mustard (SM) is a chemical warfare agent that causes erythema and blistering of the skin with a latency of several hours. Although SM is known for almost 200 years the cellular mechanisms involved in the damaging process are not fully understood. There is evidence that changes in nitric oxide (*NO), reactive oxygen species (ROS) and reactive nitrogen species (RNS) might be involved in the damaging process.To find out more about the pathophysiology of SM, /the authors/ investigated the initial formation of biochemical markers of nitrosative and oxidative stress as well as activation (translocation from plasma-membrane) and upregulation of eNOS and iNOS, respectively. Human immortalized keratinocytes (HaCaT cell line) were exposed to SM (100 uM or 300 uM) for 30 min. Cells were fixed after 1hr, 3hr or 6hr of incubation in SM-free medium and immunostained. Live cell experiments were performed using the NO-sensitive dye DAF2-DA. In order to assess cell viability after BH(4) supplementation, /investigators/ analyzed apoptosis using CDD-ELISA. SM significantly increased biochemical markers of nitrosative and oxidative stress already 1hr after exposure. Moreover, the NO producing enzymes eNOS and iNOS showed concentration- and time-dependent changes in their activation or expression levels. Initially, live cell imaging experiments could not confirm NO production after SM exposure. Only when cells were supplemented with tetrahydrobiopterine, stable NO production was detectable. Apoptotic activity was increased due to SM exposure and could be reduced after BH(4) treatment. Our data point towards concentration- and time-dependent formation of iNOS and activation of eNOS due to translocation from plasma-membrane. Live cell experiments yielded first indications of catalytic decoupling of NOS that could be reversed by supplementation with tetrahydrobiopterin (BH(4)). Addition of BH(4) 1hr after SM exposure significantly decreased apoptosis compared to the unsupplemented control. The biochemical sequelae to chloroethyl mustard exposure correspond very well to toxic processes initiated by free radicals. Additionally, mustard solutions contain spontaneously formed cyclic onium ions which produce carbon free radicals when reduced electrochemically. Therefore, /the authors/ hypothesized that the onium ions of sulfur or nitrogen mustards might produce carbon free radicals upon being reduced enzymatically, and that these radicals might constitute a metabolic activation. /The au

Mechanism of action

...it has been shown that the activation of particular T2R bitter taste receptors is partially involved with the bitter aftertaste sensation of saccharin and acesulfame-K. ... /This study/ addressed the question of whether /they/ could stimulate transient receptor potential vanilloid-1 (TRPV1) receptors, as these receptors are activated by a large range of structurally different chemicals. Moreover, TRPV1 receptors and/or their variants are found in taste receptor cells and in nerve terminals throughout the oral cavity. Hence, TRPV1 activation could be involved in the ... aftertaste or even contribute to the poorly understood metallic taste sensation. Using Ca(2+) imaging on TRPV1 receptors heterologously expressed in the human embryonic kidney (HEK) 293 cells and on dissociated primary sensory neurons,... /it was found/ that in both systems, .../sweeteners/ activate TRPV1 receptors, and, moreover, they sensitize these channels to acid and heat. ... /it was/also found that TRPV1 receptors were activated by CuSO(4), ZnSO(4), and FeSO(4), three salts known to produce a metallic taste sensation. In summary, .../the/ results identify a novel group of compounds that activate TRPV1 and, consequently, provide a molecular mechanism that may account for off tastes of sweeteners and metallic tasting salts.

Mechanism of action

Sorbitol exerts its laxative effect by drawing water into the large intestine, thereby stimulating bowel movements. ... Sorbitol exerts hygroscopic and/or local irritant action, drawing water from tissues into feces and reflexly stimulating evacuation. The polyol pathway consists of two enzymes aldose reductase (AR) and sorbitol dehydrogenase (SDH); the former is the first enzyme in the polyol pathway, that catalyzes the reduction of glucose to sorbitol, the latter is the second one, that converts sorbitol to fructose using by NAD(+) as a cofactor. ... SDH activity, the second step in the polyol pathway, might make a greater contribution to the etiology of diabetic retinopathy than does the first step involving AR. /This paper proposes/ a novel hypothesis that polymorphisms of SDH gene may be correlated with SDH gene expression levels in diabetic retinas, thus being a valuable genetic marker for diabetic retinopathy. It has been reported that sorbitol induces apoptosis in several cancer cell lines. ... In /this/ study, the intracellular signaling pathways of sorbitol-induced apoptosis in human K562 cells were investigated using both morphological analysis and DNA fragmentation technique. In this study, we demonstrated that sorbitol-induced apoptosis in human K562 cells is a concentration- and time-dependent manner. This sorbitol-induced apoptosis in human K562 cells was also accompanied by the up-regulation of Bax, and down-regulation of p-Bcl-2, but no effect on the levels of Bcl-X(L). Moreover, the sorbitol treatment resulted in a significant reduction of mitochondria membrane potential, increase in the release of mitochondrial cytochrome c (cyt c), and activation of caspase 3. Furthermore, treatment with caspase 3 inhibitor (z-DEVD-fmk) was capable of preventing the sorbitol-induced caspase 3 activity and cell death. These results clearly demonstrate that the induction of apoptosis by sorbitol involves multiple cellular/molecular pathways and strongly suggest that pro- and anti-apoptotic Bcl-2 family proteins, mitochondrial membrane potential, mitochondrial cyt c, and caspase 3, they all participate in sorbitol-induced apoptotic process in human K562 cells. Chronic diabetic complications, in particular, nephropathy, peripheral and autonomic neuropathy, "diabetic foot," retinopathy, and cardiovascular disease, remain the major cause of morbidity and mortality in patients with diabetes mellitus. Growing evidence indicates that both increased activity of the sorbitol pathway of glucose metabolism and enhanced oxidative stress are the leading factors in the pathogenesis of diabetic complications. The relation between the two mechanisms remains the area of controversy. One group has reported that increased sorbitol pathway activity has a protective rather than detrimental role in complication-prone tissues because the pathway detoxifies toxic lipid peroxidation products. Others put forward a so-called "unifying hypothesis" suggesting that activation of several major pathways implicated in diabetic complications (eg, sorbitol pathway) occurs due to increased production of superoxide anion radicals in mitochondria and resulting poly(ADP-ribose) polymerase activation. This review (a) presents findings supporting a key role for the sorbitol pathway in oxidative stress and oxidative stress-initiated downstream mechanisms of diabetic complications, and (b) summarizes experimental evidence against a detoxifying role of the sorbitol pathway, as well as the "unifying concept."

Mechanism of action

Although systemically applied nanoparticles are quickly taken up by phagocytic cells, mainly macrophages, the interactions between engineered nanoparticles and macrophages are still not well defined. ...Therefore ... the uptake of diagnostically used carboxydextran-coated superparamagnetic iron oxide nanoparticles of 60 nm (SPIO) and 20 nm (USPIO) by human macrophages /was analyzed/. By pharmacological and in vitro knockdown approaches, the principal uptake mechanism for both particles was identified as clathrin-mediated, scavenger receptor A-dependent endocytosis... /Iron oxide nanoparticles/ ... /It has been/ suggested that ferric oxide serves as a carcinogenic cofactor either by retarding the clearance of inhaled carcinogens or by inducing cytopathological changes which make the cells of the respiratory tract more prone to develop cancer when exposed to carcinogenic substances.