Demtris Cream

Indications

• Oral candidiasis
• Perioral fungal infections
• Oropharyngeal candidiasis

Dosage

Children: 100,000 units by mouth 4 times a day, usually for 7 days, continued for 48 hours after lesions have resolved.

Adults: 100,000 units by mouth 4 times a day, usually for 7 days, continued for 48 hours after lesions have resolved.

Mechanism of action

Nystatin is a channel-forming ionophore that binds to ergosterol, a sterol found in fungal cell membranes, creating membrane-spanning pores. This disrupts the membrane's integrity, resulting in the leakage of intracellular components and loss of electrochemical gradients essential for cell function, leading to cell death.

Pharmacodynamics

Nystatin exhibits both fungistatic and fungicidal activity against a wide range of yeasts and yeast-like fungi, particularly _Candida albicans_. Resistance is minimal with _Candida albicans_ but may develop in other _Candida_ species. It is ineffective against bacteria, protozoa, or viruses and has significant systemic toxicity, limiting its use to topical and oral applications.

Pharmacokinetics

Nystatin is poorly absorbed from the gastrointestinal tract, which allows it to exert its effects locally within the gut and oral cavity. Because of its limited systemic absorption, it is primarily used for local treatment of fungal infections. The drug is not metabolized systemically and is excreted unchanged in the feces.

Contra-indications

• Infants with impaired swallowing
• Acute porphyrias

Adverse effects

• Abdominal distress
• Angioedema
• Diarrhoea
• Face oedema
• Nausea
• Sensitisation
• Skin reactions
• Stevens-Johnson syndrome
• Vomiting

Precautions

• Caution in patients with acute porphyrias
• Use with care in patients with a history of hypersensitivity to nystatin or other polyene antifungals

Pregnancy

Nystatin is generally considered safe in pregnancy; however, it should be used only if clearly needed and prescribed by a healthcare provider.

Breast-feeding

Nystatin is excreted in breast milk but is considered safe for use during breastfeeding as it is poorly absorbed systemically.

Storage

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

Formulations

• Nystatin oral suspension 100,000 units/ml
• Nystatin tablets
• Nystatin capsules

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

• Bowel sterilization before surgery
• Hepatic coma
• Topical infections caused by susceptible organisms

Dosage

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

Adults: By mouth: 1 g every 1 hour for 4 hours, then 1 g every 4 hours for 2–3 days. For hepatic coma: Up to 4 g daily in divided doses usually for 5–7 days.

Mechanism of action

Neomycin sulfate binds to the 30S ribosomal subunit of bacteria, leading to the misreading of mRNA and the inhibition of protein synthesis. This disrupts the production of essential proteins needed for bacterial growth and function, ultimately resulting in cell death.

Pharmacodynamics

Neomycin demonstrates bactericidal activity against susceptible bacteria. Its efficacy is enhanced in alkaline environments, which is why it is often used in combination with other agents for surgical prophylaxis. The drug is primarily effective against a range of gram-negative organisms, including Escherichia coli and Klebsiella species, but also has some activity against gram-positive organisms.

Pharmacokinetics

Neomycin is poorly absorbed from the gastrointestinal tract, and its systemic absorption is minimal when administered orally. In cases of systemic use, such as intramuscular or intravenous administration, neomycin is distributed widely in the body but is primarily excreted unchanged in the urine. The elimination half-life varies but is generally around 2 to 3 hours in individuals with normal renal function. Monitoring of serum concentrations is essential to prevent toxicity, especially in patients with renal impairment.

Adverse effects

• neurotoxicity
• ototoxicity
• nephrotoxicity
• allergic reactions
• skin rashes
• hearing loss

Interactions

• other nephrotoxic drugs
• loop diuretics
• neuromuscular blocking agents

Precautions

• monitor renal function
• use cautiously in patients with hearing impairment
• avoid concurrent use with other ototoxic medications
• ensure adequate hydration

Pregnancy

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

Breast-feeding

Use caution; neomycin can be absorbed systemically and may affect the nursing infant.

Storage

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

Formulations

• oral tablets
• topical ointments
• injectable solutions

Indications

• Eczema
• Psoriasis
• Contact dermatitis
• Allergic dermatitis
• Seborrheic dermatitis

Dosage

Children: Refer to specific product information or clinical guidelines for appropriate dosing in children, as it varies by formulation and condition treated.

Adults: Refer to specific product information or clinical guidelines for appropriate dosing, as it varies by formulation and condition treated.

Mechanism of action

Acetonide exerts its effects by binding to glucocorticoid receptors in the cytoplasm of target cells, leading to the translocation of the receptor-ligand complex into the nucleus. This complex then influences the expression of specific genes, resulting in decreased production of pro-inflammatory cytokines and increased production of anti-inflammatory proteins. This modulation of gene expression contributes to its anti-inflammatory and immunosuppressive effects.

Pharmacodynamics

The pharmacodynamics of acetonide involve its ability to inhibit the migration of leukocytes to sites of inflammation, reduce the production of inflammatory mediators such as prostaglandins and leukotrienes, and suppress the immune response. The potency and duration of action can vary based on the specific formulation and concentration used.

Pharmacokinetics

Acetonide is absorbed through the skin when applied topically, with systemic absorption depending on the formulation, application area, and duration of use. It undergoes hepatic metabolism, and its metabolites are excreted primarily through the urine. The half-life and clearance rates can vary based on individual patient factors and specific formulations.

Contra-indications

• Hypersensitivity to acetonide or any component of the formulation.
• Active or untreated infections at the site of application.

Adverse effects

• Local irritation or burning sensation at the application site.
• Skin thinning or atrophy with prolonged use.
• Systemic effects such as adrenal suppression with high doses or prolonged therapy.

Interactions

• Increased risk of systemic effects when used with other corticosteroids.
• Potentially altered metabolism when administered with CYP3A4 inhibitors or inducers.

Precautions

• Use with caution in patients with a history of tuberculosis or other infections.
• Monitor for signs of adrenal insufficiency in patients on high doses.
• Avoid application to large areas of the body or under occlusive dressings.

Pregnancy

Acetonide should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Consult with a healthcare professional before use.

Breast-feeding

Limited data available. Use with caution as it may be excreted in breast milk. Consult with a healthcare professional before use.

Storage

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

Formulations

• Topical cream
• Topical ointment
• Topical solution

Indications

• Mild skin irritations
• Superficial cuts
• Allergies
• Insect bites
• Fungal infections (e.g., athlete's foot)
• Sore throat
• Hemorrhages
• Peptic ulcers
• Acne

Dosage

Children: Refer to the BNF for Children for appropriate dosing information for paediatric patients, as dosages will depend on the specific condition and formulation used.

Adults: Refer to specific product guidelines for dosage information, as aluminum formulations can vary. Generally, topical applications are used as directed for symptom relief.

Mechanism of action

Aluminum acetate acts as an astringent, causing shrinkage or constriction of body tissues following topical application. This effect occurs through osmotic flow of water away from the area of application, leading to decreased mucous secretions and blood serum discharge. Astringents like aluminum also promote mild coagulation of skin proteins, providing protective effects on the skin and aiding in the healing of minor skin irritations.

Pharmacodynamics

Aluminum compounds exert their effects primarily through their astringent properties, which can lead to reduced inflammation and secretion. The local application of aluminum results in a protective barrier on the skin and mucous membranes, which can diminish symptoms associated with irritation, such as itching or discomfort. Astringents are often indicated in conditions that require the drying of exudates or the protection of damaged skin.

Pharmacokinetics

Aluminum is poorly absorbed through the gastrointestinal tract when ingested, as most aluminum compounds are not soluble in water. When applied topically, aluminum is absorbed minimally, allowing it to act locally without significant systemic effects. The elimination of aluminum occurs primarily through the kidneys, with small amounts excreted in feces. It is important to monitor aluminum levels in patients with renal impairment, as they may be at risk of accumulation and toxicity.

Pregnancy

The safety of aluminum compounds during pregnancy has not been established. Use only if clearly needed.

Breast-feeding

Aluminum is excreted in breast milk. Caution should be exercised when administering to breastfeeding mothers.

Storage

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

Formulations

• Aluminum Acetate solution
• Aluminum Hydroxide gel

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

• Dry skin
• Skin irritation
• Eczema
• Dermatitis
• Cosmetic applications as a moisturizer and thickening agent

Dosage

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

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

Mechanism of action

Dimethicone works by forming a protective layer on the skin, which helps to seal in moisture and protect the skin from irritants. Its anti-foaming properties are due to its ability to reduce surface tension, allowing gas bubbles to coalesce and escape more easily, thus diminishing the formation of foam in solutions.

Pharmacodynamics

Dimethicone exhibits emollient properties, which means it can soften and soothe the skin. It acts by creating a barrier that prevents transepidermal water loss, thereby enhancing hydration. Its non-irritating nature makes it suitable for sensitive skin, and it does not clog pores, making it a preferred choice in many dermatological preparations.

Pharmacokinetics

Dimethicone is not absorbed systemically; it remains on the skin surface and does not penetrate into the deeper layers of the skin. This characteristic makes it effective as a topical agent. Because it is not metabolized or excreted by the body, its pharmacokinetic profile is primarily focused on its local effects rather than systemic absorption.

Adverse effects

• Allergic reactions
• Skin irritation
• Gastrointestinal discomfort

Precautions

• Use with caution in patients with a history of allergic reactions to silicone-based compounds
• Monitor for any signs of adverse reactions during treatment

Pregnancy

Dimethicone is generally considered safe for use during pregnancy, as it is not absorbed systemically.

Breast-feeding

Dimethicone is considered safe for use during breastfeeding, as it is not absorbed and is unlikely to affect breastfed infants.

Storage

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

Formulations

• Topical creams
• Lotions
• Ointments
• Oral suspensions

Indications

• Monitoring respiratory function
• Assessment of metabolic status
• Management of respiratory acidosis
• Management of respiratory alkalosis

Dosage

Children: Dosing for interventions related to carbon dioxide levels in pediatric patients should be guided by clinical protocols and the BNF for Children.

Adults: Dosing for interventions related to carbon dioxide levels is typically based on clinical assessment and individual patient needs. Refer to clinical guidelines for specific scenarios.

Mechanism of action

Carbon dioxide acts primarily as a signaling molecule in the body, influencing respiratory drive and blood pH. It is produced during cellular respiration and is a critical component of the bicarbonate buffering system, which helps maintain acid-base homeostasis. Elevated levels of CO2 in the blood stimulate ventilation in the lungs, increasing the rate of gas exchange and facilitating the removal of excess CO2.

Pharmacodynamics

The pharmacodynamic effects of dioxides, particularly carbon dioxide, are closely related to its concentration in the blood. As CO2 levels increase, it leads to respiratory acidosis, which can stimulate the respiratory centers in the brain to increase ventilation. Conversely, low levels of CO2 can cause respiratory alkalosis, potentially leading to decreased respiratory drive. CO2 also plays a role in vasodilation and can affect blood flow and pressure through its influence on smooth muscle tone.

Pharmacokinetics

Carbon dioxide is produced endogenously during metabolic processes and is transported in the bloodstream primarily in three forms: dissolved in plasma, as bicarbonate ions (HCO3-), and bound to hemoglobin. The half-life of CO2 in the bloodstream is very short due to its rapid exchange with alveolar gas in the lungs. The elimination of CO2 occurs through exhalation, making it a dynamic component of respiratory physiology.

Pregnancy

Data on the effects of dioxide during pregnancy are limited. Caution is advised due to potential risks associated with exposure.

Breast-feeding

Limited data are available regarding the excretion of dioxide in human milk. Caution is recommended.

Storage

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

Indications

• Nutritional supplementation
• Herbal therapy for various conditions
• Preservation of medicinal properties of plants

Dosage

Children: Dosage for dried herbal preparations in children should be approached cautiously and is best determined by a healthcare professional. Refer to paediatric guidelines for specific dosing recommendations.

Adults: Dosage for dried herbal preparations varies widely depending on the specific herb and its intended use. Refer to specific guidelines or reputable sources for dosing information.

Mechanism of action

The mechanism of action for dried herbal preparations varies depending on the specific plant material involved. Generally, the active constituents in dried herbs can exert their effects through various pathways, such as modulating neurotransmitter systems, influencing metabolic pathways, and acting on specific receptors in the body. For instance, flavonoids, terpenes, and alkaloids found in certain dried herbs can exhibit anti-inflammatory, antioxidant, or antimicrobial properties.

Pharmacodynamics

The pharmacodynamics of dried drugs depend on their specific chemical constituents. These compounds can affect physiological functions, such as modulating inflammatory responses, enhancing immune function, or affecting neurotransmission. The effects can vary widely based on the type of herb, the method of drying, and the concentration of active ingredients.

Pharmacokinetics

The pharmacokinetics of dried herbal preparations can vary significantly based on the specific herb used. Generally, after ingestion, the active compounds are absorbed in the gastrointestinal tract, metabolized primarily by the liver, and then excreted through urine or feces. The bioavailability of these compounds can be influenced by factors such as the form of the preparation (e.g., powder, extract), the presence of other food substances, and individual patient characteristics.

Pregnancy

Safety during pregnancy has not been established. Consult a healthcare provider before use.

Breast-feeding

Consult a healthcare provider before use during breastfeeding.

Storage

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

Mechanism of action

Ethylenediamine acts as a gamma-aminobutyric acid (GABA) agonist by enhancing the binding of labeled diazepam to rat forebrain membrane preparations in a bicuculline-sensitive manner. Although it has significantly lower potency compared to GABA, it serves as an inhibitor of beta-alanine uptake in the cerebral cortex. Additionally, ethylenediamine facilitates the release of labeled GABA from glial cells in the retina, indicating its involvement in neurotransmitter modulation.

Pharmacodynamics

Ethylenediamine exhibits weak GABAergic activity, being 700-800 times less potent than GABA itself in enhancing diazepam binding. Its primary action is as an inhibitor of beta-alanine uptake, which may have implications for neurotransmitter balance in the central nervous system. The compound's effects on GABA release suggest a role in the modulation of inhibitory neurotransmission, although further studies are necessary to fully elucidate its pharmacodynamic profile.

Pharmacokinetics

The pharmacokinetics of ethylenediamine are not extensively documented in the literature. However, as a small organic molecule, it is likely to be absorbed readily upon administration. The distribution, metabolism, and excretion pathways are not well characterized, warranting further investigation to elucidate its pharmacokinetic properties.

Pregnancy

There are no well-controlled studies in pregnant women. Ethylenediamine should only be used if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

It is not known whether ethylenediamine is excreted in human milk. Caution should be exercised when administering to nursing mothers.

Storage

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

Indications

• Angina pectoris
• Heart failure
• Hypertensive emergencies
• Myocardial infarction

Dosage

Children: Dosing in children is not well established; refer to

Adults: For acute angina, 0.3 to 0.6 mg sublingually. For transdermal patches, doses vary based on the specific product; consult guidelines for individualized dosing.

Mechanism of action

Nitroglycerin is converted by mitochondrial aldehyde dehydrogenase in vascular smooth muscle cells to nitric oxide (NO). NO activates guanylate cyclase, leading to the conversion of guanosine triphosphate (GTP) to cyclic guanosine 3',5'-monophosphate (cGMP). cGMP induces relaxation of vascular smooth muscle, which results in vasodilation and increased blood flow, particularly to the heart. This mechanism reduces myocardial oxygen requirements and alleviates angina symptoms.

Pharmacodynamics

Nitroglycerin causes relaxation of vascular smooth muscles, leading to both arteriolar and venous dilation. This results in increased myocardial blood flow, reduced cardiac preload and afterload, and lowered myocardial wall stress. Additionally, it alleviates coronary artery spasms and decreases systemic vascular resistance and blood pressure. Tolerance may develop with prolonged use, reducing efficacy due to desensitization of smooth muscle and potential inhibition of mitochondrial aldehyde dehydrogenase.

Pharmacokinetics

Nitroglycerin is rapidly absorbed and undergoes significant first-pass metabolism when administered orally. It has a half-life of about 1-4 minutes when given intravenously. The onset of action varies depending on the route of administration, with sublingual forms acting within minutes and transdermal patches providing sustained release. The drug is metabolized primarily in the liver and excreted in urine as metabolites.

Contra-indications

• Hypersensitivity to nitroglycerin or any of its components
• Severe anemia
• Increased intracranial pressure
• Hypotension
• Cardiomyopathy with obstructive lesions
• Severe aortic stenosis

Adverse effects

• Headache
• Dizziness
• Hypotension
• Tachycardia
• Nausea
• Flushing
• Methemoglobinemia

Interactions

• Concurrent use with phosphodiesterase type 5 inhibitors (e.g., sildenafil, tadalafil) may lead to severe hypotension
• Antihypertensives may enhance the hypotensive effect of nitroglycerin
• Alcohol may increase the risk of hypotension
• Other vasodilators may have additive effects

Precautions

• Use with caution in patients with renal or hepatic impairment
• Monitor blood pressure regularly
• Consider potential for tolerance with prolonged use
• Should not be abruptly discontinued after long-term use

Pregnancy

Nitroglycerin should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Limited data available.

Breast-feeding

Nitroglycerin 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 moisture and heat.

Formulations

• Sublingual tablets
• Transdermal patches
• Oral extended-release capsules
• Intravenous infusion
• Topical ointment

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

Dosage

Children: Refer to specific guidelines for pediatric dosing; consult the BNF for Children for accurate dosage information.

Adults: Refer to specific guidelines for use; dosage may vary based on the context of use.

Mechanism of action

Hydroxide ions act primarily as bases, neutralizing acids to form water and salts. They participate in various biochemical pathways, including selenium metabolism and the degradation of reactive oxygen species. Hydroxide can influence enzyme activity and stability by altering the pH of the environment, thereby affecting metabolic reactions.

Pharmacodynamics

Hydroxide ions can impact biological processes by changing the local pH, which influences enzyme activity, ion transport, and the solubility of other compounds. Their ability to neutralize acids can help regulate physiological pH, contributing to homeostasis in living organisms.

Pharmacokinetics

As an inorganic ion, hydroxide does not undergo traditional pharmacokinetic processes like absorption, distribution, metabolism, or excretion. Instead, it is rapidly equilibrated in biological fluids and participates in acid-base reactions, having immediate effects on the local environment.

Pregnancy

There is limited information regarding the use of hydroxide during pregnancy. Consult a healthcare professional for advice.

Breast-feeding

Limited data is available on the excretion of hydroxide in breast milk. Consult a healthcare professional before use.

Storage

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

Indications

• Preservative in pharmaceuticals
• Preservative in cosmetics
• Food preservative

Dosage

Children: Refer to specific product guidelines for concentrations and usage recommendations, as there are no standardized dosing regimens for methylparaben due to its use primarily as a preservative.

Adults: Refer to specific product guidelines for concentrations and usage recommendations, as there are no standardized dosing regimens for methylparaben due to its use primarily as a preservative.

Mechanism of action

Methylparaben functions as an antimicrobial agent by disrupting the cell membrane of bacteria and fungi, leading to cell lysis and death. It exerts its effects by inhibiting the enzyme activity necessary for microbial metabolism, which ultimately prevents the growth of these microorganisms.

Pharmacodynamics

The pharmacodynamics of methylparaben involve its ability to inhibit the growth of a wide range of bacteria and fungi. It is typically effective against gram-positive bacteria and some yeast species. The compound is often used in combination with other preservatives to enhance its antimicrobial efficacy and broaden its spectrum of activity.

Pharmacokinetics

Methylparaben is rapidly absorbed through the skin and mucous membranes, with metabolism primarily occurring in the liver. It is conjugated to form glucuronide and sulfate metabolites, which are then excreted in the urine. The compound has a relatively short half-life, and its systemic exposure is low when used in topical applications.

Adverse effects

• Allergic reactions including rash, itching, and swelling
• Contact dermatitis
• Irritation at the site of application

Precautions

• Use with caution in patients with known allergies to parabens
• Should not be applied to broken or inflamed skin

Pregnancy

Limited data available; use only if clearly needed and benefits outweigh risks.

Breast-feeding

Limited data available; consult healthcare provider before use.

Storage

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

Formulations

• Topical creams
• Lotions
• Ointments
• Cosmetic products

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

• Bacterial infections caused by aerobic organisms
• Topical treatment of skin infections

Mechanism of action

Neomycin binds to specific proteins and 16S rRNA within the 30S ribosomal subunit of susceptible bacteria. This binding interferes with the decoding site, causing misreading of mRNA and leading to the incorporation of incorrect amino acids into polypeptides. As a result, nonfunctional or toxic peptides are produced, and polysomes are disrupted into nonfunctional monosomes. Neomycin's bactericidal action is characterized by its ability to irreversibly bind to the 30S ribosomal subunit, thereby inhibiting bacterial protein synthesis.

Pharmacodynamics

Neomycin is primarily active against aerobic bacteria and is not effective against fungi, viruses, or most anaerobic bacteria. It mediates its bactericidal effects by inhibiting protein synthesis, which suppresses bacterial growth and survival. Following oral administration, neomycin exhibits a duration of bactericidal activity lasting between 48 to 72 hours. It is particularly useful in treating infections caused by strains of E. coli and Klebsiella, and it also acts to reduce colonic bacterial populations in patients with hepatic coma.

Pharmacokinetics

Neomycin is poorly absorbed from the gastrointestinal tract when taken orally, which limits its systemic availability and enhances its utility in targeting colonic bacteria. It is generally not used parenterally due to its potential for nephrotoxicity and ototoxicity. The duration of action following oral administration can last from 48 to 72 hours, and it is primarily excreted unchanged in the urine. Caution should be exercised when using neomycin in patients with renal impairment, as the risk of toxicity increases.

Adverse effects

• Nephrotoxicity
• Ototoxicity
• Allergic reactions
• Diarrhea
• Nausea
• Vomiting

Interactions

• neomycin+digoxin: Unknown (decreases absorption)
• neomycin+sorafenib: Unknown (decreases exposure)

Precautions

• Use with caution in patients with renal impairment
• Monitor renal function during therapy
• Evaluate hearing function in long-term use

Pregnancy

Neomycin is classified as category D; it should be used only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

Neomycin is excreted in breast milk; caution should be exercised when administered to nursing mothers.

Storage

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

Formulations

• Topical ointment
• Cream
• Eye drops
• Oral tablets

Indications

• Constipation
• Bowel preparation prior to surgical procedures or diagnostic tests

Dosage

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

Adults: Refer to specific guidelines or BNF for detailed dosing information.

Mechanism of action

Polyethylene glycol works by osmotically retaining water in the intestinal lumen, which increases the water content of the stool. This enhances the passage of stool through the intestines and promotes bowel movements. The high molecular weight of polyethylene glycol prevents its absorption in the gastrointestinal tract, ensuring that it remains in the lumen to exert its effects.

Pharmacodynamics

The pharmacodynamic profile of polyethylene glycol involves its ability to increase stool water content, thereby reducing stool consistency and facilitating easier passage. It does not stimulate intestinal motility directly but rather relies on the osmotic effect to promote bowel evacuation. The onset of action typically occurs within 24 to 96 hours after ingestion.

Pharmacokinetics

Polyethylene glycol is not absorbed systemically, and its pharmacokinetics are characterized by its presence solely in the gastrointestinal tract. It is excreted unchanged in the stool. The volume of polyethylene glycol administered can influence the effectiveness and timing of its action, but its absorption is negligible, making systemic side effects rare.

Adverse effects

• Abdominal cramping
• Diarrhea
• Nausea
• Vomiting
• Bloating
• Flatulence

Precautions

• Use with caution in patients with gastrointestinal disorders or bowel obstruction.
• Ensure adequate hydration during use to prevent dehydration.

Pregnancy

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

Breast-feeding

Polyethylene glycol is excreted in breast milk in very small amounts and is generally regarded as safe during breastfeeding.

Storage

Store at room temperature, away from moisture and heat.

Formulations

• Powder for oral solution
• Liquid formulation

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.

Indications

• Preservative in topical pharmaceutical preparations
• Preservative in cosmetic products
• Preservative in food products

Dosage

Children: Refer to specific product guidelines for appropriate dosing as dosages may vary based on formulation and intended use.

Adults: Refer to specific product guidelines for appropriate dosing as dosages may vary based on formulation and intended use.

Mechanism of action

Propylparahydroxybenzoate acts as a preservative by inhibiting the growth of microorganisms. Its mechanism involves the disruption of the microbial cell membrane and interference with energy production processes within the cell. This leads to a decrease in microbial viability and replication, effectively preventing contamination in products.

Pharmacodynamics

The pharmacodynamics of propylparahydroxybenzoate involve its ability to permeate microbial cell membranes, where it disrupts essential biochemical processes. Its efficacy is influenced by factors such as pH, concentration, and temperature. It is typically effective in lower pH environments, which is common in many cosmetic and pharmaceutical formulations.

Pharmacokinetics

Propylparahydroxybenzoate is generally poorly absorbed through the skin or gastrointestinal tract when used in topical or oral formulations. When absorbed, it can undergo hydrolysis to form p-hydroxybenzoic acid. The compound is primarily excreted in urine. The half-life and specific metabolic pathways may vary based on individual factors and the formulation used.

Adverse effects

• Allergic reactions
• Skin irritation
• Contact dermatitis

Precautions

• Use with caution in individuals with known hypersensitivity to parabens
• Avoid use in children with sensitive skin or open wounds

Pregnancy

Propylparahydroxybenzoate is generally considered safe during pregnancy, but should be used only if clearly needed.

Breast-feeding

Considered safe during breastfeeding, but should be used with caution.

Storage

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

Formulations

• Topical formulations (creams, lotions)
• Oral preparations (as a food preservative)

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

• Food preservation
• Cosmetic preservation
• Pharmaceutical preservation

Dosage

Children: Refer to applicable regulations and guidelines for specific usage limits, typically not exceeding 0.1% to 0.3% in food products.

Adults: Refer to applicable regulations and guidelines for specific usage limits, typically not exceeding 0.1% to 0.3% in food products.

Mechanism of action

Sorbic acid exerts its antimicrobial effects by inhibiting the enzyme activity required for yeast and mold growth. It disrupts the metabolic pathways of these microorganisms, preventing their reproduction and leading to cell death. The undissociated form of sorbic acid penetrates the microbial cell membrane, where it lowers the intracellular pH, thus inhibiting vital cellular processes.

Pharmacodynamics

Sorbic acid is effective against a wide range of fungi and some bacteria. Its antimicrobial activity is pH-dependent, exhibiting greater efficacy at lower pH levels. The compound is particularly effective in acidic environments, making it suitable for use in acidic food products. The inhibitory concentration varies depending on the type of microorganism, with molds generally being more susceptible than bacteria.

Pharmacokinetics

Sorbic acid is poorly absorbed in the gastrointestinal tract when ingested, leading to minimal systemic exposure. It is primarily excreted unchanged in the urine. The half-life of sorbic acid in the body is short, which correlates with its rapid elimination. The compound does not accumulate in tissues, making it safe for short-term consumption at low doses.

Adverse effects

• Allergic reactions
• Skin irritation
• Gastrointestinal disturbances

Precautions

• Use with caution in patients with known allergies to sorbates
• Should be used in moderation to avoid potential gastrointestinal upset

Pregnancy

Safety during pregnancy has not been established; consult a healthcare provider before use.

Breast-feeding

Consult a healthcare provider before use while breastfeeding.

Storage

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

Formulations

• Sorbic acid
• Potassium sorbate

Indications

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

Dosage

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

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

Mechanism of action

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

Pharmacodynamics

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

Pharmacokinetics

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

Adverse effects

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

Precautions

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

Pregnancy

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

Breast-feeding

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

Storage

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

Formulations

• Oral solution
• Syrup

Indications

• Orthopedic implants
• Dental implants
• Prosthetic devices
• Surgical instruments

Mechanism of action

Titanium does not have a specific mechanism of action as it is not a drug in the traditional sense. Instead, its biocompatibility allows it to integrate with biological tissues without eliciting significant immune responses, making it suitable for use in implants and prosthetic devices. The presence of titanium ions can influence biological processes, including cell proliferation and differentiation.

Pharmacodynamics

Titanium itself does not exhibit pharmacodynamics as it is not administered as a drug. Its interactions within biological systems are primarily mechanical and structural, providing support and stability in orthopedic and dental applications. The biocompatibility of titanium allows for favorable tissue integration and reduced rejection rates compared to other materials.

Pharmacokinetics

As titanium is not a pharmacological agent, traditional pharmacokinetic parameters such as absorption, distribution, metabolism, and excretion do not apply. Titanium is typically utilized in solid forms, such as implants, where it remains localized and does not undergo metabolism or systemic circulation.

Pregnancy

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

Breast-feeding

There is limited data on the excretion of titanium in breast milk. Consult a healthcare professional before use.

Storage

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

Indications

• Asthma
• Allergic rhinitis
• Rheumatoid arthritis
• Systemic lupus erythematosus
• Dermatitis
• Psoriasis
• Inflammatory bowel disease

Dosage

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

Adults: Refer to BNF for specific dosing recommendations based on condition and formulation.

Mechanism of action

Triamcinolone inhibits phospholipase A2 on cell membranes, preventing the breakdown of lysosomal membranes of leukocytes. This action reduces the formation of arachidonic acid, leading to decreased expression of cyclooxygenase and lipoxygenase, which inhibits the synthesis of prostaglandins and leukotrienes. Additionally, triamcinolone inhibits nuclear factor kappa-B, reducing pro-inflammatory signals such as interleukin-6 and interleukin-8. It interacts with specific intracellular receptor proteins to alter the expression of corticosteroid-responsive genes, leading to the synthesis of proteins like lipocortin that further inhibit inflammatory pathways.

Pharmacodynamics

Triamcinolone exhibits significant anti-inflammatory effects through multiple mechanisms, including suppression of immune cell migration and modulation of inflammatory mediator production. Its effects can lead to reduced edema, erythema, and pain associated with inflammatory processes. The drug’s action is mediated by its ability to influence gene expression in target tissues, resulting in a broad range of effects on the immune response and inflammation.

Pharmacokinetics

Triamcinolone is well absorbed following parenteral administration, with peak plasma concentrations typically observed within a few hours. It has a relatively long half-life, which allows for sustained therapeutic effects. The drug is metabolized primarily in the liver and excreted via the kidneys. Its pharmacokinetic profile may vary depending on the route of administration and the specific formulation used.

Interactions

• mitotane+triamcinolone: Moderate (decreases exposure)
• rifampicin+triamcinolone: Moderate (decreases exposure)
• cobicistat+triamcinolone: Unknown (increases exposure)
• idelalisib+triamcinolone: Unknown (increases exposure)
• clarithromycin+triamcinolone: Unknown (increases exposure)

Pregnancy

Corticosteroids, including triamcinolone, should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. They may cause fetal harm, particularly when used in high doses or for prolonged periods in the second and third trimesters.

Breast-feeding

Triamcinolone is excreted in human milk, and caution should be exercised when administering to nursing mothers. The benefits of breastfeeding should be weighed against the potential risk of adverse effects on the infant.

Storage

Store at room temperature, away from light and moisture. Do not freeze.

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

Nystatin is a channel-forming ionophore, meaning it exerts its therapeutic effect via formation of a membrane-spanning pore in the fungal plasma membrane. The formation of this pore results in a change in membrane permeability that allows for leakage of intracellular contents and the subsequent disruption of electrochemical gradients necessary for proper cell function. Selectivity for fungal cells over mammalian cells is due to nystatin’s greater binding affinity for ergosterol, a key sterol found in fungal cell walls, as opposed to its mammalian counterpart, cholesterol. Nystatin exerts its antifungal activity by binding to sterols in the fungal cell membrane. The drug is not active against organisms (e.g., bacteria) that do not contain sterols in their cell membrane. As a result of this binding, the membrane is no longer able to function as a selective barrier, and potassium and other cellular constituents are lost. ... /Antimicrobial/ agents that act directly on the cell membrane of the microorganism, affecting permeability and leading to leakage of intracellular compounds; these include ... the polyene antifungal agents nystatin ... which bind to cell-wall sterols ...

Pharmacodynamics

Nystatin is an antifungal that is both fungistatic and fungicidal in vitro against a wide variety of yeasts and yeast-like fungi. It exerts its antifungal effects via disruption of the fungal cell membrane. Resistance to nystatin is minimal in _Candida albicans_, but tends to develop in other species of _Candida_. Nystatin carries no significant activity against bacteria, protozoa, or viruses. It carries significant systemic toxicity and is currently unavailable in a formula appropriate for systemic use - its efficacy is currently restricted, therefore, to topical, oral, and gastrointestinal infections.

Mechanism of action

Aluminum Acetate is an astringent. An astrignent is a chemical that tends to shrink or constrict body tissues, usually locally after topical medicinal application. The shrinkage or constriction is through osmotic flow of water (or other fluids) away from the area where the astringent was applied. Astringent medicines cause shrinkage of mucous membranes or exposed tissues and are often used internally to check discharge of blood serum or mucous secretions. This can happen with a sore throat, hemorrhages, diarrhea, or with peptic ulcers. Externally applied astringents, which cause mild coagulation of skin proteins, dry, harden, and protect the skin. Acne sufferers are often advised to use astringents if they have oily skin. Astringents also help heal stretch marks and other scars. Mild astringent solutions are used in the relief of such minor skin irritations as those resulting from superficial cuts, allergies, insect bites, or fungal infections such as athlete's foot. Excessive dietary aluminum has been proposed to be a factor contributing to several neurological disorders in humans. Six 8-week-old female Swiss Webster mice were fed for 10 wk purified diets containing 100 (control), 500 or 1000 ug aluminum/g diet. Brain and liver lipid peroxidation was determined by evaluating the production of 2-thiobarbituric acid reactive substances in brain and liver homogenates in the presence or absence of 50 uM ferrous iron. 2-Thiobarbituric acid reactive substances production in the absence of iron in brain homogenates from mice fed the 1000 ug/g diet was higher (30%) than that in the 100 ug/g control group (3.1 vs 2.4 nmol 2-thiobarbituric acid reactive substances/mg protein). The addition of ferrous iron increased 2-thiobarbituric acid reactive substances production in brain homogenates from all 3 dietary groups. The iron induced 2-thiobarbituric acid reactive substances production was 26% higher in the 1000 ug/g brain homogenates than in the 100 ug/g group (4.9 vs 3.9 nmol 2-thiobarbituric acid reactive substances/mg protein). Brain 2-thiobarbituric acid reactive substances production in the presence and absence of iron was similar between the 100 and 500 ug/g aluminum groups. 2-Thiobarbituric acid reactive substances production in liver homogenates measured either with or without iron was similar for the 3 groups. These results show that, in mice, dietary aluminum intoxication leads to increased brain 2-thiobarbituric acid reactive substance production, suggesting that enhanced lipid peroxidation may be one possible mechanism underlying the neurological damage associated with increased tissue aluminum. Evidence is presented indicating that dementias are associated with a relative insufficiency of magnesium in the brain. Such insufficiency may be attributable to low intake or retention of magnesium; high intake of a neurotoxic metal, such as aluminum, which inhibits activity of magnesium requiring enzymes; or impaired transport of magnesium and/or enhanced transport of the neurotoxic metal into brain tissue. It is proposed that Alzheimer's disease involves a defective transport process, characterized by both an abnormally high incorporation of aluminum and an abnormally low incorporation that an altered serum protein contributes to the progression of Alzheimer's disease by having a greater affinity for aluminum than for magnesium, in contrast to the normal protein, which binds magnesium better than aluminum. The altered protein crosses the blood-brain barrier more efficiently than the normal protein and competes with the normal protein in binding to brain neurons. Binding of the altered protein to the target neurons would both facilitate aluminum uptake and impede magnesium uptake. Evidence suggests that albumin is the serum protein that is altered. Aluminum is established as a neurotoxin, although the basis for its toxicity is unknown. It recently has been shown to alter the function of the blood-brain barrier, which regulates ex

Mechanism of action

Ethylenediamine (EDA) acted as a gamma-aminobutyric acid (GABA) agonist by enhancing (3)H-labeled diazepam binding to well-washed rat forebrain membrane prepn in a bicuculline-sensitive manner, although its potency was 700-800 fold less than that of gamma-aminobutyric acid. Ethylenediamine was more than 3750-fold weaker than gamma-aminobutyric acid as a displacer of (3)H-gamma-aminobutyric acid bound to membrane receptors & was more than 40-fold weaker than gamma-aminobutyric acid at (3)H-gamma-aminobutyric acid uptake sites. Its most potent action was as an inhibitor of beta-alanine uptake into rat cerebral cortex slices. The release of (3)H gamma-aminobutyric acid (GABA) from Mueller (glial) cells was studied in the rat retina by a double isotope-labeling technique in which Mueller cells are preloaded with (3)H-gamma-aminobutyric acid while a population of neurons is prelabeled with (14)C-labeled glycine. The effects of 2 depolarizing agents, high K+ and veratridine, and the gamma-aminobutyric acid mimetic, ethylenediamine (EDA), on transmitter release from glial cells and neurons were simultaneously determined. Ethylenediamine released (3)H-gamma-aminobutyric acid readily, whereas little (14)C-glycine release was observed.

Mechanism of action

Nitroglycerin is converted by mitochondrial aldehyde dehydrogenase in smooth muscle cells to nitric oxide (NO), a potent vasodilator. NO activates the enzyme guanylate cyclase, which converts guanosine triphosphate (GTP) to cyclic guanosine 3',5'-monophosphate (cGMP) in vascular smooth muscle and other tissues. cGMP is an endogenous vasodilator of vascular smooth muscle: it causes protein kinase-dependent phosphorylation and activates downstream cascades that promote relaxation and increased blood flow in veins, arteries and cardiac tissue. An _in vitro_ study using mouse aorta suggests that nitric oxide, an active metabolite of nitroglycerin, targets the natriuretic peptide receptors. The drugs used to treat angina alleviate symptoms by increasing blood flow to the ischemic myocardium and/or by reducing myocardial oxygen requirements. ... /Nitrates/ reduce myocardial oxygen requirements through their effects on the systemic circulation. Their major systemic action is a reduction in venous tone, which leads to pooling of blood in peripheral veins, decreased venous return, and reduced ventricular volume and myocardial tension (preload). /Org nitrates/ Although it predominately affects vascular smooth muscle /nitroglycerin/, the bronchioles, gastrointestinal tract (including biliary system), ureters, and uterus are affected. Free radicals of nitric oxide may activate guanylate cyclase, resulting in increased synthesis of cyclic GMP. Nitric oxide may combine with sulfhydryl groups in the endothelium and produce S-nitrosothiols, which stimulate guanylate cyclase production. N-acetyl-cycteine may enhance this process by providing a source of sulfhydryl groups. Cyclic GMP appears to reduce stored calcium and interfere with calcium-activated smooth muscle contractions. Organic nitrates... lead to the formation of the reactive free radical nitric oxide, which can activate guanylyl cyclase and increase the synthesis of cyclic GMP in smooth muscle and other tissues... A cyclic GMP-dependent protein kinase catalyzes the phosphorylation of various proteins in smooth muscle. Eventually, the light chain of myosin is dephosphorylated. Phosphorylation of the myosin chain regulates the maintenance of the contractile state in smooth muscle. Nitrates also may alter the prostaglandin system by inhibiting thromboxane synthetase and permitting preferential formation of prostacyclin over thromboxane A2. Both of these two short-acting vasoactive substances are formed from prostaglandin precursors. Prostacyclin is a potent vasodilator which causes smooth muscle relaxation through phosphorylation of the myosin light chain kinase. This reduces its ability to to be activated by calciun and calmodulin.

Pharmacodynamics

Nitroglycerin causes the relaxation of vascular smooth muscles, causing arteriolar and venous dilatation. It increases blood flow to the myocardium and reduces cardiac preload and afterload, decreasing myocardial wall stress and ameliorating anginal symptoms. Nitroglycerin also reduces coronary artery spasm, decreasing systemic vascular resistance as well as systolic and diastolic blood pressure. Like other organic nitrates, repeated and prolonged administration of nitroglycerin can lead to the development of tolerance or desensitization of vascular smooth muscle to further nitroglycerin-induced vasorelaxation. This loss of efficacy may be associated with the inhibition of mitochondrial aldehyde dehydrogenase, which is an important enzyme involved in the bioactivation of nitroglycerin. Nitroglycerin tolerance may be accompanied by pro-oxidant effects, endothelial dysfunction, and increased sensitivity to vasoconstrictors.

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

Framycetin binds to specific 30S-subunit proteins and 16S rRNA, four nucleotides of 16S rRNA and a single amino acid of protein S12. This interferes with decoding site in the vicinity of nucleotide 1400 in 16S rRNA of 30S subunit. This region interacts with the wobble base in the anticodon of tRNA. This leads to interference with the initiation complex, misreading of mRNA so incorrect amino acids are inserted into the polypeptide leading to nonfunctional or toxic peptides and the breakup of polysomes into nonfunctional monosomes. Like other aminoglycoside antibiotic drugs, neomycin inhibits bacterial ribosomes by binding to the 30S ribosomal subunit of susceptible bacteria and disrupting the translational machinery of bacterial protein synthesis. Bacterial translation is normally initiated by the mRNA binding to the 30S ribosomal subunit and subsequent binding with 50S subunit for elongation. 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/ A class of angiogenesis inhibitor has emerged from our mechanistic study of the action of angiogenin, a potent angiogenic factor. Neomycin, an aminoglycoside antibiotic, inhibits nuclear translocation of human angiogenin in human endothelial cells, an essential step for angiogenin-induced angiogenesis. The phospholipase C-inhibiting activity of neomycin appears to be involved, because U-73122, another phospholipase C inhibitor, has a similar effect. In contrast, genistein, oxophenylarsine, and staurosporine, inhibitors of tyrosine kinase, phosphotyrosine phosphatase, and protein kinase C, respectively, do not inhibit nuclear translocation of angiogenin. Neomycin inhibits angiogenin-induced proliferation of human endothelial cells in a dose-dependent manner. At 50 microM, neomycin abolishes angiogenin-induced proliferation but does not affect the basal level of proliferation and cell viability. Other aminoglycoside antibiotics, including gentamicin, streptomycin, kanamycin, amikacin, and paromomycin, have no effect on angiogenin-induced cell proliferation. Most importantly, neomycin completely inhibits angiogenin-induced angiogenesis in the chicken chorioallantoic membrane at a dose as low as 20 ng per egg. These results suggest that neomycin and its analogs are a class of agents that may be developed for anti-angiogenin therapy. ... 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/

Pharmacodynamics

Framycetin is used for the treatment of bacterial eye infections such as conjunctivitis. Framycetin is an antibiotic. It is not active against fungi, viruses and most kinds of anaerobic bacteria. Framycetin works by binding to the bacterial 30S ribosomal subunit, causing misreading of t-RNA, leaving the bacterium unable to synthesize proteins vital to its growth. Framycetin is useful primarily in infections involving aerobic bacteria bacteria. Neomycin mediates its bactericidal action by inhibiting bacterial protein synthesis, thereby suppressing the growth and survival of susceptible bacteria. Following oral administration, the duration of bactericidal activity of neomycin ranged from 48 to 72 hours. By decreasing colonic bacteria that produce ammonia, neomycin was shown to be effective as an adjunctive therapy in hepatic coma to improve neurologic symptoms. Neomycin is active against both gram positive and gram negative organisms, including the major _E. coli_ species resident in the colon as well as the enteropathogenic forms of _E. coli_. It is also active against _Klebsiella_-_Enterobacter_ group. Resistant strains of _E. coli_, _Klebsiella_ and _Proteus spp_. may emerge from neomycin therapy. Neomycin has no antifungal activity and has some activity against some protozoa.

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.

Mechanism of action

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

Mechanism of action

Corticosteroids like triamcinolone inhibit phospholipase A2 on cell membranes, preventing the breakdown of lysosomal membranes of leukocytes, which in turn prevent the formation of arachidonic acid, which decrease expression of cyclooxygenase and lipoxygenase, inhibiting synthesis of prostaglandins and leukotrienes. Anti-inflammatory activity occurs via reversal of vascular dilation and reducing permeability, which prevents macrophage and leukocyte migration. Triamcinolone also inhibits nuclear factor kappa-B, which decreases the production of pro-inflammatory signals such as interleukin-6, interleukin-8, and monocyte chemoattractant protein-1. Glucocorticoids are capable of suppressing the inflammatory process through numerous pathways. They interact with specific intracellular receptor proteins in target tissues to alter the expression of corticosteroid-responsive genes. Glucocorticoid-specific receptors in the cell cytoplasm bind with steroid ligands to form hormone-receptor complexes that eventually translocate to the cell nucleus. There these complexes bind to specific DNA sequences and alter their expression. The complexes may induce the transcription of mRNA leading to synthesis of new proteins. Such proteins include lipocortin, a protein known to inhibit PLA2a and thereby block the synthesis of prostaglandins, leukotrienes, and PAF. Glucocorticoids also inhibit the production of other mediators including AA metabolites such as COX, cytokines, the interleukins, adhesion molecules, and enzymes such as collagenase. /Glucocorticoids/ Corticosteroids diffuse across cell membranes and complex with specific cytoplasmic receptors. These complexes then enter the cell nucleus, bind to DNA (chromatin), and stimulate transcription of messenger RNA (mRNA) and subsequent protein synthesis of various inhibitory enzymes responsible for the anti-inflammatory effects of topical corticosteroids. These anti-inflammatory effects include inhibition of early processes such as edema, fibrin deposition, capillary dilatation, movement of phagocttes into the area, and phagocytic activities. Later processes, such as capillary production, collagen deposition, and keloid formation also are inhibited by corticosteroids. The overall actions of topical corticosteroids are catabolic. /Corticosteroids (topical)/ The potent anti-inflammatory action may be due to an inhibition of the secretion of growth factors, endothelial activating and other cytokines from lymphocytes, eosinophils, macrophages, fibroblasts, and mast cells. The results are decreased influx of inflammatory cells into the bronchial walls, due in part to inhibition of expression of adhesion molecules on the endothelium and in the tissue. Decreased activation and survival of eosinophils in the lung tissue and a reduction in numbers of mast cells are further effects. Corticosteroids may inhibit release of mediators from basophils and enzymes from macrophages. There is decreased permeability through vasoconstriction and direct inhibition of endothelial cell contradiction. Beta-adrenergic-receptor numbers may be increased, which results in an enhanced response to beta-adrenergic bronchodilators and reduced down-regulation of beta-receptors after prolonged beta-agonist exposure. Inhaled corticosteroids also inhibit mucus secretion in airways, possibly by a direct action on submucosal gland cells and an indirect inhibitory effect caused by the reduction in inflammatory mediators that stimulate mucus secretion. The amount and viscosity of sputum are reduced. /Corticosteroids (inhalation-local/

Pharmacodynamics

Triamcinolone is a corticosteroid with anti-inflammatory properties. These properties are used to treat inflammation in conditions that affect various organs and tissues. Triamcinolone should not be administered as an epidural injection.