Antifungals Flashcards Preview

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Flashcards in Antifungals Deck (27):
1

How are pathogenic fungals classified

Yeast
Moulds/filamentous - hyphae, mycelium, septa

2

What disease does candida albicans cause?

Thrush (yeast)

3

What disease does cryptococcus neoformans

Meningitis in immunosuppressed

4

Targets of anti-fungals

Cell wall
Cell membrane
Protein synthesis
Mitosis
DNA synthesis

5

What makes up fungal cell membranes?

Ergosterol

6

What makes up fungal cell walls

Beta- 1,3 - glucan

7

How is ergosterol synthesised (name the components of synthesis)

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

(enzymes squalene epoxidase and lanosterol 14 a demthylase = potential targets)

8

What enzyme makes Beta 1,3 glucan

Beta 1,3 glucan synthase (potential targets)

9

Anti fungal classes - name all 5...

Polyenes
Allylamines
Azoles
Echinocandins

10

Name 2 examples of polyenes

Nystatin (very toxic) - only for superficial infection (oral/vaginal thrush) - not absorbed orally but very toxic

Amphotericin B (serious systemic infections) - given by IV (parentally), not orally

11

Polyenes - mode of action

associates with ergosterol, resulting in the formation of pores. This results in cell leakage and loss of membrane integrity, resulting in cell death

Remember 'P' = plasma membrane

12

What does Amphotericin B effect and name its adverse effects

- Kills most fungi of clinical important
-allergic reactions and nephrotoxicity

13

Example of allylamine (only one!) and adverse effect

Terbinafine - athletes foot - liver toxicity (RARE!)

14

Mode of action of allylamines

Inhibits ergosterol synthesis - blocks squalene epoxidase

15

What are allylamines used for?

superficial fungal infections (dermatophyte)
- topical - athletes foot (tinea pedis)
- oral - scale ringworm (tine cupids)

16

Name the 2 types of azoles

Imidazole's - 2 N atoms - v toxic
Triazoles - 3 N atoms - less toxic, systemic use common

17

What is the mode of action of Azoles

Block ergosterol synthesis - block lanosterol 14a demethylase

18

Give example of an Imidazole

Clotrimazole

(CLOT - RIM - AZOLE)

19

Give examples of Triazoles

Fluconazoles (Flu-CON-azole) - does not kill aspergillis
Intraconazoles (intra-CON-azole)
Voriconazoles (vori- CON-azole)

-

20

Adverse effects of azoles

- hepatotoxicity (hepatitis)
- Interact with Cytochrome P450 enzymes (increases conc of all drugs metabolised by Cy P-450)

21

What fungal infections are the following used for..
- Fluconazoles
- Intraconazoles/Voriconazoles
- Posconazole/isavuconazole

Fluconazoles - yeasts ONLY
Intraconazoles/Voriconazoles - Yeasts and aspergillis
Posconazole/isavuconazole - all!!

22

What is clotrimazole used for?

Vaginal thrush

23

What is the mode of action of echinocandins?

Blocks beta 1,3 gluten synthase (prevents construction of fungal cell wall)

24

What does/does not Echinocandins effect?

- effects aspergillus and candida
- misses some moulds and cryptococcus

25

Adverse effects of echinocandins?

minimal - because there are no things similar to beta 1,3 glucan synthase - very selective toxicity

26

Why do we do therapeutic drug monitoring?

Minimise toxicity while ensuring efficacy

27

What antifungal drugs require TDM?

- 5-flurocytosine
- intraconazole
- voriconzaole

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