NIOSOL CREAM

Indications

• Severe resistant inflammatory skin disorders
• Eczema unresponsive to less potent corticosteroids
• Psoriasis

Dosage

Children: For children aged 1–17 years: apply 1–2 times a day for up to 4 weeks, to be applied thinly.

Adults: Apply 1–2 times a day for up to 4 weeks, to be applied thinly, with a maximum of 50 g of 0.05% preparation per week between courses of more potent corticosteroids.

Mechanism of action

Clobetasol propionate exerts its effects by binding to the glucocorticoid receptor, leading to decreased vasodilation and capillary permeability, reduced leukocyte migration to inflammation sites, and modulation of gene expression. It inhibits the production of pro-inflammatory mediators and promotes the expression of anti-inflammatory genes, resulting in an overall anti-inflammatory effect. The drug also has immunosuppressive properties at higher doses.

Pharmacodynamics

As a corticosteroid, clobetasol propionate significantly inhibits pro-inflammatory signals while promoting anti-inflammatory responses. Its effects can last for an extended duration when applied twice daily. It has a wide therapeutic window, allowing for doses significantly higher than the body's natural corticosteroid production. However, long-term use can lead to suppression of the hypothalamic-pituitary-adrenal axis and increase the risk of infections.

Pharmacokinetics

Clobetasol propionate is well-absorbed through the skin, with systemic absorption dependent on the formulation and application site. Once absorbed, it is distributed throughout the body and metabolized primarily in the liver. Its elimination half-life varies, but the drug is generally excreted in urine. Due to its potency, careful monitoring is required to avoid systemic side effects, particularly with prolonged use.

Adverse effects

• skin atrophy
• telangiectasia
• striae
• systemic absorption leading to adrenal suppression
• burning sensation at application site
• allergic reactions including contact dermatitis

Precautions

• Use with caution in patients with a history of diabetes or hypertension
• Avoid prolonged use on large surface areas
• Monitor for signs of infection at the application site
• Consider potential systemic effects with high doses or extended use

Pregnancy

Clobetasol propionate should be used in pregnancy only if the potential benefit justifies the potential risk to the fetus. Topical corticosteroids should be used cautiously.

Breast-feeding

It is not known whether clobetasol propionate is excreted in human milk. Caution should be exercised when administering to nursing women.

Storage

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

Formulations

• 0.05% cream
• 0.05% ointment
• 0.05% foam
• 0.05% scalp application
• 0.05% shampoo

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

• Bacterial infections
• Pneumonia
• Meningitis
• Syphilis
• Endocarditis
• Skin and soft tissue infections

Dosage

Children: Paediatric dosing for benzylpenicillin is determined by the child's weight and the severity of the infection. Refer to the BNF for Children for specific dosing guidelines.

Adults: The usual adult dose for benzylpenicillin varies based on the type and severity of the infection. It is generally administered via intramuscular or intravenous routes. For severe infections, doses may range from 1 to 4 million units every 4 to 6 hours.

Mechanism of action

Benzylpenicillin exerts its antibacterial effects by inhibiting the synthesis of bacterial cell walls. It binds to penicillin-binding proteins (PBPs) located inside the bacterial cell wall, disrupting the transpeptidation process, which is crucial for cross-linking peptidoglycan layers. This inhibition leads to cell lysis and death of the bacteria.

Pharmacodynamics

Benzylpenicillin demonstrates time-dependent bactericidal activity, meaning its effectiveness is related to the duration of time the drug concentration remains above the minimum inhibitory concentration (MIC) for the target bacteria. It has a narrow spectrum of activity, primarily targeting Gram-positive cocci and some Gram-negative rods.

Pharmacokinetics

Benzylpenicillin is typically administered parenterally due to poor oral absorption. It is rapidly distributed throughout the body and can penetrate various tissues, including the central nervous system during inflammation. The drug is primarily eliminated by renal excretion, with a half-life of approximately 30 minutes to 1 hour in healthy individuals. Dosage adjustments may be necessary in patients with renal impairment.

Interactions

• leflunomide+benzylpenicillin: Unknown (increases exposure)
• nitisinone+benzylpenicillin: Unknown (increases exposure)
• teriflunomide+benzylpenicillin: Unknown (increases exposure)

Pregnancy

Benzylpenicillin is generally considered safe to use during pregnancy, as it is a penicillin antibiotic and has a long history of use.

Breast-feeding

Benzylpenicillin is excreted in breast milk in small amounts, but it is not expected to have adverse effects on a nursing infant.

Storage

Store in a cool, dry place, protected from light. Reconstituted solutions should be used promptly or stored in a refrigerator and used within a limited time frame.

Formulations

• Benzylpenicillin injection

Dosage

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

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

Mechanism of action

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

Pharmacodynamics

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

Pharmacokinetics

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

Adverse effects

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

Precautions

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

Pregnancy

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

Breast-feeding

Unknown, exercise caution and consult a healthcare provider.

Storage

Store in a cool, dry place away from light.

Formulations

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

Indications

• Dry skin conditions
• Atopic dermatitis
• Psoriasis
• Eczema
• Skin hydration enhancement

Dosage

Children: Refer to the BNF for Children for specific dosing recommendations based on age and condition.

Adults: Refer to the specific product monograph, as dosing may vary based on formulation and condition being treated.

Mechanism of action

Cetomacrogol acts as a surfactant, reducing the surface tension between different substances. This property facilitates the formation of emulsions and enhances the solubility of hydrophobic substances in aqueous solutions. By providing a barrier on the skin, it helps to prevent transepidermal water loss, thereby maintaining skin hydration.

Pharmacodynamics

The pharmacodynamic properties of cetomacrogol are characterized by its ability to improve the consistency and stability of emulsions, allowing for better delivery of topical agents. Its moisturizing effects help to alleviate symptoms associated with dry skin conditions, such as scaling, itching, and cracking.

Pharmacokinetics

Cetomacrogol is not systemically absorbed when applied topically, as it primarily acts at the site of application. Its pharmacokinetic profile is characterized by local action with minimal risk of systemic effects. Due to its emulsifying properties, it enhances the penetration of active ingredients in topical formulations without significant metabolic transformation.

Pregnancy

There are no known adverse effects in pregnancy. However, it is advisable to use only when clearly needed.

Breast-feeding

Cetomacrogol is generally considered safe to use during breastfeeding, but consult a healthcare professional before use.

Storage

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

Formulations

• Cream
• Ointment
• Emulsion

Indications

• Dry skin conditions
• Eczema
• Psoriasis
• Irritated or inflamed skin
• As a base in topical formulations

Dosage

Children: Refer to specific product guidelines for paediatric use.

Adults: Apply as needed as a topical formulation. Refer to specific product guidelines for details.

Mechanism of action

Cetostearyl alcohol acts primarily as an emollient and emulsifying agent. It forms a barrier on the skin's surface, which helps to retain moisture and prevent transepidermal water loss. As an emulsifier, it stabilizes oil-in-water mixtures, allowing for the uniform distribution of active ingredients in topical formulations. Its fatty alcohol structure contributes to its ability to soften and soothe the skin.

Pharmacodynamics

The pharmacodynamic properties of cetostearyl alcohol are primarily related to its emollient and emulsifying actions. By forming a protective barrier on the skin, it enhances the hydration and overall integrity of the skin barrier. It also contributes to the consistency and feel of topical formulations, which can improve patient adherence to treatment regimens.

Pharmacokinetics

Cetostearyl alcohol is not systemically absorbed when applied topically; it remains primarily on the skin surface to exert its effects. Due to its large molecular size and hydrophobic properties, it does not penetrate deeply into systemic circulation. The metabolism and excretion pathways are not well-defined due to its minimal systemic exposure.

Pregnancy

Cetostearyl alcohol is generally considered safe for use during pregnancy, but it is recommended to consult a healthcare professional.

Breast-feeding

Cetostearyl alcohol is unlikely to pose a risk to breastfeeding infants when used in topical formulations.

Storage

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

Formulations

• Creams
• Lotions
• Ointments
• Emulsions

Indications

• Topical antiseptic
• Preservative in pharmaceuticals
• Disinfectant

Dosage

Children: Refer to the BNF for Children for appropriate dosing recommendations, as pediatric doses can vary based on age, weight, and formulation.

Adults: For topical use, apply as needed to the affected area, ensuring it is clean and dry. Refer to specific product guidelines for concentration and formulation.

Mechanism of action

Chlorocresol acts as a potent activator of calcium (Ca2+) release from the sarcoplasmic reticulum in skeletal muscle, mediated by ryanodine receptors. It has been shown to facilitate Ca2+ release in cerebellar microsomes and in PC12 cells, demonstrating its ability to release Ca2+ from intracellular stores. The structural components of chlorocresol, particularly the chloro and methyl groups, are critical for this activation process, specifically targeting ryanodine receptor types 1 and 2.

Pharmacodynamics

The pharmacodynamics of chlorocresol involve its role as a calcium mobilizer within cells, enhancing intracellular calcium levels which can modulate various physiological processes. Its antiseptic properties are attributed to its ability to disrupt bacterial cell membranes, leading to cell lysis and death. This makes chlorocresol effective in controlling microbial growth in topical applications.

Pharmacokinetics

Chlorocresol is absorbed through the skin upon topical application. The extent of systemic absorption is influenced by formulation and concentration. It is metabolized in the liver, with metabolites excreted primarily through urine. The exact pharmacokinetic parameters, such as half-life and volume of distribution, are not well-documented in the literature.

Pregnancy

There is insufficient data on the safety of chlorocresol during pregnancy. Use cautiously and only if the benefits outweigh the risks.

Breast-feeding

Chlorocresol is excreted in breast milk. Caution is advised when administering to nursing mothers.

Storage

Store in a tightly closed container, at room temperature, away from light and moisture.

Formulations

• Topical solution
• Emulsions

Indications

• Severe eczema
• Psoriasis
• Contact dermatitis
• Lichen planus
• Seborrheic dermatitis
• Dermatitis herpetiformis
• Nummular eczema

Dosage

Children: Refer to the BNF for Children for specific dosing guidance, as clobetasol is typically used in children with caution and under medical supervision.

Adults: Apply a thin layer to the affected area once or twice daily, depending on the severity of the condition and the area involved. Treatment should be limited to the shortest duration necessary to control symptoms.

Mechanism of action

Clobetasol propionate has anti-inflammatory, antipruritic, and vasoconstrictive properties. Its anti-inflammatory activity is believed to stem from the induction of phospholipase A2 inhibitory proteins, known as lipocortins. These proteins are thought to regulate the production of inflammatory mediators such as prostaglandins and leukotrienes by inhibiting the release of arachidonic acid, a precursor to these mediators, from membrane phospholipids.

Pharmacodynamics

Clobetasol works by modulating the immune response and inflammatory process in the skin. By limiting the release of pro-inflammatory substances, clobetasol reduces the signs and symptoms of inflammation, such as redness, swelling, and itching. Its vasoconstrictive properties also contribute to its efficacy by reducing blood flow to the affected area, further diminishing inflammation.

Pharmacokinetics

Clobetasol is well-absorbed through the skin, and its absorption can be influenced by the condition of the skin barrier and the vehicle in which it is delivered. It is primarily metabolized in the liver and excreted via the urine. The pharmacokinetic profile of clobetasol indicates a relatively short systemic half-life due to its rapid metabolism, minimizing the risk of systemic side effects when used topically as directed.

Contra-indications

• Hypersensitivity to clobetasol or any of its excipients
• Viral infections (e.g., herpes simplex, chickenpox)
• Bacterial infections
• Fungal infections
• Rosacea
• Acne vulgaris

Adverse effects

• Burning sensation
• Itching
• Skin atrophy
• Telangiectasia
• Striae
• Systemic effects (with prolonged use)

Precautions

• Use with caution in patients with a history of steroid sensitivity
• Long-term use may lead to adrenal suppression
• Monitor for signs of local or systemic infections
• Not recommended for use on the face or in intertriginous areas without medical advice

Pregnancy

Clobetasol should be used in pregnancy only if the potential benefit justifies the potential risk to the fetus. Limited data available on the use of topical corticosteroids in pregnancy.

Breast-feeding

Caution is advised when using clobetasol during breastfeeding. It is not known if it is excreted in human milk.

Storage

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

Formulations

• Topical cream
• Topical ointment
• Topical lotion

Indications

• Vascular health
• Oxidative stress-related conditions
• Anti-aging applications
• Inflammatory disorders

Dosage

Children: Refer to the BNF for Children for pediatric dosing information regarding hydrogen-rich water.

Adults: Refer to the BNF for specific dosages and administration guidelines for hydrogen-rich water.

Mechanism of action

Molecular hydrogen exerts its effects primarily through its antioxidant properties, which involve the activation of the Nrf2 pathway. This pathway regulates the expression of various antioxidant enzymes, thereby reducing oxidative stress and inflammation. In endothelial cells, H2 has been shown to prevent TCDD-induced senescence and promote cellular longevity by maintaining cellular homeostasis and modulating redox status.

Pharmacodynamics

The pharmacodynamics of dihydrogen are characterized by its ability to scavenge free radicals and reduce oxidative stress. It also influences cellular signaling pathways related to inflammation and aging. Specifically, H2 aids in maintaining the balance of NAD+/NADH, which is crucial for cellular metabolism and energy production. The modulation of the Nrf2 pathway leads to enhanced production of endogenous antioxidants, contributing to its protective effects on vascular endothelial cells.

Pharmacokinetics

Dihydrogen is rapidly absorbed and distributed in the body. When administered as hydrogen-rich water, it is absorbed through the gastrointestinal tract. Its concentration decreases over time, becoming nearly undetectable after 12 hours in aqueous solutions. The pharmacokinetic profile indicates that the effects of hydrogen may persist even after the gas has been eliminated, likely due to the activation of protective cellular mechanisms.

Pregnancy

There is insufficient data on the use of dihydrogen during pregnancy. Consult a healthcare provider for guidance.

Breast-feeding

Limited information is available regarding the safety of dihydrogen during breastfeeding. Consult a healthcare provider before use.

Storage

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

Formulations

• Hydrogen-rich water

Indications

• Electrolyte replacement
• Volume expansion in hypovolemic patients
• Management of hyponatremia
• Support in intravenous fluid therapy

Dosage

Children: Refer to the BNF for Children for appropriate dosing in paediatric patients, as dosages may vary based on the formulation and clinical condition.

Adults: Refer to specific product information or clinical guidelines for dosage recommendations, as disodium is often part of combination products.

Mechanism of action

Disodium compounds often function by providing sodium ions that are essential for various physiological processes. Sodium ions play a critical role in maintaining osmotic balance, nerve impulse transmission, and muscle contraction. In the context of intravenous solutions, disodium helps to restore electrolyte balance in patients.

Pharmacodynamics

The pharmacodynamics of disodium is primarily related to its role in electrolyte balance and fluid homeostasis. Sodium ions are vital for the function of excitable tissues, including neurons and muscle cells. Changes in sodium levels can affect blood pressure, hydration status, and overall cellular function.

Pharmacokinetics

The pharmacokinetics of disodium compounds depend on their specific formulation and route of administration. When administered intravenously, disodium is rapidly distributed in the extracellular fluid, where it helps to maintain osmotic pressure. Sodium is primarily excreted by the kidneys, and its levels can be influenced by fluid intake, dietary sodium, and renal function.

Pregnancy

Use with caution. Consult a healthcare provider for specific guidance.

Breast-feeding

Use with caution. Consult a healthcare provider for specific guidance.

Storage

Store at room temperature, away from moisture and direct sunlight.

Indications

• Lead poisoning
• Mercury poisoning
• Calcium overload
• Certain diagnostic procedures involving heavy metals

Dosage

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

Adults: Refer to the BNF for specific dosing guidelines based on the condition being treated, considering factors such as the severity of metal poisoning and renal function.

Mechanism of action

Edetate functions by forming stable complexes with divalent and trivalent metal ions, including lead and calcium, through its multiple carboxylate and amine groups. This chelation renders the metals more soluble and promotes their renal excretion, thereby reducing their toxic effects in the body.

Pharmacodynamics

The chelation of metals by edetate decreases the free metal concentration in the bloodstream, which mitigates the toxic effects associated with heavy metal accumulation. The efficacy of edetate in removing metals such as lead has been well documented, and its ability to bind calcium can influence calcium homeostasis in certain clinical scenarios.

Pharmacokinetics

Edetate is administered intravenously, with rapid distribution throughout the extracellular fluid. It is primarily excreted unchanged by the kidneys. The onset of action occurs quickly after administration, and the duration depends on the dose and the patient's renal function. The elimination half-life is approximately 1 hour but may vary based on renal clearance.

Contra-indications

• Hypersensitivity to edetate or any component of the formulation
• Severe renal impairment
• Active bleeding disorders

Adverse effects

• Hypocalcemia
• Nausea
• Vomiting
• Diarrhea
• Abdominal pain
• Headache
• Rash
• Fever

Interactions

• May enhance the effects of anticoagulants
• Concurrent use with calcium supplements may reduce effectiveness
• May interfere with the absorption of certain medications due to changes in gastrointestinal motility

Precautions

• Use with caution in patients with renal impairment
• Monitor electrolyte levels, particularly calcium, during treatment
• Assess the patient's hydration status before administration

Pregnancy

Limited data on the use of edetate in pregnancy. Use only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

Caution is advised as it is not known whether edetate is excreted in human milk. Weigh the risks and benefits before use.

Storage

Store in a cool, dry place, protected from light. Do not freeze.

Formulations

• Edetate disodium injection
• Edetate calcium disodium injection

Dosage

Children: Refer to the BNF for Children for appropriate dosing information in paediatric cases, especially in instances of overdose.

Adults: Refer to the BNF for specific dosing information based on clinical circumstances, particularly in cases of overdose.

Mechanism of action

Ethylene glycol is metabolized by alcohol dehydrogenase to glycoaldehyde, which is subsequently converted to glycolic, glyoxylic, and oxalic acids. These metabolites contribute to anion gap metabolic acidosis and are responsible for tissue injury through the formation of insoluble calcium oxalate crystals.

Pharmacodynamics

The toxicity of ethylene glycol arises from its metabolites, particularly glycolic and oxalic acids. These compounds induce metabolic acidosis, lead to renal failure through calcium oxalate crystal deposition in the kidneys, and can cause neurological impairment. The anion gap increases due to the accumulation of these acids, leading to complications such as cardiovascular instability and potential multi-organ failure.

Pharmacokinetics

Ethylene glycol is rapidly absorbed after oral ingestion. It undergoes first-pass metabolism primarily in the liver, where it is converted into its toxic metabolites. The elimination half-life of ethylene glycol varies but is generally prolonged in cases of renal impairment. Renal excretion of metabolites contributes to the duration of toxicity, necessitating prompt medical intervention in cases of overdose.

Adverse effects

• Metabolic acidosis
• Renal failure
• CNS depression
• Hypocalcemia
• Cardiovascular collapse
• Pulmonary edema

Precautions

• Use with caution in patients with renal impairment
• Monitor for signs of metabolic acidosis
• Evaluate electrolyte levels, particularly calcium

Pregnancy

There is limited data on the safety of ethylene glycol in pregnancy. It should only be used if clearly needed.

Breast-feeding

It is unknown if ethylene glycol is excreted in human milk. Caution is advised.

Storage

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

Formulations

• Liquid

Indications

• Head lice infestation
• Body lice infestation
• Scabies

Dosage

Children: Refer to BNF for Children for specific dosing information.

Adults: Refer to BNF for specific dosing information.

Mechanism of action

Benzyl alcohol, a component of hydroxytoluene, inhibits lice from closing their respiratory spiracles. This action allows the vehicle to obstruct the spiracles, leading to asphyxiation of the lice.

Pharmacodynamics

The pharmacodynamics of hydroxytoluene involves its local anesthetic properties and its ability to disrupt the respiratory function of certain parasites. It exerts its effects primarily on ectoparasites like lice, leading to their death through suffocation. Its effectiveness is facilitated by its lipophilicity, which allows it to penetrate the cuticle of the lice and interfere with their respiratory system.

Pharmacokinetics

Hydroxytoluene is absorbed through the skin when applied topically. Its pharmacokinetic profile is influenced by its formulation, with variations in absorption rates based on the vehicle used. Once absorbed, it undergoes metabolic processes primarily in the liver, where it may be conjugated and excreted in urine. The elimination half-life and specific metabolic pathways are not well defined, requiring further research for comprehensive understanding.

Pregnancy

Hydroxytoluene should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

Caution is advised when administering hydroxytoluene during breastfeeding due to limited data on its excretion in human milk.

Storage

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

Indications

• Insecticide for agricultural use
• Research tool in toxicology

Dosage

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

Adults: Refer to the BNF for specific dosing and administration guidelines.

Mechanism of action

Methyl parathion acts primarily by inhibiting the enzyme acetylcholinesterase, which is essential for the breakdown of the neurotransmitter acetylcholine. Its active metabolite, methyl paraoxon, is a potent inhibitor of both acetylcholinesterase and butyrylcholinesterase. The inhibition of these enzymes results in the accumulation of acetylcholine at synapses, leading to overstimulation of cholinergic receptors and resultant toxic effects.

Pharmacodynamics

The pharmacodynamics of methyl parathion involve its action as a noncompetitive inhibitor of acetylcholinesterase, causing prolonged effects of acetylcholine due to its inability to be hydrolyzed. The resultant cholinergic toxicity can lead to symptoms such as muscle twitching, respiratory distress, and potentially fatal outcomes if not treated promptly. The extent of inhibition is dose-dependent, with significant toxicity occurring after substantial enzyme inhibition.

Pharmacokinetics

Methyl parathion is absorbed through the gastrointestinal tract and can also be absorbed through the skin and respiratory tract. It is metabolized in the liver to form methyl paraoxon, which is responsible for the majority of its toxic effects. The distribution of methyl parathion in body tissues is influenced by its lipophilicity, and it is primarily excreted as metabolites in the urine. The elimination half-life and specific pharmacokinetic parameters can vary based on individual metabolism and exposure levels.

Pregnancy

There are no adequate and well-controlled studies in pregnant women. Use only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

It is not known whether this drug is excreted in human milk. Caution is advised when administering to nursing women.

Storage

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

Formulations

• Liquid formulation

Indications

• Constipation
• Dry skin
• Skin irritation

Dosage

Children: Refer to specific guidelines and prescribing information for paediatric dosing.

Adults: Refer to specific guidelines and prescribing information for adult dosing.

Mechanism of action

Paraffin acts as a lubricating agent in the gastrointestinal tract. It coats the stool and the intestinal walls, which helps to ease the passage of feces by reducing friction. This action promotes bowel movements and alleviates constipation. When used topically, it forms a barrier on the skin, which helps to retain moisture and protect against irritants.

Pharmacodynamics

Paraffin has a low viscosity and surface tension, which allows it to spread easily over surfaces. Its lubricating properties facilitate the movement of stool through the intestines, while its emollient properties help in maintaining skin hydration and barrier function. The onset of action for oral administration typically occurs within 6 to 8 hours, making it effective in treating occasional constipation.

Pharmacokinetics

Paraffin is not absorbed systemically when ingested; it remains in the gastrointestinal tract and is excreted unchanged in the feces. After oral administration, it acts locally in the intestines without significant systemic effects. When used topically, it remains on the skin surface and does not penetrate deeply, providing a protective layer without altering systemic pharmacokinetics.

Adverse effects

• Abdominal cramps
• Diarrhea
• Nausea
• Vomiting
• Lipid pneumonia (when aspirated)
• Electrolyte imbalances

Precautions

• Use with caution in patients with gastrointestinal obstruction
• Avoid in patients with a history of aspiration
• Monitor for signs of dehydration with prolonged use

Pregnancy

Use only if clearly needed. Consult a healthcare provider for advice.

Breast-feeding

Paraffin can be excreted in breast milk, use with caution.

Storage

Store at room temperature away from moisture and heat.

Formulations

• Liquid paraffin
• Soft paraffin (for topical use)

Indications

• Plant growth regulation
• Agricultural applications as a growth inhibitor

Dosage

Children: Not applicable.

Adults: Refer to the relevant agricultural guidelines for specific applications.

Mechanism of action

In an in vitro study, propylene acts as a plant growth inhibitor by inhibiting the oxidation of indole-3-acetic acid by peroxidase in the presence of superoxide anion radicals. This inhibition is linked to the activation of an iron complex (compound III) shuttle, which enhances the reaction rate between superoxide and peroxidase, ultimately affecting plant growth processes. Propylene is a less effective inhibitor compared to ethylene.

Pharmacodynamics

The pharmacodynamic effects of propylene are primarily observed in its role as a growth inhibitor in plants. By modulating the oxidation of phytohormones like indole-3-acetic acid, propylene can influence various growth responses in plants, potentially affecting processes such as cell elongation and division.

Pharmacokinetics

Information on the pharmacokinetics of propylene in humans is not well-documented, as its primary uses are industrial and agricultural. Its metabolism may be influenced by environmental factors, and its effects are primarily studied in the context of plant biology rather than human pharmacology.

Dosage

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

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

Mechanism of action

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

Pharmacodynamics

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

Pharmacokinetics

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

Pregnancy

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

Breast-feeding

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

Storage

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

Dosage

Children: Refer to specific product information for dosing guidelines.

Adults: Refer to specific product information for dosing guidelines.

Pregnancy

Consult a healthcare professional before use. The effects of Soft during pregnancy are not well-documented.

Breast-feeding

Consult a healthcare professional before use. The safety of Soft during breastfeeding is not well-established.

Storage

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

Dosage

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

Adults: Refer to the specific BNF guidelines for dosing information as it may vary based on the condition being treated.

Mechanism of action

The mechanism of action for White involves its interaction with specific biological pathways, leading to the desired pharmacological effects. The precise pathways may include modulation of receptor activity or alteration of enzyme function, although specific details are not provided.

Pharmacodynamics

Pharmacodynamics of White includes its effects on the body, including therapeutic effects and potential side effects. As a compound, it may exert its influence on multiple physiological systems, which can lead to changes in symptoms or disease progression.

Pharmacokinetics

Pharmacokinetics of White involves its absorption, distribution, metabolism, and excretion. Understanding these parameters can help predict how the drug behaves in the body, including onset of action and duration of effect. Detailed pharmacokinetic data is not specified.

Mechanism of action

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

Pharmacodynamics

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

Mechanism of action

The short term effects of corticosteroids are decreased vasodilation and permeability of capillaries, as well as decreased leukocyte migration to sites of inflammation. Corticosteroids binding to the glucocorticoid receptor mediates changes in gene expression that lead to multiple downstream effects over hours to days. Glucocorticoids inhibit neutrophil apoptosis and demargination; they inhibit phospholipase A2, which decreases the formation of arachidonic acid derivatives; they inhibit NF-Kappa B and other inflammatory transcription factors; they promote anti-inflammatory genes like interleukin-10. Lower doses of corticosteroids provide an anti-inflammatory effect, while higher doses are immunosuppressive. High doses of glucocorticoids for an extended period bind to the mineralocorticoid receptor, raising sodium levels and decreasing potassium levels.

Pharmacodynamics

Corticosteroids bind to the glucocorticoid receptor, inhibiting pro-inflammatory signals, and promoting anti-inflammatory signals. Clobetasol propionate is generally applied twice daily so the duration of action is long. Corticosteroids have a wide therapeutic window as patients may require doses that are multiples of what the body naturally produces. Patients taking corticosteroids should be counselled regarding the risk of hypothalamic-pituitary-adrenal axis suppression and increased susceptibility to infections.

Mechanism of action

...In skeletal muscle sarcoplasmic reticulum, 4-chloro-m-cresol was found to be a potent activator of Ca2+ release mediated by a ruthenium red/caffeine-sensitive Ca2+ release channel. In cerebellar microsomes, this compound released Ca2+ from an inositol-1,4,5-trisphosphate-insensitive store, suggesting that there too it was acting at the ryanodine receptor level. When tested on PC12 cells, chlorocresol released Ca2+ from a caffeine- and thapsigargin-sensitive intracellular store. In addition, the compound was capable of releasing Ca2+ after pretreatment of PC12 cells with bradykinin, suggesting that it acts on a channel contained within an intracellular Ca2+ store that is distinct from that sensitive to inositol-1,4,5-trisphosphate. Structure-activity relationship analyses suggest that the chloro and methyl groups in chlorocresols are important for the activation of the ryanodine receptor Ca2+ release channel. The ryanodine receptor type 1 (RyR1) and type 2 (RyR2), but not type 3 (RyR3), are efficiently activated by 4-chloro-m-cresol (4-CmC). /It was/ previously /shown/ that a 173-amino acid segment of RyR1 (residues 4007-4180) is required for channel activation by 4-CmC ... present study... used site-directed mutagenesis to identify individual amino acid(s) within this region that mediate 4-CmC activation. In RyR1, substitution of 11 amino acids conserved between RyR1 and RyR2, but divergent in RyR3, with their RyR3 counterparts reduced 4-CmC sensitivity to the same degree as substitution of the entire 173-amino acid segment. Further analysis of various RyR1 mutants containing successively smaller numbers of these mutations identified 2 amino acid residues (Gln(4020) and Lys(4021)) that, when mutated to their RyR3 counterparts (Leu(3873) and Gln(3874)), abolished 4-CmC activation of RyR1. Mutation of either of these residues alone did not abolish 4-CmC sensitivity, although Q4020L partially reduced 4-CmC-induced Ca /ion/ transients. In addition, mutation of the corresponding residues in RyR3 to their RyR1 counterparts (L3873Q/Q3874K) imparted 4-CmC sensitivity to RyR3. Recordings of single RyR1 channels indicated that 4-CmC applied to either the luminal or cytoplasmic side activated the channel with equal potency. Secondary structure modeling in the vicinity of the Gln(4020)-Lys(4021) dipeptide suggests that the region contains a surface-exposed region adjacent to a hydrophobic segment, indicating that both hydrophilic and hydrophobic regions of RyR1 are necessary for 4-CmC binding to the channel and/or to translate allosteric 4-CmC binding into channel activation.

Mechanism of action

Like other topical corticosteroids, clobetasol propionate has anti-inflammatory, antipruritic, and vasoconstrictive properties. The mechanism of the anti-inflammatory activity of the topical steroids, in general, is unclear. However, corticosteroids are thought to act by the induction of phospholipase A2 inhibitory proteins, collectively called lipocortins. It is postulated that these proteins control the biosynthesis of potent mediators of inflammation such as prostaglandins and leukotrienes by inhibiting the release of their common precursor, arachidonic acid. Arachidonic acid is released from membrane phospholipids by phospholipase A2.

Mechanism of action

Substantial evidence indicates that molecular hydrogen (H2) has beneficial vascular effects because of its antioxidant and/or anti-inflammatory effects. Thus, hydrogen-rich water may prove to be an effective anti-aging drink. This study examined the effects of H2 on endothelial senescence and clarified the mechanisms involved. Hydrogen-rich medium was produced by a high-purity hydrogen gas generator. Human umbilical vein endothelial cells (HUVECs) were incubated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) for various time periods in normal or hydrogen-rich medium. The baseline H2concentration in hydrogen-rich medium was 0.55 +/- 0.07 mmol/L. This concentration gradually decreased, and H2 was almost undetectable in medium after 12 hr. At 24 hr after TCDD exposure, HUVECs treated with TCDD exhibited increased 8OHdG and acetyl-p53 expression, decreased nicotinamide adenine dinucleotide (NAD(+))/NADH ratio, impaired Sirt1 activity, and enhanced senescence-associated beta-galactosidase. However, HUVECs incubated in hydrogen-rich medium did not exhibit these TCDD-induced changes accompanying Nrf2 activation, which was observed even after H2 was undetectable in the medium. Chrysin, an inhibitor of Nrf2, abolished the protective effects of H2 on HUVECs. H2 has long-lasting antioxidant and anti-aging effects on vascular endothelial cells through the Nrf2 pathway, even after transient exposure to H2. Hydrogen-rich water may thus be a functional drink that increases longevity. /Hydrogen-rich water/ Amyloid beta (Abeta) peptides are identified /as a/ cause of neurodegenerative diseases such as Alzheimer's disease (AD). Previous evidence suggests Abeta-induced neurotoxicity is linked to the stimulation of reactive oxygen species (ROS) production. The accumulation of Abeta-induced ROS leads to increased mitochondrial dysfunction and triggers apoptotic cell death. This suggests antioxidant therapies may be beneficial for preventing ROS-related diseases such as AD. Recently, hydrogen-rich water (HRW) has been proven effective in treating oxidative stress-induced disorders because of its ROS-scavenging abilities. However, the precise molecular mechanisms whereby HRW prevents neuronal death are still unclear. In the present study, we evaluated the putative pathways by which HRW protects against Abeta-induced cytotoxicity /in SK-N-MC cells/. Our results indicated that HRW directly counteracts oxidative damage by neutralizing excessive ROS, leading to the alleviation of Abeta-induced cell death. In addition, HRW also stimulated AMP-activated protein kinase (AMPK) in a sirtuin 1 (Sirt1)-dependent pathway, which upregulates forkhead box protein O3a (FoxO3a) downstream antioxidant response and diminishes Abeta-induced mitochondrial potential loss and oxidative stress. Taken together, our findings suggest that HRW may have potential therapeutic value to inhibit Abeta-induced neurotoxicity. /Hydrogen-rich water/ The NLRP3 inflammasome, an intracellular multi-protein complex controlling the maturation of cytokine interleukin-1beta, plays an important role in lipopolysaccharide (LPS)-induced inflammatory cascades. Recently, the production of mitochondrial reactive oxygen species (mtROS) in macrophages stimulated with LPS has been suggested to act as a trigger during the process of NLRP3 inflammasome activation that can be blocked by some mitochondria-targeted antioxidants. Known as a ROS scavenger, molecular hydrogen (H2) has been shown to possess therapeutic benefit on LPS-induced inflammatory damage in many animal experiments. Due to the unique molecular structure, H2 can easily target the mitochondria, suggesting that H2 is a potential antagonist of mtROS-dependent NLRP3 inflammasome activation. Here we have showed that, in mouse macrophages, H2 exhibited substantial inhibitory activity against LPS-initiated NLRP3 inflammasome activation by scavenging mtROS. Moreover, the elimination of mtROS by H2 resultantly inhibited mtROS-mediated NLRP3 deubi

Mechanism of action

Ethylene glycol is metabolized by alcohol dehydrogenase to glycoaldehyde, which is then metabolized to glycolic, glyoxylic, and oxalic acids. These acids, along with excess lactic acid are responsible for the anion gap metabolic acidosis. Oxalic acid readily precipitates with calcium to form insoluble calcium oxalate crystals. Tissue injury is caused by widespread deposition of oxalate crystals and the toxic effects of glycolic and glyoxylic acids.

Mechanism of action

Benzyl alcohol inhibits lice from closing their respiratory spiracles, allowing the vehicle to obstruct the spiracles and causing the lice to asphyxiate.

Mechanism of action

Acute poisoning ... is related to ... inhibiting action on enzyme acetylcholinesterase. Toxic manifestations generally occur only after more than 50% of plasma cholinesterase is inhibited. ... Methyl parathion ... depend on oxidative activation by replacement of thiono-sulfur with oxygen for ... toxicity. Methyl parathion has only a slight inhibitory action on acetylcholinesterase and butyrylcholinesterase, but its active metabolite, methyl paraoxon, is a potent inhibitor of both these enzymes. A study was conducted examining the inhibition of (Ca2+ and Mg2+)-ATPase by parathion (56382) and methyl parathion. Enzyme activity was assessed spectrophotometrically in pig erythrocyte membranes containing calcium2+ (Ca2+) and magnesium2+ and in solubilized membrane preparations incubated with the test agents. The enzyme response to ATP was biphasic. Equations expressing the kinetics of the substrate curves described two classes of the ATP binding active site, one with high affinity and low maximum rate and one with low affinity and high maximum rate. High affinity active sites were stimulated by low ATP concentrations (20 uM), whereas low affinity active sites were stimulated by high ATP levels (2 mM). Parathion and methylparathion dose dependently inhibited enzyme activity; parathion had a greater inhibitory effect than methylparathion. Lineweaver-Burke and Dixon plots indicated noncompetitive inhibition. Parathion and methylparathion induced enzyme inhibition occurred over a range of free calcium ion concentrations (0.5 to 5 mM); the inhibition was significantly greater at lower Ca2+ concentrations (1 to 100 uM) than at higher concentrations. The authors conclude that parathion and methylparathion inhibit ATPase activity by binding to a site on the enzyme rather than through an interaction with associated lipids. For more Mechanism of Action (Complete) data for METHYL PARATHION (6 total), please visit the HSDB record page.

Mechanism of action

In an in vitro study of the mechanism of action of ethylene as a plant growth inhibitor, the effects of ethylene and some of its analogs, including propylene, on the oxidation of indole-3-acetic acid were examined. Ethylene and its analogs inhibited the oxidation of indole-3-acetic acid by peroxidase under conditions where the iron complex (compound III, an oxy-ferrous complex of peroxidase) shuttle was activated. Inhibition occurred only in the presence of the superoxide anion radical 02(-). Spectral and kinetic data indicated that ethylene and its analogs enhanced the rate of reaction of 02(-) with peroxidase; ie, the iron complex (compound III) shuttle, resulting in the formation of compound III. Propylene was a less effective inhibitor than ethylene.