FUBEN ORAL SUSPENSION

Indications

• Pain and inflammation in musculoskeletal disorders
• Mild to moderate pain including dysmenorrhea
• Postoperative analgesia
• Dental pain
• Migraine
• Fever

Dosage

Adults: Initially 300–400 mg 3–4 times a day; increase if necessary up to 600 mg 4 times a day; maintenance 200–400 mg 3 times a day, may be adequate.

Mechanism of action

The exact mechanism of action of ibuprofen is unknown. However, it is considered a non-selective inhibitor of cyclooxygenase (COX), which is involved in the synthesis of prostaglandins and thromboxane. By inhibiting COX-1 and COX-2, ibuprofen decreases the production of prostaglandins that mediate inflammation, pain, and fever, while COX-1 inhibition may lead to gastrointestinal side effects.

Pharmacodynamics

Ibuprofen exerts its analgesic effects through multiple pathways involved in both acute and chronic inflammation. It reduces pain and inflammation by inhibiting the synthesis of prostanoids via COX-1 and COX-2. The pain relief is believed to be mediated through both peripheral effects at the site of injury and central effects within the nervous system, particularly affecting pain transmission pathways. Additionally, ibuprofen has antipyretic effects linked to its action on prostanoid synthesis in the hypothalamus.

Pharmacokinetics

Ibuprofen is rapidly absorbed from the gastrointestinal tract, with peak plasma concentrations typically occurring within 1 to 2 hours after oral administration. It is extensively metabolized in the liver, primarily by oxidation, and has an elimination half-life of approximately 2 to 4 hours. The drug is excreted mainly in the urine, with a small proportion eliminated unchanged. Renal impairment may affect ibuprofen clearance, necessitating caution in patients with compromised kidney function.

Contra-indications

• History of hypersensitivity to aspirin or any other NSAID
• Severe renal impairment
• Severe hepatic impairment
• Active peptic ulcer disease
• Caution in patients with asthma, angioedema, urticaria, or rhinitis precipitated by NSAIDs

Adverse effects

• Gastrointestinal ulceration
• Nausea
• Vomiting
• Diarrhea
• Dizziness
• Rash
• Headache
• Tinnitus
• Visual impairment
• Fluid retention
• Increased blood pressure

Interactions

• Increased risk of gastrointestinal bleeding with other NSAIDs or anticoagulants
• May reduce the antihypertensive effect of ACE inhibitors
• May increase serum levels of lithium
• May enhance the effects of other anticoagulants
• Caution with corticosteroids due to increased risk of gastrointestinal side effects

Precautions

• Use with caution in patients with mild to moderate hepatic impairment
• Use with caution in patients with mild to moderate renal impairment
• Monitor for signs of gastrointestinal bleeding
• Avoid use during the third trimester of pregnancy

Pregnancy

Avoid unless the potential benefit outweighs the risk. Avoid during the third trimester due to the risk of closure of the fetal ductus arteriosus and possibly persistent pulmonary hypertension of the newborn.

Breast-feeding

Small amounts are present in milk. Manufacturer advises to avoid unless necessary.

Storage

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

Formulations

• Tablets (200 mg, 400 mg)
• Oral suspension (100 mg/5 mL)
• Gel (5%) for topical application
• Suppositories (various strengths)

Indications

• Constipation
• Bowel cleansing

Dosage

Children: Child 1–11 months: 1 g as required, Child 1–11 years: 2 g as required, Child 12–17 years: 4 g as required.

Adults: 4 g as required, usually administered rectally.

Mechanism of action

When administered rectally, glycerol exerts a hygroscopic and/or local irritant action, drawing water from the tissues into the feces and reflexively stimulating evacuation. It decreases intraocular pressure by creating an osmotic gradient between the blood and intraocular fluid, causing fluid to move from the aqueous and vitreous humors into the bloodstream. Glycerol is classified as a hyperosmotic laxative and may also have lubricating and fecal softening effects.

Pharmacodynamics

Glycerol is commonly classified as an osmotic laxative, acting through its local irritant effects and possibly having lubricating and fecal softening actions. Glycerol suppositories usually produce effects within 15 to 30 minutes, providing quick relief from constipation.

Pharmacokinetics

Glycerol is rapidly absorbed through the gastrointestinal tract. It is metabolized in the liver and other tissues, with a half-life that varies depending on the route of administration. Following rectal administration, glycerol is primarily excreted in urine. The pharmacokinetics may vary based on dosage forms and individual patient factors.

Contra-indications

• Acute abdominal conditions
• Acute inflammatory bowel disease
• Intestinal obstruction
• Severe dehydration

Adverse effects

• Abdominal cramps
• Asthenia
• Gastrointestinal disorders
• Hypermagnesaemia
• Skin reactions
• Urine discolouration

Precautions

• Avoid prolonged contact with skin, especially in incontinent patients or infants wearing nappies due to the risk of irritation and excoriation.
• Excessive use may cause diarrhea and related effects such as hypokalaemia.

Pregnancy

Manufacturers advise avoidance due to limited information available.

Breast-feeding

Manufacturers advise avoidance as there is no information available.

Storage

Store at room temperature, away from direct sunlight.

Formulations

• Glycerol 1g suppositories
• Glycerol 2g suppositories
• Glycerol 4g suppositories
• Glycerol oral suspension

Indications

• Food preservative
• Treatment of urea cycle disorders
• Metabolic disorders involving benzoyl-CoA

Dosage

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

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

Mechanism of action

Benzoate acts mainly by inhibiting the growth of bacteria and fungi through its ability to lower the pH, creating an environment that is less favorable for microbial growth. It is also involved in metabolic pathways where it helps in the conjugation of toxic substances, facilitating their excretion from the body.

Pharmacodynamics

Benzoate is known for its antimicrobial properties, which are particularly effective against a wide range of fungi and bacteria. Its efficacy as a preservative is due to its ability to penetrate microbial cell membranes and disrupt their metabolic processes. Additionally, it has been observed to modulate various metabolic pathways, particularly those associated with aromatic compound degradation.

Pharmacokinetics

After ingestion, benzoate is rapidly absorbed in the gastrointestinal tract. It is metabolized primarily in the liver, where it undergoes conjugation with glycine to form hippurate, which is then excreted in the urine. The half-life of benzoate varies depending on individual metabolic rates but is generally short due to its efficient conversion and excretion.

Pregnancy

There is limited data on the use of benzoate in pregnancy. Consultation with healthcare professionals is advised before use.

Breast-feeding

Limited data is available on the excretion of benzoate in breast milk. Caution is recommended when administering to nursing mothers.

Storage

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

Indications

• Food coloring
• Cosmetic applications
• Pharmaceutical preparations

Dosage

Children: Carmoisine is used as a coloring agent and does not have a conventional dosage. Its use is based on regulatory guidelines for food and cosmetic products.

Adults: Carmoisine is used as a coloring agent and does not have a conventional dosage. Its use is based on regulatory guidelines for food and cosmetic products.

Mechanism of action

Carmoisine functions by absorbing certain wavelengths of light, resulting in the perception of color. It contains azo groups (-N=N-), which are responsible for its chromophoric properties. The dye does not have a pharmacological mechanism of action as it is primarily utilized for aesthetic purposes rather than therapeutic effects.

Pharmacodynamics

As a coloring agent, carmoisine does not exert therapeutic pharmacodynamic effects. Its primary role is to enhance the visual appeal of products. In some individuals, it may lead to allergic reactions, particularly in those with sensitivities to food additives.

Pharmacokinetics

Carmoisine is absorbed through the gastrointestinal tract when ingested. The bioavailability and metabolism data specific to carmoisine are limited, as it is primarily considered an inert substance. The dye is excreted unchanged in the urine, and its elimination half-life has not been well studied.

Pregnancy

Carmoisine is generally considered safe for use in food products during pregnancy. However, it should be used with caution, and potential risks should be assessed.

Breast-feeding

Carmoisine is not known to be excreted in breast milk; however, it is advisable to monitor for any potential adverse reactions in breastfeeding infants.

Storage

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

Indications

• Acidulant in food and beverages
• Preservative in pharmaceutical formulations
• pH adjuster in various chemical preparations

Dosage

Children: Refer to product-specific guidelines for appropriate dosing based on formulation and indication.

Adults: Refer to product-specific guidelines for appropriate dosing based on formulation and indication.

Mechanism of action

Citric acid acts by chelating metal ions, which can enhance the solubility of certain compounds and improve their bioavailability. It also contributes to the acidity of the environment, which can influence enzymatic activity and metabolic pathways, particularly in the degradation of citronellol.

Pharmacodynamics

Citric acid exhibits mild pharmacological effects primarily attributed to its role in metabolic processes. It aids in the regulation of pH levels, which can impact enzymatic reactions and biochemical pathways. The acid's chelating properties may help to reduce the toxicity of certain metal ions in biological systems.

Pharmacokinetics

Citric acid is rapidly absorbed after oral administration and is metabolized in the liver. It undergoes conversion to various metabolites in the citric acid cycle, contributing to energy production. The elimination primarily occurs through urine, with minimal accumulation in the body.

Pregnancy

Citric acid is generally regarded as safe during pregnancy when used in food amounts. However, consult a healthcare provider for advice on medicinal use.

Breast-feeding

Citric acid is considered safe during breastfeeding when consumed in food amounts. For medicinal use, consult a healthcare provider.

Storage

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

Mechanism of action

The precise mechanism of action is not well-documented in the provided resources. However, compounds with similar molecular structures often interact with biological pathways through modulation of neurotransmitter systems or receptor activity.

Pharmacodynamics

Pharmacodynamics for compounds like Colour typically involve interactions at the cellular level, influencing physiological responses through receptor binding and modulation of signaling pathways. The specific effects and potency would depend on the context of use and formulation.

Pharmacokinetics

Information on the pharmacokinetics of Colour, including absorption, distribution, metabolism, and excretion, is not provided in the available resources. Generally, pharmacokinetic properties will vary significantly based on formulation and route of administration.

Pregnancy

Safety in pregnancy has not been established. Use only if the benefits outweigh the risks.

Breast-feeding

Caution is advised. There are no adequate studies in breastfeeding women.

Storage

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

Indications

• Electrolyte replacement
• Volume expansion in hypovolemic patients
• Management of hyponatremia
• Support in intravenous fluid therapy

Dosage

Children: Refer to the BNF for Children for appropriate dosing in paediatric patients, as dosages may vary based on the formulation and clinical condition.

Adults: Refer to specific product information or clinical guidelines for dosage recommendations, as disodium is often part of combination products.

Mechanism of action

Disodium compounds often function by providing sodium ions that are essential for various physiological processes. Sodium ions play a critical role in maintaining osmotic balance, nerve impulse transmission, and muscle contraction. In the context of intravenous solutions, disodium helps to restore electrolyte balance in patients.

Pharmacodynamics

The pharmacodynamics of disodium is primarily related to its role in electrolyte balance and fluid homeostasis. Sodium ions are vital for the function of excitable tissues, including neurons and muscle cells. Changes in sodium levels can affect blood pressure, hydration status, and overall cellular function.

Pharmacokinetics

The pharmacokinetics of disodium compounds depend on their specific formulation and route of administration. When administered intravenously, disodium is rapidly distributed in the extracellular fluid, where it helps to maintain osmotic pressure. Sodium is primarily excreted by the kidneys, and its levels can be influenced by fluid intake, dietary sodium, and renal function.

Pregnancy

Use with caution. Consult a healthcare provider for specific guidance.

Breast-feeding

Use with caution. Consult a healthcare provider for specific guidance.

Storage

Store at room temperature, away from moisture and direct sunlight.

Indications

• Lead poisoning
• Mercury poisoning
• Calcium overload
• Certain diagnostic procedures involving heavy metals

Dosage

Children: Refer to the BNF for Children for appropriate dosing information tailored for paediatric patients.

Adults: Refer to the BNF for specific dosing guidelines based on the condition being treated, considering factors such as the severity of metal poisoning and renal function.

Mechanism of action

Edetate functions by forming stable complexes with divalent and trivalent metal ions, including lead and calcium, through its multiple carboxylate and amine groups. This chelation renders the metals more soluble and promotes their renal excretion, thereby reducing their toxic effects in the body.

Pharmacodynamics

The chelation of metals by edetate decreases the free metal concentration in the bloodstream, which mitigates the toxic effects associated with heavy metal accumulation. The efficacy of edetate in removing metals such as lead has been well documented, and its ability to bind calcium can influence calcium homeostasis in certain clinical scenarios.

Pharmacokinetics

Edetate is administered intravenously, with rapid distribution throughout the extracellular fluid. It is primarily excreted unchanged by the kidneys. The onset of action occurs quickly after administration, and the duration depends on the dose and the patient's renal function. The elimination half-life is approximately 1 hour but may vary based on renal clearance.

Contra-indications

• Hypersensitivity to edetate or any component of the formulation
• Severe renal impairment
• Active bleeding disorders

Adverse effects

• Hypocalcemia
• Nausea
• Vomiting
• Diarrhea
• Abdominal pain
• Headache
• Rash
• Fever

Interactions

• May enhance the effects of anticoagulants
• Concurrent use with calcium supplements may reduce effectiveness
• May interfere with the absorption of certain medications due to changes in gastrointestinal motility

Precautions

• Use with caution in patients with renal impairment
• Monitor electrolyte levels, particularly calcium, during treatment
• Assess the patient's hydration status before administration

Pregnancy

Limited data on the use of edetate in pregnancy. Use only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

Caution is advised as it is not known whether edetate is excreted in human milk. Weigh the risks and benefits before use.

Storage

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

Formulations

• Edetate disodium injection
• Edetate calcium disodium injection

Dosage

Children: Refer to the BNF for Children for appropriate dosing information in paediatric cases, especially in instances of overdose.

Adults: Refer to the BNF for specific dosing information based on clinical circumstances, particularly in cases of overdose.

Mechanism of action

Ethylene glycol is metabolized by alcohol dehydrogenase to glycoaldehyde, which is subsequently converted to glycolic, glyoxylic, and oxalic acids. These metabolites contribute to anion gap metabolic acidosis and are responsible for tissue injury through the formation of insoluble calcium oxalate crystals.

Pharmacodynamics

The toxicity of ethylene glycol arises from its metabolites, particularly glycolic and oxalic acids. These compounds induce metabolic acidosis, lead to renal failure through calcium oxalate crystal deposition in the kidneys, and can cause neurological impairment. The anion gap increases due to the accumulation of these acids, leading to complications such as cardiovascular instability and potential multi-organ failure.

Pharmacokinetics

Ethylene glycol is rapidly absorbed after oral ingestion. It undergoes first-pass metabolism primarily in the liver, where it is converted into its toxic metabolites. The elimination half-life of ethylene glycol varies but is generally prolonged in cases of renal impairment. Renal excretion of metabolites contributes to the duration of toxicity, necessitating prompt medical intervention in cases of overdose.

Adverse effects

• Metabolic acidosis
• Renal failure
• CNS depression
• Hypocalcemia
• Cardiovascular collapse
• Pulmonary edema

Precautions

• Use with caution in patients with renal impairment
• Monitor for signs of metabolic acidosis
• Evaluate electrolyte levels, particularly calcium

Pregnancy

There is limited data on the safety of ethylene glycol in pregnancy. It should only be used if clearly needed.

Breast-feeding

It is unknown if ethylene glycol is excreted in human milk. Caution is advised.

Storage

Store in a tightly closed container at room temperature, away from heat and moisture.

Formulations

• Liquid

Indications

• Insecticide for agricultural use
• Research tool in toxicology

Dosage

Children: Refer to the BNF for Children for specific dosing and administration guidelines.

Adults: Refer to the BNF for specific dosing and administration guidelines.

Mechanism of action

Methyl parathion acts primarily by inhibiting the enzyme acetylcholinesterase, which is essential for the breakdown of the neurotransmitter acetylcholine. Its active metabolite, methyl paraoxon, is a potent inhibitor of both acetylcholinesterase and butyrylcholinesterase. The inhibition of these enzymes results in the accumulation of acetylcholine at synapses, leading to overstimulation of cholinergic receptors and resultant toxic effects.

Pharmacodynamics

The pharmacodynamics of methyl parathion involve its action as a noncompetitive inhibitor of acetylcholinesterase, causing prolonged effects of acetylcholine due to its inability to be hydrolyzed. The resultant cholinergic toxicity can lead to symptoms such as muscle twitching, respiratory distress, and potentially fatal outcomes if not treated promptly. The extent of inhibition is dose-dependent, with significant toxicity occurring after substantial enzyme inhibition.

Pharmacokinetics

Methyl parathion is absorbed through the gastrointestinal tract and can also be absorbed through the skin and respiratory tract. It is metabolized in the liver to form methyl paraoxon, which is responsible for the majority of its toxic effects. The distribution of methyl parathion in body tissues is influenced by its lipophilicity, and it is primarily excreted as metabolites in the urine. The elimination half-life and specific pharmacokinetic parameters can vary based on individual metabolism and exposure levels.

Pregnancy

There are no adequate and well-controlled studies in pregnant women. Use only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

It is not known whether this drug is excreted in human milk. Caution is advised when administering to nursing women.

Storage

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

Formulations

• Liquid formulation

Dosage

Adults: Refer to specific guidelines for management of methyl mercaptan exposure, as there are no established therapeutic doses due to its toxicity.

Mechanism of action

Methyl mercaptan exerts its toxic effects primarily through the reversible inhibition of cytochrome c oxidase, similar to mechanisms observed in cyanide and hydrogen sulfide poisoning. It also inhibits brain sodium and potassium ATPase activity. These mechanisms contribute to its potential to induce coma and other neurological disturbances. Additionally, methyl mercaptan has been implicated in the pathogenesis of hepatic coma, indicating its impact on liver function and metabolism. The compound stabilizes erythrocyte membranes against hypotonic hemolysis at low concentrations, which may be linked to its anesthetic properties.

Pharmacodynamics

The pharmacodynamics of methyl mercaptan involve its ability to disrupt normal cellular respiratory processes and membrane stability. The inhibition of cytochrome c oxidase leads to impaired oxidative phosphorylation, causing cellular hypoxia. Furthermore, its effect on sodium and potassium ATPase can disrupt ionic balance within cells, potentially leading to cellular dysfunction and death. The compound's anesthetic-like effects differentiate it from common anesthetics, particularly in its toxicity profile, as it can elicit significant adverse reactions even at lower concentrations.

Pharmacokinetics

The pharmacokinetics of methyl mercaptan are not extensively characterized in clinical literature, but it is known to be rapidly absorbed through inhalation. Once in the body, it is likely metabolized by the liver, consistent with its involvement in hepatic coma. The gas is highly soluble in water and biological fluids, which may facilitate its distribution throughout tissues. Elimination pathways are not well defined, but it is presumed to be excreted through respiration and potentially other metabolic routes.

Pregnancy

There is limited information on the safety of methyl mercaptan in pregnancy. It is advisable to avoid exposure whenever possible due to potential risks.

Breast-feeding

The effects of methyl mercaptan during breastfeeding are not well studied. Caution is recommended due to the potential for unknown risks.

Storage

Store in a cool, dry place away from light and heat. Ensure containers are tightly sealed to prevent exposure and contamination.

Indications

• Emulsifying agent in drug formulations
• Stabilizer for parenteral preparations
• Solubilizer for hydrophobic drug compounds
• Ingredient in topical formulations

Dosage

Children: Refer to specific product guidelines, as dosing varies based on formulation and intended use.

Adults: Refer to specific product guidelines, as dosing varies based on formulation and intended use.

Mechanism of action

Polysorbate functions primarily as an emulsifying agent. It reduces the surface tension between immiscible liquids, allowing them to mix more easily. This property is particularly useful in stabilizing emulsions and suspensions, facilitating the delivery of active pharmaceutical ingredients in various formulations.

Pharmacodynamics

Polysorbate does not exert pharmacological effects in the traditional sense, as it does not bind to specific receptors to elicit a physiological response. Instead, it plays a crucial role in modifying the physical properties of drug formulations, thereby enhancing drug delivery and absorption. Its ability to solubilize drugs enhances their bioavailability, particularly for poorly soluble compounds.

Pharmacokinetics

Polysorbate is generally considered to be non-toxic and is not absorbed to a significant extent when administered orally. It is metabolized by the liver and excreted primarily through the gastrointestinal tract. The pharmacokinetic profile may vary depending on the route of administration and the specific formulation in which it is used.

Adverse effects

• Allergic reactions
• Skin irritation
• Gastrointestinal disturbances

Precautions

• Use cautiously in patients with known allergies to polysorbates or related compounds
• Monitor for allergic reactions in susceptible individuals

Pregnancy

Polysorbate is generally considered safe for use during pregnancy, but consult with a healthcare provider for specific cases.

Breast-feeding

Polysorbate is considered safe during breastfeeding, but consult with a healthcare provider for individual advice.

Storage

Store at room temperature, away from direct sunlight and moisture.

Formulations

• Polysorbate 20
• Polysorbate 80

Indications

• Plant growth regulation
• Agricultural applications as a growth inhibitor

Dosage

Children: Not applicable.

Adults: Refer to the relevant agricultural guidelines for specific applications.

Mechanism of action

In an in vitro study, propylene acts as a plant growth inhibitor by inhibiting the oxidation of indole-3-acetic acid by peroxidase in the presence of superoxide anion radicals. This inhibition is linked to the activation of an iron complex (compound III) shuttle, which enhances the reaction rate between superoxide and peroxidase, ultimately affecting plant growth processes. Propylene is a less effective inhibitor compared to ethylene.

Pharmacodynamics

The pharmacodynamic effects of propylene are primarily observed in its role as a growth inhibitor in plants. By modulating the oxidation of phytohormones like indole-3-acetic acid, propylene can influence various growth responses in plants, potentially affecting processes such as cell elongation and division.

Pharmacokinetics

Information on the pharmacokinetics of propylene in humans is not well-documented, as its primary uses are industrial and agricultural. Its metabolism may be influenced by environmental factors, and its effects are primarily studied in the context of plant biology rather than human pharmacology.

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

• Antioxidant support
• Anti-inflammatory effects
• Potential cancer prevention
• Support for cardiovascular health
• Glycemic control

Dosage

Children: Refer to specific dietary guidelines. No standard therapeutic dose established.

Adults: Refer to specific dietary guidelines. No standard therapeutic dose established.

Mechanism of action

The bioactive compounds in raspberries, such as ellagic acid, quercetin, and anthocyanins, exert their effects through various mechanisms. They are known to scavenge free radicals, modulate cell signaling pathways, and influence gene expression related to inflammation and cancer progression. These compounds may also enhance the activity of certain detoxifying enzymes in the body.

Pharmacodynamics

Raspberry exhibits antioxidant activity, which helps protect cells from oxidative stress and damage caused by free radicals. The anti-inflammatory properties are attributed to the inhibition of pro-inflammatory cytokines and enzymes, thereby reducing inflammation. Additionally, some studies suggest that components of raspberry may influence lipid metabolism and improve glycemic control.

Pharmacokinetics

The bioactive compounds in raspberries are subject to digestion and metabolism, with absorption occurring primarily in the intestine. The specific pharmacokinetics of raspberry compounds can vary based on the individual compound, but generally, they are rapidly absorbed and can be detected in plasma shortly after consumption. The half-life of these compounds can vary significantly depending on the specific component and individual metabolic factors.

Adverse effects

• Allergic reactions
• Gastrointestinal upset
• Diarrhea

Precautions

• Use with caution in individuals with known allergies to berries.
• Consult a healthcare provider before use in patients with diabetes due to potential effects on blood sugar levels.

Pregnancy

Raspberries are generally considered safe during pregnancy when consumed in moderate amounts as part of a healthy diet.

Breast-feeding

Raspberries are safe to consume while breastfeeding, but excessive intake should be avoided.

Storage

Store in a cool, dry place. Fresh raspberries should be refrigerated and consumed within a few days.

Formulations

• Fresh raspberries
• Dried raspberries
• Raspberry extract
• Raspberry juice

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

• 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

Indications

• Used as a thickening agent in food products
• Utilized in pharmaceutical formulations as a stabilizer
• Employed in cosmetics for texture improvement
• Applied in industrial products for its viscosity properties

Dosage

Children: Refer to specific product guidelines for appropriate use. Xanthan is used in formulations as a thickener or stabilizer, and dosage should be evaluated based on the specific product and formulation.

Adults: Refer to specific product guidelines for appropriate use. Xanthan is typically used in small quantities as a thickener or stabilizer in food and pharmaceutical products.

Mechanism of action

Xanthan functions primarily as a thickener and stabilizer. It acts by interacting with water molecules to form a gel-like consistency, which enhances the texture and stability of products. Its unique rheological properties allow it to maintain viscosity under varying conditions, which is beneficial in food and pharmaceutical applications.

Pharmacodynamics

Xanthan's action is primarily physical rather than pharmacological. It does not exert a direct therapeutic effect but influences the delivery and stability of active ingredients in formulations. The gel formation and viscosity changes help ensure the uniform distribution of substances in liquid formulations, which can improve the effectiveness of the drug delivery.

Pharmacokinetics

As xanthan is a polysaccharide, it is not absorbed in the gastrointestinal tract when ingested. It passes through the digestive system largely unchanged. In terms of metabolism, xanthan is broken down by colonic bacteria, resulting in short-chain fatty acids. Its pharmacokinetic profile indicates that it has a low bioavailability due to its large molecular size and structure.

Pregnancy

There is insufficient data on the use of xanthan during pregnancy. Consult a healthcare professional before use.

Breast-feeding

There is insufficient data on the excretion of xanthan in human milk. Consult a healthcare professional before use.

Storage

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

Formulations

• Xanthan gum powder

Mechanism of action

When administered rectally, glycerin exerts a hygroscopic and/or local irritant action, drawing water from the tissues into the feces and reflexively stimulating evacuation. Glycerin decreases intraocular pressure by creating an osmotic gradient between the blood and intraocular fluid, causing fluid to move out of the aqueous and vitreous humors into the bloodstream. Glycerin (glycerol) and sorbitol are hyperosmotic laxatives. When administered rectally, glycerin and sorbitol exert a hygroscopic and/or local irritant action, drawing water from the tissues into the feces and reflexly stimulating evacuation. The extent to which the simple physical distention of the rectum and the hygroscopic and/or local irritant actions are responsible for the laxative effects of some of these drugs is not known. Only extremely high oral doses of sorbitol (25 g daily) or glycerin exert laxative action. /Glycerin/ decreases intraocular pressure by creating an osmotic gradient between the blood and intraocular fluid, causing fluid to move out of the aqueous and vitreous humors into the bloodstream. The physicochemical effects of a series of alkanols, alkanediols and glycerol on erythrocyte shape and hemolysis at 4 and 20 degrees C were examined. We calculated the dielectric constant of the incubation medium, Ds, and the dielectric constant of the erythrocyte membrane Dm in the presence of organic solutes. The ratio Ds/Dm = -38.48 at 20 degrees C defines the normal biconcave shape in a medium without hemolytic agents. A decrease in Ds/Dm favors externalization or internalization with consequent hemolysis. Alkanols and alkanediols convert biconcave erythrocytes into echinocytes, which is accompanied by an increase in the projected surface area. Glycerol converts biconcave erythrocytes into stomatocytes, which was accompanied by a marginal decrease in the projected surface area. Progressive externalization in alkanols and alkanediols or internalization in glycerol resulted in a decrease in the projected surface area and the formation of smooth spheres. The degree of shape change induced was related to the degree of hemolysis and the ratio Ds/Dm. A decrease in temperature reduced both the degree of shape change and hemolysis. .../Thus/ physicochemical toxicity may be a result of a temperature dependent hydrophobic interaction between the organic solutes and the membrane and is best interpreted by the ability of the solutes to change Ds and Dm.

Pharmacodynamics

Glycerin is commonly classified as an osmotic laxative but may act additionally or alternatively through its local irritant effects; it may also have lubricating and fecal softening actions. Glycerin suppositories usually work within 15 to 30 minutes.

Mechanism of action

The exact mechanism of action of ibuprofen is unknown. However, ibuprofen is considered an NSAID and thus it is a non-selective inhibitor of cyclooxygenase, which is an enzyme involved in prostaglandin (mediators of pain and fever) and thromboxane (stimulators of blood clotting) synthesis via the arachidonic acid pathway. Ibuprofen is a non-selective COX inhibitor and hence, it inhibits the activity of both COX-1 and COX-2. The inhibition of COX-2 activity decreases the synthesis of prostaglandins involved in mediating inflammation, pain, fever, and swelling while the inhibition of COX-1 is thought to cause some of the side effects of ibuprofen including GI ulceration. IBUPROFEN AT 25 MG/KG IV INCREASED THE PRIMARY AND TOTAL HEMOSTATIC PLUG FORMATION TIME IN RABBIT EAR CHAMBERS WITH LASER-INDUCED INJURY. THE SAME DOSE INCREASED THE NUMBER OF CUMULATIVE EMBOLI OVER A 10 MINUTE PERIOD AFTER A LASER INJURY TO ARTERIOLES. IN DOGS, DOSES OF 10, 25, AND 50 MG/KG DID NOT ENHANCE THE RELEASE OF (125)I-LABELED FIBRIN DEGRADATION PRODUCTS FROM THE THROMBI AFTER INCUBATION IN PLASMIN, BUT THE LARGEST DOSE SIGNIFICANTLY DECREASED THE THROMBUS WEIGHT 90 AND 180 MINUTES AFTER DRUG ADMINISTRATION. THUS, IBUPROFEN HAD AN INHIBITORY EFFECT ON PLATELET FUNCTION IN VIVO AND IN LARGE DOSES DIMINISHED THE THROMBUS WEIGHT. L-Arginine (L-arg) exhibits multiple biological properties and plays an important role in the regulation of different functions in pathological conditions. Many of these effects could be achieved on this amino acid serving as a substrate for the enzyme nitric oxide synthase (NOS). At the gastrointestinal level, recent reports revealed its protective activities involving a hyperemic response increasing the gastric blood flow. The aim of this study was to characterize the relationship between NOS activity/expression and prostaglandin changes (PGs) in rats gastric mucosa, with L-arg associated resistance to the nonsteroidal anti-inflammatory drug (NSAID) ibuprofen (IBP). The protective effect of oral L-arg (100 mg/kg body wt), administerred together with IBP (100 mg/kg body wt, per os), was evident enough 90 min after drug administration, although a significant protection persisted for more than 6 hr. Pretreatment with N(G)-nitro-L-arginine (L-NNA) (40 mg/kg body wt, intraperitoneally), a competitive inhibitor of constitutive NOS, partly altered the protection afforded by the amino acid. In contrast, no changes could be observed after inducible NOS inhibition [aminoguanidine (AG) 50 mg/Kg body wt, intraperitoneally). L-arg, plus IBP, produced a significant increase of the cyclic GMP (cGMP) response in tissue samples from rat stomach, 90 min and 6 h after drug administration. iNOS activity and mRNA expression were higher in IBP-treated rats, and no differences were observed in inducible responses in the L-arg plus IBP group. No variations in the cNOS activity and expression were found among the different groups of animals assayed. The measurement of mucosal PGE2 content confirmed that biosynthesis of the eicosanoid is maintained by L-arg for over 90 min after IBP, while a total inhibition was observed 6 hr later. The mechanisms of the L-arg protective effect on the damaged induced by IBP could be explained by the different period after drug administration. The early phase is mediated by cyclooxygenase/prostaglandins pathway (COX/PGs) although NO liberated by cNOS and the guanylate cyclase/cGMP pathway could be also relevant. The later phase implicates inhibition of the iNOS/NO response. We previously showed the non-steroidal anti-inflammatory drug (NSAID) ibuprofen suppresses inflammation and amyloid in the APPsw (Tg2576) Tg2576 transgenic mouse. The mechanism for these effects and the impact on behavior are unknown. We now show ibuprofen's effects were not mediated by alterations in amyloid precursor protein (APP) expression or oxidative damage (carbonyls). Six months ibuprofen treatment in Tg+ females caused a decrease in open fie

Pharmacodynamics

Ibuprofen has multiple actions in different inflammatory pathways involved in acute and chronic inflammation. The main effects reported in ibuprofen are related to the control of pain, fever and acute inflammation by the inhibition of the synthesis of prostanoids by COX-1 and COX-2. Pain relief is attributed to peripheral affected regions and central nervous system effects in the pain transmission mediated by the dorsal horn and higher spinothalamic tract. Some reports have tried to link the pain regulation with a possible enhancement on the synthesis of endogenous cannabinoids and action on the NMDA receptors. The effect on pain has been shown to be related to the cortically evoked potentials. The antipyretic effect is reported to be linked to the effect on the prostanoid synthesis due to the fact that the prostanoids are the main signaling mediator of pyresis in the hypothalamic-preoptic region. The use of ibuprofen in dental procedures is attributed to the local inhibition of prostanoid production as well as to anti-oedemic activity and an increase of plasma beta-endorphins. Some reports have suggested a rapid local reduction of the expression of COX-2 in dental pulp derived by the administration of ibuprofen. The administration of ibuprofen in patients with rheumatic diseases has shown to control joint symptoms. Ibuprofen is largely used in OTC products such as an agent for the management of dysmenorrhea which has been proven to reduce the amount of menstrual prostanoids and to produce a reduction in the uterine hypercontractility. As well, it has been reported to reduce significantly the fever and the pain caused by migraines. This effect is thought to be related to the effect on platelet activation and thromboxane A2 production which produces local vascular effects in the affected regions. This effect is viable as ibuprofen can enter in the central nervous system. In the investigational uses of ibuprofen, it has been reported to reduce neurodegeneration when given in low doses over a long time. On the other hand, its use in Parkinson disease is related to the importance of inflammation and oxidative stress in the pathology of this condition. The use of ibuprofen for breast cancer is related to a study that shows a decrease of 50% in the rate of breast cancer.

Mechanism of action

Ethylene glycol is metabolized by alcohol dehydrogenase to glycoaldehyde, which is then metabolized to glycolic, glyoxylic, and oxalic acids. These acids, along with excess lactic acid are responsible for the anion gap metabolic acidosis. Oxalic acid readily precipitates with calcium to form insoluble calcium oxalate crystals. Tissue injury is caused by widespread deposition of oxalate crystals and the toxic effects of glycolic and glyoxylic acids.

Mechanism of action

Acute poisoning ... is related to ... inhibiting action on enzyme acetylcholinesterase. Toxic manifestations generally occur only after more than 50% of plasma cholinesterase is inhibited. ... Methyl parathion ... depend on oxidative activation by replacement of thiono-sulfur with oxygen for ... toxicity. Methyl parathion has only a slight inhibitory action on acetylcholinesterase and butyrylcholinesterase, but its active metabolite, methyl paraoxon, is a potent inhibitor of both these enzymes. A study was conducted examining the inhibition of (Ca2+ and Mg2+)-ATPase by parathion (56382) and methyl parathion. Enzyme activity was assessed spectrophotometrically in pig erythrocyte membranes containing calcium2+ (Ca2+) and magnesium2+ and in solubilized membrane preparations incubated with the test agents. The enzyme response to ATP was biphasic. Equations expressing the kinetics of the substrate curves described two classes of the ATP binding active site, one with high affinity and low maximum rate and one with low affinity and high maximum rate. High affinity active sites were stimulated by low ATP concentrations (20 uM), whereas low affinity active sites were stimulated by high ATP levels (2 mM). Parathion and methylparathion dose dependently inhibited enzyme activity; parathion had a greater inhibitory effect than methylparathion. Lineweaver-Burke and Dixon plots indicated noncompetitive inhibition. Parathion and methylparathion induced enzyme inhibition occurred over a range of free calcium ion concentrations (0.5 to 5 mM); the inhibition was significantly greater at lower Ca2+ concentrations (1 to 100 uM) than at higher concentrations. The authors conclude that parathion and methylparathion inhibit ATPase activity by binding to a site on the enzyme rather than through an interaction with associated lipids. For more Mechanism of Action (Complete) data for METHYL PARATHION (6 total), please visit the HSDB record page.

Mechanism of action

... The primary mechanisms by which methyl mercaptan has caused death and induces coma appear to reside with its reversible inhibition of cytochrome c oxidase (as in cyanide and hydrogen sulfide poisoning) and its inhibition of brain sodium and potassium ATPase activity. Methanethiol (CH3SH) has been implicated in the pathogenesis of hepatic coma. Studies are presented to identify the possible biochemical basis of anesthesia-like effects of methanethiol and those features, which distinguish such effects from common anesthetics and may represent the basis of its toxicity. CH3SH was found to stabilize erythrocyte membranes against hypotonic hemolysis at relatively low concentrations. At 37 degrees C the AH25 value for human erythrocyte antihemolysis was observed at a concentration of 0.34 mumol of CH3SH bound per mg of erythrocyte protein. Similar results were obtained with rat erythrocytes. This property of CH3SH is in common with other anesthetic agents. Anesthetic agents also inhibit the membrane-associated Na+, K+-adenosine triphosphatase (ATPase); however, for effective and nontoxic agents of this type the inhibition of ATPase activity is elicited at concentrations which are at least an order of magnitude higher than those which influence the membrane stability characterized by the antihemolysis effect. CH3SH was also found to inhibit the membrane Na+,K+-ATPase activity. The I25 value for the inhibition of human erythrocyte ATPase activity was obtained at CH3SH concentration of 0.12 mM which corresponded to 0.3 umol of CH3SH bound per mg of erythrocyte membrane protein. Rat erythrocyte membrane ATPase was somewhat more sensitive to CH3SH. In all cases, the binding of CH3SH to erythrocytes occurred primarily on the membrane. These results indicate that no differential exists with respect to the dose-response of these two activities associated with human erythrocyte membrane. Pulpal disease is intimately associated with the immune system's response to bacteria products. Clinical pathology is mediated in part by the production of pyrogenic cytokines, especially interleukin (IL)-1, tumor necrosis factor (TNF)-alpha, and IL-6. Methyl mercaptan (CH3SH), a volatile sulfur compound produced by anaerobic Gram-negative bacteria, has been shown to contribute to the production of IL-1 by human mononuclear cells. In this report, /the authors/ investigated the production of IL-1, TNF-alpha, and IL-6 by human pulp fibroblasts when stimulated for various periods of time with lipopolysaccharide (LPS) with or without the presence of CH3SH. We found that LPS and CH3SH had no effect on the production of IL-1 or TNF-alpha. However, LPS stimulated IL-6 production, and this production was augmented when CH3SH was present. /It was concluded/ that the volatile sulfur compound CH3SH plays a role in activation and modulation of the immune response through its role in production of IL-6. Hydrogen sulfide (H2S) and methyl mercaptan (CH3SH) are the volatile sulfur compounds (VSC) that were investigated for a possible role in the etiology of periodontal disease. The results show that the permeability of porcine non-keratinized sublingual mucosa is increased by up to 75% or 103% following exposure to H2S and CH3SH, respectively. The effect may be attributed to VSC reaction with tissue components resulting in alteration in the integrity of the tissue barrier. The increase in permeability of the mucosa to (35)S-Na2SO4 was dependent on both the time of exposure and concentration of VSC in the head-space. The (35)S-H2S was retained by the mucosal tissue and was able to penetrate the intact layers consisting of non-keratinized epithelium, basal membrane, and connective tissue. Treatment of the mucosa with 0.22% ZnCl2, either prior to or after exposure to CH3SH, nullified the effect of CH3SH and restored the permeability to a state similar to that observed in control 95% air/5% CO2 systems. For more Mechanism of Action (Complete) data for METHYL MERCAPTAN (10 t

Mechanism of action

In an in vitro study of the mechanism of action of ethylene as a plant growth inhibitor, the effects of ethylene and some of its analogs, including propylene, on the oxidation of indole-3-acetic acid were examined. Ethylene and its analogs inhibited the oxidation of indole-3-acetic acid by peroxidase under conditions where the iron complex (compound III, an oxy-ferrous complex of peroxidase) shuttle was activated. Inhibition occurred only in the presence of the superoxide anion radical 02(-). Spectral and kinetic data indicated that ethylene and its analogs enhanced the rate of reaction of 02(-) with peroxidase; ie, the iron complex (compound III) shuttle, resulting in the formation of compound III. Propylene was a less effective inhibitor than ethylene.

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."