COFFDEX SYRUP

Mechanism of action

Amaranth, as an azo dye, exerts its effect primarily through its interaction with cellular components, where it can bind to proteins and nucleic acids. This interaction can lead to changes in cellular functions and may induce oxidative stress. The exact pathways of its action are not fully elucidated, but it is believed to influence metabolic processes related to color stability and absorption in various mediums.

Pharmacodynamics

The pharmacodynamics of amaranth involves its role as a coloring agent. It does not possess pharmacological activity in the traditional sense, as it is not used for therapeutic purposes. The dye's stability in acidic and neutral conditions allows it to retain its color in food products, but it does not interact with biological systems in a manner that would produce a pharmacological response.

Pharmacokinetics

The pharmacokinetic profile of amaranth is not well defined due to its nature as a food additive rather than a pharmaceutical compound. However, it is generally assumed that upon consumption, amaranth can be absorbed in the gastrointestinal tract, potentially metabolized in the liver, and excreted via the kidneys. The extent of absorption and metabolism may vary based on individual factors and the form in which it is ingested.

Pregnancy

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

Breast-feeding

Safety during breastfeeding is not established. Consult healthcare provider before use.

Storage

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

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

• Dry eye syndrome
• Ocular surface disorders
• Topical lubrication
• Pharmaceutical excipients in formulations

Dosage

Children: Refer to specific product guidelines, as doses may vary by formulation and indication.

Adults: Refer to specific product guidelines, as doses may vary by formulation and indication.

Mechanism of action

Carboxymethyl cellulose acts by forming a viscous gel when it comes into contact with water. This gel-like consistency helps to retain moisture, providing lubrication and protection to ocular surfaces. The polymer's ability to bind water makes it effective at enhancing the viscosity of formulations, which can prolong the retention time of active ingredients in contact with the affected tissues.

Pharmacodynamics

Carboxymethyl cellulose exhibits its effects primarily through its physical properties rather than specific biochemical interactions. Its high viscosity contributes to a protective barrier on mucosal surfaces, aiding in the alleviation of dryness and irritation. The gel-forming property helps to maintain hydration and can facilitate the healing process of epithelial tissues.

Pharmacokinetics

Carboxymethyl cellulose is not significantly absorbed through the gastrointestinal tract or ocular surfaces. Its action is mainly local, with minimal systemic absorption. The polymer is excreted unchanged, and its viscosity and gel-forming capabilities are maintained until it is cleared from the application site through natural processes such as blinking or swallowing.

Adverse effects

• Allergic reactions
• Skin irritation
• Gastrointestinal disturbances
• Headache
• Dizziness

Precautions

• Use with caution in patients with known allergies to carboxymethyl derivatives
• Monitor for potential allergic reactions
• Consider potential interactions with other medications

Pregnancy

Safety during pregnancy has not been established. Use only if potential benefits justify the risks.

Breast-feeding

It is not known whether carboxymethyl is excreted in human milk. Caution should be exercised.

Storage

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

Formulations

• Carboxymethyl cellulose sodium (CMC) - commonly used as a thickening agent in various formulations

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

• Allergic rhinitis
• Urticaria (hives)
• Hay fever
• Allergic conjunctivitis
• Common cold symptoms

Dosage

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

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

Mechanism of action

Chlorphenamine exerts its effects by antagonizing the H1 histamine receptors, leading to a reduction in the physiological effects of histamine, a mediator released during allergic reactions. This blockade results in decreased vascular permeability, reduced bronchoconstriction, and inhibition of other effects mediated by histamine. Additionally, chlorphenamine can cross the blood-brain barrier, contributing to its sedative effects.

Pharmacodynamics

The pharmacodynamic effects of chlorphenamine include antiallergic actions, sedation, and anticholinergic effects. By inhibiting H1 receptors, chlorphenamine alleviates symptoms of allergic rhinitis and urticaria. The sedative action is due to its central nervous system penetration, which can lead to drowsiness and decreased alertness. It may also exhibit mild anticholinergic properties, leading to dry mouth and blurred vision in some patients.

Pharmacokinetics

Chlorphenamine is well-absorbed from the gastrointestinal tract, with peak plasma concentrations typically achieved within 1-2 hours after oral administration. It has a half-life of approximately 12-15 hours, allowing for once or twice daily dosing in many cases. The drug is metabolized primarily in the liver and excreted in the urine. Its pharmacokinetic profile may be affected by factors such as age, liver function, and concurrent medications.

Contra-indications

• Hypersensitivity to chlorphenamine or any of its constituents
• Severe asthma or bronchospasm
• Use in neonates or premature infants

Adverse effects

• Drowsiness
• Dizziness
• Dry mouth
• Blurred vision
• Constipation
• Urinary retention
• Increased appetite

Interactions

• CNS depressants may enhance sedative effects
• Monoamine oxidase inhibitors (MAOIs) may prolong and intensify anticholinergic effects
• Alcohol may increase sedation

Precautions

• Caution in patients with glaucoma, prostatic hypertrophy, or urinary retention
• Use with caution in elderly patients due to increased sensitivity
• May impair physical or mental abilities required for operating machinery or driving

Pregnancy

Use only if clearly needed, as safety in pregnancy has not been established.

Breast-feeding

Excreted in breast milk, caution is advised when administered to nursing mothers.

Storage

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

Formulations

• Tablets
• Syrup
• Injectable solution

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

• Cough
• Pseudobulbar affect

Dosage

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

Adults: Refer to the BNF for specific dosing guidelines based on the formulation and clinical context.

Mechanism of action

Dextromethorphan acts as a low-affinity uncompetitive antagonist of NMDA receptors and as an agonist at sigma-1 receptors. It also antagonizes α3/β4 nicotinic receptors. The clinical effects are thought to arise from NMDA receptor blockade and serotonin (5-HT) uptake inhibition, which may lead to increased serotonin receptor stimulation. However, the precise mechanisms by which these actions translate into therapeutic effects remain incompletely understood.

Pharmacodynamics

Dextromethorphan is considered an opioid-like molecule with a moderate therapeutic window, indicating that while it is effective at standard doses, higher doses can lead to intoxication. It has a moderate duration of action, making it suitable for use in cough management. Due to its potential for abuse and risk of intoxication, patients are advised to use it cautiously.

Pharmacokinetics

Dextromethorphan is metabolized primarily in the liver through the cytochrome P450 enzyme system, leading to the formation of its active metabolite, dextrorphan. The pharmacokinetics may be influenced by individual variations in metabolic pathways, which can affect the drug's efficacy and safety profile.

Contra-indications

• Hypersensitivity to dextromethorphan or any of its components
• Concurrent use with monoamine oxidase inhibitors (MAOIs)
• Severe respiratory insufficiency or asthma
• Persistent cough due to smoking, emphysema, or chronic bronchitis

Adverse effects

• Dizziness
• Nausea
• Vomiting
• Drowsiness
• Confusion
• Constipation
• Abdominal discomfort
• Euphoria or dysphoria
• Serotonin syndrome (when used with serotonergic drugs)

Interactions

• May interact with MAOIs, leading to serious side effects
• Potential interactions with other CNS depressants, leading to increased sedation
• May enhance the effects of alcohol
• Can interact with medications that affect serotonin levels, increasing the risk of serotonin syndrome

Precautions

• Use with caution in patients with a history of substance abuse
• Monitor use in patients with hepatic impairment
• Caution advised in patients with a history of seizures
• Should not be used in children under 2 years unless directed by a physician

Pregnancy

Dextromethorphan should be used during pregnancy only if clearly needed. Consult a healthcare provider for advice.

Breast-feeding

Dextromethorphan is excreted in breast milk. Caution is advised when administered to nursing mothers.

Storage

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

Formulations

• Oral syrup
• Tablets
• Capsules
• Lozenges

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

Indications

• Respiratory conditions (e.g., asthma, chronic obstructive pulmonary disease)
• Cough (e.g., as an antitussive)
• Anxiety and sleep disorders (when associated with specific formulations)

Dosage

Children: Refer to the BNF for Children for appropriate dosing information, as it is determined based on weight and age for the specific formulation.

Adults: Refer to the specific product monograph for dosing information, as it varies based on the drug formulation and indication.

Mechanism of action

Hydrobromides often act as competitive antagonists or agonists at specific receptor sites, depending on the drug involved. The exact mechanism can vary widely, but many hydrobromide-containing drugs modulate neurotransmitter activity, impacting various pathways in the body such as those involved in the central nervous system or respiratory function. The metabolic pathways include Phase I reactions primarily mediated by cytochrome P450 enzymes, which facilitate the functionalization and clearance of these compounds.

Pharmacodynamics

The pharmacodynamics of hydrobromide salts are largely determined by the specific drug they are associated with. Generally, hydrobromides may exhibit effects such as sedation, bronchodilation, or antitussive actions. The efficacy and adverse effects are influenced by the drug's receptor selectivity, affinity, and the pharmacological properties inherent to the parent compound.

Pharmacokinetics

Hydrobromides typically exhibit variable pharmacokinetic profiles depending on the specific drug formulation. They are generally absorbed rapidly following oral administration, with peak plasma concentrations occurring within a few hours. Metabolism primarily occurs in the liver through cytochrome P450 enzymes, particularly CYP2E1, among others. The elimination half-life varies but is often in the range of several hours, allowing for once or twice-daily dosing in many formulations. Excretion is usually via the kidneys, with metabolites being eliminated in urine.

Pregnancy

There are no adequate and well-controlled studies in pregnant women. Use only if clearly needed and the potential benefits justify the potential risks to the fetus.

Breast-feeding

Caution is advised; consider the importance of the drug to the mother against potential risks to the breastfeeding infant.

Storage

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

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

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

• 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

Mechanism of action

Dextromethorphan is a low-affinity uncompetitive NMDA antagonist and sigma-1 receptor agonist. It is also an antagonist of α3/β4 nicotinic receptors. However, the mechanism by which dextromethorphan's receptor agonism and antagonism translate to a clinical effect is not well understood. Dextromethorphan (DXM) is the dextro isomer of levomethorphan, a semisynthetic morphine derivative. Although structurally similar to other /CNS depressants/, DXM does not act as a mu receptor opioid (eg, morphine, heroin). DXM and its metabolite, dextrorphan, act as potent blockers of the N-methyl-d-aspartate (NMDA) receptor. Amantadine and dextromethorphan suppress levodopa (L-DOPA)-induced dyskinesia (LID) in patients with Parkinson's disease (PD) and abnormal involuntary movements (AIMs) in the unilateral 6-hydroxydopamine (6-OHDA) rat model. These effects have been attributed to N-methyl-d-aspartate (NMDA) antagonism. However, amantadine and dextromethorphan are also thought to block serotonin (5-HT) uptake and cause 5-HT overflow, leading to stimulation of 5-HT(1A) receptors, which has been shown to reduce LID. We undertook a study in 6-OHDA rats to determine whether the anti-dyskinetic effects of these two compounds are mediated by NMDA antagonism and/or 5-HT(1A) agonism. In addition, we assessed the sensorimotor effects of these drugs using the Vibrissae-Stimulated Forelimb Placement and Cylinder tests. Our data show that the AIM-suppressing effect of amantadine was not affected by the 5-HT(1A) antagonist WAY-100635, but was partially reversed by the NMDA agonist d-cycloserine. Conversely, the AIM-suppressing effect of dextromethorphan was prevented by WAY-100635 but not by d-cycloserine. Neither amantadine nor dextromethorphan affected the therapeutic effects of L-DOPA in sensorimotor tests. We conclude that the anti-dyskinetic effect of amantadine is partially dependent on NMDA antagonism, while dextromethorphan suppresses AIMs via indirect 5-HT(1A) agonism. Combined with previous work from our group, our results support the investigation of 5-HT(1A) agonists as pharmacotherapies for LID in PD patients. Dextromethorphan (DM) is a dextrorotatory morphinan and an over-the-counter non-opioid cough suppressant. We have previously shown that DM protects against LPS-induced dopaminergic neurodegeneration through inhibition of microglia activation. Here, we investigated protective effects of DM against endotoxin shock induced by lipopolysaccharide/d-galactosamine (LPS/GalN) in mice and the mechanism underlying its protective effect. Mice were given multiple injections of DM (12.5 mg/kg, s.c.) 30 min before and 2, 4 hr after an injection of LPS/GalN (20 ug/700 mg/kg). DM administration decreased LPS/GalN-induced mortality and hepatotoxicity, as evidenced by increased survival rate, decreased serum alanine aminotransferase activity and improved pathology. Furthermore, DM was also effective when it was given 30 min after LPS/GalN injection. The protection was likely associated with reduced serum and liver tumor necrosis factor alpha (TNF-alpha) levels. DM also attenuated production of superoxide and intracellular reactive oxygen species in Kupffer cells and neutrophils. Real-time RT-PCR analysis revealed that DM administration suppressed the expression of a variety of inflammation-related genes such as macrophage inflammatory protein-2, CXC chemokine, thrombospondin-1, intercellular adhesion molecular-1 and interleukin-6. DM also decreased the expression of genes related to cell-death pathways, such as the DNA damage protein genes GADD45 and GADD153. In summary, DM is effective in protecting mice against LPS/GalN-induced hepatotoxicity, and the mechanism is likely through a faster TNF-alpha clearance, and decrease of superoxide production and inflammation and cell-death related components. This study not only extends neuroprotective effect of DM, but also suggests that DM may be a novel compound for the therapeutic intervention for sepsis. /The

Pharmacodynamics

Dextromethorphan is an opioid-like molecule indicated in combination with other medication in the treatment of coughs and pseudobulbar affect. It has a moderate therapeutic window, as intoxication can occur at higher doses. Dextromethorphan has a moderate duration of action. Patients should be counselled regarding the risk of intoxication.

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

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

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

...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.