Glycerin Lemon and Honey

Indications

• Skin disinfection
• Preparation of skin before injections
• Cleansing minor wounds

Dosage

Children: Apply to the skin as required; consult product literature for specific guidance.

Adults: Apply to the skin as required for disinfection.

Mechanism of action

Alcohol exerts its antiseptic effect by denaturing proteins, disrupting cell membranes, and dehydrating microbial cells, leading to cell lysis and death.

Pharmacodynamics

Alcohol has broad-spectrum antimicrobial activity, effective against bacteria, fungi, and viruses. Its efficacy is influenced by concentration, with higher concentrations generally being more effective.

Pharmacokinetics

Alcohol is rapidly absorbed through the skin and mucous membranes. It is metabolized primarily in the liver, with a half-life that varies based on the individual's metabolic rate and the amount consumed.

Contra-indications

• Concomitant use with lithium
• Regular use in neonates
• Patients with severe burns when diathermy has been preceded by application of alcoholic skin disinfectants

Adverse effects

• Eye erythema
• Punctate keratitis
• Cytotoxicity
• Eye discolouration

Interactions

• Increases risk of visual disturbances with antiepileptics
• Increases concentration with methylphenidate
• Increases risk of facial flushing and skin irritation with topical pimecrolimus
• Increases concentration with retinoids
• Increases concentration with acitretin
• Increases risk of facial flushing and skin irritation with topical tacrolimus
• Decreases antidiuretic effect with vasopressin

Precautions

• Avoid regular application to inflamed or broken skin or mucosa
• Avoid broken skin
• Flammable

Pregnancy

Sufficient iodine may be absorbed to affect the fetal thyroid in the second and third trimester.

Breast-feeding

Avoid regular or excessive use.

Storage

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

Formulations

• Betadine 2.5% dry powder spray
• Industrial methylated spirit
• Povidone-Iodine 25 mg per 1 gram

Indications

• Nutritional supplement
• Source of healthy fats
• Culinary ingredient
• Potential use in managing cholesterol levels
• Allergen (in allergic reactions)

Dosage

Children: Refer to established dietary guidelines for intake as a food source.

Adults: Refer to established dietary guidelines for intake as a food source.

Mechanism of action

The primary mechanism of action of arachis oil involves its high content of unsaturated fatty acids, particularly oleic acid. These fatty acids may help in modulating lipid metabolism, reducing inflammation, and providing energy. Arachis also contains antioxidants such as resveratrol and vitamin E, which may contribute to its health benefits through their protective effects against oxidative stress.

Pharmacodynamics

Arachis exhibits various pharmacodynamic properties owing to its nutritional composition. The unsaturated fatty acids present in arachis can positively influence cholesterol levels, potentially lowering LDL cholesterol and raising HDL cholesterol. The presence of bioactive compounds may also contribute to anti-inflammatory effects, enhancing cardiovascular health and possibly reducing the risk of chronic diseases.

Pharmacokinetics

Arachis is primarily consumed orally, and its components are absorbed in the gastrointestinal tract. The fatty acids are metabolized in the liver, and the rate of absorption can be influenced by the presence of other dietary components. The bioavailability of nutrients in arachis can be affected by its processing methods, such as roasting, which may alter the absorption of certain vitamins and minerals.

Contra-indications

• Hypersensitivity to peanuts or any of its components
• History of severe allergic reactions to other legumes

Adverse effects

• Anaphylaxis in sensitive individuals
• Skin reactions such as urticaria or eczema
• Gastrointestinal disturbances including nausea or diarrhea

Precautions

• Use with caution in individuals with a history of food allergies
• Consider potential for cross-reactivity with other legumes

Pregnancy

Arachis can be consumed during pregnancy unless there is a known allergy to peanuts. It is a source of protein and healthy fats, but caution is advised in allergic individuals.

Breast-feeding

Arachis can be consumed during breastfeeding, but mothers should monitor for any allergic reactions in the infant, especially if there is a family history of allergies.

Storage

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

Formulations

• Raw peanuts
• Peanut oil
• Peanut butter

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.

Dosage

Children: Refer to specific formulations and usages, as dosing can vary widely depending on the application and regulatory guidelines.

Adults: Refer to specific formulations and usages, as dosing can vary widely depending on the application and regulatory guidelines.

Mechanism of action

Butylated hydroxyanisole (BHA) and butylated hydroxytoluene (BHT) act as antioxidants by inhibiting the oxidation of lipids. They scavenge free radicals and donate hydrogen atoms to reactive species, thus stabilizing and preventing oxidative damage to cellular components. This action helps to protect the integrity of cell membranes and prevent the formation of harmful peroxides.

Pharmacodynamics

The pharmacodynamic properties of butylated compounds are primarily related to their antioxidant activity. They exhibit a dose-dependent ability to inhibit lipid peroxidation, which is crucial in protecting cells from oxidative stress. Furthermore, they may modulate certain biochemical pathways involved in cell signaling and apoptosis, although these effects are less well-characterized.

Pharmacokinetics

Butylated compounds are absorbed from the gastrointestinal tract following oral ingestion. They undergo metabolic processing primarily in the liver, where they are conjugated and excreted in urine. The half-life of butylated compounds in humans is variable, influenced by factors such as dosage and individual metabolism. Accumulation in tissues is generally low, but prolonged exposure may lead to higher tissue concentrations.

Adverse effects

• Gastrointestinal disturbances
• Allergic reactions
• Potential carcinogenic effects with prolonged exposure

Precautions

• Use with caution in patients with a history of hypersensitivity to butylated compounds
• Avoid prolonged exposure due to potential toxicity

Pregnancy

Limited data available, use only if the benefits outweigh the risks.

Breast-feeding

Unknown, exercise caution and consult a healthcare provider.

Storage

Store in a cool, dry place away from light.

Formulations

• Butylated hydroxytoluene (BHT)
• Butylated hydroxyanisole (BHA)

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

• Use as a non-nutritive sweetener
• Sugar substitute for individuals requiring caloric restriction
• Dietary management in diabetes

Dosage

Children: Paediatric dosing is not established for cyclamate as it is used as an artificial sweetener. Consult product

Adults: The use of cyclamate as a sweetener does not have a specified dose; it is typically used in amounts sufficient to achieve the desired sweetness in food and beverage products. Refer to product guidelines for specific usage.

Mechanism of action

Cyclamate interacts with the sweet taste receptor, which is a heterodimer of two G protein-coupled receptors, T1R2 and T1R3. The interaction occurs primarily through binding sites located in the transmembrane domain of T1R3. This binding initiates a signaling cascade that results in the perception of sweetness. The specific amino acid interactions within the receptor are crucial for the activity of cyclamate and its sweetening effect.

Pharmacodynamics

Cyclamate is characterized by its ability to activate sweet taste receptors, leading to a sweet taste sensation without providing calories. Its potency allows for low concentrations to achieve desired sweetness levels, making it a popular choice for reducing caloric intake in sweetened foods and beverages. Cyclamate does not elicit a significant glycemic response, making it suitable for individuals managing their blood sugar levels.

Pharmacokinetics

Cyclamate is rapidly absorbed from the gastrointestinal tract and is metabolized primarily in the liver. It undergoes hydrolysis and is converted into cyclohexylamine. The half-life of cyclamate is relatively short, and it is excreted primarily in the urine. The pharmacokinetics of cyclamate may vary based on individual metabolic rates and dietary factors.

Pregnancy

Cyclamate is not recommended during pregnancy due to insufficient data on safety.

Breast-feeding

Cyclamate is considered safe during breastfeeding, but caution is advised as data is limited.

Storage

Store in a cool, dry place away from light.

Formulations

• Cyclamate is available in various formulations including tablets and powder.

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

• Cough associated with colds
• Bronchitis
• Respiratory tract infections
• Other conditions with excessive mucus production

Dosage

Children: Refer to the BNF for Children for specific dosing guidelines based on age and

Adults: The typical adult dose is 200-400 mg orally every 4 hours as needed, not exceeding 2.4 g per day.

Mechanism of action

Guaifenesin is believed to function by increasing mucus secretion and acting as an irritant to gastric vagal receptors. This action recruits efferent parasympathetic reflexes that stimulate glandular exocytosis, resulting in a less viscous mucus mixture. Consequently, this may provoke coughing, facilitating the clearance of congealed mucopurulent material from obstructed airways, thereby improving respiratory function. Additionally, it is thought to enhance the output of phlegm and bronchial secretions by reducing their viscosity and adhesiveness, thus promoting ciliary action and improving the efficiency of the cough reflex.

Pharmacodynamics

Guaifenesin acts as an expectorant that enhances the output of phlegm and bronchial secretions by decreasing their adhesiveness and surface tension. By increasing the flow of less viscous gastric secretions, it promotes ciliary action, leading to more productive coughs. This mechanism ultimately aids in the removal of accumulated secretions from the upper and lower airways, making coughs less frequent and more effective.

Pharmacokinetics

Guaifenesin is rapidly absorbed from the gastrointestinal tract and is metabolized in the liver. It has a relatively short half-life, with peak plasma concentrations typically occurring within one hour of administration. The drug is eliminated primarily through renal excretion, with both unchanged drug and metabolites being excreted in the urine.

Adverse effects

• Nausea
• Vomiting
• Dizziness
• Headache
• Rash
• Gastrointestinal discomfort

Precautions

• Caution in patients with chronic cough associated with smoking, asthma, or emphysema
• Use with caution in patients with a history of gastrointestinal disorders

Pregnancy

Guaifenesin is categorized under FDA pregnancy category C. Risk cannot be ruled out; consult a healthcare provider.

Breast-feeding

Limited data available; exercise caution and consult a healthcare provider before use.

Storage

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

Formulations

• Oral solution
• Tablet
• Extended-release tablet
• Syrup

Indications

• Solar lentigines
• Hyperpigmented lesions
• Other related skin disorders characterized by increased melanin production

Dosage

Children: Refer to BNF for Children for specific dosage guidance for paediatrics.

Adults: Refer to BNF for specific dosage guidance for adults.

Mechanism of action

Mequinol is considered a melanocytotoxic chemical that, upon oxidation in melanocytes, leads to the formation of toxic compounds such as quinones. These cytotoxic agents can damage and destroy pigment-producing cells (melanocytes), resulting in skin depigmentation. The presence of glutathione and glutathione S-transferase in skin cells offers a protective mechanism against the toxicity, but the combination of mequinol with tretinoin can inhibit this protective response, enhancing the depigmentation effect.

Pharmacodynamics

Mequinol's pharmacodynamic profile reveals its ability to induce cellular toxicity in melanocytes, leading to the destruction of pigment cells and subsequent depigmentation of the skin. The drug's action is characterized by the formation of cytotoxic quinones after oxidation, which, while detrimental to melanocytes, is a primary mechanism for its therapeutic efficacy in addressing hyperpigmentation.

Pharmacokinetics

The pharmacokinetics of hydroxyanisole have not been extensively detailed in the provided sources. Typically, topical agents like mequinol are expected to have limited systemic absorption, with localized action on the skin. The duration of action and specific metabolic pathways for mequinol are not specified, indicating a need for further research to fully understand these aspects.

Pregnancy

Use is not recommended during pregnancy due to potential risks.

Breast-feeding

Caution is advised; the effects on a nursing infant are unknown.

Storage

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

Formulations

• Topical solution
• Cream

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

Dosage

Children: Refer to BNF for Children for specific recommendations regarding the consumption of orange juice in children.

Adults: There is no standard dosage for orange juice as it is typically consumed as a beverage. Moderation is advised, especially for individuals on certain medications.

Mechanism of action

The exact mechanism of action of orange juice is not fully understood, but it is known to contain compounds that can influence the metabolism of certain drugs. For instance, it may affect the activity of cytochrome P450 enzymes, particularly CYP3A4, which can alter the pharmacokinetics of medications.

Pharmacodynamics

Orange juice is known to enhance the bioavailability of certain nutrients and may influence the pharmacological effects of some drugs. Its high vitamin C content contributes to various physiological functions, including antioxidant activity, which may indirectly support overall health.

Pharmacokinetics

The pharmacokinetics of orange juice itself are not extensively studied, but it is generally absorbed well through the gastrointestinal tract. The compounds in orange juice can affect the absorption and metabolism of medications, leading to varied clinical effects depending on the drug in question.

Interactions

• orange juice + celiprolol: Unknown (decreases exposure)

Formulations

• juice
• whole fruit

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

• Providing energy in dietary supplementation
• Enhancing flavor in food products
• Replacement of carbohydrates in certain medical nutrition therapies

Dosage

Children: Refer to general dietary guidelines for carbohydrate intake in children. No specific dosing guidelines provided.

Adults: Refer to general dietary guidelines for carbohydrate intake. No specific dosing guidelines provided.

Mechanism of action

Sugar is metabolized in the body to provide energy. Upon ingestion, sucrose is broken down by the enzyme sucrase into its constituent monosaccharides, glucose and fructose, which are then absorbed into the bloodstream. These monosaccharides can be utilized by cells for energy or stored as glycogen in the liver and muscles.

Pharmacodynamics

As a simple carbohydrate, sugar elevates blood glucose levels rapidly after consumption, leading to increased insulin secretion from the pancreas. This insulin facilitates the uptake of glucose by tissues, promoting energy production. The rapid increase in blood sugar can provide quick energy but may also lead to potential negative effects on metabolism and weight if consumed in excess.

Pharmacokinetics

After oral administration, sugar is quickly hydrolyzed in the gastrointestinal tract. Peak plasma glucose concentrations typically occur within 30 minutes to 2 hours post-ingestion, depending on the amount consumed and individual metabolism. The half-life of glucose in the bloodstream is relatively short, as it is rapidly taken up by tissues or converted into glycogen.

Pregnancy

Sugar is generally considered safe for use during pregnancy, but excessive intake should be avoided to prevent gestational diabetes and excessive weight gain.

Breast-feeding

Sugar is safe during breastfeeding; however, excessive consumption should be avoided.

Storage

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

Formulations

• Granulated sugar
• Brown sugar
• Powdered sugar
• Liquid sugar

Dosage

Children: Refer to product-specific guidelines or consult a healthcare professional.

Adults: Refer to product-specific guidelines or consult a healthcare professional.

Pregnancy

There is limited data on the safety of Sunset during pregnancy, thus it should be used only if clearly needed and prescribed by a healthcare provider.

Breast-feeding

Due to the lack of sufficient studies, it is advised to consult a healthcare professional before using Sunset while breastfeeding.

Storage

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

Indications

• Acne vulgaris
• Chlamydia infections
• Respiratory tract infections
• Urinary tract infections
• Skin and soft tissue infections
• Periodontal disease

Dosage

Children: Refer to the

Adults: Refer to official dosing guidelines or the BNF for specific indications and dosing regimens, as dosages may vary based on the type and severity of the infection.

Mechanism of action

Tetratome exerts its antibacterial effects by binding to the 30S ribosomal subunit of bacteria, inhibiting the binding of aminoacyl-tRNA to the mRNA-ribosome complex. This action disrupts protein synthesis, which is essential for bacterial growth and replication. The inhibition of protein synthesis leads to bacteriostatic effects, allowing the host's immune system to eliminate the infection.

Pharmacodynamics

The pharmacodynamics of tetratome are characterized by its ability to inhibit bacterial protein synthesis, which is crucial for bacterial growth. The drug demonstrates a time-dependent killing effect, meaning that the duration of exposure to the drug is more important than the peak concentration achieved. Tetracycline also exhibits some post-antibiotic effects, where bacterial growth remains suppressed for a period after drug removal.

Pharmacokinetics

Tetratome is well absorbed from the gastrointestinal tract, with peak plasma concentrations occurring within 2 to 4 hours after oral administration. Its bioavailability can be affected by food, calcium, and iron, which can chelate the drug and reduce absorption. Tetracycline is widely distributed throughout body tissues and fluids, with a volume of distribution of approximately 1.5 L/kg. The drug is primarily excreted in the urine, with a half-life of about 6 to 12 hours, depending on renal function. It is contraindicated in patients with renal impairment due to the risk of accumulation and toxicity.

Pregnancy

There is limited data on the safety of tetratome during pregnancy. It should be used only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

It is unknown whether tetratome is excreted in human breast milk. Caution should be exercised when administered to a nursing mother.

Storage

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

Pregnancy

No specific data available, consult a healthcare professional.

Breast-feeding

No specific data available, consult a healthcare professional.

Storage

Store in a cool, dry place away from light.

Mechanism of action

Ethanol affects the brain’s neurons in several ways. It alters their membranes as well as their ion channels, enzymes, and receptors. Alcohol also binds directly to the receptors for acetylcholine, serotonin, GABA, and the NMDA receptors for glutamate. The sedative effects of ethanol are mediated through binding to GABA receptors and glycine receptors (alpha 1 and alpha 2 subunits). It also inhibits NMDA receptor functioning. In its role as an anti-infective, ethanol acts as an osmolyte or dehydrating agent that disrupts the osmotic balance across cell membranes. ... Ethanol is known to affect a large number of membrane proteins that participate in signaling pathways such as neurotransmitter receptors, enzymes, and ion channels, and there is extensive evidence that ethanol interacts with a variety of neurotransmitters. The major actions of ethanol involve enhancing the inhibitory effects of gamma-aminobutyric acid (GABA) at GABAa receptors and blockade of the N-methyl-D-aspartate (NMDA) subtype of glutamate, an excitatory amine acid (EAA) receptor. Animal studies indicate that the acute effects of ethanol result from competitive inhibition of glycine binding to NMDA receptor and disruption of glutamatergic neurotransmission by inhibiting the response of the NMDA receptor. Persistent glycine antagonism and attenuation of glutamatergic neurotransmission by chronic ethanol exposure results in tolerance to ethanol by enhancing EAA neurotransmission and NMDA receptor upregulation. The latter appears to involve selective increases in NMDA R2B subunit concentrations and other molecular changes in specific brain loci. The abrupt withdrawal of ethanol thus produces a hyperexcitable state that leads to the ethanol withdrawal syndrome and excitotoxic neuronal death. GABA-mediated inhibition, which normally acts to limit excitation, is eliminated during ethanol withdrawal syndrome and further intensifies this excitation. In addition, NMDA receptors function to inhibit the release of dopamine in the nucleus accumbens and mesolimbic structures, which modulate the reinforcing action of addictive xenobiotics such as ethanol. By inhibiting NMDA receptor activity, ethanol could increase dopamine release from the nucleus accumbens and ventral tegmental area and could thus create dependence. Chronic ethanol administration also results in tolerance, dependence, and an ethanol withdrawal syndrome, mediated, in part, by desensitization and or downregulation of GABAa receptors. The development of alcoholic ketoacidosis (AKA) requires that a combination of physical and physiologic events occur. The normal response to starvation and depletion of hepatic glycogen stores is for amino acids to be converted to pyruvate. Pyruvate can serve as a substrate for gluconeogenesis, be converted to acetyl-CoA, which can enter the Krebs cycle or can be utilized in various biosynthetic pathways (eg, fatty acid, ketone bodies, cholesterol, and acetylcholine) ... Ethanol metabolism generates NADH, resulting in an excess of reducing potential. This high redox state favors the conversion of pyruvate to lactate, diverting pyruvate from being a substrate for gluconeogenesis. To compensate for the lack of normal metabolic substrates, the body mobilizes fat from adipose tissue and increased fatty acid metabolism as an alternative source of energy. This response is mediated by a decrease in insulin and an increased secretion of glucagon, catecholamines, growth hormone, and cortisol. Fatty acid metabolism results in the formation of acetyl-CoA and it combines with the excess acetate that is generated from ethanol metabolism to form acetoacetate. Most of the acetoacetate is reduced to beta-hydroxybutyrate due to the excess reducing potential or high redox state of the cell. Volume depletion interferes with the renal elimination of acetoacetate and beta-hydroxybutyrate, and contributes to the acidosis. An elevated lactate concentration may result from shunting from pyruvate or

Pharmacodynamics

Alcohol produces injury to cells by dehydration and precipitation of the cytoplasm or protoplasm. This accounts for its bacteriocidal and antifungal action. When alcohol is injected in close proximity to nerve tissues, it produces neuritis and nerve degeneration (neurolysis). Ninety to 98% of ethanol that enters the body is completely oxidized. Ethanol is also used as a cosolvent to dissolve many insoluble drugs and to serve as a mild sedative in some medicinal formulations. Ethanol also binds to GABA, glycine, NMDA receptors and modulates their effects. Ethanol is also metabolised by the hepatic enzyme alcohol dehydrogenase.

Mechanism of action

The sweet taste receptor is a heterodimer of two G protein coupled receptors, T1R2 and T1R3. Previous experimental studies using sweet receptor chimeras and mutants show that there are at least three potential binding sites in this heterodimeric receptor. Receptor activity toward the artificial sweeteners aspartame and neotame depends on residues in the amino terminal domain of human T1R2. In contrast, receptor activity toward the sweetener cyclamate and the sweet taste inhibitor lactisole depends on residues within the transmembrane domain of human T1R3. Furthermore, receptor activity toward the sweet protein brazzein depends on the cysteine rich domain of human T1R3. The sweet protein brazzein [recombinant protein with sequence identical with the native protein lacking the N-terminal pyroglutamate (the numbering system used has Asp2 as the N-terminal residue)] activates the human sweet receptor, a heterodimeric G-protein-coupled receptor composed of subunits Taste type 1 Receptor 2 (T1R2) and Taste type 1 Receptor 3 (T1R3). In order to elucidate the key amino acid(s) responsible for this interaction, we mutated residues in brazzein and each of the two subunits of the receptor. The effects of brazzein mutations were assayed by a human taste panel and by an in vitro assay involving receptor subunits expressed recombinantly in human embryonic kidney cells; the effects of the receptor mutations were assayed by in vitro assay. We mutated surface residues of brazzein at three putative interaction sites: site 1 (Loop43), site 2 (N- and C-termini and adjacent Glu36, Loop33), and site 3 (Loop9-19). Basic residues in site 1 and acidic residues in site 2 were essential for positive responses from each assay. Mutation of Y39A (site 1) greatly reduced positive responses. A bulky side chain at position 54 (site 2), rather than a side chain with hydrogen-bonding potential, was required for positive responses, as was the presence of the native disulfide bond in Loop9-19 (site 3). Results from mutagenesis and chimeras of the receptor indicated that brazzein interacts with both T1R2 and T1R3 and that the Venus flytrap module of T1R2 is important for brazzein agonism. With one exception, all mutations of receptor residues at putative interaction sites predicted by wedge models failed to yield the expected decrease in brazzein response. The exception, hT1R2 (human T1R2 subunit of the sweet receptor):R217A/hT1R3 (human T1R3 subunit of the sweet receptor), which contained a substitution in lobe 2 at the interface between the two subunits, exhibited a small selective decrease in brazzein activity. However, because the mutation was found to increase the positive cooperativity of binding by multiple ligands proposed to bind both T1R subunits (brazzein, monellin, and sucralose) but not those that bind to a single subunit (neotame and cyclamate), we suggest that this site is involved in subunit-subunit interaction rather than in direct brazzein binding. Results from this study support a multi-point interaction between brazzein and the sweet receptor by some mechanism other than the proposed wedge models.

Mechanism of action

Although the exact mechanism of action of guaifenesin may not yet be formally or totally elucidated, it is believed that expectorants like guaifenesin function by increasing mucus secretion. Moreover, it is also further proposed that such expectorants may also act as an irritant to gastric vagal receptors, and recruit efferent parasympathetic reflexes that can elicit glandular exocytosis that is comprised of a less viscous mucus mixture. Subsequently, these actions may provoke coughing that can ultimately flush difficult to access, congealed mucopurulent material from obstructed small airways to facilitate a temporary improvement for the individual. Consequently, while it is generally proposed that guaifenesin functions as an expectorant by helping to loosen phlegm (mucus) and thin bronchial secretions to rid the bronchial passageways of bothersome mucus and make coughs more productive, there has also been research to suggest that guaifenesin possesses and is capable of demonstrating anticonvulsant and muscle relaxant effects to some degree possibly by acting as an NMDA receptor antagonist. Guaifenesin is thought to act as an expectorant by increasing the volume and reducing the viscosity of secretions in the trachea and bronchi. Thus it may increase the efficiency of the cough reflex and facilitate removal of the secretions; however, objective evidence for this is limited and conflicting. By increasing respiratory tract fluid, guaifenesin reduces the viscosity of tenacious secretions and acts as an expectorant. Guaifenesin, a commonly used agent for the treatment of cough, is termed an expectorant since it is believed to alleviate cough discomfort by increasing sputum volume and decreasing its viscosity, thereby promoting effective cough. Despite its common usage, relatively few studies, yielding contrasting results, have been performed to investigate the action and efficacy of guaifenesin. To evaluate the effect of guaifenesin on cough reflex sensitivity. Randomized, double-blind, placebo-controlled trial. Fourteen subjects with acute viral upper respiratory tract infection (URI) and 14 healthy volunteers. On 2 separate days, subjects underwent capsaicin cough challenge 1 to 2 hr after receiving a single, 400-mg dose (capsules) of guaifenesin or matched placebo. Measurements and results: The concentration of capsaicin inducing five or more coughs (C(5)) was determined. Among subjects with URI, mean (+/- SEM) log C(5) after guaifenesin and placebo were 0.92 +/- 0.17 and 0.66 +/- 0.14, respectively (p = 0.028). No effect on cough sensitivity was observed in healthy volunteers. /The/ results demonstrate that guaifenesin inhibits cough reflex sensitivity in subjects with URI, whose cough receptors are transiently hypersensitive, but not in healthy volunteers. Possible mechanisms include a central antitussive effect, or a peripheral effect by increased sputum volume serving as a barrier shielding cough receptors within the respiratory epithelium from the tussive stimulus.

Pharmacodynamics

Guaifenesin is categorized as an expectorant that acts by enhancing the output of phlegm (sputum) and bronchial secretions via decreasing the adhesiveness and surface tension of such material. Furthermore, guaifenesin elicits an increased flow of less viscous gastric secretions that subsequently promote ciliary action - all actions that ultimately change dry, unproductive coughing to coughs that are more productive and less frequent. Essentially, by decreasing the viscosity and adhesiveness of such secretions, guaifenesin enhances the efficacy of mucociliary activity in removing accumulated secretions from the upper and lower airway.

Mechanism of action

Solar lentigines and related hyperpigmented lesions are localized, pigmented, macular lesions of the skin, usually on the areas of the body which have been chronically exposed to sunlight. These lesions are characterized by increased numbers of active melanocytes and increased melanin production. Although the mechanism of action of mequinol is not fully elucidated, when employed as an active ingredient in combination with other agents like tretinoin in skin depigmentation products, a synergy between a number of potential mechanisms is proposed. Firstly, mequinol is in fact considered a melanocytotoxic chemical which when oxidized in melanocytes results in the formation of toxic compounds like quinones. Such cytotoxic agents are subsequently capable of damaging and destroying pigment cells, which results in skin depigmentation of solar lentigines or other related hyperpigmented lesions. Nevertheless, skin cells are naturally capable of protecting themselves against such cytotoxic entities by endogenous intracellular glutathione (GSH). This protection is elicited through the enzymatic action of glutathione S-transferase (GST), which is responsible for the conjugation of agents toxic to glutathione. Conversely, tretinoin has been observed to serve as a potent inhibitor of mammalian GSTs and to be capable of reducing the level of intracellular GSH in various cells. As a result, the combination of mequinol with tretinoin seemingly allows for a synergistic enhancement of a melanocytotoxic effect that involves the inhibition and impairment of GSH and GST cytoprotection. Secondly, even though mequinol is a substrate for the enzyme tyrosinase and therefore acts as a competitive inhibitor of the formation of melanin precursors by way of tyrosinase facilitated reactions, the clinical significance of this action is unknown. We examined changes in the levels of chaperone proteins to evaluate the toxic effects of environmental chemicals in human cells in vitro. Some chaperones are up-regulated by estrogenic chemicals, but the effect is not necessarily dependent on the receptor. Thus we also investigated whether a chemical-induced change in chaperone protein expression is human estrogen receptor (hER)-dependent or not, using cultured human cell lines transfected with hERalpha cDNA or an empty vector. In the hERalpha-expressed cells, the protein levels of the heat shock protein 27 (HSP27), the glucose-regulated protein 78 (GRP78/BiP), and GRP94 increased after exposure to beta-estradiol (E(2)) (from 10(-9)M to 10(-6)M) and bisphenol A (BPA) (from 10(-6)M to 10(-5)M). On the other hand, the increase was not observed in the cells without hERalpha expression. These results suggest that the E(2)- and BPA-induced increase in the protein levels were hERalpha dependent. We next examined the effect of four phenolic chemicals similar in structure to BPA, and found that among them, 4-methoxyphenol (from 10(-6)M to 10(-5)M) increased the levels of the chaperone proteins with hERalpha dependency. Thus the human cultured cells would be suitable for evaluating whether an increase in chaperone proteins occurs upon exposure to environmental chemicals and whether the effect is ER-dependent. Many of the well-known depigmenting agents such as hydroquinone and 4-hydroxyanisole are, in fact, melanocytotoxic chemicals which are oxidized in melanocytes to produce highly toxic compounds such as quinones. These cytotoxic compounds are responsible for the destruction of pigment cells, which results in skin depigmentation. However, cells are capable of protecting themselves against cytotoxic agents by intracellular glutathione (GSH). This protection takes place under the enzymatic action of the detoxification enzyme glutathione S-transferase (GST), which is responsible for the conjugation of toxic species to GSH. The depigmenting effect of hydroquinone is shown to be potentiated by buthionine sulfoximine (BSO) and cystamine as the result of the reduction of intracel

Pharmacodynamics

Mequinol is in fact considered a melanocytotoxic chemical which when oxidized in melanocytes results in the formation of toxic entities like quinones. Such cytotoxic compounds subsequently have the potential to damage and destroy pigment cells, therefore causing skin depigmentation. In response, skin cells are naturally capable of protecting themselves against such cytotoxic agents with the help of endogenous intracellular glutathione and the detoxification action of glutathione S-transferase on the cytotoxic compounds. Regardless, it is consequently by way of this seemingly negative and damaging pharmacodynamic profile by which the mechanism of action of mequinol is sometimes described.

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.