Systemic

Amphotericin B
Amphotericin B is poorly absorbed orally and may only be given intravenously for systemic fungal infections.
Mechanism of Action -- The primary sterol in fungi is ergosterol whereas in mammals it is cholesterol.  Amphotericin B binds to ergosterol, destroying fungal membrane integrity.  The structure of the drug forms a large oval, one side of which is lipophilic.  This side binds to the ergosterol.  The other side is hydrophilic.  The binding of additional molecules will form a pore in the fungal membrane, allowing the efflux of intracellular fungal ions and macromolecules.  At lower doses this action is fungistatic.  At higher concentrations amphotericin will exert fungicidal activity.

Spectrum of Activity -- Amphotericin is a broad spectrum anti-fungal with activity against Candida spp., Cryptococcus, Histoplasma, Blastomyces, Coccidioides, and Aspergillus.

Adverse Effects -- Amphotericin may produce severe side effects including fever, chills, muscle spasm, vomiting, headache, hypotension, hypokalæmia, and thrombophlebitis.  These actions are common upon IV infusion.  They may be attenuated by either pre- or concurrent-administration of antipyretics, antihistaminics, glucocorticoids, and heparin.  Other adverse reactions include nephrotoxicity and hepatotoxicity.  Continuous infusion of normal saline between doses of amphotericin will minimise the risk for nephrotoxicity.
 

Flucytosine (5-FC)  -- Flucytosine is available only for oral administration.
Mechanism of Action -- Flucytosine is metabolised to 5-fluorouracil.  In the fungal cell, this is further metabolised to 5-fluorodeoxyuridinemonophosphate (5-F-dUMP) and 5-fluorouridinetriphosphate (5-FUTP).  The former inhibits DNA synthesis while the later inhibits RNA synthesis, thereby inhibiting fungal replication and protein synthesis respectively.

Spectrum -- Flucytosine is most effective against Cryptococcus and some spp. of Candida.  It is used only in combination with other antifungals (i.e. amphotericin) when is shows greater efficacy, possibly due to increased entry into the fungal cell by the pores created by amphotericin or other compromises in membrane integrity.

Adverse Effects -- Flucytosine may cause GI upset, anæmias, nephrotoxicity, ataxia, and paræsthesias.  At least some of these effects may be mediated by the anti-metabolite action of 5-fluorouracil.

Griseofulvin -- Griseofulvin is used orally to provide systemic treatment for dermal fungal infections.  It is moderately well absorbed.  Taking the drug with a fatty meal will greatly increase its absorption.  Additionally, it is available in microsize and ultramicrosize formulations, which also increases the absorption of the drug.
 Mechanism of Action -- Griseofulvin is fungistatic.  It inhibits fungal mitosis by inhibiting mitotic spindle formation (similar to colchicine).  It is highly distributed to dermal tissues (keratophilic), which is beneficial in the treatment of dermal fungal infections.  NOTE that therapy is long term (up to one year) and that the fungus may return when the drug is discontinued.  This is due at least in part to the fungistatic nature of griseofulvin.

Spectrum -- Griseofulvin is effective against Microsporum, Epidermophyton, and Trichophyton spp. (All of which are common spp. of fungus that cause dermal infections.)  It is predominantly used in the treatment of onychomycosis (tinea unguium or fungal infection of the nail bed).

Adverse Effects -- Headache is the most common side effect.  It usually diminishes with continued therapy.

Imidazole/Triazole Antifungals -- The mechanism of action and spectrum of agents belonging to these two chemical classes of anti-fungals are identical.  The primary difference between the classes is that the newer triazole antifungals are metabolised at a slower rate than the older imidazoles.  Additionally, the triazoles exhibit fewer side effects and at a reduced incidence than the imidazoles.  The triazole antifungals include terconazole, itraconazole, and fluconazole.  All others are imidazoles.  The imidazole/triazole antifungals that are available for systemic use include ketoconazole (oral), miconazole (parenteral), itraconazole (oral), and fluconazole (oral and parenteral).
Mechanism of Action -- These agents inhibit the enzyme 14-alpha-demethylase, a cytochrome P₄₅₀ enzyme that catalyses the synthesis of ergosterol.  Consequently, ergosterol synthesis is inhibited and membrane integrity and function is compromised.

Spectrum -- These classes of antifungals are effective against some spp. of Candida (including albicans), Cryptococcus, Blastomyces, Histoplasma, Coccidioides, and the dermatophytes (including Trychophyton and other species that commonly cause cutaneous fungal infections).

Adverse Effects -- These drugs primarily cause GI upset.   They may also inhibit mammalian cytochrome P₄₅₀ enzymes, resulting in inhibition of cortisone, androgen, and œstrogen synthesis.  Side effects that may arise from these actions include gynecomastia, menstrual irregularities, infertility, and adrenal insufficiency.  Ketoconazole is the agent with the greatest incidence of these side effects (it may even be used as a treatment in mild Cushing's disease).  These agents may also precipitate torsade de pointes when administered with the non-sedating antihistaminics (again ketoconazole is the most prominent, although the others may pose a danger for arrhythmias).

Allylamines -- One antifungal in this chemical class is used systemically for fungal infections.
Terbinafine
Mechanism of Action -- Terbinafine inhibits the fungal enzyme squalene 2, 3 epoxidase, which ultimately decreases the synthesis of ergosterol, thus structurally and functionally compromising the fungal cell membrane.  Like griseofulvin, it is also keratophilic, allowing distribution to infected areas.

Spectrum -- Terbinafine is a broad spectrum antifungal agent.  However it is used primarily for the treatment of onychomycoses.

Adverse Effects -- The primary side effects of terbinafine is GI upset.  It does not inhibit human microsomal enzymes.

Oral Thrush
Oral thrush or candidiasis is an infection of the mouth and upper throat by Candida albicans.
Nystatin -- Nystatin is poorly absorbed from the GI tract.
Mechanism of Action -- Nystatin works by a mechanism similar to that of amphotericin.
Spectrum -- Similar to amphotericin
Adverse Effects -- When used as directed, nystatin is relatively side effect free.  The most frequently reported side effects are bad taste and dry mouth (these are rare).

Vaginal Candidiasis
Imidazole/Triazole Antifungals -- Clotrimazole, butaconazole, miconazole (available as a 3-day regimen), terconazole (3-day regimen), and tioconazole (1-day regimen).

Nystatin is also available for use in vaginal candidiasis.

Adverse Effects -- Vulvovaginal burning, irritation, itching.

 

Dermatological Infections -- Athlete's foot (tinea pedis), jock itch (tinea cruris), barber's itch (tinea barberis), and scalp itch (tinea capitis) are the most common infections treated with topical antifungals.

Imidazole/Triazole -- ketoconazole, miconazole, econazole, clotrimazole, oxiconazole, and sulconazole.
Allylamine -- terbinafine, naftifine
Macromolecular -- nystatin and amphotericin

Tolnaftate -- The mechanism of action of tolnaftate is unknown.  It is presumed to interfere with membrane structure and function.  This is an older drug that is still effective in the treatment of some fungal infections.  However, some resistant strains have developed to the efficacy of tolnaftate.

Haloprogin -- The mechanism of action is unknown, but also presumed to act in a similar manner (cell wall integrity).  There is a higher incidence of cutaneous side effects with haloprogin, including irritation, burning, vesiculation (blisters), scaling, and itching.  It is generally used when the infection is unresponsive to other antifungals.

Ciclopirox

Mechanism of Action -- At low concentrations ciclopirox inhibits fungal uptake of amino acids.  At higher concentrations it alters membrane structure and function.

Spectrum -- Ciclopirox is effective against numerous fungal infections but is used primarily in the treatment of tinea versicolour, which is resistant to most other agents.

Older Topical Antifungals
Undecylenic Acid -- The mechanism is unknown.  It is not as effective as the newer agents, due at least in part to resistant strains of fungi.  The drug is yellow and chronic use may stain the patient's skin.

Clioquinol (Iodochlorhydroxyquin) -- A derivative of chloroquine, this drug works by a mechanism similar to chloroquine (inhibition of DNA structure/function).  It is also less effective than newer agents and may also stain the skin yellow.  It may also produce irritation at the application site.

Triacetin -- Fungistatic by an unknown mechanism.

Gentian Violet -- This dye is also fungistatic.  Application will cause temporary staining of the skin or clothes.  If gentian violet is applied to an area of ulceration, it may permanently stain the skin ("tatooing").

Benzoic Acid (Often used with Salicylic Acid) -- The former is fungistatic while the later has beneficial keratolytic effects.

Natamycin -- an antibiotic similar to the aminoglycosides.  Natamycin binds to the fungal membrane, compromising its structural and functional integrity.  It is relatively side effect free.