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Flashcards in Antifungal 1 Deck (50)
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1

Yeasts shape

oval or round

2

Yeasts grow via

budding

3

Molds composed of

hyphae

4

Dimporphic fungi (syndromes)

  1. Sporotrichosis
  2. Coccidiodiomycosis
  3. Paracoccidioidomycosis
  4. Blastomycosis
  5. Chromoblastomycosis
  6. Histoplasmosis

5

Cells of fungi that are pathogenic in humans are...

nonmotile and have a rigid cell wall

 

(usually containing chitin and polysaccharides)

6

Two exceptions to the "non-transmissible" rule

Ringworm of scalp

Neonatal candida

7

Dermatomycoses live on ___ tissue

keratinized

8

Antifungals to treat dermatomycoses

Tolnaftate

Clotrimazole

Griseofulvin

9

Tolnaftate MOA

Inhibits squalene epoxidase

10

Why doesn't inhibition of squalene epoxidase affect mammillian cells as much as fungi?

The fungal enzye is more sensitive to the drug

11

Steps in ergosterol synthesis

  • Squalene

(squalene epoxidase) 

  • Protonated squalene
  • Lanosterol
  • Ergosterol

12

Other squalene epoxidase inhibitors

Terbenafine

Naftifine

Butenafine

13

Clotrimazole MOA

Inhibits +++Fe-CYP450

which catalyzes the 14a-demethylation of lanosterol

14

Normal intermediate between Lanosterol and Ergosterol contains______

COOH group on D ring

15

How do azoles (like clotrimazole) block CYP450 during ergosterol synthesis

The electrons on N bind to the Fe3+ on CYP450. 

 

This happens more readily with fungal enzyme than with humans

16

Two other examples of -azole antifungal agents

Miconazole

Ketoconazole

17

___ used for systemic treatment of dermatomycoses

Griseofulvin

18

Griseofulvin MOA

Disrupts the mitotic spindle by binding to polymerized MTs to inhibit mitosis

19

Griseofulvin is used for this (possibly long term)

Onychomycoses

Treatment lasts up to a year since keratin in old tissue may support fungal growth.

20

Antifungals to treat systemic infections

Amphoteracin B

Flucytosine

Itraonazole

Fluconazole

Echinocandins

21

AMP B contains __ and ___

lipophilic polyene region and hydrophilic polyalcohol region

22

AMP B must be administered ____ . Why?

IV 

Poor water solubility

23

Major Amp B acute reaction

Fever and Chills

24

Major Amp limiting toxicities

Nephrotoxicity

hypokalemia

25

AmpB is ___ for treatment of ____

broad spec

deep mycoses

26

AmpB MOA

binds directly to ergosterol in fungal membranes

 

Opens pores that let out small organic molecules

27

AmpB - binding ergosterol vs cholesterol

10x more strongly

28

Fluorocytosine MOA

Susceptible fungi convert:

5FC >> 5FU >> 5 fluorodeoxyuridine monophosphate

29

5FDUMP function

inhibits thymidylate synthase

(inhibits DNA synth)

30

Mechanism of DUMP to DTMP conversion

  • Michael addition >> enolate created
  • added to iminium in methyleneTHF (thiss eliminates THF)
  • Uracil derivative formed
  • Delivery of hydride from THF to the uracil intermediate (via Michael reation)
  • Generates enolate >> eliminates the enzyme = product