Antifungals

Question 1

How are pathogenic fungals classified

Answer 1

Yeast

Moulds/filamentous - hyphae, mycelium, septa

Question 2

What disease does candida albicans cause?

Answer 2

Thrush (yeast)

Question 3

What disease does cryptococcus neoformans

Answer 3

Meningitis in immunosuppressed

Question 4

Targets of anti-fungals

Answer 4

Cell wall 
Cell membrane 
Protein synthesis
Mitosis 
DNA synthesis

Question 5

What makes up fungal cell membranes?

Answer 5

Ergosterol

Question 6

What makes up fungal cell walls

Answer 6

Beta- 1,3 - glucan

Question 7

How is ergosterol synthesised (name the components of synthesis)

Answer 7

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

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

Question 8

What enzyme makes Beta 1,3 glucan

Answer 8

Beta 1,3 glucan synthase (potential targets)

Question 9

Anti fungal classes - name all 5…

Answer 9

Polyenes
Allylamines
Azoles
Echinocandins

Question 10

Name 2 examples of polyenes

Answer 10

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

Question 11

Polyenes - mode of action

Answer 11

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

Question 12

What does Amphotericin B effect and name its adverse effects

Answer 12

• Kills most fungi of clinical important

- allergic reactions and nephrotoxicity

Question 13

Example of allylamine (only one!) and adverse effect

Answer 13

Terbinafine - athletes foot - liver toxicity (RARE!)

Question 14

Mode of action of allylamines

Answer 14

Inhibits ergosterol synthesis - blocks squalene epoxidase

Question 15

What are allylamines used for?

Answer 15

superficial fungal infections (dermatophyte)

• topical - athletes foot (tinea pedis)
• oral - scale ringworm (tine cupids)

Question 16

Name the 2 types of azoles

Answer 16

Imidazole’s - 2 N atoms - v toxic

Triazoles - 3 N atoms - less toxic, systemic use common

Question 17

What is the mode of action of Azoles

Answer 17

Block ergosterol synthesis - block lanosterol 14a demethylase

Question 18

Give example of an Imidazole

Answer 18

Clotrimazole

CLOT - RIM - AZOLE

Question 19

Give examples of Triazoles

Answer 19

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

-

Question 20

Adverse effects of azoles

Answer 20

• hepatotoxicity (hepatitis)

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

Question 21

What fungal infections are the following used for..

• Fluconazoles
• Intraconazoles/Voriconazoles
• Posconazole/isavuconazole

Answer 21

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

Question 22

What is clotrimazole used for?

Answer 22

Vaginal thrush

Question 23

What is the mode of action of echinocandins?

Answer 23

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

Question 24

What does/does not Echinocandins effect?

Answer 24

• effects aspergillus and candida

- misses some moulds and cryptococcus

Question 25

Adverse effects of echinocandins?

Answer 25

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

Question 26

Why do we do therapeutic drug monitoring?

Answer 26

Minimise toxicity while ensuring efficacy

Question 27

What antifungal drugs require TDM?

Answer 27

- 5-flurocytosine - intraconazole - voriconzaole