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Flashcards in Anti-fungals Deck (32)
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1

What are the various temperature dependent morphologies of dimorphic fungi?

1) Yeast at body temp
2) Mold at room temp

2

What is the structure and function of the fungal cell wall?

- Structure:
- Polysaccharides (~90%)
- Proteins and glycoproteins (~10%)
-Functions:
Provides shape, rigidity, strength and protection from osmotic shock

3

What is the structure and function of the fungal cell MEMBRANE?

- Structure:
- Phospholipids
- Sterol (ergosterol)
- Functions:
- Protects cytoplasm
- Regulates the intake and secretion of solutes
- Facilitates capsule and cell wall synthesis

4

What is the mechanism of action of Azoles?

Inhibit the rate limiting step in ergosterol synthesis

5

What are the drug interactions associated with Azoles?

- Azole’s increase levels of many drugs including cyclosporine / tacrolimus, antihistamines, oral hypoglycemics, warfarin…
- Rifampin and other CYP 450 enzyme inducers decrease azole levels

6

What are the adverse drug reactions of Azoles?

GI upset, Hepatitis, Rash, Headache

7

How is Fluconazole administered and how is it absorbed?

- Administration: IV, oral tabs and oral soln
- Absorption: GI absorption and CNS penetration (50-60% serum)

8

Which drug has the least drug interactions of all the Azoles?

Fluconazole

9

What toxicity is associated with Fluconazole?

H/A, alopecia, n/v,anorexia, hepatitis (rare), rash

10

What fungi are sensitive to fluconazole?

Drug of choice for Candida albicans, mild to moderate Cryptococcus neoformans

11

Which fungi are resistant to fluconazole?

C. krusei, T. glabrata (usually dose dependant)

12

How is itraconzole administered and absorbed?

- Administratio: IV, oral caps and soln.
- Poor GI absorption (caps are worst) and CNS penetration

13

Which drug has the MOST drug interactions of all the Azoles?

Itraconzaole

14

What toxicities are associated with itraconazole?

- Headache, Nausea/vomiting, diarrhea, rash, hypokalemia, adrenal insufficiency, impotence, gynecomastia,leg edema, hepatitis (rare), CHF (rare)

15

What are the indications for itraconazole?

-Most yeast, many molds and most dimorphics
-Drug of choice for Histoplasma

16

How does voriconazole extend the spectrum of azoles?

Extends spectrum to molds

17

Describe the bioavailability of voriconazole?

Excellent bioavailability and CNS penetration

18

What toxicities are associated with Voriconazole?

Visual disturbances (24%), hepatitis (13%), Rash (6%)

19

What are the indications for voriconazole?

Aspergillus sp., Candida sp., Cryptococcus, dimorphics, Scedosporidium, Fusarium…
- Drug of choice for aspergillus
- Prophylaxis during neutropenia and GVHD

20

What is the mechanism of action of the polyenes?

- Bind to ergosterols in cell membrane and form membrane channels w/ increased permeability causing a resultant leakage of intracellular components

21

What fungi are sensitive to amphotericin B?

- Candida sp, Cryptococcus neoformans, dimorphics, Aspergillus sp, mucormycosis

22

Which fungi are resistant to amphotericin B?

- C. lusitaniae C. guilliermondi, P. boydii and A. terrius
- Less sensitive: C. krusei

23

What drug interactions are associated with amphotericin B?

Concurrent nephrotoxic agents

24

What toxicities are associated with Amphotericin B?

- Renal, infusion related rxn’s (fever and rigors), anemia (↓ erythropoetin)

25

How does Amphotericin B lead to renal toxicity?

1) Direct damage of distal tubular membranes leading to wasting of Na+, K+, and Mg++
2) Tubular-glomerular feedback: Further constriction of arterioles
3) Constriction of the afferent arterioles leading to decreased glomerular filtration

26

What type of Amphotericin B has decreased renal toxicity?

- Lipid Based Amphotericin B
- Require higher doses to achieve the same therapeutic effect as AmphoB

27

What is the mechanism of action of Echinocandin?

- Inhibition of Beta (1,3)-D-glucan synthesis in the fungal cell wall

28

What fungi are sensitive/resistant to Echinocandin?

1) Sensitive: Candida sp., Aspergillus sp.
2) Resistant: Poor activity against Mucor, Cryptococcus

29

What echinocandin is given IV only?

Caspofungin

30

What adverse drug reactions are associated with Caspofungin?

fever, rash, n/v, phlebitis, hepatitis (all rare)