Dermovate cream

Indications

• Constipation
• Bowel cleansing

Dosage

Children: Child 1–11 months: 1 g as required, Child 1–11 years: 2 g as required, Child 12–17 years: 4 g as required.

Adults: 4 g as required, usually administered rectally.

Mechanism of action

When administered rectally, glycerol exerts a hygroscopic and/or local irritant action, drawing water from the tissues into the feces and reflexively stimulating evacuation. It decreases intraocular pressure by creating an osmotic gradient between the blood and intraocular fluid, causing fluid to move from the aqueous and vitreous humors into the bloodstream. Glycerol is classified as a hyperosmotic laxative and may also have lubricating and fecal softening effects.

Pharmacodynamics

Glycerol is commonly classified as an osmotic laxative, acting through its local irritant effects and possibly having lubricating and fecal softening actions. Glycerol suppositories usually produce effects within 15 to 30 minutes, providing quick relief from constipation.

Pharmacokinetics

Glycerol is rapidly absorbed through the gastrointestinal tract. It is metabolized in the liver and other tissues, with a half-life that varies depending on the route of administration. Following rectal administration, glycerol is primarily excreted in urine. The pharmacokinetics may vary based on dosage forms and individual patient factors.

Contra-indications

• Acute abdominal conditions
• Acute inflammatory bowel disease
• Intestinal obstruction
• Severe dehydration

Adverse effects

• Abdominal cramps
• Asthenia
• Gastrointestinal disorders
• Hypermagnesaemia
• Skin reactions
• Urine discolouration

Precautions

• Avoid prolonged contact with skin, especially in incontinent patients or infants wearing nappies due to the risk of irritation and excoriation.
• Excessive use may cause diarrhea and related effects such as hypokalaemia.

Pregnancy

Manufacturers advise avoidance due to limited information available.

Breast-feeding

Manufacturers advise avoidance as there is no information available.

Storage

Store at room temperature, away from direct sunlight.

Formulations

• Glycerol 1g suppositories
• Glycerol 2g suppositories
• Glycerol 4g suppositories
• Glycerol oral suspension

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

• Topical emulsions
• Creams
• Ointments

Dosage

Children: Refer to specific product guidelines for appropriate concentrations and application methods, as paediatric dosing may vary.

Adults: Dosage varies based on formulation and intended use. Refer to specific product guidelines for appropriate concentrations and application methods.

Mechanism of action

Arlacel acts by reducing the surface tension at the interface between oil and water, thus facilitating the formation and stabilization of emulsions. It forms a protective layer around dispersed droplets, preventing coalescence and improving product stability.

Pharmacodynamics

As a surfactant, Arlacel enhances the bioavailability of lipophilic drugs by improving their dispersion in aqueous solutions. Its emulsifying properties allow for a more uniform distribution of active ingredients in topical formulations, leading to improved therapeutic efficacy.

Pharmacokinetics

The pharmacokinetics of Arlacel is not well-documented in terms of absorption, distribution, metabolism, and excretion as it is primarily used topically. However, it is generally considered safe with low systemic absorption when applied to intact skin. Its emulsifying properties facilitate the delivery of drugs but do not significantly alter their pharmacokinetics.

Pregnancy

There is no specific information available regarding the use of Arlacel in pregnancy. Consult healthcare providers for guidance.

Breast-feeding

There is no specific information available regarding the use of Arlacel during breastfeeding. Consult healthcare providers for guidance.

Storage

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

Indications

• Skin moisturization
• Wound healing
• Chapped lips
• Eczema
• Dry skin conditions

Dosage

Children: Refer to specific formulations and guidelines for pediatric use. Dosage may vary based on the formulation and the specific product being used.

Adults: For topical application, beeswax is typically used in formulations at concentrations ranging from 10% to 50%, depending on the desired texture and properties of the product.

Mechanism of action

Beeswax functions primarily as an emollient, forming a protective barrier on the skin that prevents moisture loss. Its composition allows it to mix well with oils and other ingredients, enhancing the stability and texture of formulations. Beeswax also exhibits some antibacterial properties, making it beneficial in topical applications.

Pharmacodynamics

The emollient properties of beeswax help to soften and soothe the skin. It can improve skin hydration and elasticity, and its barrier-forming capability aids in protecting the skin from environmental irritants. Additionally, beeswax's low water solubility and high melting point contribute to its effectiveness as a thickening agent in various formulations.

Pharmacokinetics

Beeswax is not absorbed systemically in significant amounts when applied topically. It remains on the skin surface, where it exerts its emollient effects. Due to its composition, beeswax is stable and does not readily degrade under normal storage conditions. Its physical properties allow for a slow release of active ingredients in topical formulations.

Adverse effects

• Allergic reactions in sensitive individuals
• Skin irritation with topical application

Precautions

• Use with caution in individuals with known allergies to bee products
• Avoid use in open wounds or broken skin

Pregnancy

Considered safe for use during pregnancy when applied topically, but should be used with caution.

Breast-feeding

Generally regarded as safe for topical use during breastfeeding.

Storage

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

Formulations

• Beeswax pellets
• Beeswax pastilles
• Beeswax blocks

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

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

Dosage

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

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

Mechanism of action

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

Pharmacodynamics

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

Pharmacokinetics

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

Pregnancy

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

Breast-feeding

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

Storage

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

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

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

• Used as an emulsifying agent in pharmaceutical formulations
• Used in food products for texture and stability
• May be indicated in topical preparations to enhance drug absorption

Dosage

Children: Refer to specific product guidelines as doses can vary widely based on formulation and intended use.

Adults: Refer to specific product guidelines as doses can vary widely based on formulation and intended use.

Mechanism of action

Monostearate functions primarily as a surfactant. It reduces the surface tension between components in a mixture, allowing for better emulsification of oils and water. This action enhances the dispersion of active ingredients and improves their absorption in the gastrointestinal tract.

Pharmacodynamics

As an emulsifier, monostearate facilitates the formation of stable emulsions, which can lead to improved drug delivery and absorption. Its ability to enhance solubility of lipophilic compounds can result in increased bioavailability of certain drugs, making them more effective.

Pharmacokinetics

Monostearate is generally considered non-toxic and is metabolized by the body through hydrolysis into glycerol and stearic acid. It is poorly absorbed in the gastrointestinal tract due to its large molecular structure, and any absorbed amounts may be further metabolized or excreted. The onset and duration of action depend on the formulation in which it is used.

Pregnancy

Monostearate is generally considered safe for use during pregnancy, but it is important to consult with a healthcare provider for personalized advice.

Breast-feeding

Monostearate is typically regarded as safe during breastfeeding, but a healthcare provider should be consulted to ensure no adverse effects on the infant.

Storage

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

Formulations

• Monostearate powder
• Monostearate capsules
• Monostearate ointment

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.

Indications

• Diabetes mellitus
• Hypothyroidism
• Adrenal insufficiency
• Growth hormone deficiency
• Hypoparathyroidism

Dosage

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

Adults: Refer to the specific BNF for guidance on dosing based on the drug being substituted.

Mechanism of action

Substitutes function by replenishing the levels of specific hormones or substances that the body is not producing adequately. For instance, insulin substitutes facilitate glucose uptake into cells, thereby decreasing blood sugar levels in diabetic patients. Hormonal substitutes like levothyroxine mimic the action of naturally occurring hormones, regulating metabolic processes and maintaining homeostasis.

Pharmacodynamics

The pharmacodynamics of substitutes depend on the specific substance being replaced. Generally, these agents bind to specific receptors in target tissues, eliciting a biological response that aims to restore normal physiological functions. The efficacy of hormone substitutes is closely related to their ability to match the normal physiological levels and rhythms of the hormones they replace, thus minimizing adverse effects.

Pharmacokinetics

Pharmacokinetics of substitutes varies widely based on the specific drug. Typically, these drugs exhibit absorption, distribution, metabolism, and elimination characteristics that are tailored to mimic natural substances. For example, insulin is rapidly absorbed after subcutaneous injection and has a short half-life, necessitating multiple daily doses. In contrast, levothyroxine has a longer half-life and is usually administered once daily. The dosing and administration routes are designed to achieve therapeutic levels while minimizing the risk of toxicity.

Pregnancy

Consult a healthcare professional before use, as safety during pregnancy is not well established.

Breast-feeding

Consult a healthcare professional before use, as safety during breastfeeding is not well established.

Storage

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

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

When administered rectally, glycerin exerts a hygroscopic and/or local irritant action, drawing water from the tissues into the feces and reflexively stimulating evacuation. Glycerin decreases intraocular pressure by creating an osmotic gradient between the blood and intraocular fluid, causing fluid to move out of the aqueous and vitreous humors into the bloodstream. Glycerin (glycerol) and sorbitol are hyperosmotic laxatives. When administered rectally, glycerin and sorbitol exert a hygroscopic and/or local irritant action, drawing water from the tissues into the feces and reflexly stimulating evacuation. The extent to which the simple physical distention of the rectum and the hygroscopic and/or local irritant actions are responsible for the laxative effects of some of these drugs is not known. Only extremely high oral doses of sorbitol (25 g daily) or glycerin exert laxative action. /Glycerin/ decreases intraocular pressure by creating an osmotic gradient between the blood and intraocular fluid, causing fluid to move out of the aqueous and vitreous humors into the bloodstream. The physicochemical effects of a series of alkanols, alkanediols and glycerol on erythrocyte shape and hemolysis at 4 and 20 degrees C were examined. We calculated the dielectric constant of the incubation medium, Ds, and the dielectric constant of the erythrocyte membrane Dm in the presence of organic solutes. The ratio Ds/Dm = -38.48 at 20 degrees C defines the normal biconcave shape in a medium without hemolytic agents. A decrease in Ds/Dm favors externalization or internalization with consequent hemolysis. Alkanols and alkanediols convert biconcave erythrocytes into echinocytes, which is accompanied by an increase in the projected surface area. Glycerol converts biconcave erythrocytes into stomatocytes, which was accompanied by a marginal decrease in the projected surface area. Progressive externalization in alkanols and alkanediols or internalization in glycerol resulted in a decrease in the projected surface area and the formation of smooth spheres. The degree of shape change induced was related to the degree of hemolysis and the ratio Ds/Dm. A decrease in temperature reduced both the degree of shape change and hemolysis. .../Thus/ physicochemical toxicity may be a result of a temperature dependent hydrophobic interaction between the organic solutes and the membrane and is best interpreted by the ability of the solutes to change Ds and Dm.

Pharmacodynamics

Glycerin is commonly classified as an osmotic laxative but may act additionally or alternatively through its local irritant effects; it may also have lubricating and fecal softening actions. Glycerin suppositories usually work within 15 to 30 minutes.

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

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

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.