Core Microbiology - Anti-fungal Agents (5)

Question 1

Fungi classification

Answer 1

1. Moulds/filamentous fungi

2. Yeast

Question 2

Dimorphic fungi

Answer 2

Exist as mould and yeast

Question 3

Erogsterol

Answer 3

In fungal cell membranes, forms clusters within phospholipid bilayer, regulates membrane permeability

Question 4

Ergosterol biosynthesis

Answer 4

Squalene > (Squalene epoxidase) > Lanosterol > (Lanosterol 14a demethylase) > Ergosterol

Question 5

B-1,3-glucans

Answer 5

Large polymers of UDP-glucose, form a fibrous network on inner surface of wall, snythesised by B-1,3-glucan synthase

Question 6

Antifungal classes

Answer 6

Polyenes, Allylamines, Azoles, Echinocandins, others..

Question 7

Polyenes mode of action

Answer 7

Association with ergosterol, forms pore-like molecular aggregates, loss of membrane integrity and leakage of K+, cell death

Question 8

Examples of Polygenes

Answer 8

Amphotericin B and Nystatin

Question 9

Amphotericin B spectrum of activity

Answer 9

Most fungi - Aspergillus, Candida, Cryptococcus (Parenterally)

Question 10

Amphotericin B adverse effects

Answer 10

Allergic reactions, nephrotoxicity (reversible), not completely selective to fungi

Question 11

Lipid associated Amphotericin B (AmB) different formulations

Answer 11

Liposomal AmB (L-AmB), AmB lipid complex (ABLC), AmB colloidal disperson (ABCD)

Question 12

Lipid associated Amphotericin B (AmB) pros

Answer 12

Minimises delivery of AmB to kidney cells (liver, spleen and lymph nodes)

Question 13

Nystatin

Answer 13

Too toxin for systemic use, superficial infections - oral/vaginal candidiasis

Question 14

Allylamines mode of action

Answer 14

Inhibit erogsterol synthesis (Squalene epoxidase)

Question 15

Allylamines examples

Answer 15

Terbinafine

Question 16

Terbinafine spectrum

Answer 16

Broad in vitro

Question 17

Terbinafine adverse effects

Answer 17

Liver toxicity (Jaundice, hepatitis)

Question 18

Allylamines clinical use

Answer 18

Dermatophyte infections (superficial)

Topical - athletes foot (tinea pedis), tinea corporis (trunk, legs, arm/skin), tinea cruris (groin)

Systemic - scalp ringworm (tinea capitis), onychomycosis (nail)

Question 19

Azoles

Answer 19

5-membered ring

Question 20

Examples

Answer 20

• Imidazoles (2N)

- Triazoles (3N)

Question 21

Azoles mode of action

Answer 21

Inhibit ergosterol synthesis (Lanosterol 14a-demethylase)

Question 22

Azoles spectrum

Answer 22

Broad - yeasts and filamentous fungi (except Fluconazole/Aspergillus)

Question 23

Imidazoles

Answer 23

Toxic, rarely used systemically (ketoconazole)

Question 24

Examples of Imidazoles

Answer 24

Clotrimazole (Canesten), Miconazole, Ketoconazole

Question 25

Examples of Triazoles

Answer 25

Fluconazole, Itraconazole, Voriconazole, Posaconazole, Isavuconazole

Question 26

Azoles adverse effects

Answer 26

Hepatotoxicity

Question 27

Azoles drug interactions

Answer 27

Inhibition of Cytochrome P-450 enzymes - increases concentration of all drugs metabolised by Cy P-450 enzymes

Question 28

Imidazoles clinical use

Answer 28

Superficial infections - Candidiasis or dermatophyte infections

Question 29

Triazoles clinical use

Answer 29

Systemic - aspergillosis and candidiasis

Question 30

Echinocandins mode of action

Answer 30

Inhibition of B-1,3-glucan synthase, construction of severely abnormal cell wall

Question 31

Examples of Echinocandins

Answer 31

Andiulafungin, Caspofungin, Micafungin

Question 32

Echinocandins spectrum of activity

Answer 32

Aspergillus and Candida (not certain moulds and cryptococcus) - serious as iv

Question 33

Echinocandins adverse effects

Answer 33

Skin rash, nausea, vomiting, headache, diarrhoea

Question 34

5-fluorocytosine (5-FC)

Answer 34

Synthetic analogue of cytosine (pyrimidine nucleoside), developed as anti-cancer drug

Question 35

5-FC mode of action

Answer 35

Entry into cells requires fungal cytosine permeases, converted to 5-fluorouracil and 5-fluorodeoxyuridine monophosphate (inhibit RNA/protein synthesis and DNA synthesis)

Question 36

5-FC spectrum of activity

Answer 36

Yeasts only (Candida and Cryptococcus)

Question 37

5-FC adverse effects

Answer 37

Bone marrow suppression, selective toxicity is incomplete - 5FU anti-cancer

Question 38

5-FC clinical use

Answer 38

Cryptococcal meningitis (combination with AmB)

Question 39

Griseofulvin mode of action

Answer 39

Inhibition of fungal mitosis

Question 40

Griseofulvin spectrum of activity

Answer 40

Dermatophytes

Question 41

Griseofulvin clinical use

Answer 41

Dermatophyte infections in children requiring system treatment (kerion, onychomycosis)

Question 42

Antifungal drugs that require therapeutic drug monitoring

Answer 42

- Itraconazole - 5-FC (bone marrow) - Voriconazole (liver)