Antifungals Flashcards
what is the component of fungal cell walls that humans don’t have, making it a good drug target
ergosterol
what are the 3 classes of antifungals
antibiotics (amphotericin B)
antimetabolite (pyrimidine analog)
azoles
is amphotericin B fungicidal or fungistatic
fungicidal
what is the mechanism of action for amphotericin B
it binds to ergosterol and forms pores, allowing for the leakage of cell content and death of the fungal cell
is amphotericin B able to cross the BBB
no
is amphotericin B polar or nonpolar
polar so it is water soluble and can’t cross the cell membrane, given IV
amphotericin B is used for topical actions for __ infections
GI
amphotericin B can lead to __ toxicty
renal
how is amphotericin B prepared to decrease its toxicity
bound to liposomes which have low affinity to human tissue and therefore bind poorly
amphotericin B is the drug of choice for what fungal infections
serious and life threatening
what is the acute/immediate reaction of amphotericin B due to IV infusion
release of histamine leads to fever, chills, vomiting, HA, etc.
how can the acute/immediate reaction due to amphotericin B be reduced
by slowing the rate of IV infusion and using a test dose of 1mg
what is the adverse effect of amphotericin B that occurs in most people
nephrotoxicity–>tubular acidosis, hypokalemia and hypomagnesaemia
flucytosine is a pyrimidine antimetabolite which is an analog of __
5-fluorouracil
is flucytosine fungistatic or fungicidal
fungistatic
is flucytosine able to cross the BBB
yes
what is the mechanism of action of flucytosine
it inhibits fungal thymidylate synthetase, inhibiting RNA and DNA synthesis
amphotericin B is used synergistically with flucytosine. why
amphotericin B produces pores and increases the penetration of 5-fluorouracil into the fungal cell
what does it mean to say that flucytosine has a narrow therapeutic window
at high concentration it produces more toxic effects and at low concentration it develops resistance
what is the mechanism of action of azole drugs
inhibition of 14-alpha demethylase leads to inhibition of demethylation and leakage of cell contents
mutation in what gene can lead to azole drug resistance
ERG11
what are 2 adverse reactions of ketaconazole azole drugs
blockage of androgen receptors–> impotence, decreased libido, gynecomastia, and menstrual irregularities
disulfiram like reactions
amphotericin B should not be combined with what other drug
azoles
fluconazole is useful for meningitis due to the fact that it has __
good CSF permeability
fluconazole is as efficacious as amphotericin B at preventing __
candidemia in ICU patients
what is the drug of choice for cryptococcal meningitis
fluconazole
itraconazole has poor __ and __
absorption (enhance with food)
CSF penetration
what is the broadest spectrum of azole
itraconazole
itraconazole is the drug of choice for what 3 fungal infections
histoplasmosis
blastomycosis
sporothrichosis
what are 2 adverse effects of itraconazole
hepatotoxicity
should be avoided in pregnancy
what drug is effective in fluconazole resistant candidiasis
vorconazole
what is an adverse effect of posaconazole
hyperaldosteronism
what is the mechanism of action of echinocandin drugs
inhibits beta 1,3 D-glucan synthase leading to inhibition of 1,3 beta-glucan synthesis, preventing integrity of fungal cell wall and leading to lysis of the fungal cells
what is the mechanism of action of echinocandin drugs
inhibits beta 1,3 D-glucan synthase leading to inhibition of 1,3 beta-glucan synthesis, preventing integrity of fungal cell wall and leading to lysis of the fungal cell
what is the mechanism of resistance to echinocandins
amino acid changes in fks subunits of glucan synthase
are echinocandins fungicidal or fungistatic
fungicidal
capsofungin, an echinocandin, is used in what 3 cases
disseminated and mucocutaneous candida infections
empirical and stem cell transplants
salvage therapy in invasive aspergillosis
griseofulvin is used for what type of mycotic infections
superficial
what is the mechanism of action of griseofulvin
it binds to microtubules and prevents spindle formation, inhibiting fungal mitosis
*it prevents infection of new tissue, not the tissue that is already infected
how can the absorption of griseofulvin be increased
give with fatty food
why is prolonged therapy required with griseofulvin
it is required until the infected tissue is replaced by new healthy skin or nail
what is the main adverse effect of griseofulvin
disulfiram like reaction
what is the mechanism of action of allylamine
it inhibits squalene epoxidase and ergosterol synthesis, leading to the accumulation of squalene which is toxic to fungus
what is the drug of choice for dermatophytosis (especially for onychomycosis)
terbinafine
