Banol

Indications

• Support cardiovascular health
• Aid in digestion
• Provide quick energy
• Enhance nutrient intake
• Support muscle function

Dosage

Children: For children, bananas can be offered as a healthy snack or added to meals. There is no specific dosing, but one banana per day is a common recommendation.

Adults: There is no specific dosing for bananas, but including 1-2 bananas as part of a balanced diet can be beneficial.

Mechanism of action

The primary active components in bananas include potassium, which helps regulate fluid balance, muscle contractions, and nerve signals. The dietary fiber in bananas aids in digestion by promoting regular bowel movements and supporting gut health. Additionally, the antioxidants found in bananas may help reduce oxidative stress and inflammation in the body.

Pharmacodynamics

Bananas exhibit pharmacodynamic properties primarily through their nutrient content. The potassium in bananas plays a crucial role in maintaining normal blood pressure and heart function. The soluble fiber helps regulate blood sugar levels by slowing the absorption of sugar, while the presence of vitamins and antioxidants contributes to overall health and well-being.

Pharmacokinetics

Bananas are digested and absorbed in the gastrointestinal tract. The carbohydrates are broken down into sugars, which are then absorbed into the bloodstream. The potassium and other vitamins are also absorbed through the intestinal lining. The effects of consuming bananas can be seen relatively quickly, particularly in terms of energy provision due to their carbohydrate content.

Pregnancy

Bananas are generally considered safe to eat during pregnancy and can provide essential nutrients like potassium and vitamin B6.

Breast-feeding

Bananas are safe during breastfeeding, providing important vitamins and minerals.

Storage

Store bananas at room temperature. They can be kept in the refrigerator to slow ripening, but the skin may darken.

Indications

• Dry eye syndrome
• Keratoconjunctivitis sicca
• Ocular surface disorders
• Topical lubrication in surgical procedures
• As a vehicle for drug delivery in ophthalmic formulations

Dosage

Children: Refer to specific product guidelines for dosing, as formulations may vary.

Adults: Refer to specific product guidelines for dosing, as formulations may vary.

Mechanism of action

Carboxymethylcellulose works primarily by increasing the viscosity of solutions, which helps to maintain moisture in the eye and other tissues. It forms a gel-like layer that reduces friction and enhances comfort in dry conditions, making it ideal for treating dry eye syndrome and other conditions requiring lubrication.

Pharmacodynamics

Carboxymethylcellulose exhibits mucomimetic properties, meaning it mimics natural mucin, enhancing the stability and retention of tears on the ocular surface. Its viscosity contributes to prolonged contact time with the eye, thus improving the therapeutic effect for conditions such as xerophthalmia and keratitis.

Pharmacokinetics

Carboxymethylcellulose is not significantly absorbed into systemic circulation when used topically. Its pharmacokinetic profile is characterized by local action, with retention on the tissue surfaces it is applied to, leading to prolonged effects in the targeted areas.

Pregnancy

Safety during pregnancy has not been established. Use only if clearly needed and the benefits outweigh the risks.

Breast-feeding

Caution is advised; it is unknown if carboxymethyl cellulose is excreted in human milk.

Storage

Store at room temperature, away from moisture and heat.

Indications

• Constipation
• Dietary fiber supplementation
• Irritable bowel syndrome
• Diverticular disease
• Weight management

Dosage

Children: Refer to appropriate guidelines for specific dosage; generally taken with adequate fluid intake.

Adults: Refer to appropriate guidelines for specific dosage; generally taken with adequate fluid intake.

Mechanism of action

Cellulose acts primarily as a bulk-forming laxative. It absorbs water in the intestines, which increases stool bulk and stimulates peristalsis, thus facilitating bowel movements. Additionally, cellulose is not digestible by human enzymes, leading to fermentation by gut bacteria, which may enhance gut health and alter gut microbiota composition.

Pharmacodynamics

Cellulose increases stool weight and frequency of bowel movements. It works by retaining water in the intestines, leading to softer stools and improved passage through the gastrointestinal tract. The bulking effect of cellulose can help alleviate constipation and promote overall digestive health. It may also play a role in cholesterol reduction and glycemic control through its effects on digestion and absorption of nutrients.

Pharmacokinetics

Cellulose is not absorbed into the bloodstream due to its indigestible nature. Instead, it passes through the gastrointestinal tract, where it adds bulk to the stool. Its fermentation by colonic bacteria produces short-chain fatty acids, which may have beneficial effects on colon health. The onset of action for cellulose as a laxative can vary but is generally within 24 to 72 hours after ingestion.

Adverse effects

• Bloating
• Flatulence
• Diarrhea
• Abdominal discomfort

Precautions

• Use with caution in patients with a history of gastrointestinal disorders.
• Monitor for potential allergic reactions in sensitive individuals.

Pregnancy

Cellulose is generally considered safe during pregnancy as it is a non-toxic, indigestible fiber.

Breast-feeding

Cellulose is also considered safe during breastfeeding; it is excreted in breast milk in negligible amounts.

Storage

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

Formulations

• Powder
• Capsules
• Tablets
• Granules

Indications

• Enhancement of taste in food and beverages
• Improvement of palatability in nutritional products
• Masking undesirable flavors in medications

Dosage

Children: There is no specific pediatric dosage for flavor agents as they are used as needed to improve the taste of food and beverages.

Adults: There is no specific dosage for flavor agents as they are used as needed to achieve the desired taste and aroma in food and beverages.

Mechanism of action

Flavor compounds interact with taste receptors on the tongue, stimulating the sensory neurons responsible for taste perception. This interaction influences the overall flavor profile of food and beverages, enhancing the eating experience. Some flavors may also have a psychological effect, stimulating appetite or evoking pleasant memories associated with certain tastes.

Pharmacodynamics

While flavor agents are primarily used for sensory enhancement in food, their pharmacodynamic effects are minimal as they are not designed to elicit a pharmacological response. However, certain flavors may influence digestion and metabolism indirectly by enhancing saliva production or affecting gut motility. The enjoyment of flavored products can also lead to increased food intake and satisfaction.

Pharmacokinetics

Flavour compounds are typically ingested and metabolized by the body. Their absorption rates can vary depending on their chemical structure and formulation. Once ingested, they may be rapidly metabolized in the liver and other tissues, with excretion primarily via urine. The specific pharmacokinetic profiles of flavor agents can vary significantly based on their source and chemical properties.

Pregnancy

Flavours are generally considered safe for use during pregnancy, but specific assessments should be made based on the type of flavouring agent.

Breast-feeding

Most flavouring agents are deemed safe during breastfeeding, although it's advisable to consult healthcare professionals regarding specific ingredients.

Storage

Store in a cool, dry place away from direct sunlight and heat sources. Ensure that the container is tightly sealed to prevent contamination.

Indications

• Constipation
• Preparation for surgical or diagnostic procedures involving the rectum
• Decreasing intraocular pressure in certain ocular conditions

Dosage

Children: For children aged 2 to 6 years, 2 g to 5 g of glycerin may be used as a suppository. Children aged 6 to 12 years may use 5 g to 10 g as needed. For specific pediatric dosing, please refer to the BNF for Children.

Adults: For rectal use, 4 g to 10 g of glycerin may be administered as a suppository as needed.

Mechanism of action

When administered rectally, glycerin draws water from the tissues into the feces due to its hygroscopic action, which reflexively stimulates bowel evacuation. Additionally, glycerin creates an osmotic gradient that leads to a decrease in intraocular pressure by facilitating fluid movement from the aqueous and vitreous humors into the bloodstream.

Pharmacodynamics

Glycerin is classified as an osmotic laxative, which acts to retain water in the fecal matter, softening stools and making them easier to pass. Its local irritant effects also contribute to its laxative properties. Glycerin suppositories typically produce a bowel movement within 15 to 30 minutes of administration.

Pharmacokinetics

Glycerin is readily absorbed from the gastrointestinal tract when taken orally and is metabolized primarily in the liver. It is distributed widely throughout the body, with excretion occurring primarily via the kidneys. The onset of action for glycerin when used as a laxative is relatively quick, particularly when used rectally.

Contra-indications

• Severe dehydration
• Severe renal impairment
• Intestinal obstruction
• Appendicitis

Adverse effects

• Abdominal cramps
• Diarrhea
• Nausea
• Vomiting
• Electrolyte imbalance

Interactions

• May enhance the effects of other laxatives
• Caution with concurrent use of diuretics due to potential electrolyte imbalance

Precautions

• Use with caution in patients with renal impairment
• Monitor electrolytes in patients with prolonged use
• Not recommended for long-term use

Pregnancy

Glycerin is generally considered safe during pregnancy but should be used under medical advice.

Breast-feeding

Glycerin is excreted in breast milk in small amounts and is considered safe for use while breastfeeding.

Storage

Store at room temperature, away from moisture and heat.

Formulations

• Glycerin suppositories
• Glycerin oral solution

Indications

• Hyperlipidemia
• Dyslipidemia
• Prevention of cardiovascular disease
• Familial hypercholesterolemia

Dosage

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

Adults: Refer to the specific prescribing information or guidelines for detailed dosing recommendations based on individual patient needs and conditions.

Mechanism of action

Nipastat works by inhibiting the enzyme HMG-CoA reductase, which plays a central role in the biosynthesis of cholesterol in the liver. By blocking this enzyme, nipastat reduces the production of cholesterol and increases the uptake of LDL cholesterol from the bloodstream, thereby lowering overall cholesterol levels.

Pharmacodynamics

Nipastat exhibits dose-dependent effects on lipid profiles, decreasing LDL cholesterol and triglyceride levels while increasing HDL cholesterol. Additionally, it has been shown to have anti-inflammatory properties, which may contribute to its cardiovascular protective effects. The therapeutic effects generally manifest within a few weeks of initiation of therapy.

Pharmacokinetics

Nipastat is well absorbed from the gastrointestinal tract, with peak plasma concentrations typically occurring within 1 to 4 hours after oral administration. It undergoes extensive first-pass metabolism in the liver, leading to significant variability in plasma levels. The drug is primarily eliminated via hepatic metabolism and is excreted in the bile, with a half-life ranging from 1 to 3 hours. Factors such as age, liver function, and concurrent medications can influence its pharmacokinetic profile.

Pregnancy

There is limited data on the use of nipastat during pregnancy. It should only be used if clearly needed and the benefits outweigh the risks.

Breast-feeding

It is unknown whether nipastat is excreted in human milk. Caution should be exercised when administering to nursing mothers.

Storage

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

Indications

• Enterobiasis (pinworm infection)
• Ascariasis (roundworm infection)
• Other intestinal helminth infections

Dosage

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

Adults: Refer to specific guidelines or the BNF for dosing recommendations, as doses may vary based on the type of helminthic infection.

Mechanism of action

Pamoate works by depolarizing the neuromuscular junctions of the parasites, leading to paralysis. It binds to nicotinic acetylcholine receptors on the parasite's muscle cells, causing sustained muscle contraction followed by paralysis. This mechanism prevents the parasites from maintaining their grip on the intestinal wall, resulting in their expulsion from the host.

Pharmacodynamics

The pharmacodynamic profile of pamoate highlights its specific action on the neuromuscular system of parasites. Unlike some other anthelmintics, pamoate does not have systemic absorption, which limits its effects to the intestinal lumen. This targeted action minimizes potential side effects in the host while effectively eliminating the parasites.

Pharmacokinetics

Pamoate is poorly absorbed from the gastrointestinal tract, with minimal systemic circulation. The drug remains predominantly in the intestinal lumen, where it exerts its anthelmintic effects. Its elimination half-life is relatively short, and it is primarily excreted unchanged in the feces. Due to its limited absorption, pamoate does not typically require dose adjustments in renal impairment.

Contra-indications

• Hypersensitivity to pamoate or any of its components
• Severe liver disease
• Severe renal impairment

Adverse effects

• Gastrointestinal disturbances (nausea, vomiting, diarrhea)
• Dizziness
• Headache
• Fatigue
• Allergic reactions (rash, itching)
• Abdominal pain

Interactions

• May interact with other medications that affect liver enzymes
• Potential for increased toxicity when used with other hepatotoxic agents

Precautions

• Caution in patients with a history of liver or renal disease
• Monitor for signs of toxicity
• Use with caution in elderly patients

Pregnancy

The safety of pamoate during pregnancy has not been established. Use only if clearly needed and the benefits outweigh the risks.

Breast-feeding

There is limited information on the excretion of pamoate in human milk. A decision should be made to discontinue nursing or discontinue the drug, considering the importance of the drug to the mother.

Storage

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

Formulations

• Oral tablets
• Suspensions
• Powders for reconstitution

Indications

• Enterobiasis (pinworm infection)
• Ascariasis (roundworm infection)
• Ancylostomiasis (hookworm infection)
• Other intestinal nematode infections

Dosage

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

Adults: Refer to the BNF for specific dosing guidelines.

Mechanism of action

Pyrantel acts as a depolarizing neuromuscular blocking agent in susceptible helminths. It binds to nicotinic acetylcholine receptors at the neuromuscular junction, causing a persistent depolarization. This leads to paralysis of the parasites, allowing for their elimination from the host through peristalsis.

Pharmacodynamics

Pyrantel has a selective action on the neuromuscular system of the parasites, which makes it effective with minimal toxicity to the host. It is not absorbed significantly from the gastrointestinal tract, which enhances its safety profile. The drug's action results in the paralysis of the worms and their subsequent expulsion from the intestines.

Pharmacokinetics

Pyrantel is poorly absorbed from the gastrointestinal tract, with less than 10% of an oral dose being systemically available. The drug primarily exerts its effects locally in the gut. Its half-life is approximately 1 to 2 hours, and it is mostly excreted unchanged in the feces. The minimal systemic absorption limits the risk of systemic side effects.

Contra-indications

• Known hypersensitivity to pyrantel or any of its components
• Severe liver disease

Adverse effects

• Nausea
• Vomiting
• Diarrhea
• Abdominal cramps
• Headache
• Dizziness
• Rash
• Insomnia

Interactions

• May interact with piperazine, as concurrent use can reduce the effectiveness of pyrantel
• The effects of pyrantel may be diminished in patients taking cholinesterase inhibitors

Precautions

• Use with caution in patients with liver dysfunction
• Evaluate for potential allergic reactions prior to administration
• Monitor for signs of intestinal obstruction, especially in patients with existing gastrointestinal conditions

Pregnancy

Pyrantel is classified as pregnancy category C. It should only be used when clearly needed and the benefits outweigh the risks.

Breast-feeding

Pyrantel is excreted in breast milk, and caution should be exercised when administering to nursing mothers.

Storage

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

Formulations

• Tablets
• Suspension

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

• Used as an emulsifier in pharmaceutical formulations
• Improving the solubility of poorly soluble drugs
• Stabilizing emulsions in topical and oral medications
• Used in laboratory settings as a surfactant

Dosage

Children: Dosage varies based on formulation and intended use, refer to specific product guidelines.

Adults: Dosage varies based on formulation and intended use, refer to specific product guidelines.

Mechanism of action

Tween works by reducing the surface tension of the liquid it is mixed with, allowing for better mixing of hydrophilic and hydrophobic substances. This property makes it effective in enhancing the delivery of drugs that are poorly soluble in water. Tween can also stabilize emulsions by forming a protective layer around droplets, preventing them from coalescing.

Pharmacodynamics

As a surfactant, Tween enhances the solubility of lipophilic compounds and improves the absorption of drugs through biological membranes. Its application in drug formulation can lead to increased bioavailability and improved therapeutic effects, especially for poorly soluble drugs.

Pharmacokinetics

Tween is generally not absorbed significantly in the gastrointestinal tract when ingested. Instead, it has a local effect in the gastrointestinal tract and may influence the absorption of other compounds. The metabolism of Tween is not well characterized, and its excretion primarily occurs through feces. The overall pharmacokinetic profile is influenced by the specific formulation in which it is used.

Pregnancy

Tween (polysorbate 20) is generally considered safe for use during pregnancy. However, it should be used only when clearly needed and after consultation with a healthcare provider.

Breast-feeding

Tween is considered safe for use during breastfeeding. Its absorption and systemic exposure are minimal, but it is advisable to consult a healthcare provider.

Storage

Store at room temperature, away from moisture and heat. Keep tightly closed in a cool, dry place.

Indications

• Dehydration
• Electrolyte imbalance
• Hydration therapy

Dosage

Children: Refer to the BNF for Children for specific guidance on hydration and fluid requirements in paediatric patients.

Adults: The dosage of water varies according to individual needs, typically based on factors such as age, sex, weight, and activity level. The general recommendation is to consume adequate fluids to maintain hydration, often estimated at approximately 2.5 liters per day for adults, including all sources of fluid intake.

Mechanism of action

Water functions primarily as a solvent, enabling the dissolution and transport of various solutes within biological systems. It participates in hydrolysis reactions, where it contributes to the breakdown of complex molecules, and is involved in thermoregulation and metabolic processes.

Pharmacodynamics

Water is essential for maintaining cellular turgor and function. It regulates osmotic balance and is involved in enzymatic reactions as a reactant or product. The presence of water influences the structure and function of biomolecules, impacting enzymatic activity and metabolic pathways.

Pharmacokinetics

Water is absorbed primarily in the gastrointestinal tract, with rapid distribution throughout the body. Its elimination occurs through urine, sweat, and respiration, with the rate of loss influenced by environmental factors and physiological conditions. The body maintains water balance through mechanisms involving thirst and hormonal regulation.

Pregnancy

Water is essential for life and is considered safe during pregnancy. Adequate hydration is crucial for maternal health and fetal development.

Breast-feeding

Water is safe for breastfeeding mothers and is vital for maintaining hydration while nursing.

Storage

Store in a cool, dry place. Ensure that the container is clean and free from contaminants.

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

...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."