Antifungals

Question 1

what is the component of fungal cell walls that humans don’t have, making it a good drug target

Answer 1

ergosterol

Question 2

what are the 3 classes of antifungals

Answer 2

antibiotics (amphotericin B)
antimetabolite (pyrimidine analog)
azoles

Question 3

is amphotericin B fungicidal or fungistatic

Answer 3

fungicidal

Question 4

what is the mechanism of action for amphotericin B

Answer 4

it binds to ergosterol and forms pores, allowing for the leakage of cell content and death of the fungal cell

Question 5

is amphotericin B able to cross the BBB

Answer 5

no

Question 6

is amphotericin B polar or nonpolar

Answer 6

polar so it is water soluble and can’t cross the cell membrane, given IV

Question 7

amphotericin B is used for topical actions for __ infections

Answer 7

GI

Question 8

amphotericin B can lead to __ toxicty

Answer 8

renal

Question 9

how is amphotericin B prepared to decrease its toxicity

Answer 9

bound to liposomes which have low affinity to human tissue and therefore bind poorly

Question 10

amphotericin B is the drug of choice for what fungal infections

Answer 10

serious and life threatening

Question 11

what is the acute/immediate reaction of amphotericin B due to IV infusion

Answer 11

release of histamine leads to fever, chills, vomiting, HA, etc.

Question 12

how can the acute/immediate reaction due to amphotericin B be reduced

Answer 12

by slowing the rate of IV infusion and using a test dose of 1mg

Question 13

what is the adverse effect of amphotericin B that occurs in most people

Answer 13

nephrotoxicity–>tubular acidosis, hypokalemia and hypomagnesaemia

Question 14

flucytosine is a pyrimidine antimetabolite which is an analog of __

Answer 14

5-fluorouracil

Question 15

is flucytosine fungistatic or fungicidal

Answer 15

fungistatic

Question 16

is flucytosine able to cross the BBB

Answer 16

yes

Question 17

what is the mechanism of action of flucytosine

Answer 17

it inhibits fungal thymidylate synthetase, inhibiting RNA and DNA synthesis

Question 18

amphotericin B is used synergistically with flucytosine. why

Answer 18

amphotericin B produces pores and increases the penetration of 5-fluorouracil into the fungal cell

Question 19

what does it mean to say that flucytosine has a narrow therapeutic window

Answer 19

at high concentration it produces more toxic effects and at low concentration it develops resistance

Question 20

what is the mechanism of action of azole drugs

Answer 20

inhibition of 14-alpha demethylase leads to inhibition of demethylation and leakage of cell contents

Question 21

mutation in what gene can lead to azole drug resistance

Answer 21

ERG11

Question 22

what are 2 adverse reactions of ketaconazole azole drugs

Answer 22

blockage of androgen receptors–> impotence, decreased libido, gynecomastia, and menstrual irregularities

disulfiram like reactions

Question 23

amphotericin B should not be combined with what other drug

Answer 23

azoles

Question 24

fluconazole is useful for meningitis due to the fact that it has __

Answer 24

good CSF permeability

Question 25

fluconazole is as efficacious as amphotericin B at preventing __

Answer 25

candidemia in ICU patients

Question 26

what is the drug of choice for cryptococcal meningitis

Answer 26

fluconazole

Question 27

itraconazole has poor __ and __

Answer 27

absorption (enhance with food) CSF penetration

Question 28

what is the broadest spectrum of azole

Answer 28

itraconazole

Question 29

itraconazole is the drug of choice for what 3 fungal infections

Answer 29

histoplasmosis blastomycosis sporothrichosis

Question 30

what are 2 adverse effects of itraconazole

Answer 30

hepatotoxicity should be avoided in pregnancy

Question 31

what drug is effective in fluconazole resistant candidiasis

Answer 31

vorconazole

Question 32

what is an adverse effect of posaconazole

Answer 32

hyperaldosteronism

Question 33

what is the mechanism of action of echinocandin drugs

Answer 33

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

Question 34

what is the mechanism of action of echinocandin drugs

Answer 34

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

Question 35

what is the mechanism of resistance to echinocandins

Answer 35

amino acid changes in fks subunits of glucan synthase

Question 36

are echinocandins fungicidal or fungistatic

Answer 36

fungicidal

Question 37

capsofungin, an echinocandin, is used in what 3 cases

Answer 37

disseminated and mucocutaneous candida infections empirical and stem cell transplants salvage therapy in invasive aspergillosis

Question 38

griseofulvin is used for what type of mycotic infections

Answer 38

superficial

Question 39

what is the mechanism of action of griseofulvin

Answer 39

it binds to microtubules and prevents spindle formation, inhibiting fungal mitosis *it prevents infection of new tissue, not the tissue that is already infected

Question 40

how can the absorption of griseofulvin be increased

Answer 40

give with fatty food

Question 41

why is prolonged therapy required with griseofulvin

Answer 41

it is required until the infected tissue is replaced by new healthy skin or nail

Question 42

what is the main adverse effect of griseofulvin

Answer 42

disulfiram like reaction

Question 43

what is the mechanism of action of allylamine

Answer 43

it inhibits squalene epoxidase and ergosterol synthesis, leading to the accumulation of squalene which is toxic to fungus

Question 44

what is the drug of choice for dermatophytosis (especially for onychomycosis)

Answer 44

terbinafine