6 Antifungals

Question 0

what is the main use of amphotericin B

Answer 0

synergistically works with flucytosine

it binds to ergosterol and produced a pore allowing flucytosine to get into the fungus

Question 1

antifungals for systemic mycoses

Answer 1

1. amphotericin B
2. Flucytosine (5FC) + amphotericin B
3. ketoconazole
4. Fluconazole
5. Caspofungin
6. Itraconazole

Question 2

if you hear broad spectrum antifungal for systemic mycoses you would think

Answer 2

amphotericin B
	good vs:
		1. CANDIDA ALBICANS
		2. histoplasma capsulatum
		3. cryptococcus neoformans
		4. coccidioides immitis
		5. blastomyces dermatitidis

Question 3

if you need a very broad spectrum antifungal for system mycoses you think

Answer 3

itraconazole
	used for:
		1. AIDS ASSOCIATED HISTOPLASMOSIS
		2. DOC FOR BLASTOMYCOSIS
		3. aspergillosis
		4. candidemia
		5. coccidioidomycosis
		6. cryptococcosis

Question 4

want to treat AIDs patient who develops histoplasmosis, pro would give

Answer 4

itraconazole–> bc its used for AIDS related histoplasmosis

Question 5

MOA of amphotericin B

Answer 5

binds to sterol in cell membrane and forms channels/pores K+ and Mg2+ leak out of cell–> cell death

Question 6

why is amphotericin B not used that much anymore

Answer 6

it has a high TI= low doses can be toxic

Question 7

what is one of the only antifungals for systemic infs that cant get into the CSF

Answer 7

1. amphertericin B
2. ketoconazole
3. itraconazole

Question 8

how would you administer amphitericin B for fungal meningitidis?

Answer 8

intra-thecally= in the space between the spinal cord

Question 9

MOA of Flucytosine

Answer 9

5FU–>5FdUMP= false nucleotide

inhibits THYMIDYLATE SYNTHETASE–> no thymidylic acid–> which is an essential DNA product–> w/o this the cell dies

Question 10

what 2 organisms can flu-cytosine be used against

Answer 10

1. cryptococcus neoformans

2. candida

Question 11

what is the cause of side effects the flucytosine

Answer 11

5-FU is formed from 5-FC

• 5-FU= formed by intestinal organisms
• -> CAUSES HEPATOLOGICAL TOXICITY

5FU–> liver problems

Question 12

which systemic anti-fungal do you have to adjust for in ppl with renal failure

Answer 12

flucytosine= 5FC

Question 13

whats the purpose of conjugating flucytosine with amphotericin B

Answer 13

amphotericin B affects cell permeability which opens a poor in the fungi and allows flucytosine to get better penetration

Question 14

MOA of all -azoles

Answer 14

has C-14-demethylase= p450 -

• it prevents production of ergosterol (blocks the demethylation fo Ianosterol–> ergosterol)
• which causes the cell to die

Question 15

ketoconazole is synergistic with…

Answer 15

acidic environment/Coca Cola–> improves the absorption of ketoconazole

Question 16

which 2 drugs would you not use for fungal meningitidis

Answer 16

1. ketoconazole

2. itraconazole

Question 17

which systemic antifungal would you see used to treat the prostate and what are the side effects?

Answer 17

ketoconazole

–> need to give in REALLY HIGH DOSES–>causes decreased testerosterone levels–> IMPOTENCE

Question 18

why might you use fluconazole

Answer 18

it has good CSF penetration–> which means its a good drug for fungal meningitidis
=DOC for fungal meningitidis
DOC–> cryptococcus neoformans= encapsulated fungi

Question 19

why would you use fluconazole during pregnancy

Answer 19

it is a p450 - and a potent teratogen

if you dont want mutant babies–> dont give fluconazole

Question 20

what pts would you possible see resistance to fluconazole

Answer 20

HIV + patients

Question 21

which drug has anti-androgen properties

Answer 21

ketoconazole= decreased testosterone–> IMPOTENCE

Question 22

MOA of caspofungin

Answer 22

• formation of Beta (1,3)-D glucans–> which are found in the fungal cell cell

Question 23

if you have an azole resistant C. albicans you might think of treating with

Answer 23

Caspofungin

Question 24

what are the other uses of caspofungins

Answer 24

1. azole resistant C. albicans 2. aspergillus fumigatus--> opportunist infection of LRT 3. P carini 4. H capsulatum

Question 25

caspofungins can cause

Answer 25

histamine release

Question 26

how would you administer caspofungin

Answer 26

IV infusion over 1 hr

Question 27

when would you give itraconazole over ketoconazole?

Answer 27

if you have a male that doesnt want impotence or a case of AIDs associated histoplasmosis, or if pt has kidney disease bc itraconazole is extensively metabolized in the liver if pt has HTN or edema already present--> wouldnt give itraconazole bc it would exacerbate the pts symptoms

Question 28

what is the broadest spectrum azole

Answer 28

posa-con-azole= PUSSY

Question 29

used to treat superficial mycotic infections

Answer 29

1. griseo-fulvin 2. ter-bin-afine 3. nystatin

Question 30

MOA of griseofulvin

Answer 30

disrupts miotic spindle--> - mitosis | -accumulates in infected newly synthesized keratin containing tissues--. making them unsuitable for growth of fungi

Question 31

which antifungal would you use against the dermatophytes= 1. tricho-phyton 2. epidermo-phyton 3. microsporum

Answer 31

griseofulvin

Question 32

if you give griseofulvin what might you want to watch for to make sure it doesnt interfere with the drug?

Answer 32

phenobarbital= barbiturate= sleep and anticonvulsant

Question 33

side effect of griseofulvin

Answer 33

p450 inducer--> increases the metabolism of other drugs

Question 34

why is griseofulvin not used alot

Answer 34

the pt has to take it for months--> yr (multiple times a day) which results in decreased patient compliance

Question 35

which antifungals are bad for pregnant women?

Answer 35

1. flucytosine | 2. griseofulvin

Question 36

how do you administer griseofulvin

Answer 36

oral fine crystalline preps are absorbed from the GI tract CAN PROMOTE ABSORPTION IF TAKE WITH HIGH FAT MEAL

Question 37

is see acute polyphyria (issue with heme production) and hepatic issues, you might as it the patients on

Answer 37

griseofulvin

Question 38

MOA of terbinafine

Answer 38

- fungal enzyme= squalene epoxidase--> accumulation of squalene(sterol), which is toxic to the fungi

Question 39

how can you administer terbinafine?

Answer 39

1. orally | 2. topical gel

Question 40

MOA of nystatin

Answer 40

similar to amphotericin B--> binds to sterol and produced pore

Question 41

what is the only use of nystatin?

Answer 41

topical use of candida | swish and swallow for oral candida

Question 42

what are the topical antifungals

Answer 42

1. keto-conazole 2. mi-conazole 3. ter-conazole 4. clotrim-azole

Question 43

which topical antifungals can be used vaginally

Answer 43

1. miconazole--> monistat 2. terconazole 3. clotrimazole

Question 44

which topical antifungal is only used vaginally

Answer 44

terconazole

Question 45

what is the use of topical antifungals

Answer 45

the tineas 1. tinea corporis= body 2. tinea cruris 3. tinea versicolor 4. cutaneous candidiasis

Question 46

MOA topical antifungals

Answer 46

same as ketochonazole c-14 alpha demethylase--> which inhibits conversion of Ianosterol to ergosterol no ergosterol= disrupt membrane function--> increased membrane perm.