How does fluconazole work?

If you want to kill micro-organisms in the external world, you can take your pick of nasty chemicals to throw at them; most will work just fine. However, if you want to kill a micro-organism that is inside of you, you’ll understandably want to avoid yourself becoming collateral damage. It therefore makes sense to try to target something specific to the micro-organism’s metabolism, so that you won’t get affected in the process.

This rationale applies to most of the antimicrobials we doctors prescribe, and fluconazole is no exception. Fluconazole is one of the triazoles, a group that also includes itraconazole and several related antifungals. Their fungus-specific target is something called ergosterol. Fungi use it as a component of their cell membranes, where it serves a similar purpose to that of cholesterol in human cell membranes.

What fluconazole does is to inhibit an enzyme responsible for the production of ergosterol. This results in a toxic build up of precursors, and culminates in the inhibition of the fungus’ ability to grow and divide.

[If you really want more details (and I for one don’t), the relevant step is the conversion of lanosterol to ergosterol, and the enzyme is the cytochrome-P450-dependent 14-α-demethylase.]

Reference: Overview of Antifungal Agents