Chapter 35: Fungal Infections

Question 1

Flucytosine MOA?

Answer 1

converted to 5 FdUMP, which goes on to inhibit thymidylate sythase –> inhibit DNA synthesis!

Question 2

Flucytosine is used to treat 1) 2) 3) ?

Answer 2

fluCytosine –> the three Cs

Candiasis
Cyptococcosis
Chromomycosis

Question 3

How does flucytosine resistance manifest?

Answer 3

mutations in cytosine permease/deaminase lead to resistance

Question 4

Which antifungal drug works by binding to tubulin and and a microtubule assc protein, thus disrupting assembly of the mitotic spindle?

Answer 4

Griseofulvin

Grizzly-fulvin comes in and RIPS APART THE MITOTIC SPINDLE!!!

Question 5

Griseofulvin is used to treat __? But cannot

Answer 5

skin hair or nail infections

caused by trichophyton, microsporum, epidermophyton

Question 6

You cannot use griseofulvin in patients with what medical conditions?

Answer 6

pregnancy; porphyria; hepatic failure

Question 7

Giving barbituates with griseofulvin causes what?

Answer 7

increases GI absorption of griseofulvin

Question 8

Which inhibitor of squalene epoxidase has a really long half life (~300 hr) because it accumulates in the nails, skin, and fat?

Answer 8

terbinafine

Question 9

What is the drug of choice for onychomycosis (nail fungus tinea unguum)?

Answer 9

terbinafine

Question 10

What class of drugs are used to treat the “tineas?”

Answer 10

squalene epoxidase inhibitors –> “fines”
terbinaFINE, naftiFINE, butenaFINE

that chick Tinea is sooo FINE!

Question 11

Which inhibitor of sqaulene epoxidase is available only as a cream or gel?

Answer 11

naftifine

Question 12

A lot of stuff interferes with ketoconazole - what?

Answer 12

amphotericin B
oral triazolam
anything that decreases gastric acidity
inhibits p450 so anyting like warfarin, h1 antihistamines…

Question 13

which imidazole antifungal is NOT used for superficial eye infections?

Answer 13

ketoconazole

Question 14

triazole antifungals include –?

Answer 14

fluconazole
itraconazole
posaconazole
terconazole
noriconazole

Question 15

which triazole can be used to treat aspergillosis, blastomycosis, cadidiasis, histoplasmosis, onychomycosis?

Answer 15

itraconazole

Question 16

Which triazole does not penetrate the CSF but may have strong effects on the meninges anyways?

Answer 16

intraconazole

Question 17

amphotericin B MOA?

Answer 17

binds to ergosterol and forms pores that alter fungal membrane stability

Question 18

what are the major adverse effects of amphotericin B?

Answer 18

renal toxicity
cytokine storm (fever, chills, hypotension)

Question 19

What measures are taken to reduce renal toxicity of ampho B?

Answer 19

lipid formulations reduce drug exposure to the proximal tubule

Question 20

Ampho B should be combined with what other antifungal to tx acute cryptococcal meningitis?

Answer 20

flucytosine

Question 21

Which ergosterol inhibitor is used to treat only mucocutaneous candidiasis?

Answer 21

nystatin

Question 22

what is the MOA of the “fungins”

Answer 22

noncomp inhibition of B 1 3 D glucans synthesis –> disrupts cell wall integrity

Question 23

Echinocandins, the “fungins” are fungicidal against ___ and fungistatic against ___?

Answer 23

candidiasis species

aspergillus species

Question 24

CSF sample reveals crytococcus neoformans. Tx begins with ampho B for two weeks then you switch to oral tx with __? Why?

Answer 24

fluconazole

bc it has good CNS penetration (unlike itraconazole and ketoconazole…so are not used to tx meningitis)