Fungal Treatment

Question 1

nosocomial infections

Answer 1

hospital

Question 2

3 main types of fungal diseases

Answer 2

-Candida spp.
-Aspergillus spp.
-Cryptococcus spp.

Question 3

what does Griesofluvin taregt

Answer 3

microtubulin formation

Question 4

what does Flucytosine target

Answer 4

RNA and DNA synthesis

Question 5

What do Echinocandins target

Answer 5

beta-glucan synthesis

Question 6

What do Polyenes target

Answer 6

ergosterol of cell membrane

Question 7

What do Allylamines target

Answer 7

ergosterol cell membrane

Question 8

What do Azoles target

Answer 8

Ergosterol cell membrane

Question 9

What drugs target microtubulin formation

Answer 9

Griesofluvin

Question 10

What drug targets RNA and DNA synthesis

Answer 10

Flucytosine

Question 11

What drugs target beta-glucan synthesis

Answer 11

Echinocandins

Question 12

What drugs target cell membrane via ergosterol

Answer 12

-Polyenes
-Allylamines
-Azoles

Question 13

What type of fungi does Griseofulvin target

Answer 13

-Dermatophytes

Question 14

What is the mechanism of Griseofulvin

Answer 14

-binds to keratin precursor of skin and nails
-taken up by fungi
-binds to microtubules
-mitosis arrests at metaphase

Question 15

How is Griseofulvin taken

Answer 15

Orally

Question 16

What fungi does Flucytosine target

Answer 16

-Candida
-Cryptococcus

Question 17

Flucytosine mechanism

Answer 17

-converted to 5-fluorouracil by fungi cytosine deaminase
-is a pyrimidine analogue
-inhibits DNA and RNA synthesis

Question 18

Examples of a Pyrimidine analogue

Answer 18

5-fluorouracil

Question 19

What are pyrimidine analogues

Answer 19

Antimetabolites that inhibit DNA and RNA synthesis

Question 20

What fungi are Echinocandins used for

Answer 20

-Candida
-Aspergillus

Question 21

For what fungi are Echinocandins fungistatic

Answer 21

Aspergillus spp.

Question 21

For what fungi is Echinocandins fungicidal

Answer 21

Candida spp.

Question 22

Echinocandins mechanism

Answer 22

-Non-competitively inhibit beta-1,3-D-glucan synthase
-Resistance from osmotic forces lost
-Cell lysis
-Host immune response enhanced

Question 23

What do Polyenes bind

Answer 23

directly to ergosterol

Question 24

Allylamines effect

Answer 24

-inhibits sterol biosynthesis -via inhibit ERG1

Question 25

Azoles effect

Answer 25

-inhibit sterol biosynthesis -via inhibit ERG11, CYP51

Question 26

How does Polyene affect the membrane

Answer 26

-binds to ergosterol -causes gaps in membrane -leaking of contents or less ergosterol

Question 27

Examples of Polyenes

Answer 27

-Amphotericin B -Nyastatin

Question 28

How could Polyenes be dangerous to humans

Answer 28

-may bind to cholesterol -risk of human toxicity

Question 29

Examples of Allylamines

Answer 29

Terbinafine

Question 30

Allylamines mechanism

Answer 30

-inhibits squalene epoxidase -squalene accumulates -depletion in amount of ergosterol -Fungistatic

Question 31

How can Allylamines possibly be harmful to humans

Answer 31

-can inhibit human squalene epoxidase -toxicity

Question 32

What is the most widely used and first course of treatment for fungi infections

Answer 32

Azoles

Question 33

What type of pathogen are Azoles usually used for

Answer 33

Primary pathogens

Question 34

What antifungal is commonly used for plant infections

Answer 34

Azoles

Question 35

Topically used Azoles

Answer 35

-Ketoconazole -Miconazole -Clotrimazole

Question 36

Azoles affective against resistant fungi

Answer 36

-Voriconazole -Posaconazole

Question 37

Azoles mechanism

Answer 37

-inhibits sterol 14alpha demethylase -Ergosterol depletion -accumulation of bulky sterols -fungiSTATIC

Question 38

Azoles risk to humans

Answer 38

-May also interact with other CYPs -toxicity

Question 39

What is CYP51

Answer 39

-Cytochrome p450 enzyme -contains haem required for catalysis

Question 40

What does Azole bind to on CYP51

Answer 40

directly to haem moiety and inhibiting its function

Question 41

How has Azole resistance arisen

Answer 41

-prophylactics given to immunocompromised patients

Question 42

Prophylactic meaning

Answer 42

Preventative

Question 43

Azole resistance mechanisms

Answer 43

1) Alterations of target sites (CYP51) 2)Alteration of metabolic pathway (ERG3) 3) Reduced drug accumulation

Question 44

How do fungi alter target site for Azole

Answer 44

1) Point mutations in CYP51 2) Overexpression of CYP51

Question 45

How do fungi alter metabolic pathway for Azole

Answer 45

-mutations in other sterol pathway genes (ERG3) -ergosterol still made

Question 46

How is Candida spp. resistant to Azole

Answer 46

-CYP51 point mutations -overexpression of CYP51 -Overexpression of efflux -ERG3 mutations

Question 47

How is Aspergillus spp. resistant to Azole

Answer 47

-CYP51 point mutations -Overexpression of CYP51 -Overexpression of efflux

Question 48

How is Cryptococcus spp. resistant to Azole

Answer 48

-CYP51 point mutations -Overexpression of CYP51 -Overexpression of efflux

Question 49

how is Histoplasma capsulatum resistant to Azole

Answer 49

-CYP51 point mutations

Question 50

What fungi are urgent threats to resistance

Answer 50

Candida Auris

Question 51

What fungi are a serious threat to resistance

Answer 51

The Candida species

Question 52

What fungi are on watchlist to resistance

Answer 52

-for Azole -Aspergillus fumigatus

Question 53

How is Azole resistance mechanism determined

Answer 53

-Sterol analysis -DNA sequencing

Question 54

How can Azole efficacy be predicted/tested

Answer 54

-Vitro = ligand binding, catalysis studies -Silico = modeling

Question 55

What does in Vitro mean

Answer 55

In glass - outside of living organism

Question 56

What does in silico mean

Answer 56

using computers

Question 57

Further issues of Azoles

Answer 57

-Toxicity/side effects -Resistance due to agricultural use -Cross-resistance with polyenes