4 Antifungals Flashcards Preview

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Flashcards in 4 Antifungals Deck (27):
1

What are the subclassifications of fungi?

Filamentous (form mycelium from hyphae).
Yeasts.
Dimorphic.
(and pneumocystis jiroveci)

2

What is the main component in the lipid membrane of fungi? What does it do?

Ergosterol. Forms clusters. Regulates membrane permeability.

3

How is ergosterol synthesised?

Squalene -> squalene epoxidase -> lanosterol -> lanosterol 14 alpha demethylase -> ergosterol

4

What forms the majority of a fungal cell wall and how is it made?

Beta-1,3-glucans. A polymer of UDP-glucose. Forms fibrous network. Synthesised by Beta-1,3-glucan synthase.

5

What are the five classes of antifungals?

Polyenes.
Allylamines.
Azoles.
Echinocandins.
Others.

6

What is the mode of action of polyenes? 2 examples.

Associate with ergosterol. Form pores, membrane loses integrity and leaks K+.

Amphotericin B and Nystatin.

7

What are the adverse effects of Am B?

Allergic reactions.
Severe (but reversible) nephrotoxicity.

8

What are the formulations of ApB and why do they exist?

Liposomal AmB (L-AmB)
AmB lipid complex (ABLC)
AmB colloidal dispersion (ABCD)

Minimise delivery of AmB to kidney cells.

9

How is AmB used clinically?

AmB - parenterally for systemic infections (aspergillosis, cryptococcosis, candidiasis).

10

How is Nystatin clinically used?

Too toxic for systemic use.

Superficial infections - candidiasis.

11

How do Allylamines function? 1 example.

Inhibit ergosterol synthesis via squalene epoxidase.

Terbinafine.

12

Adverse effects of Allylamines?

Liver toxicity

13

Clinical use of Allylamines?

Dermatophyte infections.
Oral: scalp ringworm, onychomycosis
Topical: athletes foot, tine corporis/cruris

14

How are azoles structured?

Synthetic compounds containing 5-membered azole ring.

Imidazole's: 2 N's
Triazoles: 3N's

15

How do azoles work?

Inhibit ergosterol synthesis via Lanosterol 14alpha demethylase.

16

1 imidazole example.

3 triazole examples.

Clotrimazole.

Fluconazole, Itraconazole, Voriconazole.

17

Adverse effects of azole use.

Hepatotoxicity.
Life threatening hepatitis (1/10,000)
Inhibition of cytochrome P-450 enzymes.

18

What are azoles clinically used for?

Imidazoles: superficial infections (candidiasis).
Triazoles: systemic infections (aspergillosis, candidiasis).

19

Which azole only works against yeasts?

Fluconazole

20

How do echinocandins work? 1 example.

Inhibit beta-1,3-glucan synthase. Severley abnormal cell wall constructed.

Anidulafungin.

21

What are the adverse effects of echinocandins?
What do they work against?

Minimal.

Aspergillus and Candida.

22

What is the structure of 5-fluorocytosine?
How is it selectively toxic?

Synthetic analogue of cytosine.
Requires fungal cytosine permease enzyme.

23

How does 5-fluorocytosine work?

Converted to 5-florouracil and 5-fluorodeoxyuridine.

Inhibits RNA/protein synthesis.

24

What are the adverse effects of 5-fluorocytosine?

Bone marrow suppression (developed as an anti-cancer drug).

25

What is 5-fluorocytosine clinically used for?

Cryptococcal meningitis (with AmB).

26

How does Griseofulvin work and what is it used for?

Inhibition of fungal mitosis.
Used for dermatophyte infections requiring systemic treatment.

27

Which fungal drugs require therapeutic monitoring and why?

Itraconazole (needs to b above).
5-fluorocytosine (needs to be below).
Voriconazole (for both reasons).

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