Antifungals

For a review of mycology, see here: Mycology

Amphotericin B

Binds to ergosterol to attack the cell wall. Poor GI absorption, so it is always given via IV. Only given for severe, systemic, life-threatening fungal infections

Amphotericin B deoxycholate

First generation. Nephrotoxic.

Amphotericin B lipid preparation

More commonly used. Less nephrotoxic.

Toxicity

Can cause acute symptoms of fever, rigors, hypotension, tachypnea, and thrombophlebitis. Chronically, kidney damage and electrolyte abnormalities (hypokalemia, hypomagnesemia, metabolic acidosis) can occur.

Flucytosine (5-FC)

Converted in fungal cells to 5-FU which inhibits Thymidylate Synthetase, required for DNA synthesis.

It is the empiric treatment of Cryptococcal meningitis and used in conjunction with Amphotericin B. After 2 weeks, Fluconazole is used as maintenance therapy to prevent relapse.

Azoles

Inhibits ergosterol synthesis via Lanosine-14-alpha demethylase, attacking the cell membrane.

Worth noting is that azoles can inhibit CYP3A4 and CYP2C9, which will increase drug concentration.

Fluconazole

Treats yeast infections, especially Candida, Cryptococcus, and Coccidioides immitis. Has high oral bioavailability. However, it has teratogenic effects.

Used for Cryptococcal meningitis maintenance therapy (after Flucytosine).

Itraconazole

Not used as often any more because of low bioavailability. Must be taken with an acidic beverage.

Good for the endemic mycoses after initial treatment with Amphotericin B.

Voriconazole

Covers a wide range of fungi, but is the optimal treatment for Aspergillus.

Side effects include abnormal liver biomarkers (AST/ALT), visual effects (color perception is off), photosensitivity, and Squamous Cell Carcinoma.

Posaconazole

Covers a wide range of fungi, including Candida, Aspergillus and Mucormycosis.

Isavuconazole

Newer azole, good for Aspergillus and Mucormycosis.

Echinocandins

Attacks the fungal cell wall (Glucan) directly. Echinocandins inhibit 1, 3-beta-D-glucan synthase.

Caspofungin, Micafungin, and Anidulafungin

Targets Candida and is especially indicated for Azole resistant Candida. Only administered via IV.

Griseofulvin

Binds to microtubules, and inhibits mitosis in metaphase. A topical antifungal used for Dermatophytes.