ANTI FUNGI

NURUL FEBRIANI

Program Studi Ilmu Kesehatan Mata

FK UNDIP/RSUP Dr.Kariadi Semarang
ANTIFUNGAL TARGET
 Anti fungal target :
1. Cell wall
2. Plasma membrane
3. Nucleic acid systhesis
POLYENE
• Lipophilic
• Antibiotics to bind to sterols in the cell membrane of susceptible
fungi, an interaction that results in damage to the membrane and
leakage of essential nutrients.
• Other antifungals (such as flucytosine and the imidazoles) and even
other antibiotics (such as tetracycline and rifampin) can enter through
the damaged membrane, yielding synergistic effects.
Natamycin

● Natamycin and amphotericin B are 2 examples

of polyene macrolide antibiotics. Natamycin is
available as a 5% suspension for topical
ophthalmic use (once per hour). Local
hypersensitivity reactions of the conjunctiva
and eyelid and corneal epithelial toxicity may
occur.
Amphotericin B
• Amphotericin B may be reconstituted at 0.25%–0.5% in sterile water (with
deoxycholate to improve solubility) for topical use (every 30 minutes).
• It may also be administered systemically for disseminated disease, although careful
monitoring for renal and other toxicities is required.
• Drugs penetrate the cornea poorly.
• They have been used topically against various filamentous fungi, including species
of Aspergillus, Cephalosporium, Curvularia, Fusarium, and Penicillium, as well as
the yeast Candida albicans. Systemic amphotericin B has been reported as useful in
treating systemic Aspergillus, Blastomyces, Candida, Coccidioides, Cryptococcus,
and Histoplasma infections.
Mechanism of action
• Interacts with
ergosterols in
membrane cell →
forms pores →
increase membrane
permeability and
allow leakage of
intracellular ions &
macromolecules
from fungal cell →
cell death.
■ Indikasi:
Candida , Aspergillus, Cryptococcus
Blastomyces, Histoplasma,Coccidioides

■ Sediaan:
1.Solution 0,1-0,5% (Topikal), encerkan
dengan air atau dextrose 5%
2. injeksi subkonjunctiva/intravitreal/iv:
0,8-1 mg
IMIDAZOLES AND TRIAZOLES
• The imidazole- and triazole-derived antifungal drugs also increase
fungal cell-membrane permeability and interrupt membrane-bound
enzyme systems.
• The triazoles have less effect on human sterol synthesis, as well as a
longer half-life, than the imidazoles, and they are being more actively
developed.
IMIDAZOL
MICONAZOL
miconazole is available in a 1% solution that may be injected
subconjunctivally (5 mg/0.5 mL, once or twice daily) or applied
topically. Miconazole penetrates the cornea poorly.

• Indikasi: Infeksi Candida, Aspergillus, dan Cryptococcus

 Ketoconazol
• Ketoconazole is available in 200-mg tablets for oral therapy (once or
twice daily).
• Ketoconazole normally penetrates the blood–brain barrier and,
presumably, the blood–ocular barrier poorly, but therapeutic levels
can be achieved in inflamed eyes.
Mechanism of action
• Interaction with
cytochrome P-450
enzyme →
inhibition of
synthesis
ergosterol →
disrupts membrane
function, increases
permeability →
death cell.
TRIAZOLE
Itraconazole
• an expanded antifungal spectrum
• less systemic toxicity,
• has largely replaced ketoconazole. However, there is an extensive and
growing list of potentially dangerous drug interactions with itraconazole that
should be consulted prior to instituting systemic therapy.

Fluconazol
• Fluconazole, another triazole, may also increase the plasma concentrations
of other medications.
Vorikonazole

• Oral voriconazole is rapidly replacing other

antifungals
• Excellent intraocular penetration and broad-
spectrum coverage.
• The imidazole and triazole antifungals act
against various species of Aspergillus,
Coccidioides, Cryptococcus, and Candida.
• Dosis :
1.1% (solution) → topical.
2.200 mg oral 2x/hari
3.3 – 6 mg/kg intravena setiap 12 jam

Efek samping :
– Mual
– Muntah
– Gangguan hati
– Anafilaksis
– Gagal ginjal
 Flucytosine
• Flucytosine (5-fluorocytosine) is converted by some species of
fungal cells to 5-fluorouracil by cytosine deaminase, and then
to 5-fluorodeoxyuridylate.
• This last compound inhibits thymidylate synthase, an important
enzyme in DNA synthesis.
• Host cells lack cytosine deaminase activity and are less
affected.
• Only fungi that have both a permease to facilitate flucytosine
penetration and a cytosine deaminase are sensitive to
flucytosine.
• Flucytosine is taken orally at 50–150 mg/kg daily,
divided every 6 hours.
• Although the drug is well absorbed and penetrates
the blood–ocular barrier well, most Aspergillus and
half of Candida isolates are resistant to it.
• Flucytosine is used primarily as an adjunct to
systemic amphotericin B therapy.
 REFERENSI

- AAO The Eye M.D. Association. 2016. Ocular

Pharmacotherapeutics. Fundamentals and Principles of
Ophtalmology, BCSC Section 2.
 TERIMA KASIH

MOHON BIMBINGAN DAN SARAN