Antifungals Flashcards
what are the 5 main types of antifungals and give an example
- polyenes (amphotericin B)
- azoles (itraconazole)
- pneumocandins and echinocandins (caspofungin)
- pyrimidines
- drugs used for dermatophytosis (terbinafine)
what is the toxicity and relative spectrum of polyenes? are they fungistatic or fungicidal?
broad spectrum
high systemic toxicity
fungicidal
what is the toxicity and relative spectrum of azoles? are they fungistatic or fungicidal?
very low toxicity
broad spectrum
fungistatic
are pneumocandins/echinocandins high or low toxicity?
low toxicity
what is the newest class of antifungal drugs
pneumocandins/echinocandins
what is the cell target for:
a) pneumocandins
b) azoles
c) polyenes
a) pneumocandins: cell wall
b) azoles: plasma membrane
c) polyenes: plasma membrane
how do the cell targets of antibacterials differ from antifungals
antibacterials are commonly protein synthesis or cell wall synthesis whereas antifungals are very commonly plasma membrane
what allows us to target the plasma membrane of fungi (what is different about the plasma membrane compared to animals cells)
they contain ergosterol instead of cholesterol
what are the two “formulations” of amphotericin B (a polyene) and what is the therapeutic difference
1) bile salts: will be eliminated in the kidneys and can cause kidney damage
2) lipid: will be eliminated in the reticuloendothelial system and can be used to target infections there
what is the absorption and distribution of amphotericin B
poor oral; given IV; distributes in extracellular fluid but poor CNS penetration
what is the half life of amphotericin B
LONG (26h in dogs)
what is the spectrum of amphotericin B and what is its main use(s)? how do we usually give it? how does use differ in large animals?
broad (not against dermatophytes); due to toxicity it is usually used topically or for life-threatening systemic mycoses; we usually give one dose of this followed by doses of azoles; not used in food animals and rarely used in equine
what is the main adverse effect of amphotericin B
dose-dependent nephrotoxicity (worse with bile salt formulations, better with lipid formulations)
how should we go about administering amphotericin B
slow (4-6h) in dextrose-containing IV fluid, may be good to give NaCl fluids before administration to lessen renal toxicity
what antifungal can you not give a pregnant dog
azoles (teratogenic)
what is the bioavailability of azoles
good oral bioavailability
what are the two “types” of azoles and an example? how do we use them?
1) imidazoles (ex. ketoconazole)
2) triazoles (ex. itraconazole)
Triazoles better for systemic use but both good for topical use so we use imidazoles first
what is the MoA of azoles and an important consideration due to this MoA
inhibits fungal P450 enzymes involved in ergosterol formation
it also inhibits some mammalians P450 enzymes making it inhibit the metabolism of other drugs given
why do we generally not use imidazoles systemically anymore
endocrine effects common with systemic therapy because they inhibit mammalian sterol synthesis
what drug is no longer used as an antifungal but is used to treat hyperadrenocorticism
ketoconazole (an imidazole azole)
what are the topical imidazole azoles
miconazole (otic and dermal)
clotrimazole (otic)
enilconazole (dermal)
what is caspofungin and what is it important for
echinocandin; useful against Candida spp.
what 2 classes/types of antifungals can be used synergistically against dermatophytes
terbinafine and azoles
what are the two ways to administer terbinafine
oral or topical
