Antifungals systemic

Patrician A (160) Polyene antibiotic SPK-843 (161) Antifungal (systemic mycosis) Destabilizes fungal cell membrane Phase n Kaken Pharmaceuticals 828-834... 

Fluconazole (4) (s the first member of a new generation of orally acti ve antifungal agents, highly effective in the treatment of dermal and vaginal infections [6, 7] S-Fluorocyrtosine (5) is also used to treat serious systemic fungal infections [5]... 

Stopher and Gage used size-exclusion chromatography (SEL) coupled to reversed phase HPLC for the direct injection of plasma in the analysis of an antifungal agent, voriconazole (12). Their system consisted of three columns, i.e. first a size-exclusion... 

In contrast to the wide range of antibacterial antibiotics, there are very few antifungal antibiotics that can be used systemically. Lack of toxicity is, as always, of paramount importance, but the differences in structure of, and some biosynthetic processes in, fungal cells (Chapter 2) mean that antibacterial antibiotics are usually inactive against fungi. 

Amphotericin B is particularly effective against systemic infections caused by C. albicans and Cryptococcus neoformans. It is poorly absorbed from the gastrointestinal tract and is thus usually administered by intravenous injection under strict medical supervision. Amphotericin B methyl ester (Fig. 5.15C) is water-soluble, unlike amphotericin B itself, and can be administered intravenously as a solution. The two forms have equal antifungal activity but higher peak serum levels are obtained with the ester. Although the ester is claimed to be less toxic, neurological effects have been observed. An ascorbate salt has recently been described which is water-soluble, of similar activity and less toxic. 

Combinations may also be used to extend the speetrum of a preservative system. Thus, the preservative Germall 115 has an essentially antibacterial activity and very low, if not zero, antifungal aetivity. By combining Germall 115 with parabens, whieh possess antifungal activity, a broader spectrum (antibacterial/antifungal) preservative system is obtained. 

PCP is commonly used as a wood preservative having both antifungal and insecticide properties. It has also been used in a range of areas for antifungal, antibacterial, general herbicide, and slime prevention in both industrial and consumer applications. Chronic exposure to PCP has effects on the liver, kidneys, and immune system. PCP also has the potential to cause reproductive problems and has been listed as a probable carcinogen. 

Systemic adverse effects associated with vaginal azoles are less frequent than with oral products. Local discomfort such as burning may occur with the first application. Fifteen percent of patients experience gastrointestinal side effects with orally administered antifungal agents.13 Oral ketoconazole is associated with hepatic toxicity at a rate of 1 in 15,000.14... 

Since dermatophyte hyphae seldom penetrate into the living layers of the skin, instead remaining in the stratum corneum, most infections can be treated with topical antifungals. Infections covering large areas of the body or infections involving nails or hair may require systemic therapy. Patients with chronic infections or infections that do not respond to topical therapy are also candidates for systemic therapy. 

Assess the patient s symptoms to determine if selftreatment with OTC antifungal therapy is appropriate or whether the patient should be evaluated by a practitioner. Exclusions for self-treatment include infection of nails or hair, unsuccessful initial treatment, worsening condition, signs of secondary bacterial or systemic infection, or chronic medical conditions such as diabetes, immunosuppression, or impaired circulation. 

Caffeine is the alkaloid that made coffee fruit and seed so much desired. Caffeine is probably also part of the defense system of the coffee seed, since caffeine has been recognized as an antifungal,149 a selective phytotoxin,150 and a chemosterilant toward certain insects.151... 

Several bis-heterocyclopyridines have been previously demonstrated to have various central nervous system effects <1996CHEC-II(8)967>. Pyrrolo[l, 2- ]thieno[3,2-f ]pyrazines have been demonstrated to be high-affinity ligands for 5-HT3 receptors <1996JME2068>. Pyrazolo[4,3- ]pyrrolo[ l,2-tf]pyrazines have moderate antibacterial and antifungal activity <2005M217>. 

---