Pine Tar 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

• Nitrogen supplementation in clinical nutrition
• Management of metabolic alkalosis
• Treatment of certain types of kidney disorders

Dosage

Children: Specific pediatric dosing information is not detailed in the BNF. Refer to the BNF for Children for appropriate dosing based on age and condition.

Adults: Dosage varies based on clinical indication and should be guided by specific treatment protocols. Refer to clinical guidelines for detailed dosing information.

Mechanism of action

Ammonium ions participate in various metabolic pathways, including the biosynthesis of amino acids and nucleotides. It serves as a nitrogen source for organisms, facilitating the synthesis of essential biomolecules. The presence of ammonium can influence pH levels and osmotic balance within cells, thereby affecting cellular functions and enzyme activities.

Pharmacodynamics

Ammonium affects cellular metabolism by acting as a nitrogen donor in the synthesis of organic compounds. Its role in the nitrogen cycle and as a substrate in biochemical pathways allows for the maintenance of cellular functions, including energy production and cellular growth. Alterations in ammonium levels can influence various physiological processes, including neurotransmitter synthesis and energy metabolism.

Pharmacokinetics

Ammonium is readily absorbed and distributed in biological systems. It can be produced endogenously through amino acid metabolism or obtained from dietary sources. The excretion of ammonium primarily occurs through the kidneys, where it is converted to urea for elimination. Ammonium levels are regulated by various mechanisms, including the action of renal tubular cells that either secrete or reabsorb ammonium based on the body's needs.

Indications

• Cough associated with respiratory tract infections
• Acid-base disorders
• Edema management

Dosage

Children: Refer to the BNF for Children for appropriate paediatric dosing guidelines based on age and condition.

Adults: Refer to the BNF for specific adult dosing guidelines as they depend on the indication and clinical context.

Mechanism of action

Ammonium chloride increases acidity by raising hydrogen ion concentrations. It dissociates into ammonium and chloride ions; the ammonium is converted to urea in the liver, releasing hydrogen ions that lower pH. The chloride ions displace bicarbonate in extracellular fluid, leading to acidosis and increased renal excretion of electrolytes and water, resulting in fluid mobilization.

Pharmacodynamics

Ammonium chloride acts as a systemic acidifier, facilitating the excretion of chloride and sodium, while also increasing the acidity of body fluids. The conversion of ammonium to urea in the liver with the release of hydrogen ions contributes to a decrease in blood pH, affecting acid-base balance in the body.

Pharmacokinetics

Ammonium chloride is absorbed from the gastrointestinal tract and metabolized in the liver, where it is converted to urea. The dissociated ions impact renal function, leading to increased excretion of sodium, potassium, and water. The elimination half-life and specific metabolism details are not explicitly defined.

Adverse effects

• Nausea
• Vomiting
• Abdominal pain
• Diarrhea
• Dizziness
• Headache

Interactions

• Antacids may reduce the effectiveness of ammonium chloride
• Potassium-sparing diuretics may increase the risk of hyperkalemia

Precautions

• Use with caution in patients with renal impairment
• Monitor electrolyte levels during prolonged therapy
• Consider potential for acidosis in patients with liver disease

Pregnancy

Ammonium chloride should only be used during pregnancy if the potential benefit justifies the potential risk to the fetus. Consult a healthcare provider for individualized advice.

Breast-feeding

Ammonium chloride is excreted in breast milk. Use caution and consult a healthcare provider if breastfeeding.

Storage

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

Formulations

• Oral solution
• Powder for oral solution

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: Chloroform is not indicated for pediatric use due to safety concerns and potential for toxicity. Refer to specific clinical guidelines for any related interventions or alternative agents.

Adults: Chloroform is not commonly used in clinical practice today and specific dosing recommendations should be referred to in relevant clinical guidelines or literature. It is important to note that due to its toxicity, chloroform usage is highly restricted.

Mechanism of action

Chloroform undergoes bioactivation primarily through covalent binding to lipids and proteins, particularly under anaerobic conditions with the presence of NADPH. This process is linked to the inhibition of cytochrome P450 and related mono-oxygenases, with biotransformation being mediated by phenobarbital-inducible P450 isozymes. The resultant oxidation products impair the monooxygenase system, potentially leading to protein aggregation.

Pharmacodynamics

Chloroform has a depressant effect on the central nervous system, leading to sedation and anesthesia at sufficient exposure levels. Its effect on cytochrome P450 enzymes suggests a mechanism that can alter drug metabolism and pharmacokinetics of concurrently administered medications, potentially leading to toxic accumulation or therapeutic failure.

Pharmacokinetics

Chloroform is rapidly absorbed through inhalation and dermal exposure, with distribution throughout the body, including the liver and brain. It is metabolized primarily in the liver via the cytochrome P450 system, leading to the formation of reactive intermediates. Chloroform and its metabolites are eliminated through exhalation and renal excretion, but the potential for accumulation and toxicity remains a concern.

Pregnancy

Chloroform is not recommended for use during pregnancy due to potential risks to fetal development.

Breast-feeding

Chloroform is not recommended during breastfeeding as it may be excreted in breast milk and could pose risks to the infant.

Storage

Store in a cool, dry place away from light, in a tightly sealed container.

Indications

• Acidulant in food and beverages
• Preservative in pharmaceutical formulations
• pH adjuster in various chemical preparations

Dosage

Children: Refer to product-specific guidelines for appropriate dosing based on formulation and indication.

Adults: Refer to product-specific guidelines for appropriate dosing based on formulation and indication.

Mechanism of action

Citric acid acts by chelating metal ions, which can enhance the solubility of certain compounds and improve their bioavailability. It also contributes to the acidity of the environment, which can influence enzymatic activity and metabolic pathways, particularly in the degradation of citronellol.

Pharmacodynamics

Citric acid exhibits mild pharmacological effects primarily attributed to its role in metabolic processes. It aids in the regulation of pH levels, which can impact enzymatic reactions and biochemical pathways. The acid's chelating properties may help to reduce the toxicity of certain metal ions in biological systems.

Pharmacokinetics

Citric acid is rapidly absorbed after oral administration and is metabolized in the liver. It undergoes conversion to various metabolites in the citric acid cycle, contributing to energy production. The elimination primarily occurs through urine, with minimal accumulation in the body.

Pregnancy

Citric acid is generally regarded as safe during pregnancy when used in food amounts. However, consult a healthcare provider for advice on medicinal use.

Breast-feeding

Citric acid is considered safe during breastfeeding when consumed in food amounts. For medicinal use, consult a healthcare provider.

Storage

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

Mechanism of action

The precise mechanism of action is not well-documented in the provided resources. However, compounds with similar molecular structures often interact with biological pathways through modulation of neurotransmitter systems or receptor activity.

Pharmacodynamics

Pharmacodynamics for compounds like Colour typically involve interactions at the cellular level, influencing physiological responses through receptor binding and modulation of signaling pathways. The specific effects and potency would depend on the context of use and formulation.

Pharmacokinetics

Information on the pharmacokinetics of Colour, including absorption, distribution, metabolism, and excretion, is not provided in the available resources. Generally, pharmacokinetic properties will vary significantly based on formulation and route of administration.

Pregnancy

Safety in pregnancy has not been established. Use only if the benefits outweigh the risks.

Breast-feeding

Caution is advised. There are no adequate studies in breastfeeding women.

Storage

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

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

• Allergic rhinitis
• Allergic conjunctivitis
• Urticaria

Mechanism of action

Diphenhydramine primarily functions by antagonizing H1 (Histamine 1) receptors located in various tissues, including the respiratory system, gastrointestinal tract, and central nervous system. By acting as an inverse agonist at H1 receptors, it mitigates the effects of histamine, thereby reducing allergic symptoms. As a first-generation antihistamine, it also crosses the blood-brain barrier, leading to sedative effects. Furthermore, diphenhydramine exhibits antimuscarinic activity by competitively antagonizing muscarinic acetylcholine receptors, contributing to its use in treating parkinsonian symptoms.

Pharmacodynamics

Diphenhydramine possesses anti-histaminic, anti-emetic, anti-vertigo, and sedative properties. Its antihistaminic action blocks the effects of histamine by competing for H1 receptor sites, preventing symptoms associated with histamine release. Its anti-emetic effects are due to inhibition at the medullary chemoreceptor trigger zone, while its anti-vertigo action arises from a central antimuscarinic effect on the vestibular apparatus and the vomiting center in the midbrain.

Pharmacokinetics

Diphenhydramine is well-absorbed following oral administration and reaches peak plasma concentrations within 1 to 2 hours. It is metabolized in the liver and has a half-life of approximately 4 to 8 hours, although this can vary based on individual factors. The drug is excreted primarily in the urine, with a significant portion eliminated as metabolites rather than unchanged drug. Due to its lipophilic nature, diphenhydramine readily crosses the blood-brain barrier, contributing to its sedative effects.

Contra-indications

• Severe asthma exacerbation
• Hypersensitivity to diphenhydramine or any of its components
• Newborns or premature infants

Adverse effects

• Drowsiness
• Dizziness
• Dry mouth
• Constipation
• Urinary retention
• Blurred vision
• Confusion

Interactions

• CNS depressants (e.g., alcohol, sedatives, tranquilizers) may enhance sedative effects
• MAO inhibitors can prolong and intensify anticholinergic effects

Precautions

• Use with caution in patients with glaucoma
• Prostatic hypertrophy
• Cardiovascular disease
• Elderly patients may be more sensitive to side effects

Pregnancy

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

Breast-feeding

Diphenhydramine is excreted in breast milk. Use caution when administering to nursing mothers.

Storage

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

Formulations

• Tablets
• Capsules
• Liquid formulations
• Topical preparations

Indications

• Aromatherapy
• Anxiety relief
• Mood enhancement
• Antimicrobial applications
• Pain management
• Anti-inflammatory treatments

Dosage

Children: Dosage for paediatric use of essences should be approached with caution and tailored to the child's age, weight, and condition. Refer to specific pediatric guidelines or consult a healthcare provider for appropriate dosing information.

Adults: Dosage for essences varies widely based on the specific type of essence and the intended use. It is essential to refer to specific guidelines or consult a healthcare provider for appropriate dosing information.

Mechanism of action

The mechanism of action of essences can vary depending on the specific substance in question. Generally, essential oils and herbal extracts act through a combination of phytochemical interactions, influencing neurotransmitter systems, modulating inflammation, and exhibiting antimicrobial properties. These compounds may interact with various receptors in the body, including G-protein coupled receptors and ion channels, leading to physiological responses.

Pharmacodynamics

Pharmacodynamics of essences is largely dependent on their chemical composition. Many essential oils contain terpenes, phenols, and other bioactive compounds that exhibit a range of effects such as antibacterial, antifungal, anti-inflammatory, and analgesic properties. The effects can vary based on concentration, route of administration, and individual patient factors, influencing their efficacy and safety.

Pharmacokinetics

The pharmacokinetics of essences involves absorption, distribution, metabolism, and excretion. Essential oils are typically absorbed through the skin or via inhalation and can be distributed throughout the body via the bloodstream. They are often metabolized by the liver, with various pathways leading to the formation of active or inactive metabolites. Excretion mostly occurs through urine, but some components may also be eliminated through bile or exhalation.

Pregnancy

The safety of essence during pregnancy has not been established. Consultation with a healthcare provider is recommended before use.

Breast-feeding

It is unclear whether essence is excreted in breast milk. Caution is advised, and it is best to consult a healthcare provider.

Storage

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

Indications

• Anxiety disorders
• Nausea and vomiting
• Allergic conditions
• Preoperative sedation
• Pruritus

Dosage

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

Adults: Refer to the BNF for specific dosing guidelines based on the indication and patient characteristics.

Mechanism of action

Hydroxyzine works by antagonizing the H1 histamine receptors, leading to a reduction in the effects of histamine in the body. This action helps alleviate symptoms of allergic reactions and promotes sedation. Additionally, it may exert effects on serotonin and adrenergic receptors, which could contribute to its anxiolytic properties. Hydroxyzine is also involved in various metabolic pathways, including selenium metabolism and the degradation of reactive oxygen species.

Pharmacodynamics

The pharmacodynamic effects of hydroxyzine include sedation, anxiolysis, and reduction of allergic symptoms. Its sedative effects can make it useful in managing anxiety and inducing sleep, while its antihistaminic properties help to relieve symptoms such as itching and rashes associated with allergic reactions. The onset of action is typically within 15 to 30 minutes when taken orally, with peak effects occurring within 1 to 2 hours.

Pharmacokinetics

Hydroxyzine is well absorbed from the gastrointestinal tract, with peak plasma concentrations occurring approximately 2 hours after oral administration. It is extensively metabolized in the liver, with metabolites, including cetirizine, possessing their own therapeutic effects. Hydroxyzine has a half-life of approximately 20 hours, allowing for once or twice daily dosing. It is primarily excreted in the urine, with less than 1% of the unchanged drug found in urine.

Interactions

• hydroxyzine+antiepileptics: Severe (increases risk of overheating and dehydration)
• hydroxyzine+zonisamide: Severe (increases risk of overheating and dehydration)
• hydroxychloroquine+penicillamine: Severe (increases risk of haematological toxicity)
• hydroxychloroquine+agalsidase alfa: Unknown (decreases effects)
• hydroxychloroquine+agalsidase beta: Unknown (decreases exposure)
• hydroxychloroquine+oral cholera vaccine: Unknown (decreases efficacy)
• live vaccines+hydroxy carbamide: Unknown (increases risk of generalised infection (possibly life-threatening))
• lanthanum+hydroxychloroquine: Unknown (decreases absorption)
• macrolides+hydroxychloroquine: Unknown (increases risk of serious cardiovascular adverse effects)
• hydroxychloroquine+remdesivir: Unknown (decreases effects)

Pregnancy

Safety in pregnancy has not been established. Use only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

Use with caution. Hydroxychloroquine is excreted in breast milk, and effects on the infant are unknown.

Storage

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

Formulations

• Tablets
• Oral solution

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

• Hyperthyroidism
• Graves' disease
• Thyroid storm

Dosage

Children: Refer to the BNF

Adults: The usual initial dose of propylthiouracil in adults is 300 mg per day, divided into 3 doses. The maintenance dose is typically 100-150 mg per day, adjusted based on thyroid function tests.

Mechanism of action

Propylthiouracil acts by inhibiting the enzyme thyroid peroxidase, which is involved in the iodination of tyrosine residues in thyroglobulin, a precursor of thyroid hormones. By blocking this enzyme, PTU reduces the production of thyroxine (T4) and triiodothyronine (T3), leading to decreased thyroid hormone levels in circulation. Additionally, PTU inhibits the conversion of T4 to T3 in peripheral tissues, further contributing to its antithyroid effects.

Pharmacodynamics

The pharmacodynamic effects of propylthiouracil are primarily centered around its ability to lower thyroid hormone levels, which helps alleviate symptoms of hyperthyroidism such as increased heart rate, weight loss, and anxiety. The onset of action can vary, but therapeutic effects may be observed within several weeks of initiation. Monitoring thyroid function tests is essential to assess the efficacy and adjust dosing as needed.

Pharmacokinetics

Propylthiouracil is well absorbed from the gastrointestinal tract, though its bioavailability can be affected by factors such as food intake. The drug is extensively metabolized in the liver, and its elimination half-life averages around 1-2 hours. Most of the drug is excreted in urine as metabolites. It is important to note that due to its rapid metabolism, multiple daily doses may be required to maintain therapeutic levels.

Interactions

• propylthiouracil+metyrapone: Severe (decreases effects)

Indications

• Antioxidant support
• Anti-inflammatory effects
• Potential cancer prevention
• Support for cardiovascular health
• Glycemic control

Dosage

Children: Refer to specific dietary guidelines. No standard therapeutic dose established.

Adults: Refer to specific dietary guidelines. No standard therapeutic dose established.

Mechanism of action

The bioactive compounds in raspberries, such as ellagic acid, quercetin, and anthocyanins, exert their effects through various mechanisms. They are known to scavenge free radicals, modulate cell signaling pathways, and influence gene expression related to inflammation and cancer progression. These compounds may also enhance the activity of certain detoxifying enzymes in the body.

Pharmacodynamics

Raspberry exhibits antioxidant activity, which helps protect cells from oxidative stress and damage caused by free radicals. The anti-inflammatory properties are attributed to the inhibition of pro-inflammatory cytokines and enzymes, thereby reducing inflammation. Additionally, some studies suggest that components of raspberry may influence lipid metabolism and improve glycemic control.

Pharmacokinetics

The bioactive compounds in raspberries are subject to digestion and metabolism, with absorption occurring primarily in the intestine. The specific pharmacokinetics of raspberry compounds can vary based on the individual compound, but generally, they are rapidly absorbed and can be detected in plasma shortly after consumption. The half-life of these compounds can vary significantly depending on the specific component and individual metabolic factors.

Adverse effects

• Allergic reactions
• Gastrointestinal upset
• Diarrhea

Precautions

• Use with caution in individuals with known allergies to berries.
• Consult a healthcare provider before use in patients with diabetes due to potential effects on blood sugar levels.

Pregnancy

Raspberries are generally considered safe during pregnancy when consumed in moderate amounts as part of a healthy diet.

Breast-feeding

Raspberries are safe to consume while breastfeeding, but excessive intake should be avoided.

Storage

Store in a cool, dry place. Fresh raspberries should be refrigerated and consumed within a few days.

Formulations

• Fresh raspberries
• Dried raspberries
• Raspberry extract
• Raspberry juice

Indications

• 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

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

Ammonium chloride increases acidity by increasing the amount of hydrogen ion concentrations. Ammonium chloride can be used as an expectorant due to its irritative action on the bronchial mucosa. This effect causes the production of respiratory tract fluid which in order facilitates the effective cough. The acid-forming properties of ammonium chloride result from dissociation of the salt to an ammonium cation and a chloride anion. In patients with normal hepatic function, the ammonium cation is converted to urea by the liver and a hydrogen cation is released which reacts with a bicarbonate ion to form water and carbon dioxide. The chloride anion combines with fixed bases in the extracellular fluid, thereby reducing the alkaline reserve of the body. The net result is the displacement of bicarbonate ions by chloride anions. The displacement of bicarbonate by chloride alters the bicarbonate:carbonic acid ratio if the body and acidosis results. The increased chloride concentration in the extracellular fluid produces an increased load to the renal tubules and appreciable amounts of chloride anions escape reabsorption. These anions are excreted along with cations and water. Sodium is the principal cation excreted; however, potassium excretion may also be increased to some degree. By increasing the excretion of both extracellular electrolytes and water, ammonium chloride causes a net loss of extracellular fluid and promotes the mobilization of edema fluid.

Pharmacodynamics

Systemic acidifier. In liver ammonium chloride is converted into urea with the liberation of hydrogen ions ( which lowers the pH) and chloride.

Mechanism of action

The feasibility of an oxygen-independent mechanism of chloroform bioactivation was indicated by the covalent binding to lipid and protein occurring in anaerobic incubations of chloroform and microsomes in the presence of NADPH. Under these conditions, the loss of cytochrome p450 and the inhibition of related mono-oxygenases were also observed. The chloroform anoxic biotransformation was negligible in uninduced microsomes and seemed to be catalyzed mainly by phenobarbital-inducible p450 isozymes. Biotransformation could also be supported by NADH as the source of reducing equivalents. Anaerobic metabolism of chloroform led to decreased levels of the main phenobarbital-induced p450 isozymes even at low chloroform concentration, and did not affect benzo(a)pyrene hydroxylase activity. These effects were not decreased by thiolic compounds. The oxidation products of chloroform caused a general impairment of the monoxygenase system, probably related to the formation of protein aggregates with very high molecular weight. In the presence of physiological concentrations of GSH, the targets of aerobically-produced metabolite were lipids, and, to a smaller extent, p450. At low chloroform concentrations and/or in the presence of GSH, the most changes to microsomal structures seemed to be produced by the reductively-formed intermediates.

Mechanism of action

Diphenhydramine predominantly works via the antagonism of H1 (Histamine 1) receptors. Such H1 receptors are located on respiratory smooth muscles, vascular endothelial cells, the gastrointestinal tract (GIT), cardiac tissue, immune cells, the uterus, and the central nervous system (CNS) neurons. When the H1 receptor is stimulated in these tissues it produces a variety of actions including increased vascular permeability, promotion of vasodilation causing flushing, decreased atrioventricular (AV) node conduction time, stimulation of sensory nerves of airways producing coughing, smooth muscle contraction of bronchi and the GIT, and eosinophilic chemotaxis that promotes the allergic immune response. Ultimately, diphenhydramine functions as an inverse agonist at H1 receptors, and subsequently reverses effects of histamine on capillaries, reducing allergic reaction symptoms. Moreover, since diphenhydramine is a first-generation antihistamine, it readily crosses the blood-brain barrier and inversely agonizes the H1 CNS receptors, resulting in drowsiness, and suppressing the medullary cough center. Furthermore, H1 receptors are similar to muscarinic receptors. Consequently, diphenhydramine also acts as an antimuscarinic. It does so by behaving as a competitive antagonist of muscarinic acetylcholine receptors, resulting in its use as an antiparkinson medication. Lastly, diphenhydramine has also demonstrated activity as an intracellular sodium channel blocker, resulting in possible local anesthetic properties. Antihistamines used in the treatment of allergy act by competing with histamine for H1-receptor sites on effector cells. They thereby prevent, but do not reverse, responses mediated by histamine alone. Antihistamines antagonize, in varying degrees, most of the pharmacological effects of histamine, including urticaria and pruritus. Also, the anticholinergic actions of most antihistamines provide a drying effect on the nasal mucosa. /Antihistamines/ H1 antagonists inhibit both the vasoconstrictor effects of histamine and, to a degree, the more rapid vasodilator effects mediated by activation of H1 receptors on endothelial cells (synthesis/release of NO and other mediators). /H1 Receptor Antagonists/ H1 antagonists suppress the action of histamine on nerve endings, including the flare component of the triple response and the itching caused by intradermal injection. /H1 Receptor Antagonists/ The first-generation antihistamines are widely prescribed medications that relieve allergic reactions and urticaria by blocking the peripheral histamine H(1) receptor. Overdose of these drugs often results in serious neuronal toxic effects, including seizures, convulsions and worsening of epileptic symptoms. The KCNQ/M K(+) channel plays a crucial role in controlling neuron excitability. Here, we demonstrate that mepyramine and diphenhydramine, two structurally related first-generation antihistamines, can act as potent KCNQ/M channel blockers. Extracellular application of these drugs quickly and reversibly reduced KCNQ2/Q3 currents heterologously expressed in HEK293 cells. The current inhibition was concentration and voltage dependent. The estimated IC(50) (12.5 and 48.1 microM, respectively) is within the range of drug concentrations detected in poisoned patients (30-300 microM). Both drugs shifted the I-V curve of KCNQ2/Q3 channel to more depolarized potentials and altered channel gating properties by prolonging activation and shortening deactivation kinetics. Mepyramine also inhibited the individual homomeric KCNQ1-4 and heteromeric KCNQ3/Q5 currents. Moreover, mepyramine inhibited KCNQ2/Q3 current in an outside-out patch excised from HEK293 cells and the inhibitory effect was neither observed when it was applied intracellularly nor affected by blocking phospholipase C (PLC) activity, indicating an extracellular and direct channel blocking mechanism. Finally, in cultured rat superior cervical ganglion (SCG) neurons, mepyramine reduced the

Pharmacodynamics

Diphenhydramine has anti-histaminic (H1-receptor), anti-emetic, anti-vertigo and sedative and hypnotic properties. The anti-histamine action occurs by blocking the spasmogenic and congestive effects of histamine by competing with histamine for H1 receptor sites on effector cells, preventing but not reversing responses mediated by histamine alone. Such receptor sites may be found in the gut, uterus, large blood vessels, bronchial muscles, and elsewhere. Anti-emetic action is by inhibition at the medullary chemoreceptor trigger zone. Anti-vertigo action is by a central antimuscarinic effect on the vestibular apparatus and the integrative vomiting center and medullary chemoreceptor trigger zone of the midbrain.

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/