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Flashcards in Fitz, Antifungals Deck (52)
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1

Name a polyene antifungal.

Amphoterecin B

2

What is ergosterol?

Ergosterol is what yeast cell (fungi) membranes are rich in.

3

MOA of Amphoterecin B.

Binds to ergosterol and forms membrane pores that allow leakage of electrolytes.

4

Are the membrane pores created by Amphoterecin B hydrophilic or hydrophobic?

hydrophilic membrane pores.

5

What membrane structural characteristics does Amphoterecin B affect (2)?

1. Disrupts membrane integrity
2. Increases osmotic fragility.

6

Toxicity of Amphoterecin B:
1. Onset at infusion
2. Later onset

1. Chills, fever, anemia, hypotension
2. Nephrotoxicity

7

Clearance of Amphoterecin B

renal

8

Affects of Amphoterecin B on the kidney (2)

Direct DAMAGE TO DISTAL TUBULE membrane (Na/K/Mg wasting) ---> leading to DECREASED GFR.

9

Amphoterecin B aggravates nephrotoxicity of other drugs in what conditions?

In immunocompromised - transplant, allograft, HIV, people with serious gram negative or MRSA infections.

10

Name the azoles.

1. Imidazole - ketoconazole
2. Triazole - (1st gen) Fluconazole, Itraconazole; (2nd gen) Voriconazole, Posaconazole

11

MOA of azoles

Inhibits ergosterol synthesis, the CYP450 enzyme that converts Lanosterol (excess) ---> Ergosterol (deficit)

12

Name of the CYP450 enzyme that azoles inhibit.

14-alpha-demethylase

13

Fluconazole spectrum (and what 2 bugs)

Narrow spectrum - Candida albicans, Cryptococcus

14

Clearance of Fluconazole v. Itraconazole v. Voriconazole

Fluconazole - RENAL (75%)
Itraconazole - hepatic
Voriconazole - hepatic

15

Absorption/bioavailability of Fluconazole v. Itraconazole v. Voriconazole

Fluconazole - Good (90%)
Itraconazole - Poor (50%)
Voriconazole - Good (95%)

16

CSF access of Fluconazole v. Itraconazole v. Voriconazole

Fluconazole - GOOD (so can cover crypto for meningitis)
Itraconazole - POOR solubility
Voriconazole - Good

17

CYP450 inhibition of Fluconazole v. Itraconazole v. Voriconazole

Fluconazole - Weak
Itraconazole - STRONG drug interactions
Voriconazole - Weak

18

Half life of Fluconazole v. Itraconazole v. Voriconazole

Fluconazole - ~24 hours
Itraconazole - ~21 hours
Voriconazole - non linear

19

What does Fluconazole NOT cover?
What azole does cover this?

Aspergillus
Voriconazole covers this.

20

Bugs that Fluconazole covers (2)

Candida albicans, cryptococcus (bc penetrates CSF)

21

Spectrum and Bugs that Itraconazole covers (5)

-Broad spectrum
-Covers: CANDIDA (Candida albicans, other candida), some aspergillus
-DOC: **Histo, coccidio, blasto**

22

Bugs that Voriconazole covers (3)

-Candida albicans, other candida
-DOC: **Invasive Asperigillus**

23

Mechanisms of fungal resistance to azoles.

1. Mutation of lanosterol-14-alpha-demethylase
2. Overexpression of lanosterol-14alpha-demethylase
3. Energy-dependent efflux systems
4. Decreased permeability of fungal membrane (changes in sterol/phospholipid composition)

24

Name of fungal cell wall synthesis inhibitor class and drugs (3).

Echinocandins ---> Caspofungin, Micafungin, anidulafungin.

25

MOA of echinocandins

Inhibit cell wall synthesis by inhibiting synthesis of Beta-(1,3)-glucan, leading to osmotic fragility.

26

Echinocandin method of administration and relative tolerance.

All are infused and are well tolerated (none are oral).

27

Metabolization of caspofungin

Hepatic (so can give in renal insufficient patients, dialysis, etc).

28

Use caspofungin/echinocandins for what fungi?

Serious opportunistic infections:
-Invasive candidiasis, candidemia
-Invasive ASPERGILLOSIS.

29

An AIDS pt has oropharyngeal candiasis and fails fluconazole, amphotericin B, and itraconazole. What antifungal should be administered?

Caspofungin (echinocandin)

30

What are echonocandins NOT effective against?

NOT effective against pathogenic fungal organisms
-Histoplasmosis
-Coccidiomycosis
-Fusarium spp.