Antifungals

Question 1

What are the 2 forms of pathogenic fungi?

Answer 1

Filamentous fungi and yeast

Question 2

What characterises yeast?

Answer 2

Divide by budding

Question 3

What characterises filamentous fungi?

Answer 3

Elongated cells divided by cell walls. Divide by spores

Question 4

Dimorphic fungi

Answer 4

Appear in yeast and filamentous form depending on environmental conditions

Question 5

5 antifungal targets

Answer 5

cell wall
cell membrane
protein synthesis
DNA synthesis
Mitosis

Question 6

What is the main component of fungal cell walls?

Answer 6

beta 1-3 glucan

Question 7

What is cholesterol equivalent component in the cell membrane of fungi?

Answer 7

ergosterol

Question 8

What is the function of ergosterol?

Answer 8

Regulation of membrane permeability

Question 9

Describe the formation of ergosterol

Answer 9

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

Question 10

beta 1-3 glucan is a large polymer of what?

Answer 10

UDP glucose

Question 11

What enzyme synthesises beta 1-3 glucan?

Answer 11

beta 1-3 glucan synthase

Question 12

What are the 4 classes of antifungals?

Answer 12

Polyenes
Allylamines
Azoles
Echinocondins

Question 13

Give 2 examples of polyenes

Answer 13

Amphotericine B, Nystatin (not used anymore)

Question 14

How do polyenes work?

Answer 14

Form pores in ergosterol membrane resulting in loss of membrane integrity and leakage of K+

Question 15

Give 3 of fungi that AmB treats

Answer 15

Aspergillus
Candida
Crytococcus

Question 16

Adverse effects of amphotericin B

Answer 16

allergic reactions

Nephrotoxicity- pores form in human cell membranes

Question 17

How is amphotericin B administered for serios/systermic infections?

Answer 17

Parenterally

Question 18

How do lipid-associated Amphotericin B antifungals work?

Answer 18

Combining AmB to lipids minimises its delivery to kidney cells and reduces nephrotoxicity

Question 19

In what cases is nystatin used?

Answer 19

Superficial infections e.g. oral/vaginal candidiasis

Question 20

Clear cut nodule with cavity in teh middle of it. Fungus sits in the lung and causes localised infection.

Answer 20

Pulmonary aspergillosis

Question 21

Example of allyamines

Answer 21

Terbinafine

Question 22

What is terbinafine used for?

Answer 22

Athlete’s foot-tinea pedis

Question 23

How to allyalanines work?

Answer 23

Inhibit ergosterol synthesis

Question 24

Is terbinafine broad spectrum or narrow spectrum?

Answer 24

Broad

Question 25

Adverse effects of terbinafine?

Answer 25

Liver toxicity (jaundice, hepatitis)

Question 26

Examples of dermatophyte infections that terbinafine is used to treat

Answer 26

Superficial fungal infections e.g. tinea pedis | Systemic use e.g. scalp ringworm, onychomosis

Question 27

How do azoles work?

Answer 27

Inhibit ergosterol synthesis (lanosterol 14 alpha demethylase inhibitors)

Question 28

Are azoles broad or narrow spectrum antifungals?

Answer 28

Broad

Question 29

What antifungal is not effective against aspergillus?

Answer 29

Fluconazole

Question 30

2 types of azoles

Answer 30

Imidazoles | Triazoles

Question 31

What is the difference, structurally, between imidazoles and triazoles

Answer 31

Imidazoles- 2 N atoms | Triazoles- 3 N atoms

Question 32

Which is more toxic; imidazoles or triazoles?

Answer 32

Imidazoles

Question 33

Example of an imidazole and what it's used for

Answer 33

Clotrimazole, used for candidiasis

Question 34

3 examples of triazoles

Answer 34

fluconazole itraconazole voriconazole

Question 35

Adverse effects of azoles

Answer 35

Hepatotoxicity (mild liver enzyme abnormalitis or life threatening hepatitis) Drug interactions; inhibit cytochrome p450 enzymes so conc. of drugs that are metabolised by this enzyme increase

Question 36

What types of fungi is fluconazole effective against

Answer 36

yeasts

Question 37

What types of fungi is itraconazole/vcorconazole effective against

Answer 37

yeasts | aspergillus

Question 38

What types of fungi is pasaconazole/isavuconazole effective against

Answer 38

yeasts aspergillus mucuraceous moulds

Question 39

How do echinocondins work?

Answer 39

Inhibit beta 1-3 glucan synthase resulting in the construction of severely abnormal cell walls

Question 40

Example of echinocondin

Answer 40

AnidulaFUNGIN

Question 41

What types of fungi are echinocondins effective against?

Answer 41

Aspergillus and candida, misses certain moulds and cryptococcus

Question 42

Are echinocondons used for systemic or superficial infections, and how are they administered?

Answer 42

Systemic infections, parenteral formulations only

Question 43

An antifungal that is a synthetic analogue of cytosine

Answer 43

5 fluorocytosine

Question 44

How does 5 fluorocytosine work?

Answer 44

Inhibits RNA/DNA synthesis of fungal cytosine permease- prevents entry of fungus into the cell

Question 45

What is 5 fluorocytosine effective against?

Answer 45

Yeasts e.g. Candida and cyptococcus

Question 46

Adverse effects of 5 fluorocytosine

Answer 46

bone marrow suppression

Question 47

What is 5 flurocytosine used for clinically

Answer 47

Crytococcal meningitis (in combination with AmB)

Question 48

What 3 antifungals require therapeutic drug monitoring (to minimize toxicity and maximise efficacy)

Answer 48

5 flurocytosine Itraconazole Voriconazole