Clinica Mouthwash

Indications

• Oral hygiene
• Skin antisepsis
• Bladder irrigation
• Urological surgery
• Management of infections associated with indwelling urinary catheters

Mechanism of action

Chlorhexidine's antimicrobial effects arise from its ability to disrupt microbial cell membranes. The positively charged chlorhexidine molecule interacts with negatively charged phosphate groups on microbial surfaces, compromising cell integrity and causing leakage of intracellular materials. This interaction allows chlorhexidine to enter the cell, precipitate cytoplasmic components, and ultimately induce cell death. At lower concentrations, chlorhexidine acts as a bacteriostatic agent, causing leakage of substances like potassium and phosphorus, while at higher concentrations, it exerts bactericidal effects.

Pharmacodynamics

Chlorhexidine exhibits broad-spectrum antimicrobial activity, effective against a variety of bacteria, yeasts, and viruses. Its action is dose-dependent, with lower concentrations (0.02%-0.06%) providing bacteriostatic effects, while higher concentrations (>0.12%) are bactericidal. Pharmacokinetic studies indicate that about 30% of chlorhexidine remains in the mouth after rinsing, allowing for slow release into oral fluids. This property, known as 'substantivity', helps prevent microbial colonization on surfaces like dentine, although prolonged use can lead to staining of oral surfaces.

Pharmacokinetics

Chlorhexidine is retained in the oral cavity at approximately 30% following rinsing, with a slow release into saliva. The pharmacokinetics of chlorhexidine indicate a high affinity for binding to tissues, which prolongs its antimicrobial action. The systemic absorption of chlorhexidine is minimal when used topically or as a rinse, making it safe for localized use. The elimination half-life and metabolism details are not well documented due to its primarily topical application.

Adverse effects

• Mucosal irritation
• Burning sensation
• Staining of teeth and oral surfaces
• Allergic reactions

Precautions

• Use with caution in patients with a history of hypersensitivity to chlorhexidine
• May cause irritation; discontinue if severe irritation occurs
• Staining may occur with prolonged use, particularly with oral formulations

Pregnancy

Chlorhexidine is generally considered safe for use during pregnancy; however, caution is advised and pregnant individuals should consult healthcare providers.

Breast-feeding

Chlorhexidine is considered safe during breastfeeding, but it is advisable to consult a healthcare provider.

Storage

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

Formulations

• Irrigation solution (0.02% and 0.05%)
• Capsules (various strengths)
• Catheter maintenance solution (1:5000)
• Topical solutions for oral hygiene

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

• Methemoglobinemia
• Urinary tract infections
• Surgical marking
• Treatment of certain types of cyanide poisoning

Dosage

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

Adults: Refer to the relevant clinical guidelines or the BNF for specific dosing recommendations.

Mechanism of action

Methylene blue acts as a reducing agent, converting methemoglobin back to its functional form, hemoglobin. This is primarily achieved through its action as an electron donor, facilitating the reduction of ferric iron (Fe3+) in hemoglobin to ferrous iron (Fe2+), thereby restoring its oxygen-carrying capacity. It also exhibits antimicrobial properties through its ability to generate reactive oxygen species when exposed to light, which can inhibit bacterial growth.

Pharmacodynamics

The pharmacodynamics of methylene blue involve its role in enhancing oxygen delivery in patients suffering from methemoglobinemia. By converting methemoglobin back to hemoglobin, it effectively increases the amount of hemoglobin available for oxygen transport. The drug also shows effects on the vascular system, where it can induce vasodilation and influence blood pressure.

Pharmacokinetics

Methylene blue is rapidly absorbed after intravenous administration, with peak plasma concentrations occurring within 1 to 3 hours. It is extensively distributed in body tissues and fluids, including the liver, kidneys, and lungs. The drug undergoes hepatic metabolism, primarily through the cytochrome P450 system, and is excreted mainly through urine. The half-life ranges from 5 to 24 hours, depending on the dosage and individual patient factors.

Pregnancy

Consult healthcare provider before use, as safety in pregnancy is not established.

Breast-feeding

Consult healthcare provider before use, as safety during breastfeeding is not established.

Storage

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

Dosage

Children: Refer to specific drug formulations and guidelines for dosage information.

Adults: Refer to specific drug formulations and guidelines for dosage information.

Mechanism of action

Crystalline forms of drugs can affect the rate of dissolution and absorption in the body. The mechanism of action depends on the specific drug in crystalline form, as different substances interact with biological systems in various ways, including receptor binding, enzyme inhibition, or modulation of biochemical pathways.

Pharmacodynamics

The pharmacodynamics of crystalline drugs are influenced by their solubility, stability, and the rate at which they dissolve in physiological environments. These factors determine the onset, intensity, and duration of the drug's therapeutic effects. Crystalline drugs may offer advantages in terms of prolonged release and controlled dosing compared to amorphous forms.

Pharmacokinetics

The pharmacokinetics of crystalline drugs involves their absorption, distribution, metabolism, and excretion (ADME). Crystalline drugs typically exhibit slow and steady absorption rates due to their solid state. The dissolution rate can significantly affect drug bioavailability, with more soluble crystalline forms providing quicker onset of action. Metabolism and excretion pathways vary depending on the specific drug, and crystalline forms can influence these processes based on their chemical properties.

Pregnancy

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

Breast-feeding

There is limited data on the excretion of crystals in breast milk. Caution is advised.

Storage

Store in a cool, dry place, away from light and moisture. Ensure the container is tightly closed.

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
• Decreased intraocular pressure

Dosage

Children: For children, refer to the BNF for Children for appropriate glycerin dosing guidelines.

Adults: For constipation, glycerin can be administered rectally as a suppository. Follow specific product guidelines for dosage.

Mechanism of action

When administered rectally, glycerine exerts a hygroscopic and/or local irritant action, drawing water from the tissues into the feces and reflexively stimulating evacuation. Additionally, glycerine decreases intraocular pressure by creating an osmotic gradient between the blood and intraocular fluid, leading to fluid movement out of the aqueous and vitreous humors into the bloodstream.

Pharmacodynamics

Glycerine is commonly classified as an osmotic laxative but may also exert local irritant effects, lubricating, and fecal softening actions. Its onset of action typically occurs within 15 to 30 minutes when used as a suppository.

Pharmacokinetics

Glycerine is readily absorbed and metabolized in the body. It undergoes glycerol metabolism pathways, contributing to various biochemical processes including phospholipid biosynthesis. The pharmacokinetic profile of glycerine indicates a rapid onset of action due to its osmotic properties.

Adverse effects

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

Precautions

• Use with caution in patients with renal impairment
• May cause dehydration if used excessively
• Monitor for electrolyte disturbances in prolonged use

Pregnancy

Glycerin is generally considered safe to use during pregnancy for indicated conditions. Always consult a healthcare provider before use.

Breast-feeding

Glycerin is unlikely to be harmful in breastfeeding mothers. Consult a healthcare provider for specific guidance.

Storage

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

Formulations

• Suppositories
• Oral solution

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

• Topical analgesic for muscle and joint pain
• Cough suppressant in cough drops and lozenges
• Relief of minor throat irritation
• Cooling agent in various cosmetic and personal care products

Dosage

Children: Refer to BNF for Children for specific dosing guidelines, as doses may vary based on age and formulation.

Adults: For topical use, apply a thin layer to the affected area not more than 3 to 4 times daily. For cough drops, follow the product-specific instructions as per the formulation.

Mechanism of action

Menthol acts as an agonist for the transient receptor potential subtype M8 (TRPM8), a non-selective cation channel that is activated by cold temperatures. This activation leads to calcium influx in mast cells, inducing the release of histamine, which can trigger allergic responses such as urticaria, asthma, and rhinitis. Menthol's ability to induce histamine release via TRPM8 suggests potential therapeutic applications for TRPM8 antagonists in managing cold- and menthol-induced allergies.

Pharmacodynamics

Menthol produces a cooling effect by stimulating sensory neurons that convey cold sensations. It interacts with TRPM8 channels, leading to the activation of intracellular signaling pathways that can result in vasodilation and increased blood flow to the area of application. This cooling sensation can provide symptomatic relief in conditions characterized by pain or irritation.

Pharmacokinetics

Menthol is absorbed through the skin and mucous membranes, with systemic effects depending on the route of administration. Its bioavailability can vary, and it is metabolized primarily in the liver. The elimination half-life and excretion pathways have not been extensively characterized, but menthol is generally considered to have a rapid onset of action with effects lasting for a few hours.

Adverse effects

• Allergic reactions
• Urticaria
• Asthma
• Rhinitis
• Skin irritation

Precautions

• Use with caution in patients with known allergies to menthol or related compounds
• May exacerbate asthma in sensitive individuals

Pregnancy

There are no well-controlled studies of menthol in pregnant women. Menthol should be used during pregnancy only if clearly needed.

Breast-feeding

Menthol is excreted in breast milk. Caution should be exercised when administering to nursing mothers.

Storage

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

Formulations

• Topical ointment
• Cream
• Liquid

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

• 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

Mechanism of action

Chlorhexidine’s broad-spectrum antimicrobial effects are due to its ability to disrupt microbial cell membranes. The positively charged chlorhexidine molecule reacts with negatively charged phosphate groups on microbial cell surfaces - this reaction both destroys the integrity of the cell, allowing leakage of intracellular material, and allows chlorhexidine to enter the cell, causing precipitation of cytoplasmic components and ultimately cell death. The specific means of cell death is dependent on the concentration of chlorhexidine - lower concentrations are bacteriostatic and result in leakage of intracellular substances such as potassium and phosphorous, whereas higher concentrations are bactericidal and cause cytoplasmic precipitation.

Pharmacodynamics

Chlorhexidine is a broad-spectrum antimicrobial with demonstrated activity against both gram-positive and gram-negative bacteria, yeasts, and viruses. Antimicrobial activity is dose-dependent - chlorhexidine is bacteriostatic at lower concentrations (0.02%-0.06%) and bactericidal at higher concentrations (>0.12%). Pharmacokinetic studies of oral chlorhexidine rinses indicate that approximately 30% of the active ingredient is retained in the mouth following rinsing, which is subsequently slowly released into oral fluids. This ability to adsorb to dentine, shared with tetracycline antibiotics such as [doxycycline], is known as "substantivity" and is the result of chlorhexidine's positive charge - it is likely that this substantivity plays at least some role in chlorhexidine's antimicrobial activity, as its persistence on surfaces such as dentine prevent microbial colonization. Dental chlorhexidine rinses may result in staining of oral surfaces, such as teeth. This effect is not ubiquitous and appears to be more significant with extended therapy (i.e. up to 6 months) - nevertheless, patients for whom oral staining is unacceptable should use chlorhexidine rinse with caution and for the shortest effective interval. Allergic reactions to chlorhexidine have been associated with the development of anaphylaxis.

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

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

Exposure to low temperatures often causes allergic responses or urticaria. Similarly, menthol, a common food additive is also known to cause urticaria, asthma, and rhinitis. However, despite the obvious clinical implications, the molecular mechanisms responsible for inducing allergic responses to low temperatures and menthol have not been determined. Because a non-selective cation channel, transient receptor potential subtype M8 (TRPM8) is activated by cold and menthol, we hypothesized that this channel mediates cold- and menthol-induced histamine release in mast cells. Here, we report that TRPM8 is expressed in the basophilic leukemia mast cell line, RBL-2H3, and that exposure to menthol or low temperatures induced Ca(2+) influx in RBL-2H3 cells, which was reversed by a TRPM8 blocker. Furthermore, menthol, a TRPM8 agonist, induced the dose-dependent release of histamine from RBL-2H3 cells. When TRPM8 transcripts were reduced by siRNA (small interfering RNA), menthol- and cold-induced Ca(2+) influx and histamine release were significantly reduced. In addition, subcutaneous injection of menthol evoked scratching, a typical histamine-induced response which was reversed by a TRPM8 blocker. Thus, our findings indicate that TRPM8 mediates the menthol- and cold-induced allergic responses of mast cells, and suggest that TRPM8 antagonists be viewed as potential treatments for cold- and menthol-induced allergies. /DL-Menthol/ Menthol's characteristic cooling sensation is due, in part, to the activation of sensory neurons generally termed transient receptor potential (TRP) channels, in particular transient receptor potential melastatin family member 8 (TRPM8) and transient receptor potential subfamily A, member 1 (TRPA1). Menthol acts upon TRPM8 receptors by rapidly increasing intracellular calcium and mobilizing calcium flux through the channels to induce cold response signals at the application site. Aside from its cold-inducing sensation capabilities, menthol exhibits cytotoxic effects in cancer cells, induces reduction in malignant cell growth, and engages in synergistic excitation of GABA receptors and sodium ion channels resulting in analgesia. /DL-Menthol/ In recent years, the transient receptor potential melastatin member 8 (TRPM8) channel has emerged as a promising prognostic marker and putative therapeutic target in prostate cancer. We have found that forced overexpression of TRPM8 in PC-3 cells can inhibit the cell proliferation and motility probably through the TRPM8 activation. In this study, we aimed to investigate whether activating the TRPM8 channel by its selective agonist menthol can inhibit the proliferation and motility of androgen-independent prostate cancer (AIPC) with remarkable expression of TRPM8. Menthol is a naturally occurring compound, which has been widely used in cosmetics and pharmaceutical products, and also as flavoring in food. DU145 cells are androgen-independent but have a remarkable expression of TRPM8. The demonstration of the existence of TRPM8 and the absence of TRPA1 in DU145 cells provided the foundation for the following experiments, because both TRPM8 and TRPA1 are molecular targets of menthol. The outcome of MTT assay indicated that menthol inhibited the cell growth (p < 0.01). Cell cycle distribution and scratch assay analysis revealed that menthol induced cell cycle arrest at the G(0)/G(1) phase (p < 0.01). Furthermore, menthol inhibited the migration of DU145 cells by downregulating the focal-adhesion kinase. So it suggests that the activation of the existing TRPM8 channels may serve as a potential and pragmatic treatment for those AIPC with remarkable expression of TRPM8, and menthol is a useful compound for future development as an anticancer agent. /DL-Menthol/

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.