FUNGEX

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

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.

Indications

• Antibacterial agent in personal care products
• Antiseptic in surgical settings
• Preservative in household products

Dosage

Children: For pediatric dosing, consult the BNF for Children, as specific dosages may vary based on the formulation and intended use.

Adults: Triclosan is typically used topically in various formulations. For specific dosing guidelines, refer to the product labeling or consult the BNF.

Mechanism of action

Triclosan exerts its antibacterial effects mainly by inhibiting fatty acid synthesis in bacteria. It binds to the enoyl-acyl carrier protein reductase enzyme (ENR), forming a ternary complex with NAD+. This complex cannot participate in fatty acid synthesis, leading to weakened cell membranes and ultimately cell death. Human cells are not affected as they do not possess the ENR enzyme.

Pharmacodynamics

Triclosan displays bacteriostatic activity at lower concentrations, inhibiting the growth and reproduction of bacteria. At higher concentrations, it exhibits bactericidal properties. The impact of triclosan on fatty acid metabolism is significant, as it disrupts essential lipid biosynthesis, which is crucial for maintaining bacterial cell structure and function. Additionally, triclosan has been associated with various biological effects, including potential endocrine disruption and reproductive toxicity.

Pharmacokinetics

Triclosan is generally poorly absorbed through the skin, but it can accumulate in human tissues and the environment. It is subject to metabolic processing, primarily in the liver, and is excreted through urine. The half-life of triclosan in humans varies, but it is typically around 24 hours. Environmental exposure pathways and its accumulation in aquatic organisms raise concerns regarding its ecological impact.

Adverse effects

• Skin irritation
• Allergic reactions
• Endocrine disruption
• Potential reproductive toxicity

Precautions

• Should be used with caution in individuals with a history of skin sensitivity
• Not recommended for prolonged use due to potential for skin irritation
• Avoid use in pregnant women due to potential reproductive effects

Pregnancy

Triclosan should be avoided during pregnancy due to potential adverse effects on fetal development.

Breast-feeding

Caution is advised when using triclosan while breastfeeding due to potential transfer through breast milk.

Storage

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

Formulations

• Topical creams
• Soaps
• Toothpastes
• Disinfectant solutions

Indications

• Tinea pedis (athlete's foot)
• Tinea corporis (ringworm)
• Tinea cruris (jock itch)
• Onychomycosis (fungal nail infections)

Dosage

Children: Refer to specific guidelines for dosing, as it varies based on condition and formulation.

Adults: Refer to specific guidelines for dosing, as it varies based on condition and formulation.

Mechanism of action

Undecenoic acid works by inhibiting the growth of fungi, particularly by damaging the fungal cell membrane. It interferes with the synthesis of ergosterol, an essential component of fungal cell membranes, leading to increased permeability and ultimately cell death.

Pharmacodynamics

Undecenoic acid exhibits antifungal properties, particularly against dermatophytes and yeast. It disrupts the integrity of the fungal cell membrane, which is crucial for maintaining cellular homeostasis. The drug's action leads to cellular leakage and death of the fungal cells.

Pharmacokinetics

Undecenoic acid is absorbed after oral administration, with a peak plasma concentration occurring within a few hours. It is metabolized in the liver and excreted primarily through the kidneys. The half-life of undecenoic acid is variable and can be influenced by individual metabolic differences.

Adverse effects

• Nausea
• Diarrhea
• Abdominal pain
• Skin irritation
• Headache

Precautions

• Use with caution in patients with a known allergy to undecenoic acid or its derivatives
• Monitor for gastrointestinal side effects
• Caution in patients with liver impairment

Pregnancy

There is limited data on the use of undecenoic acid during pregnancy. Consult with a healthcare provider before use.

Breast-feeding

It is not known whether undecenoic acid is excreted in human milk. Caution is advised.

Storage

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

Formulations

• Topical cream
• Capsules
• Oral solution

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.