ANTIFUNGAL DRUGS

Polyenes

Polyenes react with the sterols in fungal membranes, increasing permeability and thus damaging the organism. The most potent is amphotericin, which is used intravenously in severe systemic fungal infections. Nephrotoxicity is a major problem and dosage levels must take background renal function into account. Liposomal amphotericin is less toxic but very expensive. Nystatin is not absorbed through mucous membranes and is therefore useful for the treatment of oral and enteric candidiasis and for vaginal infection. It can only be given orally or as pessaries.

Azoles

Imidazoles such as ketoconazole, miconazole and clotrimazole are broad-spectrum antifungal drugs. They are predominantly fungistatic and act by inhibiting fungal sterol synthesis, resulting in damage to the cell wall. Ketoconazole is active orally but can produce liver damage. It is effective in candidiasis and deep mycoses including histoplasmosis and blastomycosis but not in aspergillosis and cryptococcosis.

Clotrimazole and miconazole are used topically for the treatment of ringworm and cutaneous and genital candidiasis. Econazole and tioconazole are used for the topical treatment of cutaneous and vaginal candidiasis and dermatophyte infections.

Triazoles.

These include fluconazole, voriconazole and itraconazole. Fluconazole is noted for its ability to enter CSF and is used for candidiasis and for the treatment of central nervous system (CNS) infection with Cryptococcus neoformans. Itraconazole fails to penetrate CSF. It is the agent of choice for non-life-threatening blastomycosis and histoplasmosis. It is also moderately effective in invasive aspergillosis. Toxicity is mild. The problem associated with poor absorption of the capsules in the absence of food has been overcome with the liquid formulation. Voriconazole has broad-spectrum activity that includes Candida, Cryptococcus and Aspergillus spp. and other filamentous fungi. It is available for oral and intravenous use. Adverse effects include rash, visual disturbance and abnormalities of liver enzymes. It is indicated for invasive aspergillosis and severe candida infections unresponsive to amphoteracin and fluconazole respectively.

Allylamines

Terbinafine has antifungal and anti-inflammatory activity orally and is useful for the treatment of superficial mycoses such as dermatophyte infections, onychomycosis and cutaneous candidiasis. A topical formulation is also available to treat fungal skin infections.

Echinocandins

This is a new class of antifungals which act by inhibiting the cell wall polysaccharide, glucan. Caspofungin is active against Candida spp. and Aspergillus spp. and is indicated for serious aspergillosis unresponsive to other drugs. It is administered intravenously.

Other antifungals

Flucytosine.

The fluorinated pyridine derivative, flucytosine, is used in combination with amphotericin B for systemic fungal infection. Side-effects are uncommon, although it may cause bone marrow suppression. It is active when given orally or parenterally.

Griseofulvin.

Griseofulvin, a naturally occurring antifungal, is widely used for the treatment of more extensive superficial mycoses and onychomycosis.

Amorolfine.

Amorolfine is available for the topical treatment of fungal skin and nail infections.