ANTIFUNGALS- ergosterol, beta 1,3-glucan, squalene blocker, mitosis, dna synthesis inhibitor

Drug

Mechanism

POLYENES
Amphotericin B
Nystatin

- binds ergosterol in cell

membrane (esp.
ergosterol), leading to cell
death

ECHINOCANDINS
(FUNGINS)

AZOLES- General

Inhibit beta-1,3-glucan
synthase, decreasing beta1,3-glucan production

- Inhibit fungal cytochrome

P450, decreasing
ergosterol formation

Absorption/
Kinetics
Concentration
dependent

-concentration
dependent
- not
eliminated
renally
- all have
some hepatic
metabolism
- fluconazole
excreted
renally
- time
dependent

Itraconazole

Posaconazole
OthersKetoconazole

- IV
- topical
- oral: GI
fungi (topical)

- wellabsorbed,
hepatically
metabolized
- non-linear
- SBECD of IV
form is renally
eliminated

Uses

Adverse Effects

broadest spectrum antifungal

- Candidas
- Cryptococcus neoformans

- Nephrotoxicity (renal
elimination)
- Electrolyte Wasting
- Infusion-related reactions

IV Only

Strong in vitro activity against Candida

Active against Aspergillus
Ineffective for Cryptococcus

- hepatotoxicity
- infusion-related reactions
- phlebitis
Use a cane for your HIP
(hepatotox, infusion, phlebitis)

IV
Tablets
Oral

Candidiasis
Cryptoccocus
Febrile Neutropenia- (voriconazole)
Aspergillosis(vori, itra)
Onynchomycosis- (Itraconazole)
Prophylaxis (posiconazole)

- Hepatotoxicity (p450) (all)

- Rash (ketokonazole)
- drug interaction (all)
- visual (vori)

IV
Tablets
Oral

Fluconazole

Voriconazole

Admin.

IV
Capsule
Oral Solution

IV
Capsules
Oral

Candidiasis
Cryptococcal meningitis
NOT ASPERGILLUS/NON-ALBICANS

Invasive aspergillosis
Febrile neutropenia
Yeasts- candida and Cryptococcus

VISUAL
-Visual Effects
-Visual Halluinations

Candidiasis
Cryptococcus
Aspergillosis
candidiasis
Onychomycosis
Prophylaxis of fungal infections
Mold infections
Yeast- candida, cryptococcus
Dermatologic

5- Flucytosine (5FC)

- Antimetabolite
- Deaminated within fungal
DNA inhibitor

Terbinafine
- allylamine
antifungal

- inhibits fungal squalene

metabolism ( squalene
toxic), ergosterol

Griseofulvin

- inhibits fungal mitosis

via interaction with
microtubules

-Widely
distributed,
including CNS
-Renally
excreted
40%
bioavailable
(1st pass)
-metabolized
in liver,
metabolites
excreted
renally
-non-linear
elimination

Some activity vs. aspergillus

Combination therapy for cryptococcal meningitis
Rarely used for candidiasis (non-albicans)

- topical
- oral
(terbinafine)

Clinical activity mainly for dermatophytes(EMTs)

Active against Candida, Aspergillus
Onychomycosis

Orally

Active against dermatophytes

Tx for onchomycosis (last line)

All azoles: new emergence of resistant strains in AIDS patients; resistance is otherwise fairly rare.

Bone marrow suppression

GI intolerance, rash,
hepatotoxicity

-Hepatotoxicity
-Neutropenia
-Steven-Johnson syndrome

CNS- headache