Lecture 6 Antifugals

Question 1

Dimorphic fungi grow as ____ at room temperature and as ____ in hosts

Answer 1

molds; yeasts

yeast in the heat, mold in the cold

Question 2

All fungi reproduce by forming spores through ____, during which the _____ number remains unchanged

Answer 2

mitosis;

chromosome

Question 3

Fungal colonies with only an ____ mode of spore formation are said to be in the imperfect state

Answer 3

asexual

Question 4

Sexual spores are formed by the fusion of two ___, followed by ___, which reduces the chromosome number by ____

Answer 4

nuclei; meiosis; half

Question 5

Fungi growing sexual spores are said to be in the ____ ____

Answer 5

perfect state

Question 6

2 exceptions to the rule that fungi are not transmissable person to person:

Answer 6

ringworm of scalp;

oral thrush in newborn from mother with Candida

Question 7

Mechanism of action for Tolnaftate (tinactin)

Answer 7

inhibits squalene expoxidase

Question 8

Do mammals have squalene epoxidase?

Answer 8

Yes, but tinactin has higher affinity to fungal enzyme

Question 9

According to sketchy, ____ is especially used to treat onchymycosis

Answer 9

terbinafine

Question 10

Mechanism of action for azoles:

Answer 10

inhibit 14alpha-demethylation of lanosterol, blocking its conversion to ergosterol;

Question 11

Azoles inhibit fungal ____, but can bind to the human form of this enzyme as well, _____ drug metabolism

Answer 11

CYP450; inhibiting

Question 12

_____ binds to microtubules of the mitotic spindle, inhibiting _____

Answer 12

Griseofulvin, mitosis

Question 13

Griseofulvin treats onychomycosis by depositing in newly formed _____, where it prevents fungal growth

Answer 13

keratin

Question 14

Griseofulvin should be taken with a high ___ diet to improve absorption

Answer 14

fat

Question 15

adverse effects of griseofulvin

Answer 15

photosensitivity, hypersensitivity, headache

Question 16

Amphotericin B contains a lipophillic ____ region and a hydrophillic ____ region

Answer 16

polyene; polyalcohol

Question 17

Side effects of amphoterrible:
____toxicity leading to hypo_____;
____ tension
____ and ____ (shake and bake)

Answer 17

nephro, kalemia;
hypo;
fever, chills

Question 18

mechanism of action for amphoB:

Answer 18

binds to ergosterol membrane, forming pores

Question 19

in pore formation with AmphoB, the _____ groups form the pore, attracting ions. The ____ groups bind to ergosterol

Answer 19

polyalcohol;

polyene

Question 20

What anti-fungal has the same mechanism as AmphoB

Answer 20

nystatin

Question 21

Mechanism of action of flucytosine:

Flucytosine (_______) is converted to _____ by _____ which ends up inhibiting _____

Answer 21

5-Fluorocytosine–>5 Fluorouracil by fungal cytosine deaminase; inhibits thymidylate synthase

Question 22

_____ is the molecule that inhibits thymidylate synthase

Answer 22

5-fluorodeoxyuridine monophosphate

Question 23

Why is elimination of the F on 5-fluorouracil impossible?

Answer 23

F is the most electronegative element

Question 24

5-fluorouracil is also incorporated into RNA in the place of ____, inhibiting _____ synthesis. It acts as a _____ in this way

Answer 24

uracil; protein; anti-metabolite

Question 25

Flucytosine is used in combination with AmphoB to treat ____ and _____

Answer 25

systemic Candida; cryptococcus meningitis

Question 26

Adverse effect of flucytosine

Answer 26

bone marrow supression

Question 27

flucytosine is eliminated by the ____

Answer 27

kidneys

Question 28

Fluconazole is a ___azole

Answer 28

tri

Question 29

____ has high bioavailabilty and penetrates well into the CSF; its useful in treatment of meningitis in _____ patients

Answer 29

fluconazole; aids

Question 30

How is fluconazole administered for treatment of vaginal candidiasis?

Answer 30

orally

Question 31

_____ is a racemic mixture of 4 diastereomers

Answer 31

itraconazole

Question 32

____ does not appear in the CSF and is not useful for treatment of CNS infections

Answer 32

itraconazole

Question 33

Itraconazole is the preferred treatment of nonmeningeal _____, including in AIDS patients

Answer 33

histoplasmosis

Question 34

Severe but rare side effects associated with Itraconazole:

Answer 34

heart or liver failure

Question 35

Mechanism of action for the echinocandins:

Answer 35

inhibition of 1,3-beta glucan synthase, which forms polymers

Question 36

Echcandins are synergistic with ____ and _____

Answer 36

voriconazole, amphotericin B

Question 37

Caspofungin is administered ___

Answer 37

via IV