Amphotericin membrane function disruption

Mode of action Ketoconazole interacts with C-14 a-demethylase (a cytochrome P-450 enzyme) to block demethylation of lanosterol to ergosterol, the principal sterol of fungal membranes Figure 34.4). This inhibition disrupts membrane function and increases permeability. Ketoconazole acts in an additive manner with flucytosine against Candida, but antagonizes amphotericin B s antifungal activity. 

Amphotericin B is highly lipophilic (Figure 29.14) and interacts with membrane lipid sterols, such as cholesterol, to disrupt membrane permeability. Because amphotericin is freely filtered, it achieves high concentrations in distal tubular fluid and easily forms complexes with cholesterol and other lipids present in distal tubular luminal membranes. Amphotericin effectively transforms the tight distal tubular epithelium into an epithelium leaky to water, H+ and K+. Functional abnormalities observed with amphotericin B are attenuated when the antifungal agent is administered as an emulsion formulation whereby amphotericin is incorporated into lipid... 

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