ID Lecture 50: Pharmacology of Antifungal Agents | Quizlet

Polyene antifungals

Amphotericin B

Nystatin

Natamycin

Azole antifungals

Fluconazole

Ketoconazole

Voriconazole

Itraconazole

Posaconazole

Isavuconazonium sulfate

Echinocandins

Caspofungin

Micafungin

Anidulafungin

Allylamines

Butenafine

Naftifine

Terbinafine

Nystatin

topical macrocyclic lactone with hydrophilic (top) and hydrophobic (bottom) regions

Natamycin

topical macrocyclic lactone with hydrophilic (top) and hydrophobic (bottom) regions

Amphotericin B

systemic macrocyclic lactone with hydrophilic (top) and hydrophobic (bottom) regions

MOA of Polyene antifungals

affinity for sterol-containing membranes (ergosterol) so they can insert themselves into the membrane and disrupt function

What does polyene antifungals cover?

Aspergillus

Blastomyces

Candida

Coccidioides

Cryptococcus

Histoplasma

Mucorales

Amphotericin B ADRs

Nephrotoxicity

Infusion-related reactions

Electrolyte imbalances

What are the different formulations of Amphotericin B?

Deoxycholate

Colloidal dispersion

Lipid complex

Liposomal

What are the mechanisms of resistance against Amphotericin B?

replacement of ergosterol in the cell membrane with precursors

What are the topical polyenes?

Nystatin

Natamycin

ADRs of Nystatin

Rash

Itching

Burning

Diarrhea

Abdominal pain

ADRs of Natamycin

Local irritation

Visual disturbances

MOA of Azole antifungals

inhibition of 14a-demethylase to inhibit ergosterol biossynthesis

What is the structure of azole antifungals?

Imidazole and triazole

What do azole antifungals cover (SOA)?

Candida

Cryptococcus

Blastomyces

Histoplasma

Coccidioides

What are the mechanisms of resistance against azole antifungals?

Altered active site on target (erg11 mutations)

Ketoconazole

systemic azole used for candidiasis (not first line)

ADRs of Ketoconazole

Adrenal gland problems

Liver Injury

Corticosteroid suppression

Which azole antifungals are P-gp inhibitors?

Itraconazole

Ketoconazole

Posaconazole

How is Ketoconazole metabolized?

CYP3A4

Itraconazole SOA

systemic antifungal that covers Aspergillus and Candida

ADRs of Itraconazole

Hepatotoxicity

Negative inotrope

GI effects

Fluconazole SOA

systemic antifungal used for Candida, Cryptococcus, and Coccidioides

Can Fluconazole be used in pregnancy?

No - category C

ADRs of Fluconazole

N/V

HA

Rash

Abd pain

Diarrhea

Voriconazole SOA

systemic azole used for Aspergillus, fluconazole-resistant candida, and cryptococcus

Can Voriconazole be used in pregnancy?

No - teratogenic (category D)

ADRs of Voriconazole

Hepatotoxicity

QT prolongation

GI effects

Posaconazole SOA

includes mucormycosis, aspergillus, and azole-resistant candida spp

ADRs of Posaconazole

GI effects

HA

Increase LFTs (rare)

Isavuconazonium sulfate SOA

prodrug used for the treatment of aspergillus and candidiasis

Efinaconazole SOA

onchomycosis of the toenails

MOA of allylamines

inhibits squalene epoxidase to inhibit ergosterol synthesis

SOA of Allylamines

Candida

Dermatophytes

Onychomycoses

Terbinafine

allylamine

Tolnaftate

topical squalene epoxidase inhibitor used for various fungal skin infections - does NOT cover Candida

Butenafine

topical squalene epoxidase inhibitor used for dermatophytic infections

Naftifine

topical squalene epoxidase inhibitor uased for tinea skin infections

MOA of Echinocandins

inhibits fungal B-1,3-glucan synthase to interfere with fungal cell wall synthesis

SOA od Echinocandins

Candida (including azole-resistant)

Apergillus

ADRs of Echinocandins

Infusion site reactions

Caspofungin

polar macrocycle echinocandin with a lipophilic chain used for deep, invasive candida infections

Can Caspofungin be used in pregnancy?

No - category C

Micafungin

echinocandin used for deep, invasive candidiasis

Anidulafingin

echinocandin that is used for systemic and esophageal candidiasis

MOA of Flucytosine

Inhibits DNA and RNA biosynthesis by conversion to 5-fluorouracil by cytosine deaminase.

SOA of Flucytosine

Candida

Cryptococcus

Griseofulvin MOA

binds to the protein tubulin and interferes with the mitotic spindles during cell division

Ciclopirox MOA

hydroxylated pyridinone that inhibits metal-dependent enzymes within fungal cells through chelation

Tavaborole MOA

Oxabarole - inhibits leucyl-tRNA synthetase