Flucytosine is combined with amphotericin B for induction therapy of cryptococcal meningitis. The pharmacological basis for the synergy between these two drugs is:

• A Amphotericin B induces cytosine deaminase expression in Cryptococcus, accelerating flucytosine activation
• B Amphotericin B damages the fungal cell membrane, increasing permeability and uptake of flucytosine into the cell ✓
• C Amphotericin B blocks the efflux pumps that would otherwise export flucytosine from fungal cells
• D The two drugs bind adjacent sites on fungal DNA polymerase and produce additive chain termination

Explanation

Flucytosine enters fungal cells by cytosine permease, is converted by fungal cytosine deaminase to 5-fluorouracil, and then disrupts DNA and RNA synthesis. Amphotericin B binds ergosterol and creates pores in the cell membrane, which increases entry of flucytosine and potentiates its intracellular action, the classic basis for their synergistic combination in cryptococcal meningitis. Induction of cytosine deaminase and efflux blockade are not recognized mechanisms, and flucytosine acts after metabolic conversion rather than at polymerase directly.

Reference: Katzung Basic and Clinical Pharmacology, 15th ed.

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