OUR LADY OF FATIMA UNIVERSITY

COLLEGE OF PHARMACY
Valenzuela. Quezon City. Antipolo. Pampanga. Cabanatuan. Laguna

ANTIFUNGAL AGENTS
PHARMACOLOGY 2

Instructor- College of Pharmacy

COURSE FACILITATOR
 TOPIC OBJECTIVES
At the end of the session, the student should be able to:
 Classify the different antifungal agents.
 Identify the mechanism of action involved in each class
of antifungal.
 Enumerate examples from each class of antifungal and
give the uses
 WATCH THESE VIDEOS:

Easy ways to remember amphotericin B

https://www.youtube.com/watch?v=Dt8MAusfCbY

Pharmacology – ANTIFUNGAL DRUGS (MADE EASY)

https://www.youtube.com/watch?v=59aJJ6N2a3c
FUNGAL CELL STRUCTURE
 Key Terms
• glucan: any polysaccharide that is a polymer of
glucose
• ergosterol: the functional equivalent of cholesterol
found in cell membranes of fungi and some protists,
as well as, the steroid precursor of vitamin D2
• mycelium: the vegetative part of any fungus,
consisting of a mass of branching, threadlike hyphae,
often underground
• hypha: a long, branching, filamentous structure of a
fungus that is the main mode of vegetative growth
• septum: cell wall division between hyphae of a
fungus
• thallus: vegetative body of a fungus
• saprophyte: any organism that lives on dead organic
matter, as certain fungi and bacteria
• chitin: a complex polysaccharide, a polymer of N-
acetylglucosamine, found in the exoskeletons of
arthropods and in the cell walls of fungi; thought to
be responsible for some forms of asthma in humans
Types of Fungal Infection
 Antifungal Agents
• Systemic Antifungals for Systemic Infections
– Amphotericin B
– Flucytosine
– Azoles
– Echinocandins
• Systemic Antifungals for Mucocutaneous Infection
– Griseofulvin
– Terbinafine
• Topical Antifungal Therapy
– Nystatin
– Topical Azoles
– Topical Allylamines
 Amphotericin B
• Amphotericin A (not clinically used) while Amphotericin B
(only efficaceous antifungal)
• MOA:
– Ampho B binds to ergosterol and alters its permeability by
forming pores
• Antifungal with the broadest spectrum
• Used in LIFE-THREATENING systemic fungal infxn
• ADR: Renal Damage, dec RBC levels
 Flucytosine (5-FC)
• FUNGISTATIC, NARROW SPECTRUM
• MOA: taken up by the enzyme cytosine permease. It
is converted to 5-FU then to 5-FdUMP and FUTP w/c
inh DNA and RNA syn
• Use: Only restricted to candidal infxn
• ADR: Bone marrow toxicity with anemia, leukopenia
and thrombocytopenia
 Azoles
• Are synthetic cpds that can be classified as either
Imidazoles or Triazoles accdg to the number of
nitrogen atoms in the 5 membered azole ring
• MOA: reduction of ergosterol syn by inh fungal CYP 450
enzymes
• Use: BROAD spectrum, tx of ampho-resistant org
• ADR: Nontoxic, Minor GI disturbances (diarrhea), liver
enzymes abnormalities
Azoles
 Azoles

• Imidazoles – lesser degree of selectivity

– Ketoconazole (prototype)
• First oral azole introduced
• Less selective for fungal P450 than the newer azoles
– Miconazole
– Clotrimazole
 Triazoles
• Itraconazole
– Azole of choice for tx of dimorphic fungi
histoplasma
– Used extensively in dermatophytoses and
onychomycosis
• Fluconazole
• Azole of choice for treatment and 2nd prophylaxis
of cryptococcal meningitis, most commonly used
for tx of mucocutaneous candidiasis, reduce
fungal dse in bone marrow
 Triazoles
Triazoles

• Voriconazole
• Azole of choice for invasive aspergillosis
• Similar to itraconazole, Less toxic than Amphotericin
• ADR: Blurring in vision
• Posaconazole
• Last choice, NEWEST triazole, Broadest Spectrum
• Salvage therapy for invasive aspergillosis
• Only azole with activity against zygomycosis and
mucomycosis
 Echinocandins
• Newest class of antifungal agents which are large
cyclic peptides linked to a long-chain fatty acids
• MOA: inh syn of 1-3 glucan resulting in disruption
of the fungal cell wall and cell death
• ADR: Elevated liver enzymes, minor GI S/E
 Echinocandins
Echinocandins
• USE:
– Caspofungin – for disseminated and mucocutaneous
candida infxn, also for empiric antifungal therapy
during febrile neutropenia
– Micafungin – for mucocutaneous candidiasis,
prophylaxis for candida infxns in bone marrow
transplant px
– Anidulafungin – for use in esophageal candidiasis and
invasive candidiases
 Griseofulvin
• A very insoluble fungistatic drug derived from
a species of Penicillium griseofulvum
• Replaced by newer antifungal medications
such as itraconazole and terbinafine
• Used only in systemic treatment of
dermatophytosis
• ADR: allergic syndrome, induce serum
sickness, hepatitis
 Terbinafine
• A synthetic allylamine
• Used in the treatment of dermatophyses,
onchomycosis
• A KERATOPHILE medication like griseofulvin
• MOA: interferes with ergosterol biosynthesis,
inhibits the fungal enzyme squalene epoxidase
which leads to accumulation of the sterol
squalene (toxic)
• ADR: GI upset and HA
 Nystatin
• A polyene macrolide like amphotericin B
• Too toxic for pareteral admin, only TOPICAL
• Active against candida , most commonly used
for suppression of local candidal infections
(oropharyngeal thrush, vaginal candidiasis,
intertriginous candidal infxns
 Topical Azoles
• Clotrimazole and Miconazole
– Often used for vulvovaginal candidiasis,
dermatophytic infxns (tinea corporis, tinea pedis
and tines cruris)
– Oral Clotrimazole troches are available for tx of
oral thrush and are a pleasant-tasting alternative
to nystatin
– Topical and shampoo forms of ketoconazole are
useful for tx of seborrheic dermatitis and pityriasis
versicolor
 Topical antifungals
• Ciclopirox

MOA: inhibits the transport of essential elements in

the fungal cell, disrupting the synthesis of DNA,
RNA, and protein.

• Tolnaftate
MOA: distorts the hyphae and stunts mycelia
growth in susceptible fungi.
 ANY
QUESTIONS?
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OLFUAntipoloPharmacy/ (8)-661-3023 loc. 106