CP 4 - intro to antifungal Flashcards
what are the 3 types of fungi
1 - filamentous fungi
2- yeasts
3 - dimorphic fungi (in between 1 & 2)
what are some of the 5 targets for antifungal drugs
DNA synthesis, mitosis, protein synthesis, cell membrane - ergosterol, cell wall - beta 1,3-glucan
what is ergosterol
found mainly in fungal cell membranes, forms clusters within the phospholipid bilayer - role in regulating membrane permeability
how is ergosterol made?
squalene - lanosterol - ergosterol (squalene expoxidase & lanosterol 1,4 demethylase)
what is beta 1,3 glucans
50-60% dry weight of fungal cell wall - form a fibrous network on the inner surface o f the cell wall
what enzyme synthesises beta-1,3-glucan?
beta-1,3-glucan synthase
what are the 6 different classes of antifungal drugs
polyenes, allylamines, azoles, echinocandins, 5-fluorocytosine, griseofuluin
MOA for polyene
cell membrane so ergosterol - form pores and so loss of membrane integrity and cell death
what are the 2 subclasses of polyene
amphotericin B & nystatin
what fungi is amphotericin B be useful against
most fungi of medical interest - aspergillus spp. , Candida spp. cryptococcus spp.
what are some of the adverse effect of amphotericin B
allergic & nephotoxicity
what is an alternative of amphotericin B
liposomal amphotericin B - decreases nephrotoxicity
route of administration for amphotercin B
parenterally - not absorbed orally
route of administration for nystatin
too toxic for systemic use, superficial infections only
MOA for allylamines
inhibit ergosterol synthesis - squalene epoxidase
example of allylamines
terbinafine
adverse effect of allylamines
liver toxicity
clinical use of allylamines
dermatophyte infectinos - topical use - athletes foot, systemic use - scalp ringworm
MOA of azoles
inhibit ergosterol synthesis - lanesterol alpha14-demethylase (build up of non-ergosterol 14-sterol in cell membrane
what are the 2 subclasses of azoles
imidazoles, triazole
route of administration for both imidazole & triazole
imidazole - too toxic for systemic rarely used systemically
triazole - not as toxic, common systemic use
an example for imidazole
clotrimazole
examples of triazole
fluconazole, itraconazole, voriconazole
adverse effects of azoles
hepatotoxicity, drug interaction - inhibit cytochrome p-450 enzyme
clinical use for imidazole
dermatophyte infections, candidiasis
clinical use for triazole
candidasis (fluconazole), aspergillosis
MOA for echinocandins
inhibition of beta-1.3-glucan synthase - constructino of abnormal cell wall
an example of echinocandins
anidulafungin
which organism will echinocandins work against
aspergillus and candida spp.
adverse effect echinocandins
minial
clinical use for echinocandins
systemic infection - parenteral formulation
MOA for 5-fluorocytosine
analogue of cytosine - inhibit RNA/protein synthesis & DNA synthesis
which organisms will 5-fluorocytosine work against
yeasts only - candida and cryptococcus spp.
adverse effects of 5-fluorocytosine
bone marrow suppression
clinical use for 5-fluorocytosine
cryptococcus meningitis (in combination with AmB)
MOA of Griseofulvin
inhibition of fungal mitosis
adverse effect of griseofulvin
minimal
clinical use of griseofulvin
dermatophyte infections in children requiring systemic treatment
