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
Topical imidazoles that are used in dermatophytoses ?
Clotrimazole
Miconazole
Meningeal coccidiomycosis requires lifelong trx with what ?
Fluconazole
DOC for mucocutaneous infections & Cryptococcal meningitis ?
Fluconazole
Penetrates the CNS, wide therapeutic index and achieves good concentration in the urine, but is teratogenic ?
Fluconazole
Broadest spectrum of all Azoles
Itraconazole
DOC for histoplasmosis, blastomycosis and sporothricosis as well as severe esophageal candidiasis.
Itraconazole
Trx of mycetoma, coccidiomyces and paracoccidiomyces, as long as they dont involve meningitis because the drug does not cross the BBB ?
Itraconazole
DOC for aspergillosis ?
Variconazole
Inhibits CYP34A and causes visual disturbances ?
Variconazole
Used in prophylaxis in cases of neutropenia of ALL pts undergoing chemo or in transplant pts with Graft VS host disease ?
Posaconazole
Trx of mucormycosis ?
Variconazole
Posaconazole
Nystatin is the topical version of :
Amphotericin B
Griseofulvin indications ?
systemically used for dermatophytic infections (per os with fatty foods)
Drug accumulated in newly forming keratin of skin, hair and nails and protects them from new infections. Extended therapy is required.
Contraindicated in intermittent acute porphyria, causes lupus like syndrome, disulfiram-like reactions and teratogenic ?
Griseofulvin
Largely replaced by Itraconazole and Terbinafine
Microsiomal enzyme inducer decreasing efficacy of OCP, warfarin and phenobaribituates ?
Griseofulvin
