Antifungals Flashcards
Destroys ergosterol in cell membrane leading to death of cell :
Amphotericin B
Fungistatic, used orally and crosses the BBB, always administered as combination therapy, with very narrow therapeutic window :
Flucytosine
Antimetabolite
BMS, hepatotoxic
Fungicidal that has high first pass metabolism rate (BA 40%) and accumulates in breastmilk :
Terbinafine
What is the drug of choice for dermatophytoses, especially onychomycosis ?
Terbinafine
Main adverse event of Terbinafine ?
Severe hepatotoxicity
Mechanism of action of Terbinafine ?
Inhibition of squalene epoxidase (synthesis of ergosterol)
What class of antifungals prevents conversion of lanosterol to ergosterol ?
Azoles
Thus also inhibit synthesis of ergosterols, like Terbinafine, but lower in the steps.
How can you decrease nephrotoxicity associated with Amphotericin B ?
a) Give Liposomal preparation
b) Combined with flucytosine (synergy allows you to decrease dosage of Amphotericin B)
Does Amphotericin B cross the BBB ?
No.
It is still the DOC for any meningitis caused by fungal organisms - but you have to give it intrathecal.
What is the mechanism of action of Echinocandins ?
Inhibition of b-glucan synthease leading to inability to maintain cell wall made of b-glucans.
Long acting fungicidal with low toxicity that requires IV administration and indicated as salvage therapy for Aspergillosis ?
Capsofungin
What fungal microorganism has ‘‘resistance Fks strains’’ ?
C. glabrata (in immunocompromised)
Amino acid changes in Fk region (‘‘hot spots’’) of glucan-synthase which lead to decreased affinity of echinocandins to it.
C. albicans with ERG1 gene is resistant to what class of antifungals ?
Azoles
Mutated 14a-demethylase
Largely replaced by Itraconazole
Disulfiram-like reactions
Inhibition of microsomal enzymes
Antiandrogenic
Ketaconazole
3 medications in the imidazole category of Azoles ?
Ketoconazole
Clotrimazole
Miconazole