Medication Summary
The goal of pharmacotherapy is either to terminate the infection when possible or to control the infection and to reduce morbidity when cure is not possible.
Antifungal agents
Class Summary
The mechanism of action of antifungal agents differs by agent and may involve an alteration of RNA or DNA, allow for an intracellular accumulation of peroxide that is toxic to the fungal cells, or allow for intracellular potassium to be lost while intracellular sodium levels increase.
Amphotericin B (Amphocin, Fungizone)
Because of its rapid onset of action, this is the DOC for cryptococcal meningitis. Antifungal activity results from its ability to insert itself into fungal cytoplasmic membrane at sites that contain ergosterol or other sterols. Aggregates accumulate at sterol sites, resulting in an increase in cytoplasmic membrane permeability to monovalent ions (eg, potassium, sodium). At low concentrations, main effect is increased intracellular loss of potassium, resulting in reversible fungistatic activity; however, at higher concentrations, pores of 40-105 nm are produced in cytoplasmic membrane, leading to large losses of ions and other molecules. A second effect is its ability to cause auto-oxidation of cytoplasmic membrane and release of lethal free radicals. Main fungicidal activity may reside in its ability to cause auto-oxidation of cell membranes.
If therapy is supplemented by oral flucytosine, therapy can be used until the patient is afebrile and alert and spinal fluid cultures are negative for 2 wk; then, patient can be placed on fluconazole.
Flucytosine (Ancobon)
Metabolized to fluorouracil after penetrating fungal cells. Inhibits RNA and protein synthesis. Active against some Candida and Cryptococcus species and generally used in combination with amphotericin B. Always use with another active antifungal agent (eg, amphotericin B).
Fluconazole (Diflucan)
An antifungal agent active against many yeast and dimorphic fungi. In general, has poor activity against molds and filamentous fungi. Selectively inhibits fungal cytochrome P-450 and sterol C-14-alpha demethylation.
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