GEODERM Cream

Indications

• Suppression of inflammatory disorders
• Management of allergic conditions
• Congenital adrenal hyperplasia
• Inflammatory and allergic eye conditions

Dosage

Children: For children aged 1–11 months: Initially 1 mg, repeated up to 4 times in 24 hours according to response. Aged 1–5 years: Initially 2 mg, repeated up to 4 times in 24 hours according to response. Aged 6–11 years: Initially 4 mg, repeated up to 4 times in 24 hours according to response. Aged 12–17 years: 4–20 mg, repeated up to 4 times in 24 hours according to response.

Adults: Dosage varies based on condition; typically, initial doses are adjusted according to the patient's response and severity of condition.

Mechanism of action

Betamethasone exerts its effects by binding to glucocorticoid receptors, leading to modulation of gene expression and suppression of inflammatory cytokines and mediators.

Pharmacodynamics

Betamethasone reduces inflammation and immune response, which is beneficial in managing various inflammatory and allergic disorders.

Pharmacokinetics

Betamethasone is rapidly absorbed after administration, with a long half-life allowing for once-daily dosing in many cases. It is metabolized in the liver and excreted primarily in urine.

Adverse effects

• Hiccups
• Oedema
• Mood and behaviour changes
• Vision disorders
• Serious gastro-intestinal effects
• Musculoskeletal effects
• Ophthalmic effects
• Stevens-Johnson syndrome
• Myocardial rupture (following recent myocardial infarction)

Interactions

• Cobicistat + betamethasone: Unknown (increases exposure)
• Idelalisib + betamethasone: Unknown (increases exposure)
• Clarithromycin + betamethasone: Unknown (increases exposure)

Precautions

• Immunosuppression due to prolonged corticosteroid treatment
• Adrenal suppression if given for longer than 3 weeks
• Increased susceptibility to infections, including chickenpox and measles

Pregnancy

Readily crosses the placenta. Transient effect on fetal movements and heart rate.

Storage

Store at room temperature, protect from light.

Formulations

• Betamethasone sodium phosphate 4 mg per 1 ml solution for injection ampoules

Indications

• Vaginal candidiasis
• Vulval candidiasis
• Superficial fungal infections
• Otitis externa (as part of combination therapy)

Dosage

Adults: For vaginal candidiasis, 1 pessary of 500 mg can be inserted at night. Alternatively, for treatment with 1% cream, apply 2–3 times a day to the affected area for at least 14 days. For recurrent vulvovaginal candidiasis

Mechanism of action

Clotrimazole acts primarily by damaging the permeability barrier in the cell membrane of fungi. It inhibits ergosterol biosynthesis, which is essential for maintaining the integrity of fungal cell membranes. The inhibition of lanosterol 14-demethylase (CYP51) is a key mechanism behind its antifungal properties, leading to decreased ergosterol synthesis and resulting in cell membrane dysfunction. Clotrimazole also affects calcium homeostasis by inhibiting sarcoplasmic reticulum Ca2+-ATPase and blocking calcium-dependent potassium channels, contributing to its overall pharmacological effects.

Pharmacodynamics

Clotrimazole is considered a broad-spectrum antifungal that alters the permeability of fungal cell membranes, leading to inhibition of growth in pathogenic yeasts. At lower concentrations, it exhibits fungistatic properties, while at higher concentrations, it may be fungicidal against certain strains like Candida albicans. However, resistance to clotrimazole has become more common in recent years, limiting its efficacy in some populations.

Pharmacokinetics

Clotrimazole is primarily applied topically, and its absorption varies depending on the formulation and site of application. Following topical administration, systemic absorption is minimal, thereby reducing the risk of systemic side effects. The drug is metabolized in the liver and excreted via urine and feces. The pharmacokinetics may differ based on the dosing regimen and specific formulation used.

Contra-indications

• Hypersensitivity to clotrimazole or any excipients in the formulation
• Not recommended if trying to conceive due to potential damage to latex condoms and diaphragms

Adverse effects

• Skin reactions
• Vaginal burning
• Angioedema

Interactions

• Clotrimazole may increase the exposure of lomitapide, though the specific nature of this interaction is unknown

Precautions

• Avoid use in pregnancy without medical advice
• Use caution in patients with a history of hypersensitivity reactions

Pregnancy

Clotrimazole should be used during pregnancy only if clearly needed. Oral antifungal treatments should be avoided.

Breast-feeding

Clotrimazole is excreted in breast milk; caution is advised when used in breastfeeding mothers.

Storage

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

Formulations

• Clotrimazole 1% cream
• Clotrimazole 2% cream
• Clotrimazole 500 mg vaginal pessaries
• Clotrimazole 10% vaginal cream
• Clotrimazole 1% solution (ear drops)

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
• Sepsis
• Pneumonia
• Meningitis
• Endocarditis
• Biliary tract infections
• Prostatitis
• Surgical prophylaxis
• Acute diverticulitis
• Leg ulcer infections

Dosage

Adults: 3–5 mg/kg daily in 3 divided doses, or a single daily dose of 5–7 mg/kg adjusted according to serum-gentamicin concentration. For surgical prophylaxis, 1.5 mg/kg administered intraven

Mechanism of action

Gentamicin exerts its antibacterial effects through a multi-phase mechanism. Initially, it binds to negatively charged components of bacterial cell membranes, increasing membrane permeability. Following this, it enters the bacterial cell via energy-dependent transport mechanisms, where it binds to the 30S ribosomal subunit. This binding causes mistranslation of proteins and disrupts membrane integrity, resulting in bacterial cell death. The action is concentration-dependent, leading to rapid bactericidal effects.

Pharmacodynamics

Gentamicin has a rapid onset of action due to its mechanism of disrupting the bacterial cell membrane and inhibiting protein synthesis. Its effectiveness is enhanced by higher concentrations, and it demonstrates a post-antibiotic effect where bacteria remain suppressed even after drug levels fall below the minimum inhibitory concentration. The drug's efficacy is influenced by factors like the bacterial strain and its susceptibility patterns.

Pharmacokinetics

Gentamicin is usually administered intravenously or intramuscularly. It has a volume of distribution of approximately 0.25 L/kg and is not significantly protein-bound. The drug is primarily eliminated via renal excretion, with a half-life of 2 to 3 hours in individuals with normal renal function. Dosing adjustments are necessary in patients with renal impairment to avoid toxicity. Serum levels should be monitored to optimize therapeutic efficacy while minimizing toxicity.

Contra-indications

• Hypersensitivity to gentamicin or any aminoglycoside
• Severe renal impairment
• Pre-existing auditory or vestibular dysfunction

Adverse effects

• Ototoxicity (hearing loss, vertigo, tinnitus)
• Nephrotoxicity
• Neuromuscular blockade
• Allergic reactions (rash, pruritus)
• Injection site reactions

Interactions

• Gentamicin + relugolix: Unknown (increases exposure)
• Gentamicin + other nephrotoxic drugs (e.g., vancomycin, cisplatin): Increased risk of nephrotoxicity
• Gentamicin + neuromuscular blocking agents: Enhanced neuromuscular blockade

Precautions

• Monitor renal function during therapy, especially in patients with pre-existing renal impairment
• Caution in patients with pre-existing hearing loss or vestibular disorders
• Use with caution in pregnant women and during breastfeeding

Pregnancy

Use only if clearly needed and the benefit justifies the risk to the fetus. Limited data on use in pregnancy.

Breast-feeding

Gentamicin is excreted in breast milk, exercise caution when administering to breastfeeding mothers. Monitor infant for possible side effects.

Storage

Store below 25°C. Protect from light. Do not freeze.

Formulations

• Injection solution (various concentrations)
• Ophthalmic solution (0.3% w/v)
• Topical ointment (0.1% w/v)

Indications

• Pain relief
• Anti-inflammatory treatment
• Antipyretic therapy
• Vitamin supplementation
• Antioxidant therapy

Dosage

Children: Refer to specific acid formulation and context for paediatric dosing. Consult BNF for Children for accurate dosing recommendations.

Adults: Refer to specific acid formulation and context for dosing. Consult relevant guidelines or BNF for precise dosing information.

Mechanism of action

Acids typically exert their effects by participating in biochemical reactions as proton donors. For example, in the case of acetylsalicylic acid, it inhibits the enzyme cyclooxygenase (COX), leading to a decrease in the synthesis of prostaglandins, which are mediators of inflammation and pain. This mechanism reduces inflammation, alleviates pain, and can lower fever. Other acids may act through different pathways, depending on their structure and target sites.

Pharmacodynamics

The pharmacodynamic properties of acids are variable and depend on the specific acid in question. Generally, they can modulate pH levels, influence metabolic pathways, and affect cellular signaling. For instance, ascorbic acid acts as an antioxidant, protecting cells from oxidative stress, and plays a role in collagen synthesis and immune function. The effects of acids can be dose-dependent and influenced by factors such as absorption, distribution, metabolism, and excretion.

Pharmacokinetics

The pharmacokinetics of acids varies widely depending on the specific compound. Generally, they are absorbed through the gastrointestinal tract, with some, like ascorbic acid, being actively transported. Distribution occurs via systemic circulation, with binding to plasma proteins varying among different acids. Metabolism typically involves conjugation and transformation into metabolites, which may retain therapeutic properties or be inactive. Excretion is primarily renal, with many acids being eliminated as free acids or conjugated forms.

Pregnancy

The use of acid-based medications during pregnancy should be approached with caution. Some acids may have teratogenic effects, while others may be safe. Consultation with a healthcare professional is advised.

Breast-feeding

Caution is advised when using acid-based medications during breastfeeding, as some acids may pass into breast milk and affect the infant. Consultation with a healthcare provider is recommended.

Storage

Store at room temperature, away from moisture and light. Specific storage conditions may vary depending on the type of acid.

Indications

• Eczema
• Psoriasis
• Contact dermatitis
• Seborrheic dermatitis
• Atopic dermatitis

Dosage

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

Adults: Refer to relevant clinical guidelines or product information for specific dosing instructions.

Mechanism of action

Betamethasone dipropionate exerts its effects by binding to the glucocorticoid receptor, leading to the modulation of gene expression. This interaction results in the inhibition of pro-inflammatory cytokines, chemokines, and adhesion molecules, which reduces inflammation, suppresses the immune response, and promotes vasoconstriction in the affected tissues.

Pharmacodynamics

The pharmacodynamic effects of betamethasone dipropionate include a significant reduction in inflammation and immune response due to the inhibition of leukocyte infiltration at the site of inflammation. The drug also inhibits the release of arachidonic acid, subsequently decreasing the production of inflammatory mediators such as prostaglandins and leukotrienes. Its efficacy is enhanced by its high lipid solubility, allowing for better penetration through the skin layers.

Pharmacokinetics

Betamethasone dipropionate is well absorbed through the skin when applied topically. Its bioavailability is influenced by the formulation and the condition of the skin. The drug is metabolized primarily in the liver to inactive metabolites, which are excreted in the urine. The systemic absorption and effects are minimal when used as directed, but caution is advised in extensive applications or occlusive dressings, which may increase absorption.

Adverse effects

• Local skin atrophy
• Striae
• Telangiectasia
• Hypopigmentation
• Allergic contact dermatitis
• Systemic effects with prolonged use

Precautions

• Use with caution in patients with a history of diabetes mellitus
• Monitor for potential adrenal suppression with prolonged use
• Avoid application to infected areas unless treated

Pregnancy

Betamethasone dipropionate should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Limited data suggest that topical corticosteroids have low systemic absorption.

Breast-feeding

Caution is advised when using betamethasone dipropionate during breastfeeding, as it is unknown whether it is excreted in breast milk. Topical corticosteroids should be applied sparingly and avoided on the breast area to minimize ingestion by the infant.

Storage

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

Formulations

• Topical cream
• Topical ointment
• Topical lotion

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

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

• Vision correction
• Phototherapy for skin conditions (e.g., psoriasis, eczema)
• Treatment of seasonal affective disorder (SAD)
• Circadian rhythm disorders
• Wound healing

Dosage

Children: Light therapy for paediatric patients should be approached with caution and always under professional guidance. Specific dosages will depend on the individual treatment protocol and condition being addressed.

Adults: Dosage of light therapy varies based on the condition being treated and should be tailored to individual needs, typically ranging from 15 minutes to 2 hours of exposure per day depending on the specific treatment protocol.

Mechanism of action

Light affects biological systems primarily through phototransduction, which involves the conversion of light into electrical signals within photoreceptor cells in the retina. This process initiates a cascade of biochemical reactions that ultimately lead to visual perception. In addition, specific wavelengths of light can interact with various biological molecules, triggering cellular responses such as the production of vitamin D through skin exposure to UVB radiation.

Pharmacodynamics

The pharmacodynamic effects of light are highly dependent on its wavelength and intensity. Short-wavelength blue light (around 480 nm) is known to influence circadian rhythms by affecting melatonin secretion. In therapeutic settings, light can modulate biological responses, such as promoting wound healing, reducing inflammation, and alleviating symptoms of seasonal affective disorder (SAD) through bright light therapy.

Pharmacokinetics

Light does not undergo traditional pharmacokinetic processes such as absorption, distribution, metabolism, or excretion. Instead, its effects are immediate and localized, depending on the intensity and duration of exposure. The penetration depth of light varies with wavelength; for example, UV light can penetrate the skin and affect deeper tissues, while visible light primarily affects the surface layers.

Pregnancy

There is limited data on the effects of light exposure during pregnancy. However, excessive exposure to bright light can be harmful to both the mother and the developing fetus.

Breast-feeding

Light exposure is generally considered safe while breastfeeding, but excessive exposure should be avoided to prevent potential harm to the infant.

Storage

Light should be properly controlled and managed in environments where it is used, ensuring that exposure levels are safe and effective.

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

Glucocorticoids inhibit neutrophil apoptosis and demargination, and inhibit NF-Kappa B and other inflammatory transcription factors. They also inhibit phospholipase A2, leading to decreased formation of arachidonic acid derivatives. In addition, glucocorticoids promote anti-inflammatory genes like interleukin-10. Corticosteroids like betamethasone can act through nongenomic and genomic pathways. The genomic pathway is slower and occurs when glucocorticoids activate glucocorticoid receptors and initiate downstream effects that promote transcription of anti-inflammatory genes including phosphoenolpyruvate carboxykinase (PEPCK), IL-1-receptor antagonist, and tyrosine amino transferase (TAT). On the other hand, the nongenomic pathway is able to elicit a quicker response by modulating T-cell, platelet and monocyte activity through the use of existing membrane-bound receptors and second messengers. Corticosteroids interact with specific receptor proteins in target tissues to regulate the expression of corticosteroid responsive genes, thereby changing the levels and array of proteins synthesized by the various target tissues. As a consequence of the time required for changes in gene expression and protein synthesis, most effects of corticosteroids are not immediate, but become apparent after several hours. ... Although corticosteroids predominantly act to increase expression of target genes, there are well documented examples where glucocorticoids decrease transcription of target genes ... In contrast to these genomic effects, recent studies have raised the possibility that some actions of corticosteroids are immediate and are mediated by membrane-bound receptors. /Adrenocorticosteroids/ The mechanisms by which glucocorticoids inhibit glucose utilization in peripheral tissues are not fully understood. Glucocorticoids decrease glucose uptake in adipose tissue, skin, fibroblasts, thymocytes, and polymorphonuclear leukocytes; these effects are postulated to result from translocation of the glucose transporters from the plasma membrane to an intracellular location. These peripheral effects are associated with a number of catabolic actions, including atrophy of lymphoid tissue, decreased muscle mass, negative nitrogen balance, and thinning of the skin. /Adrenocorticalsteroids/ The mechanisms by which the glucocorticoids promote gluconeogenesis are not fully defined. Amino acids mobilized from a number of tissues in response to glucocorticoids reach the liver and provide substrate for the production of glucose and glycogen. In the liver, glucocorticoids induce the transcription of a number of enzymes involved in gluconeogenesis and amino acid metabolism, including phosphoenolpyruvate carboxykinase, glucose-6-phosphatase, and fructose-2,6-bisphosphatase. Analyses of the molecular basis for regulation of phosphoenolpyruvate carboxykinase gene expression have identified complex regulatory influences involving an interplay among glucocorticoids, insulin, glucagon, and catecholamine. The effects of these hormones and amines on phosphoenolpyruvate carboxykinase gene expression mirror the complex regulation of gluconeogenesis in the intact organism. /Adrenocorticalsteroids/ ... /A/ major action of corticosteroids on the cardiovascular system is to enhance vascular reactivity to other vasoactive substances. Hypoadrenalism generally is associated with hypotension and reduced response to vasoconstrictors such as norepinephrine and angiotensin II. This diminished pressor response is explained partly by recent studies in experimental systems showing that glucocorticoids increase expression of adrenergic receptors in the vascular wall. Conversely, hypertension is seen in patients with excessive glucocorticoid secretion, occurring in most patients with Cushing's syndrome and in a subset of patients treated with synthetic glucocorticoids (even those lacking any significant mineralocorticoid action). /Adrenocorticosteroids/ For more Mechanism of Action (

Pharmacodynamics

Corticosteroids bind to the glucocorticoid receptor inhibiting pro-inflammatory signals, while promoting anti-inflammatory signals. Corticosteroids have a wide therapeutic window as patients may require doses that are multiples of what the body naturally produces. Patients who require long-term treatment with a corticosteroid should be counselled regarding the risk of hypothalamic-pituitary-adrenal axis suppression and increased susceptibility to infections.

Mechanism of action

Clotrimazole acts primarily by damaging the permeability barrier in the cell membrane of fungi. Clotrimazole causes inhibition of ergosterol biosynthesis, an essential constituent of fungal cell membranes. If ergosterol synthesis is either completely or partially inhibited, the cell is no longer able to construct an intact and functional cell membrane,. Because ergosterol directly promotes the growth of fungal cells in a hormone‐like fashion, rapid onset of the above events leads to dose-dependent inhibition of fungal growth. Though decreased ergosterol, due to the inhibition of lanosterol 14-demethylase (also known as _CYP51_) is accepted to be primarily responsible for the antimycotic properties of clotrimazole, this drug also shows other pharmacological effects. These include the inhibition of sarcoplasmic reticulum Ca2+‐ATPase, depletion of intracellular calcium, and blocking of calcium‐dependent potassium channels and voltage‐dependent calcium channels. The action of clotrimazole on these targets accounts for other effects of this drug that are separate from its antimycotic activities. Clotrimazole exerts its antifungal activity by altering cell membrane permeability, apparently by binding with phospholipids in the fungal cell membrane. In contrast to polyene antibiotics (eg, amphotericin B), the action of clotrimazole is less dependent on the sterol content of the cell membrane. As a result of alteration of permeability, the cell membrane is unable to function as a selective barrier, and potassium and other cellular constituents are lost.

Pharmacodynamics

Clotrimazole is a broad-spectrum antifungal agent that inhibits the growth of pathogenic yeasts by changing the permeability of cell membranes. The action of clotrimazole is fungistatic at concentrations of drug up to 20 mcg/mL and may be fungicidal _in vitro_ against Candida albicans and other species of the genus Candida at higher concentrations. Unfortunately, resistance to clotrimazole, which was rare in the past, is now common in various patient populations. Clotrimazole is generally considered to be a fungistatic, and not a fungicidal drug, although this contrast is not absolute, as clotrimazole shows fungicidal properties at higher concentrations.

Mechanism of action

There are 3 key phases of aminoglycoside entry into cells. The first “ionic binding phase” occurs when polycationic aminoglycosides bind electrostatically to negatively charged components of bacterial cell membranes including with lipopolysaccharides and phospholipids within the outer membrane of Gram-negative bacteria and to teichoic acids and phospholipids within the cell membrane of Gram-positive bacteria. This binding results in displacement of divalent cations and increased membrane permeability, allowing for aminoglycoside entry. The second “energy-dependent phase I” of aminoglycoside entry into the cytoplasm relies on the proton-motive force and allows a limited amount of aminoglycoside access to its primary intracellular target - the bacterial 30S ribosome. This ultimately results in the mistranslation of proteins and disruption of the cytoplasmic membrane. Finally, in the “energy-dependent phase II” stage, concentration-dependent bacterial killing is observed. Aminoglycoside rapidly accumulates in the cell due to the damaged cytoplasmic membrane, and protein mistranslation and synthesis inhibition is amplified. The necessity of oxygen-dependent active transport explains why aminoglycosides are ineffective against anaerobic bacteria. Hence, aminoglycosides have both immediate bactericidal effects through membrane disruption and delayed bactericidal effects through impaired protein synthesis; observed experimental data and mathematical modeling support this two-mechanism model. Inhibition of protein synthesis is a key component of aminoglycoside efficacy. Structural and cell biological studies suggest that aminoglycosides bind to the 16S rRNA in helix 44 (h44), near the A site of the 30S ribosomal subunit, altering interactions between h44 and h45. This binding also displaces two important residues, A1492 and A1493, from h44, mimicking normal conformational changes that occur with successful codon-anticodon pairing in the A site. Overall, aminoglycoside binding has several negative effects including inhibition of translation, initiation, elongation, and ribosome recycling. Recent evidence suggests that the latter effect is due to a cryptic second binding site situated in h69 of the 23S rRNA of the 50S ribosomal subunit. Also, by stabilizing a conformation that mimics correct codon-anticodon pairing, aminoglycosides promote error-prone translation. Mistranslated proteins can incorporate into the cell membrane, inducing the damage discussed above. Aminoglycosides are usually bactericidal in action. Although the exact mechanism of action has not been fully elucidated, the drugs appear to inhibit protein synthesis in susceptible bacteria by irreversibly binding to 30S ribosomal subunits. /Aminoglycosides/ ... Aminoglycosides are aminocyclitols that kill bacteria by inhibiting protein synthesis as they bind to the 16S rRNA and by disrupting the integrity of bacterial cell membrane. Aminoglycoside resistance mechanisms include: (a) the deactivation of aminoglycosides by N-acetylation, adenylylation or O-phosphorylation, (b) the reduction of the intracellular concentration of aminoglycosides by changes in outer membrane permeability, decreased inner membrane transport, active efflux, and drug trapping, (c) the alteration of the 30S ribosomal subunit target by mutation, and (d) methylation of the aminoglycoside binding site. ... /Aminoglycosides/

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

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

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.