Pharm Topic 20: Antifungal Agents

Front 1

Nystatin

Back 1

Binds Ergosterol found in cell wall of fungi and forms pores.
Is only topical/oral
Effective against candida and cutaneous mycoses (no systematic)

Front 2

Amphotericin B

Back 2

Binds Ergosterol found in cell wall of fungi and forms pores.
Topical or systemic, does not Cx BBB
DOC for most systemic life threatening fungal infections (except aspergillous)
SE: are terrible, nephrotox

Front 3

5-Flourocytosine

Back 3

Enters cell through a Permease, then is converted to 5-florouracil via Cystosine Deaminase (not found in humans). Inhibits dUMP > dTMP necessary for DNA rep.
Given orally but not alone b/c resistance develops (give with amp B)
Works for Candida, cryptococcus, and asprigillus.
SE: BM suppression, liver, GI

Front 4

Azoles Mech and types

Back 4

Inhibit conversion of Lanosterol to Ergosterol which is necessary for fungal cell walls:
-Imidazoles:
Ketoconazole
Miconazole
Clotrimazole
-Triazoles:
Fluconazole
Intraconazole
Voriconazole
Posaconazole

Front 5

Ketoconazole

Back 5

imidazolw (old azole). Oral and topical (dandruff) Uses. Broad spectrum. Stomach must be acidic to absorb.
SE: Gynomastia, inhibits cortisol and testosterone production via p450, GI, hepatic.

Front 6

Triazole

Back 6

The triazoles are the new azoles. Less harsh SEs.
Oral or IV, broad spectrum. All enter the CSF except Intraconazole. Voriconazole is the DOC for aspergillus.
SE: No steroid interference and better GI symptoms but still has p450 interactions with other drugs.

Front 7

4 properties of all Azoles

Back 7

1) Are p450 metabolized and have drug interactions
2) Can cause hepatic disfunction
3) Should be avoided during pregnancy
4) Would antagonize Amp B and should not be used together.

Front 8

Echinocandins

Back 8

All drugs end in -fungin. Inhibit cell wall synth by inhibiting B-13 glycan synth. Effective against aspergillus and candida. Few SEs and expensive.
-Capsofungin
-Micafungin
-Anidulafungin

Front 9

Grisans

Back 9

AKA grisoflavin. Inhibits microtubules inhibiting mitosis. Given oral, binds to hair and skin and gives resistance. Used for many dermatophytes.
SE: hepatic, GI, BM supression.

Front 10

Allylamines

Back 10

(Lamicil for ex) Oral/topical, Prevents conversion of Squalie to Ergocholesterol necessary for cell wall synth. Used for onchomycoses and other tineas.
SE: GI, headaches.
-Terbiinafine
-Buterafine
-Natilfine

Front 11

5-FC resistance

Back 11

Mutate cytosine permease, mutate deaminase

Front 12

Azole resistance

Back 12

Increase efflux pumps, mutation in demethylase, up regulation of demethylase.

Front 13

Amphotericin B resistance

Back 13

Reduce amount of membrane ergosterol or alter membrane comp (rare).