CP 4 - intro to antifungal

Question 1

what are the 3 types of fungi

Answer 1

1 - filamentous fungi
2- yeasts
3 - dimorphic fungi (in between 1 & 2)

Question 2

what are some of the 5 targets for antifungal drugs

Answer 2

DNA synthesis, mitosis, protein synthesis, cell membrane - ergosterol, cell wall - beta 1,3-glucan

Question 3

what is ergosterol

Answer 3

found mainly in fungal cell membranes, forms clusters within the phospholipid bilayer - role in regulating membrane permeability

Question 4

how is ergosterol made?

Answer 4

squalene - lanosterol - ergosterol (squalene expoxidase & lanosterol 1,4 demethylase)

Question 5

what is beta 1,3 glucans

Answer 5

50-60% dry weight of fungal cell wall - form a fibrous network on the inner surface o f the cell wall

Question 6

what enzyme synthesises beta-1,3-glucan?

Answer 6

beta-1,3-glucan synthase

Question 7

what are the 6 different classes of antifungal drugs

Answer 7

polyenes, allylamines, azoles, echinocandins, 5-fluorocytosine, griseofuluin

Question 8

MOA for polyene

Answer 8

cell membrane so ergosterol - form pores and so loss of membrane integrity and cell death

Question 9

what are the 2 subclasses of polyene

Answer 9

amphotericin B & nystatin

Question 10

what fungi is amphotericin B be useful against

Answer 10

most fungi of medical interest - aspergillus spp. , Candida spp. cryptococcus spp.

Question 11

what are some of the adverse effect of amphotericin B

Answer 11

allergic & nephotoxicity

Question 12

what is an alternative of amphotericin B

Answer 12

liposomal amphotericin B - decreases nephrotoxicity

Question 13

route of administration for amphotercin B

Answer 13

parenterally - not absorbed orally

Question 14

route of administration for nystatin

Answer 14

too toxic for systemic use, superficial infections only

Question 15

MOA for allylamines

Answer 15

inhibit ergosterol synthesis - squalene epoxidase

Question 16

example of allylamines

Answer 16

terbinafine

Question 17

adverse effect of allylamines

Answer 17

liver toxicity

Question 18

clinical use of allylamines

Answer 18

dermatophyte infectinos - topical use - athletes foot, systemic use - scalp ringworm

Question 19

MOA of azoles

Answer 19

inhibit ergosterol synthesis - lanesterol alpha14-demethylase (build up of non-ergosterol 14-sterol in cell membrane

Question 20

what are the 2 subclasses of azoles

Answer 20

imidazoles, triazole

Question 21

route of administration for both imidazole & triazole

Answer 21

imidazole - too toxic for systemic rarely used systemically

triazole - not as toxic, common systemic use

Question 22

an example for imidazole

Answer 22

clotrimazole

Question 23

examples of triazole

Answer 23

fluconazole, itraconazole, voriconazole

Question 24

adverse effects of azoles

Answer 24

hepatotoxicity, drug interaction - inhibit cytochrome p-450 enzyme

Question 25

clinical use for imidazole

Answer 25

dermatophyte infections, candidiasis

Question 26

clinical use for triazole

Answer 26

candidasis (fluconazole), aspergillosis

Question 27

MOA for echinocandins

Answer 27

inhibition of beta-1.3-glucan synthase - constructino of abnormal cell wall

Question 28

an example of echinocandins

Answer 28

anidulafungin

Question 29

which organism will echinocandins work against

Answer 29

aspergillus and candida spp.

Question 30

adverse effect echinocandins

Answer 30

minial

Question 31

clinical use for echinocandins

Answer 31

systemic infection - parenteral formulation

Question 32

MOA for 5-fluorocytosine

Answer 32

analogue of cytosine - inhibit RNA/protein synthesis & DNA synthesis

Question 33

which organisms will 5-fluorocytosine work against

Answer 33

yeasts only - candida and cryptococcus spp.

Question 34

adverse effects of 5-fluorocytosine

Answer 34

bone marrow suppression

Question 35

clinical use for 5-fluorocytosine

Answer 35

cryptococcus meningitis (in combination with AmB)

Question 36

MOA of Griseofulvin

Answer 36

inhibition of fungal mitosis

Question 37

adverse effect of griseofulvin

Answer 37

minimal

Question 38

clinical use of griseofulvin

Answer 38

dermatophyte infections in children requiring systemic treatment