Lecture 6 Antifugals Flashcards
Dimorphic fungi grow as ____ at room temperature and as ____ in hosts
molds; yeasts
yeast in the heat, mold in the cold
All fungi reproduce by forming spores through ____, during which the _____ number remains unchanged
mitosis;
chromosome
Fungal colonies with only an ____ mode of spore formation are said to be in the imperfect state
asexual
Sexual spores are formed by the fusion of two ___, followed by ___, which reduces the chromosome number by ____
nuclei; meiosis; half
Fungi growing sexual spores are said to be in the ____ ____
perfect state
2 exceptions to the rule that fungi are not transmissable person to person:
ringworm of scalp;
oral thrush in newborn from mother with Candida
Mechanism of action for Tolnaftate (tinactin)
inhibits squalene expoxidase
Do mammals have squalene epoxidase?
Yes, but tinactin has higher affinity to fungal enzyme
According to sketchy, ____ is especially used to treat onchymycosis
terbinafine
Mechanism of action for azoles:
inhibit 14alpha-demethylation of lanosterol, blocking its conversion to ergosterol;
Azoles inhibit fungal ____, but can bind to the human form of this enzyme as well, _____ drug metabolism
CYP450; inhibiting
_____ binds to microtubules of the mitotic spindle, inhibiting _____
Griseofulvin, mitosis
Griseofulvin treats onychomycosis by depositing in newly formed _____, where it prevents fungal growth
keratin
Griseofulvin should be taken with a high ___ diet to improve absorption
fat
adverse effects of griseofulvin
photosensitivity, hypersensitivity, headache
Amphotericin B contains a lipophillic ____ region and a hydrophillic ____ region
polyene; polyalcohol
Side effects of amphoterrible:
____toxicity leading to hypo_____;
____ tension
____ and ____ (shake and bake)
nephro, kalemia;
hypo;
fever, chills
mechanism of action for amphoB:
binds to ergosterol membrane, forming pores
in pore formation with AmphoB, the _____ groups form the pore, attracting ions. The ____ groups bind to ergosterol
polyalcohol;
polyene
What anti-fungal has the same mechanism as AmphoB
nystatin
Mechanism of action of flucytosine:
Flucytosine (_______) is converted to _____ by _____ which ends up inhibiting _____
5-Fluorocytosine–>5 Fluorouracil by fungal cytosine deaminase; inhibits thymidylate synthase
_____ is the molecule that inhibits thymidylate synthase
5-fluorodeoxyuridine monophosphate
Why is elimination of the F on 5-fluorouracil impossible?
F is the most electronegative element
5-fluorouracil is also incorporated into RNA in the place of ____, inhibiting _____ synthesis. It acts as a _____ in this way
uracil; protein; anti-metabolite
Flucytosine is used in combination with AmphoB to treat ____ and _____
systemic Candida; cryptococcus meningitis
Adverse effect of flucytosine
bone marrow supression
flucytosine is eliminated by the ____
kidneys
Fluconazole is a ___azole
tri
____ has high bioavailabilty and penetrates well into the CSF; its useful in treatment of meningitis in _____ patients
fluconazole; aids
How is fluconazole administered for treatment of vaginal candidiasis?
orally
_____ is a racemic mixture of 4 diastereomers
itraconazole
____ does not appear in the CSF and is not useful for treatment of CNS infections
itraconazole
Itraconazole is the preferred treatment of nonmeningeal _____, including in AIDS patients
histoplasmosis
Severe but rare side effects associated with Itraconazole:
heart or liver failure
Mechanism of action for the echinocandins:
inhibition of 1,3-beta glucan synthase, which forms polymers
Echcandins are synergistic with ____ and _____
voriconazole, amphotericin B
Caspofungin is administered ___
via IV
