6 Antifungals Flashcards
what is the main use of amphotericin B
synergistically works with flucytosine
it binds to ergosterol and produced a pore allowing flucytosine to get into the fungus
antifungals for systemic mycoses
- amphotericin B
- Flucytosine (5FC) + amphotericin B
- ketoconazole
- Fluconazole
- Caspofungin
- Itraconazole
if you hear broad spectrum antifungal for systemic mycoses you would think
amphotericin B good vs: 1. CANDIDA ALBICANS 2. histoplasma capsulatum 3. cryptococcus neoformans 4. coccidioides immitis 5. blastomyces dermatitidis
if you need a very broad spectrum antifungal for system mycoses you think
itraconazole used for: 1. AIDS ASSOCIATED HISTOPLASMOSIS 2. DOC FOR BLASTOMYCOSIS 3. aspergillosis 4. candidemia 5. coccidioidomycosis 6. cryptococcosis
want to treat AIDs patient who develops histoplasmosis, pro would give
itraconazole–> bc its used for AIDS related histoplasmosis
MOA of amphotericin B
binds to sterol in cell membrane and forms channels/pores K+ and Mg2+ leak out of cell–> cell death
why is amphotericin B not used that much anymore
it has a high TI= low doses can be toxic
what is one of the only antifungals for systemic infs that cant get into the CSF
- amphertericin B
- ketoconazole
- itraconazole
how would you administer amphitericin B for fungal meningitidis?
intra-thecally= in the space between the spinal cord
MOA of Flucytosine
5FU–>5FdUMP= false nucleotide
inhibits THYMIDYLATE SYNTHETASE–> no thymidylic acid–> which is an essential DNA product–> w/o this the cell dies
what 2 organisms can flu-cytosine be used against
- cryptococcus neoformans
2. candida
what is the cause of side effects the flucytosine
5-FU is formed from 5-FC
- 5-FU= formed by intestinal organisms
- -> CAUSES HEPATOLOGICAL TOXICITY
5FU–> liver problems
which systemic anti-fungal do you have to adjust for in ppl with renal failure
flucytosine= 5FC
whats the purpose of conjugating flucytosine with amphotericin B
amphotericin B affects cell permeability which opens a poor in the fungi and allows flucytosine to get better penetration
MOA of all -azoles
has C-14-demethylase= p450 -
- it prevents production of ergosterol (blocks the demethylation fo Ianosterol–> ergosterol)
- which causes the cell to die
ketoconazole is synergistic with…
acidic environment/Coca Cola–> improves the absorption of ketoconazole
which 2 drugs would you not use for fungal meningitidis
- ketoconazole
2. itraconazole
which systemic antifungal would you see used to treat the prostate and what are the side effects?
ketoconazole
–> need to give in REALLY HIGH DOSES–>causes decreased testerosterone levels–> IMPOTENCE
why might you use fluconazole
it has good CSF penetration–> which means its a good drug for fungal meningitidis
=DOC for fungal meningitidis
DOC–> cryptococcus neoformans= encapsulated fungi
why would you use fluconazole during pregnancy
it is a p450 - and a potent teratogen
if you dont want mutant babies–> dont give fluconazole
what pts would you possible see resistance to fluconazole
HIV + patients
which drug has anti-androgen properties
ketoconazole= decreased testosterone–> IMPOTENCE
MOA of caspofungin
- formation of Beta (1,3)-D glucans–> which are found in the fungal cell cell
if you have an azole resistant C. albicans you might think of treating with
Caspofungin
what are the other uses of caspofungins
- azole resistant C. albicans
- aspergillus fumigatus–> opportunist infection of LRT
- P carini
- H capsulatum
caspofungins can cause
histamine release
how would you administer caspofungin
IV infusion over 1 hr
when would you give itraconazole over ketoconazole?
if you have a male that doesnt want impotence or a case of AIDs associated histoplasmosis, or if pt has kidney disease bc itraconazole is extensively metabolized in the liver
if pt has HTN or edema already present–> wouldnt give itraconazole bc it would exacerbate the pts symptoms
what is the broadest spectrum azole
posa-con-azole= PUSSY
used to treat superficial mycotic infections
- griseo-fulvin
- ter-bin-afine
- nystatin
MOA of griseofulvin
disrupts miotic spindle–> - mitosis
-accumulates in infected newly synthesized keratin containing tissues–. making them unsuitable for growth of fungi
which antifungal would you use against the dermatophytes=
- tricho-phyton
- epidermo-phyton
- microsporum
griseofulvin
if you give griseofulvin what might you want to watch for to make sure it doesnt interfere with the drug?
phenobarbital= barbiturate= sleep and anticonvulsant
side effect of griseofulvin
p450 inducer–> increases the metabolism of other drugs
why is griseofulvin not used alot
the pt has to take it for months–> yr (multiple times a day)
which results in decreased patient compliance
which antifungals are bad for pregnant women?
- flucytosine
2. griseofulvin
how do you administer griseofulvin
oral
fine crystalline preps are absorbed from the GI tract
CAN PROMOTE ABSORPTION IF TAKE WITH HIGH FAT MEAL
is see acute polyphyria (issue with heme production) and hepatic issues, you might as it the patients on
griseofulvin
MOA of terbinafine
- fungal enzyme= squalene epoxidase–> accumulation of squalene(sterol), which is toxic to the fungi
how can you administer terbinafine?
- orally
2. topical gel
MOA of nystatin
similar to amphotericin B–> binds to sterol and produced pore
what is the only use of nystatin?
topical use of candida
swish and swallow for oral candida
what are the topical antifungals
- keto-conazole
- mi-conazole
- ter-conazole
- clotrim-azole
which topical antifungals can be used vaginally
- miconazole–> monistat
- terconazole
- clotrimazole
which topical antifungal is only used vaginally
terconazole
what is the use of topical antifungals
the tineas
- tinea corporis= body
- tinea cruris
- tinea versicolor
- cutaneous candidiasis
MOA topical antifungals
same as ketochonazole
c-14 alpha demethylase–> which inhibits conversion of Ianosterol to ergosterol
no ergosterol= disrupt membrane function–> increased membrane perm.
