Other Antifungals

crop_square Flucytosin

Flucytosine (5-FC) is a fluorinated cytosine (pyrimidine derivate) analogue with fungistatic activity against yeasts such as and . Upon entering fungal cells, 5-FC is converted to 5-fluoruracil (5-FU) in several steps and involving the fungal enzyme cytosine deaminase. 5-FU interferes with RNA and DNA synthesis. It is not toxic to mammalian cells as they lack the enzyme cytosine deaminase. Resistances to 5-FC develop rapidly and are widespread. It is usually given in combination with other antifungals. Oral and intravenous formulations are available. 5-FC absorption from the gastrointestinal tract and bioavailability are excellent. It easily crosses the blood-brain barrier. There is no substantial hepatic metabolization. 5-FC is principally cleared by the kidneys. This drug is generally well-tolerated but prolonged use and high dosage may cause serious side effects including bone marrow suppression.

crop_square Griseofulvin

Griseofulvin is one of the oldest antifungal drugs isolated from Penicillium griseofulvum in 1939. It binds to tubulin interfering with the function of cellular microtubules. This is thought to inhibit fungal cell mitosis and nuclear acid synthesis; however, the exact mechanism of action is not understood. Griseofulvin is an oral medication that treats superficial fungal infections caused by dermatophytes . It is deposited in skin, hair, and nails. Absorption from the GI tract is poor and may be improved by fatty meals. Griseofulvin is metabolised by the liver and primarily excreted via the kidneys. Terminal half-life is about 5 days. It is a generally well-tolerated drug. Rare serious side effects include hepatotoxicity and Stevens-Johnson syndrome.

crop_square Amorolfine

Amorolfine is a morpholine derivate that has been in clinical use since the early 1980s. It interferes with ergosterol biosynthesis by inhibiting enzymes of the ergosterol pathway, D14 reductase and D7-D8 isomerase. This causes a lack of ergosterol and an intracellular accumulation of ergosterol precursors. Amorolfine is used in topical formulations to treat fungal nail infections (onychomycoses). It is active against dermatophytes like , yeasts like , ), and some moulds. Amorolfine requires weekly application for at least six months. It is available over the counter in many countries. Adverse effects include localised rashes, burning sensation and nail discolouration.