Freshburst Listerine

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

• 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

• Topical treatment of fungal infections
• Preservative in food and pharmaceutical products
• Treatment of hyperammonemia (as part of a combination therapy)

Dosage

Children: Refer to specific product guidelines and clinical protocols for pediatric dosing information.

Adults: Refer to specific product guidelines and clinical protocols for dosing information.

Mechanism of action

Benzoic acid exerts its antimicrobial effects primarily by disrupting the integrity of microbial cell membranes, leading to cell lysis. It can also inhibit certain metabolic pathways in bacteria, such as the conversion of pyruvate to acetyl-CoA, thereby limiting energy production in these organisms.

Pharmacodynamics

Benzoic acid demonstrates a concentration-dependent antibacterial and antifungal activity. The efficacy of benzoic acid is influenced by the pH of the environment; it is more effective in acidic conditions. The compound acts on a broad spectrum of microorganisms, including some bacteria and fungi, making it a useful preservative and therapeutic agent.

Pharmacokinetics

Benzoic acid is absorbed through the gastrointestinal tract when ingested and can be metabolized in the liver. It is primarily excreted in the urine as hippuric acid after conjugation with glycine. The half-life of benzoic acid varies but is generally around 1 to 2 hours. Its distribution in the body is rapid, with a volume of distribution that suggests extensive tissue binding.

Adverse effects

• Allergic reactions
• Skin irritation
• Nausea
• Vomiting
• Headache

Precautions

• Use with caution in individuals with known hypersensitivity to benzoates
• Monitor for signs of hypersensitivity reactions

Pregnancy

The safety of benzoic acid during pregnancy has not been established. Use only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

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

Storage

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

Formulations

• Topical creams
• Ointments
• Solutions

Indications

• Respiratory conditions such as bronchitis
• Cough relief
• Topical antiseptic applications
• Oral hygiene products for breath freshening

Dosage

Children: Refer to the BNF for Children for specific dosage recommendations based on age and weight.

Adults: Refer to the BNF for specific dosage recommendations based on formulation and intended use.

Mechanism of action

Eucalyptol exhibits its effects through several pathways, primarily by influencing the inflammatory response and acting as a mucolytic agent. It can enhance mucosal secretions, aiding in the clearance of mucus in the respiratory tract. Additionally, eucalyptol may exert antimicrobial effects against certain pathogens, contributing to its use in respiratory formulations.

Pharmacodynamics

Eucalyptol shows anti-inflammatory and analgesic effects, which can help alleviate symptoms associated with respiratory conditions. It has been reported to act as a bronchodilator, facilitating easier breathing by relaxing the airways. The compound may also exhibit mild analgesic properties, making it useful in topical applications for pain relief.

Pharmacokinetics

Eucalyptol is rapidly absorbed following administration, with peak plasma concentrations occurring within a short time frame. It is metabolized primarily in the liver, and its elimination half-life is relatively short. The compound is excreted mainly through urine, with some unmetabolized eucalyptol and its metabolites detectable in urine following administration.

Pregnancy

Eucalyptol is not recommended during pregnancy due to insufficient safety data.

Breast-feeding

Use with caution; the effects on breastfeeding infants are not well studied.

Storage

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

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

• Wound healing
• Skin ulceration
• Burns
• Psoriasis
• Dermatitis

Dosage

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

Adults: Refer to the BNF for specific formulations and dosing guidelines, as dosages may vary based on the condition being treated and the formulation used.

Mechanism of action

While there is no well-controlled data to formally substantiate the method of action, ongoing studies suggest that allantoin may induce a histological wound healing profile in animal models, leading to improved reestablishment of normal skin. This includes increased vasodilation, inflammatory cell presence, angiogenesis, fibroblast proliferation, and collagen deposition in treated wounds compared to untreated ones.

Pharmacodynamics

There is limited controlled data regarding the pharmacodynamic properties of allantoin. However, studies indicate that allantoin may possess moisturizing and keratolytic effects, increasing the extracellular matrix's water content and enhancing the desquamation of dead skin cells. These activities can promote cell proliferation and facilitate wound healing.

Pharmacokinetics

Specific pharmacokinetic data for allantoin in humans is limited. However, it is known to be applied topically, which suggests local absorption at the site of application. Systemic absorption is considered minimal due to its low molecular weight and hydrophilicity.

Pregnancy

There is limited data on the safety of allantoin in pregnancy. It is advisable to consult a healthcare professional before use.

Breast-feeding

Allantoin is generally considered safe during breastfeeding, but caution is recommended. Consult a healthcare professional before use.

Storage

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

Formulations

• Topical cream
• Gel
• Ointment

Indications

• Topical analgesic for minor aches and pains
• Cough and cold preparations to relieve nasal congestion
• Irritation relief in conditions such as pruritus

Dosage

Children: Refer to the BNF for Children for appropriate dosing based on age and weight.

Adults: Refer to the specific product guidelines for topical application; dosing may vary based on formulation.

Mechanism of action

Menthol primarily activates the cold-sensitive TRPM8 receptors in the skin. Upon topical application, it induces a sensation of coolness by stimulating 'cold' receptors and inhibiting calcium currents in neuronal membranes. Additionally, it may exert analgesic effects through kappa-opioid receptor agonism.

Pharmacodynamics

Menthol, as a covalent organic compound, produces a cooling sensation upon various routes of administration, including inhalation, oral ingestion, or topical application. This occurs through stimulation of cold-sensitive receptors, creating a sensory effect without an actual decrease in skin temperature.

Pharmacokinetics

L-menthol is absorbed through the skin when applied topically, and its effects can be felt rapidly. The exact pharmacokinetic parameters such as absorption rate, distribution, metabolism, and elimination are not extensively detailed in the available literature.

Adverse effects

• Skin irritation
• Allergic reactions
• Burning sensation at the application site

Precautions

• Avoid contact with eyes
• Do not apply to broken or irritated skin
• Use with caution in individuals with sensitive skin

Pregnancy

Limited data is available on the safety of menthol during pregnancy. Use only if clearly needed and prescribed by a healthcare professional.

Breast-feeding

Menthol is generally considered safe in small amounts during breastfeeding, but it is advisable to consult a healthcare professional.

Storage

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

Formulations

• Topical ointments
• Creams
• Gels
• Liquid preparations

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

• Allergic conditions
• Autoimmune diseases
• Asthma and chronic obstructive pulmonary disease (COPD)
• Certain cancers (e.g., leukemia, lymphoma)
• Skin conditions (e.g., dermatitis)
• Inflammatory bowel disease
• Multiple sclerosis exacerbations
• Severe infections requiring immunosuppression

Dosage

Children: Refer to BNF for Children for specific dosing; doses vary significantly based on the child's age, weight, and condition being treated.

Adults: Refer to BNF for specific dosing; typically, initial doses range from 4 to 48 mg depending on the severity of the condition.

Mechanism of action

Methylprednisolone exerts its effects by binding to glucocorticoid receptors, leading to the modulation of gene expression. This interaction influences the transcription of anti-inflammatory proteins while suppressing the expression of pro-inflammatory genes, ultimately resulting in reduced inflammation and immune response.

Pharmacodynamics

The pharmacodynamic effects of methylprednisolone are characterized by its ability to decrease inflammation, suppress the immune response, and affect carbohydrate metabolism. Therapeutic doses lead to various systemic effects, including modification of leukocyte distribution and inhibition of cytokine production.

Pharmacokinetics

Methylprednisolone is well absorbed after oral administration, with a bioavailability of approximately 50%. It has a volume of distribution that reflects extensive tissue binding. The drug is metabolized primarily in the liver through conjugation and reduction, and its metabolites are excreted in urine. The half-life varies based on the route of administration but is generally around 18 to 36 hours.

Adverse effects

• Increased blood pressure
• Hyperglycemia
• Weight gain
• Mood changes
• Insomnia
• Gastrointestinal disturbances
• Increased susceptibility to infections

Interactions

• methylphenidate+apraclonidine: Severe (decreases effects)
• methylthioninium chloride+bupropion: Severe (increases risk of severe hypertension)
• methylphenidate+linezolid: Severe (increases risk of elevated blood pressure)
• rasagiline+methylphenidate: Severe (increases risk of a hypertensive crisis)
• mao-inhibitors+methylphenidate: Severe (increases risk of a hypertensive crisis)
• dronedarone+methylprednisolone: Moderate (increases exposure)
• miconazole+methylprednisolone: Moderate (increases concentration)
• antifungals, azoles+methylprednisolone: Moderate (increases exposure)
• crizotinib+methylprednisolone: Moderate (increases exposure)

Precautions

• Use with caution in patients with hypertension
• Monitor blood glucose levels in diabetic patients
• Consider potential for infection risk due to immunosuppression
• Evaluate for psychiatric effects in susceptible individuals

Pregnancy

Corticosteroids may be used during pregnancy if the potential benefit justifies the risk to the fetus. Careful monitoring is advised.

Breast-feeding

Corticosteroids are excreted in breast milk; caution is advised. Monitor the infant for potential effects.

Storage

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

Formulations

• Tablets
• Injectable solutions
• Topical preparations

Mechanism of action

Methylsulphate functions as a methylating agent, transferring a methyl group to nucleophiles. This process involves the formation of a sulfonium ion, which is highly reactive and can readily react with nucleophilic sites on various substrates, leading to methylation reactions.

Pharmacodynamics

The pharmacodynamics of methylsulphate is primarily related to its role as a methylating agent in biochemical reactions. It can alter the structure and function of biological molecules, potentially affecting cellular processes and signaling pathways. However, detailed pharmacodynamic studies specific to therapeutic use are limited.

Pharmacokinetics

There is limited information on the pharmacokinetics of methylsulphate, given its typical use as a reagent in laboratory settings rather than a clinical drug. When used in chemical reactions, its reactivity and transformation into other compounds would dictate its pharmacokinetic profile, which could vary significantly based on the specific context of use.

Pregnancy

There is limited data on the use of methylsulphate in pregnancy. Consult relevant guidelines.

Breast-feeding

Data on the excretion of methylsulphate in human milk is not available. Caution is advised.

Storage

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

Indications

• Oral hygiene
• Halitosis (bad breath)
• Gingivitis
• Plaque control
• Postoperative oral care

Dosage

Children: Refer to BNF for Children for specific pediatric dosing recommendations.

Adults: Use as directed on the product label. Usually involves rinsing with 15-30 ml for 30 seconds to 1 minute, typically twice daily.

Mechanism of action

The exact mechanism of action of mouthwash is not fully understood, but it is attributed to the denaturing of lipoprotein complexes and possibly other actions. Evidence suggests that the major site of action may be the cell membrane, where agents can alter permeability, allowing the escape of enzymes, coenzymes, and metabolic intermediates. Additionally, cationic surfactants found in mouthwash can emulsify sebaceous material, facilitating the removal of dirt and bacteria. The mild desquamating effect of quaternary ammonium compounds in mouthwash aids in cleaning the oral cavity.

Pharmacodynamics

Mouthwash works by reducing the microbial load in the oral cavity and promoting a healthier environment. It can help to control plaque formation, reduce gingivitis, and provide symptomatic relief from oral conditions. The antibacterial properties of quaternary ammonium compounds contribute to the overall effectiveness in maintaining oral hygiene.

Pharmacokinetics

Mouthwash is typically used topically in the oral cavity, and its pharmacokinetics may vary based on the specific formulation. Generally, the active ingredients exert their effects locally, with minimal systemic absorption. The duration of action can depend on the formulation, frequency of use, and individual oral hygiene practices.

Pregnancy

There is limited data on the use of mouthwash during pregnancy. Consult a healthcare professional before use.

Breast-feeding

Consult a healthcare professional before use during breastfeeding, as safety has not been established.

Storage

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

Formulations

• Liquid mouthwash
• Concentrated mouthwash

Indications

• Topical drug delivery
• Emulsifying agent in pharmaceutical formulations
• Stabilizing agent in aqueous solutions
• Controlled drug release systems

Dosage

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

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

Mechanism of action

Poloxamer acts primarily by reducing the surface tension at the interface between different phases, such as oil and water. This property allows it to stabilize emulsions and improve the solubility of poorly soluble drugs. Additionally, poloxamer can form micelles in solution, encapsulating hydrophobic drugs and facilitating their delivery in the body.

Pharmacodynamics

Poloxamer exhibits surfactant properties that can enhance drug absorption and bioavailability by altering the permeability of biological membranes. Its action as a solubilizing agent can improve the pharmacological effects of drugs by ensuring they remain in a bioavailable form longer. The polymeric nature of poloxamer can also lead to sustained release of encapsulated drugs, prolonging their therapeutic effect.

Pharmacokinetics

Poloxamer is poorly absorbed when administered orally and is primarily excreted unchanged in the feces. Its absorption through the skin is minimal, making it more suitable for topical applications. The pharmacokinetics can vary based on the formulation and route of administration, with its action typically being localized rather than systemic.

Adverse effects

• Skin irritation
• Allergic reactions
• Gastrointestinal disturbances
• Headache

Precautions

• Use with caution in patients with known allergies to surfactants
• Assess for skin sensitivity before use
• Monitor for adverse reactions during therapy

Pregnancy

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

Breast-feeding

It is not known whether poloxamer is excreted in human milk. Caution is advised when administering to nursing mothers.

Storage

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

Formulations

• Poloxamer 188 (used as a surfactant in various formulations)
• Poloxamer 407 (used in pharmaceutical formulations and drug delivery systems)

Dosage

Children: Refer to specific drug formulations and product labels as purified substances can vary widely in their use and dosing.

Adults: Refer to specific drug formulations and product labels as purified substances can vary widely in their use and dosing.

Mechanism of action

The mechanism of action for purified compounds varies widely depending on the specific substance. Generally, purified drugs exert their effects by interacting with specific biological targets, such as receptors, enzymes, or ion channels, leading to a desired therapeutic effect. This interaction can involve binding to receptors to activate or inhibit signaling pathways, modulating enzymatic activity, or altering physiological processes.

Pharmacodynamics

Pharmacodynamics describes the effects of a drug on the body and the relationship between drug concentration and effect. For purified drugs, this can involve dose-response relationships and the time course of their action. The purified form often enhances potency and reduces variability in response among patients, which can lead to more predictable therapeutic outcomes. The overall effect is determined by the drug's affinity for its target, the efficacy of the drug-receptor interaction, and the downstream signaling pathways activated as a result of this interaction.

Pharmacokinetics

Pharmacokinetics involves the absorption, distribution, metabolism, and excretion (ADME) of a drug. For purified substances, absorption can be more efficient due to the absence of impurities that may affect solubility or stability. Distribution may also be enhanced, leading to higher bioavailability. Metabolism can be influenced by the structure of the purified compound, as it may be metabolized more readily by liver enzymes. Excretion typically occurs through the kidneys or liver, depending on the molecular characteristics of the purified drug.

Pregnancy

Consult with a healthcare professional, as the safety of purified forms of medications during pregnancy may vary depending on the specific substance.

Breast-feeding

Consult with a healthcare professional, as the safety of purified forms of medications during breastfeeding may vary depending on the specific substance.

Storage

Store in a cool, dry place, away from light and moisture, and keep out of reach of children.

Indications

• Adjunct in weight management
• Sugar substitute for diabetics
• Flavoring agent in various food products

Dosage

Children: Refer to the BNF for Children for specific pediatric dosing guidance. Saccharin is often used in pediatric populations as a sugar substitute but should be administered with caution and within recommended limits.

Adults: As saccharin is used as a sweetener rather than a medication, specific dosing guidelines are not typically established. The acceptable daily intake (ADI) is generally considered to be safe within the limits set by health authorities.

Mechanism of action

Saccharin activates specific T2R bitter taste receptors, which are involved in the perception of taste. Additionally, it has been shown to stimulate transient receptor potential vanilloid-1 (TRPV1) receptors, which are present in taste receptor cells and nerve terminals throughout the oral cavity. This activation may contribute to the bitter aftertaste and metallic taste sensations associated with saccharin and similar sweeteners.

Pharmacodynamics

Saccharin's primary pharmacodynamic effect is its intense sweetness, which is mediated through the activation of taste receptors. The stimulation of T2R receptors and TRPV1 channels can lead to varying taste sensations, including sweetness and bitterness. The sweet taste perception occurs through the activation of taste receptor cells that signal through gustatory pathways to the brain, allowing for the recognition of sweet flavors.

Pharmacokinetics

Saccharin is rapidly absorbed from the gastrointestinal tract and is excreted unchanged in urine. It does not undergo significant metabolism, which contributes to its safety profile as a non-caloric sweetener. The elimination half-life and pharmacokinetic parameters are not typically documented due to its minimal systemic effects in the context of sweetening agents.

Adverse effects

• Gastrointestinal disturbances
• Allergic reactions
• Headaches
• Metallic taste

Precautions

• Use with caution in patients with a history of hypersensitivity to sweeteners
• Consider potential for allergic reactions

Pregnancy

Safety during pregnancy has not been established. Use with caution and consult healthcare professionals.

Breast-feeding

Safety during breastfeeding has not been established. Consult healthcare professionals before use.

Storage

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

Formulations

• Tablets
• Powder

Indications

• Pain relief
• Fever reduction
• Inflammatory conditions such as arthritis
• Prevention of cardiovascular events in certain populations

Dosage

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

Adults: Refer to the BNF for specific dosing guidelines.

Mechanism of action

Salicylate works by inhibiting the enzyme cyclooxygenase (COX), which is involved in the synthesis of prostaglandins. Prostaglandins are lipid compounds that mediate inflammation, pain, and fever. By decreasing the production of these compounds, salicylate effectively reduces inflammation and provides analgesic and antipyretic effects.

Pharmacodynamics

The pharmacodynamic effects of salicylate include analgesia, antipyresis, and anti-inflammatory action. It reduces the sensitivity of pain receptors and inhibits the generation of pain signals. The antipyretic effect is achieved through action on the hypothalamus, leading to peripheral vasodilation and sweating, thereby reducing body temperature. The drug also modulates the immune response, contributing to its anti-inflammatory properties.

Pharmacokinetics

Salicylate is rapidly absorbed from the gastrointestinal tract following oral administration. Peak plasma concentrations are typically reached within 1 to 2 hours. It is extensively metabolized in the liver, primarily through conjugation, and its metabolites are excreted in the urine. The elimination half-life of salicylate varies depending on the dose and the presence of other medications, averaging around 2 to 3 hours at low doses, but can be prolonged at higher doses due to saturation of metabolic pathways.

Contra-indications

• Hypersensitivity to salicylates
• Active peptic ulcer disease
• Severe hepatic impairment
• Severe renal impairment
• Bleeding disorders
• Children with viral infections (due to risk of Reye's syndrome)

Adverse effects

• Gastrointestinal irritation
• Nausea
• Vomiting
• Tinnitus
• Hearing loss
• Allergic reactions
• Rash
• Asthma exacerbation
• Gastric ulceration

Interactions

• Anticoagulants (increased bleeding risk)
• Methotrexate (increased toxicity)
• NSAIDs (increased gastrointestinal side effects)
• Diuretics (reduced efficacy)
• Alcohol (increased risk of gastrointestinal bleeding)

Precautions

• Use with caution in patients with a history of gastrointestinal disease
• Monitor renal function in long-term use
• Caution in patients with asthma or allergies
• Consider alternative therapy in children with viral infections

Pregnancy

Use with caution during pregnancy, particularly in the third trimester, as it may affect fetal development.

Breast-feeding

Salicylate is excreted in breast milk; caution is advised when administering to breastfeeding mothers.

Storage

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

Formulations

• Tablets
• Oral suspension
• Topical preparations
• Suppositories

Indications

• Constipation
• Diagnostic aid in colonoscopy preparation
• Management of hyperosmolality in various conditions

Dosage

Children: For children, the dosage should be determined based on age and condition, and it is advised to refer to the BNF for Children for specific dosing guidelines.

Adults: The typical dose for adults is 30 to 150 mL of sorbitol solution (70%) taken orally, as needed, usually before bedtime.

Mechanism of action

Sorbitol exerts its laxative effect by drawing water into the large intestine, thereby stimulating bowel movements. It acts as a hygroscopic agent, pulling water from tissues into the feces, which reflexively stimulates evacuation. In metabolic pathways, sorbitol is produced from glucose via aldose reductase and is converted to fructose by sorbitol dehydrogenase, with implications in diabetic complications such as retinopathy.

Pharmacodynamics

Sorbitol's laxative effect results from its osmotic properties, which increase the water content of the stool and soften it, facilitating easier passage. Additionally, sorbitol can induce apoptosis in certain cancer cell lines, indicating potential therapeutic implications beyond its laxative use. The modulation of intracellular signaling pathways through the regulation of proteins such as Bax and Bcl-2 suggests a complex role in cellular health and disease.

Pharmacokinetics

Sorbitol is poorly absorbed in the gastrointestinal tract, which contributes to its efficacy as a laxative. It is metabolized in the liver, primarily through the polyol pathway. The absorption and distribution of sorbitol are affected by its osmotic properties, leading to increased intestinal water retention. Its elimination is primarily via renal excretion, with minimal systemic absorption, thus reducing the risk of systemic side effects.

Adverse effects

• Diarrhea
• Abdominal cramps
• Nausea
• Vomiting
• Electrolyte imbalances

Precautions

• Use with caution in patients with renal impairment
• May exacerbate gastrointestinal conditions

Pregnancy

Sorbitol is generally considered safe during pregnancy, but should be used under medical supervision.

Breast-feeding

Sorbitol is excreted in breast milk in small amounts; consult a healthcare provider before use.

Storage

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

Formulations

• Oral solution
• Syrup

Indications

• Anxiety
• Pain relief
• Inflammation
• Antimicrobial activity
• Sleep disorders
• Mood enhancement

Dosage

Children: Refer to specific product guidelines for accurate dosing information, as pediatric dosages are not well established for terpenes.

Adults: Dosage varies widely based on the specific terpene and method of administration. Refer to specific product guidelines for accurate dosing information.

Mechanism of action

Terpenes exert their effects primarily through interactions with various biochemical pathways in the body. They can modulate the endocannabinoid system, interact with serotonin receptors, and influence ion channels, such as TRP channels. This modulation can lead to effects on mood, pain perception, and inflammation. Specific terpenes may also work synergistically with cannabinoids to enhance therapeutic effects.

Pharmacodynamics

The pharmacodynamics of terpenes vary widely depending on the specific compound. Generally, terpenes may enhance the therapeutic effects of other compounds through synergy, alter neurotransmitter levels, and modulate receptor activity. Research has shown that certain terpenes can exhibit anxiolytic, analgesic, and anti-inflammatory effects, contributing to their potential use in treating various conditions. Their ability to cross the blood-brain barrier also allows them to affect central nervous system functions.

Pharmacokinetics

Terpenes are typically absorbed through various routes, including inhalation, dermal application, and oral ingestion. Once absorbed, they are metabolized primarily in the liver, although some terpenes may undergo metabolic conversion in other tissues. The elimination half-life of terpenes can vary significantly based on the specific compound, the route of administration, and individual metabolic factors. Terpenes are usually excreted in urine and feces, and their bioavailability can be influenced by factors such as formulation and presence of other compounds.

Adverse effects

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

Precautions

• Use with caution in patients with known allergies to plants or essential oils.
• Consider potential for skin irritation when using topically.
• May interact with certain medications, consult with a healthcare professional.

Pregnancy

Safety during pregnancy has not been established; use with caution and consult a healthcare professional.

Breast-feeding

Safety during breastfeeding has not been established; use with caution and consult a healthcare professional.

Storage

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

Formulations

• Essential oils
• Extracts
• Capsules
• Tinctures

Indications

• Immunological disorders
• Infections (bacterial and fungal)
• Inflammatory conditions

Dosage

Children: Refer to BNF for Children for specific dosages pertinent to paediatric patients.

Adults: Refer to BNF for specific dosages, as they can vary based on indication and formulation.

Mechanism of action

Thymol modulates macrophage activity by enhancing phagocytosis and increasing the proliferation of splenocytes, acting as a mitogen. It improves macrophage uptake capacity through increased membrane fluidity and enhances lysosomal activity. Thymol also stimulates the respiratory burst in macrophages, leading to increased generation of superoxide anions. Additionally, it shows anti-inflammatory effects by decreasing the secretion of pro-inflammatory cytokines such as TNF-alpha, IL-1beta, and PGE(2).

Pharmacodynamics

Thymol exhibits various pharmacodynamic effects including antimicrobial, antifungal, and immunomodulatory activities. Its ability to enhance macrophage function suggests a role in boosting the immune response, potentially benefiting conditions characterized by immune dysfunction. The compound also demonstrates antioxidant properties, contributing to its anti-inflammatory effects.

Pharmacokinetics

The pharmacokinetic profile of thymol is not fully characterized; however, it is known to be readily absorbed and distributed in the body due to its lipophilic nature. Metabolism occurs in the liver, with excretion primarily through the urine. The exact half-life and elimination pathways require further investigation to provide a comprehensive overview.

Pregnancy

There is insufficient data on the use of thymol during pregnancy. Caution is advised.

Breast-feeding

Limited information is available regarding the excretion of thymol in human milk. Caution is recommended.

Storage

Store in a cool, dry place away from light. 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

There is no well controlled data that can formally substantiate the method of action. However, ongoing studies suggest that there may exist a histological wound healing profile induced by allantoin in rats that leads to the amelioration and fastening of the reestablishment of normal skin. This facilitation of wound healing is supported by observations that wounds inflicted to rat subjects to which topical allantoin preparations were applied histologically demonstrated increased vasodilation, presence of inflammatory exudates, number of inflammatory cells, angiogenesis, fibroblast proliferation, and increased collagen deposition when compared to rat subjects with wounds that did not receive any allantoin administration.

Pharmacodynamics

There is no well controlled and appropriate data that can formally substantiate the pharmacodynamic properties of allantoin. Nevertheless, ongoing studies suggest that allantoin possesses moisturizing and keratolytic effects, as well as abilities to increase the water content of the extracellular matrix and enhance the desquamation of upper layers of dead skin cells, all of which are activities that can promote cell proliferation and facilitate wound healing.

Mechanism of action

Menthol primarily activates the cold-sensitive TRPM8 receptors in the skin. Menthol, after topical application, causes a feeling of coolness due to stimulation of 'cold' receptors by inhibiting Ca++ currents of neuronal membranes. It may also yield analgesic properties via kappa-opioid receptor agonism.

Pharmacodynamics

Menthol is a covalent organic compound made synthetically or obtained from peppermint or other mint oils. Menthol induces a cooling sensation on the skin upon inhalation, oral ingestion, or topical application by stimulating the cold-sensitive receptors expressed on the skin, without actually causing a drop in the skin temperature.

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

MODE OF ACTION ... NOT YET FULLY UNDERSTOOD BUT HAS BEEN ASCRIBED TO ... THE DENATURING OF LIPOPROTEIN COMPLEXES, & POSSIBLY OTHER ACTIONS. /QUATERNARY AMMONIUM COMPD/ EVIDENCE HAS BEEN PRESENTED THAT THE MAJOR SITE OF ACTION ... MAY BE THE CELL MEMBRANE, WHERE THE AGENTS MAY CAUSE CHANGES IN PERMEABILITY THAT PERMIT ESCAPE OF ENZYMES, COENZYMES, & METABOLIC INTERMEDIATES. /CATIONIC SURFACTANTS/ EMULSIFY SEBACEOUS MATERIAL, WHICH IS THEN REMOVED TOGETHER WITH DIRT & BACTERIA. THE MILD DESQUAMATING EFFECT OF THE QUATERNARY AMMONIUM COMPOUNDS AIDS IN CLEANING. /QUATERNARY AMMONIUM COMPD/

Mechanism of action

...it has been shown that the activation of particular T2R bitter taste receptors is partially involved with the bitter aftertaste sensation of saccharin and acesulfame-K. ... /This study/ addressed the question of whether /they/ could stimulate transient receptor potential vanilloid-1 (TRPV1) receptors, as these receptors are activated by a large range of structurally different chemicals. Moreover, TRPV1 receptors and/or their variants are found in taste receptor cells and in nerve terminals throughout the oral cavity. Hence, TRPV1 activation could be involved in the ... aftertaste or even contribute to the poorly understood metallic taste sensation. Using Ca(2+) imaging on TRPV1 receptors heterologously expressed in the human embryonic kidney (HEK) 293 cells and on dissociated primary sensory neurons,... /it was found/ that in both systems, .../sweeteners/ activate TRPV1 receptors, and, moreover, they sensitize these channels to acid and heat. ... /it was/also found that TRPV1 receptors were activated by CuSO(4), ZnSO(4), and FeSO(4), three salts known to produce a metallic taste sensation. In summary, .../the/ results identify a novel group of compounds that activate TRPV1 and, consequently, provide a molecular mechanism that may account for off tastes of sweeteners and metallic tasting salts.

Mechanism of action

Sorbitol exerts its laxative effect by drawing water into the large intestine, thereby stimulating bowel movements. ... Sorbitol exerts hygroscopic and/or local irritant action, drawing water from tissues into feces and reflexly stimulating evacuation. The polyol pathway consists of two enzymes aldose reductase (AR) and sorbitol dehydrogenase (SDH); the former is the first enzyme in the polyol pathway, that catalyzes the reduction of glucose to sorbitol, the latter is the second one, that converts sorbitol to fructose using by NAD(+) as a cofactor. ... SDH activity, the second step in the polyol pathway, might make a greater contribution to the etiology of diabetic retinopathy than does the first step involving AR. /This paper proposes/ a novel hypothesis that polymorphisms of SDH gene may be correlated with SDH gene expression levels in diabetic retinas, thus being a valuable genetic marker for diabetic retinopathy. It has been reported that sorbitol induces apoptosis in several cancer cell lines. ... In /this/ study, the intracellular signaling pathways of sorbitol-induced apoptosis in human K562 cells were investigated using both morphological analysis and DNA fragmentation technique. In this study, we demonstrated that sorbitol-induced apoptosis in human K562 cells is a concentration- and time-dependent manner. This sorbitol-induced apoptosis in human K562 cells was also accompanied by the up-regulation of Bax, and down-regulation of p-Bcl-2, but no effect on the levels of Bcl-X(L). Moreover, the sorbitol treatment resulted in a significant reduction of mitochondria membrane potential, increase in the release of mitochondrial cytochrome c (cyt c), and activation of caspase 3. Furthermore, treatment with caspase 3 inhibitor (z-DEVD-fmk) was capable of preventing the sorbitol-induced caspase 3 activity and cell death. These results clearly demonstrate that the induction of apoptosis by sorbitol involves multiple cellular/molecular pathways and strongly suggest that pro- and anti-apoptotic Bcl-2 family proteins, mitochondrial membrane potential, mitochondrial cyt c, and caspase 3, they all participate in sorbitol-induced apoptotic process in human K562 cells. Chronic diabetic complications, in particular, nephropathy, peripheral and autonomic neuropathy, "diabetic foot," retinopathy, and cardiovascular disease, remain the major cause of morbidity and mortality in patients with diabetes mellitus. Growing evidence indicates that both increased activity of the sorbitol pathway of glucose metabolism and enhanced oxidative stress are the leading factors in the pathogenesis of diabetic complications. The relation between the two mechanisms remains the area of controversy. One group has reported that increased sorbitol pathway activity has a protective rather than detrimental role in complication-prone tissues because the pathway detoxifies toxic lipid peroxidation products. Others put forward a so-called "unifying hypothesis" suggesting that activation of several major pathways implicated in diabetic complications (eg, sorbitol pathway) occurs due to increased production of superoxide anion radicals in mitochondria and resulting poly(ADP-ribose) polymerase activation. This review (a) presents findings supporting a key role for the sorbitol pathway in oxidative stress and oxidative stress-initiated downstream mechanisms of diabetic complications, and (b) summarizes experimental evidence against a detoxifying role of the sorbitol pathway, as well as the "unifying concept."

Mechanism of action

The potent role of thymol, a natural compound, in modulation of macrophage activity was evaluated by determining all the sequential steps involved during phagocytosis. We found a significant increase in the proliferation of splenocytes in the presence of thymol and it proved to be a good mitogen. Uptake capacity of macrophages was enhanced due to increased membrane fluidity after treatment with thymol and it also increases lysosomal activity of macrophages. Data of superoxide anion generation revealed the involvement of thymol in the generation of respiratory burst as it potentiated this property of macrophages at a concentration of 150 uM. In the case of TNF-a, IL-1beta and PGE(2) a decreased level of secretion was observed 154 pg/mL, 736.1 pg/mL, and 151 pg/mL respectively when compared with lipopolysaccharide treated cells, where the level of these cytokines was significantly high. We also determined the anti-complementary activity of thymol which showed to be more effective than rosmarinic acid. Thus, the results obtained from the study suggest the potential role of thymol as a natural immunostimulatory drug which can be used in the treatment of various immunological disorders.