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MED234 Respiratory > Fitz, Antifungals > Flashcards

Flashcards in Fitz, Antifungals Deck (52):
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.

31

Histoplasmosis is endemic to what region of the US?
DOC for this?

Central, and in locations with humid/warm soild and migratory birds.
**most common
**Itraconazole is DOC

32

Name this 4 opportunistic infections that are therapeutic indications for Triazoles

-Aspergillus
-Rhizopus
-Cryptococcus
-Candida

33

Name this 4 pathogenic infections that are therapeutic indications for Triazoles

-Histoplasmosis
-Coccidiomycosis
-Bastomycosis
-Paracoccidiodies

34

Oropharyngeal Candidasis (thrush), or immunocompromised, use what?

Itraconazole

35

Most fatal mycoses in Non-HIV patients.

Aspergillosis

36

Admin method of Ketoconazole

Pill

37

Dissolution of what two antifungals require gastric acidity?

-Pill-form of ketoconazole
-Itraconazole

38

What is a ketoconazole drug interaction?

Inhibits CYP450 drug interactions

39

A person starts taking an antifungal and comes back with decreased libido and gynecomastia. What drug was given?

Ketoconazole - Inhibits adrenal and gonadal steroid synthesis

40

Do imidazoles or triazoles disrupt testosterone synthesis?

Imidazoles.
triazoles have no endocrine abnormalities.

41

What two triazoles are strong inhibitors of hepatic CYP450 and enhance renal toxicity?

Voriconazole and Itraconazole

42

Vision disturbance, think what triazole.

voriconazole

43

When should triazoles be avoided and what damage can they cause?

Avoid in pregnancy.
All can damage liver.

44

DOC for mucormycosis

Amphotericin B

45

DOC for cryptococcal meningitis

Amphotericin B + 5-Fluorocytosine antimetabolite

46

5-FdUMP inhibits what

5-FdUMP inhibits Thymidylate Synthase = inhibition of DNA synthesis

47

5-FUTP inhibits what

5-FUTP inhibits protein synthesis

48

5-FC MOA

5-FC extracellular --(membrane bound Cytosine Permease)--> 5-FC intracellular --(cytosine deaminase)--> 5-FU ---> 5-FUMP ---> 5-FdUMP or 5-FUTP

49

Mechanisms of resistance of 5-FC

1. Intrinsic - mutation in Cytosine Permease
2. Acquired Resistance - mutation in Cytosine Deaminase

50

How do AMP-B and 5-FC work together?

Amp-B creates ergosterol pores so that more 5-FC can get in.

51

DOC for invasive fungal infection, unresponsive to other therapy

Amp-B

52

Name this fungus:
"excessive hyphal growth and dissemination"

Aspergillosis