FUNGEX COMBINATION PRODUCT DUSTING POWDER

Indications

• Vulvovaginal candidiasis
• Fungal infections
• Antiseptic for minor cuts and abrasions
• Ocular antiseptic
• Insecticide in pest control

Dosage

Adults: Refer to specific guidelines for formulations. Commonly used as a 2-3% solution

Mechanism of action

Boric acid exerts its antifungal effects by disrupting the cell membrane integrity of fungi. It interferes with the synthesis of essential cellular components, leading to cell lysis and death. The acid also has mild antibacterial properties, which can help in reducing bacterial load in infected areas. The exact molecular pathways involved in these actions are not fully elucidated, but it is known to alter the pH of the environment, making it less conducive for fungal growth.

Pharmacodynamics

Boric acid demonstrates a low toxicity profile in humans when used appropriately. Its antifungal activity is primarily effective against Candida species, and it can be used as a second-line treatment for vulvovaginal candidiasis, particularly in cases of recurrent infections. The effectiveness of boric acid is also attributed to its ability to maintain an acidic environment, which is unfavorable for the growth of many pathogens. Its antiseptic properties help in reducing inflammation and promoting healing in infected tissues.

Pharmacokinetics

Boric acid is poorly absorbed through the gastrointestinal tract but can be absorbed through the skin and mucous membranes. Once absorbed, it is distributed throughout the body, with a tendency to accumulate in various tissues, including the liver and kidneys. The elimination half-life of boric acid is variable, depending on dosage and route of administration. It is primarily excreted unchanged in the urine. Due to its potential for toxicity with high systemic exposure, it is important to adhere to recommended dosages.

Contra-indications

• Hypersensitivity to boron or any component of the formulation
• Severe renal impairment

Adverse effects

• Skin irritation or rash
• Nausea
• Vomiting
• Diarrhea
• Headache
• Fatigue
• Tremors
• Confusion

Interactions

• May interact with other topical medications
• Caution with nephrotoxic agents

Precautions

• Use with caution in patients with renal insufficiency
• Careful monitoring is advised in long-term use
• Not recommended for use in large areas of broken skin

Pregnancy

Boric acid is classified as category C. Use during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

Limited data available. It is advisable to avoid use while breastfeeding.

Storage

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

Formulations

• Topical ointment
• Powder
• Solution

Indications

• Antiseptic in personal care products
• Disinfectant in household cleaners
• Antimicrobial agent in medical devices

Dosage

Children: Refer to the BNF for Children for appropriate dosing information based on specific formulations and indications.

Adults: Refer to specific product guidelines for dosing instructions, as formulations and concentrations may vary.

Mechanism of action

Triclosan functions as a biocidal agent with multiple targets in bacterial cells. At lower concentrations, it acts as a bacteriostatic agent by inhibiting fatty acid synthesis. Triclosan binds to the enoyl-acyl carrier protein reductase enzyme (ENR), forming a ternary complex with NAD+. This complex disrupts fatty acid synthesis, leading to compromised cell membrane integrity and ultimately resulting in cell death. Importantly, humans do not possess the ENR enzyme, rendering them unaffected by triclosan's mechanism.

Pharmacodynamics

The pharmacodynamics of triclosan involve its ability to inhibit bacterial growth through interference with lipid biosynthesis. By targeting the fatty acid synthesis pathway, triclosan alters the bacterial cell membrane, which is essential for maintaining cell structure and function. Its broad-spectrum activity allows it to combat a variety of pathogens, but it may also lead to unintended effects on human health, including potential endocrine disruption and adverse reproductive outcomes.

Pharmacokinetics

Triclosan is absorbed through the skin and can be detected in human plasma and urine, indicating systemic exposure following topical application. It is metabolized in the liver, with possible conversion to glucuronide and sulfate conjugates. The elimination half-life is approximately 24 hours, and it is primarily excreted via urine. The compound has been shown to bioaccumulate in aquatic organisms, raising concerns about environmental persistence and ecological impact.

Adverse effects

• Skin irritation
• Allergic reactions
• Endocrine disruption
• Reproductive toxicity

Precautions

• Use with caution in individuals with sensitive skin
• Consider potential endocrine disruption effects
• Avoid prolonged exposure to reduce the risk of adverse effects

Pregnancy

The safety of triclosan during pregnancy has not been established; use only if clearly needed.

Breast-feeding

Triclosan is excreted in breast milk; caution should be exercised when administering to nursing mothers.

Storage

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

Formulations

• Topical creams
• Soaps
• Lotions
• Antiseptic products

Mechanism of action

Oxides do not have a single mechanism of action as they are a broad category of compounds. However, in general, metal oxides can exhibit catalytic properties, while non-metal oxides may participate in biochemical reactions by forming acids or bases upon dissolution in water.

Pharmacodynamics

The pharmacodynamics of oxides depend on the specific type of oxide and its interaction with biological systems. For instance, metal oxides may have antimicrobial properties, while certain non-metal oxides can influence metabolic pathways through their acid-base chemistry. The effects vary widely, necessitating specific studies for each oxide's role in therapeutic contexts.

Pharmacokinetics

The pharmacokinetics of oxides are also variable. Many metal oxides are poorly soluble and thus have limited absorption when ingested. Non-metal oxides, such as carbon dioxide, can be readily absorbed and utilized in metabolic processes. The distribution, metabolism, and excretion of oxides depend on their chemical form and the biological system in which they are involved.

Pregnancy

Not applicable as oxide is not a drug but a class of chemical compounds.

Breast-feeding

Not applicable as oxide is not a drug but a class of chemical compounds.

Storage

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

Mechanism of action

Triclosan is a biocidal compound with multiple targets in the cytoplasm and membrane. At lower concentrations, however, triclosan appears bacteriostatic and is seen to target bacteria mainly by inhibiting fatty acid synthesis. Triclosan binds to enoyl-acyl carrier protein reductase enzyme (ENR). This complex has increased affinity for NAD+ and forms a ternary complex. This complex is unable to participate in fatty acid synthesis, weakening the cell membrane and causing cell death. Humans do not have an ENR enzyme, and thus are not affected. Triclosan (TCS) exposure has widely adverse biological effects such as influencing biological reproduction and endocrine disorders. While some studies have addressed TCS-induced expression changes of miRNAs and their related down-stream target genes, no data are available concerning how TCS impairs miRNA expression leading us to study up-stream regulating mechanisms. Four miRNAs (miR-125b, miR-205, miR-142a and miR-203a) showed differential expression between TCS-exposure treatments and the control group; their functions mainly involved fatty acid synthesis and metabolism. TCS exposure led to the up-regulation of mature miR-125b that was concomitant with consistent changes in pri-mir-125b-1 and pri-mir-125b-3 among its 3 pri-mir-125bs. Up-regulation of miR-125b originated from direct shear processes involving the two up-regulated precursors, but not pri-mir-125b2. Increased expression of pri-mir-125b-1 and pri-mir-125b-3 resulted from nfe2l2- and c/ebpa-integration with positive control elements of promoters for the two precursors. The overexpression of transcriptional factors, nfe2l2 and c/ebpa, initiated the promoter activity for the miR-125b precursor. CpG islands and Nfe2l2 were involved in constitutive expression of mir-125b-1 and mir-125b-3. The activities of two promoter regions, -487 to -1bp for pri-mir-125b1 and -1327 to +14bp for pri-mir-125b-3 having binding sites for NFE2 and Nfe2l2/MAF:NFE2, were higher than other regions, further demonstrating that the transcriptional factor Nfe2l2 was involved in the regulation of pri-mir-125b1 and pri-mir-125b-3. TCS's estrogen activity resulted from its effects on GPER, a novel membrane receptor, rather than the classical ERa and ERbeta. These results explain, to some extent, the up-stream mechanism for miR-125b up-regulation, and also provide a guidance to future mechanistic study on TCS-exposure.