ANTI-FUNGAL DRUGS

MECHANISMS OF ACTION OF SOME

ANTI-FUNGAL DRUGS

DRUGS/CHEMOTHERAPY
A. Drugs acting on the cell membrane
1. Disrupts the integrity of the cell
membrane by binding to ergosterol

Amphotericin B/AMB (fungicidal)- most

commonly used
Nystatin (fungicidal)

DRUGS/CHEMOTHERAPY
2. Interacts with C-14, demethylase to
block demethylation of lanosterol to
ergosterol

Imidazole (Clotrimazole,
Ketoconazole, miconazole)
Triazole (Fluconazole, itraconazole))

DRUGS/CHEMOTHERAPY
B.Nuclear division blocker Griseofulvin
(fungistatic)
C. DNA synthesis blocker 5
flurocytosine/ 5FC (fungistatic)

SUPERFICIAL MYCOSES:
TREATMENT
SUPERFICIAL
MYCOSES

TREATMENT

1. Pityriasis
Versicolor

2.5% selenium sulfide for 10 min daily for 7

days
topical miconazole, itraconazole and
ketoconazole

2. Tinea Nigra
(Tinea nigra
palmaris)

topical keratolytic solutions of sulfur,

salicylic acid, or tincture of iodine

3. Black piedra

shave or cut the hairs short

4. White piedra

shave or cut the hairs short

CUTANEOUS MYCOSES:
TREATMENT
body infection therapy consist of thorough removal of
infected and dead epithelial structures and
application of a typical antifungal chemical
(Miconazole, Clotrimazole, Econazole,
Ciclopirox)
scalp infection require Griseofulvin
nail infection requires months of griseofulvin
treatment and
sometimes surgical removal of the
nail
Foot Infections
1.
Acute phase = soak in potassium permanganate
1: 5,000
until acute inflammation subsides
2. Chronic phase = apply antifungal drug

NYSTATIN

Isolated from Streptomyces; first antimycotic antibiotic.

Polyene antibiotic with broad spectrum of activity.
MOA:
Binds to sterols in fungal cell membranes, thereby
increasing membrane permeability and making the
cell
more susceptible to destruction.
Pharmacokinetic profile:
Given by oral or topical route.
ADR:
Local burning and itching (topical).
GI upset (NAV, diarrhea), renal toxicity (PO).
Therapeutic Uses: Prevention and topical treatment of
superficial candidal infections of the skin
and mucous
membranes (gums, GIT, rectum, vagina).

MOA OF NYSTATIN

GRISEOFULVIN

Fungistatic in activity.
MOA:
Inhibits fungal cell mitosis by being
accumulated in
the newly-synthesized keratincontaining tissue, thus producing multinucleated
defective cells that bind to the microtubules, thereby
disrupting mitotic spindle.
Pharmacokinetic profile:

Orally administered; t1/2:

24 hours.
Distributes to growing nails and skin, binding to keratin and
making the cells resistant to fungal infection.
Biotransformed in the liver to 6-methyl-griseofulvin; urinary
excr.

ADR:
Headache, lethargy, fatigue, blurred vision,
insomnia, GI upset, hepatotoxicity.

MOA of Griseolfulvin and

the Echinocandins

GRISEOFULVIN

Drug Interactions:

With anticoagulants reduced effectiveness of

anticoagulants because of enhanced metabolism.
With barbiturates enhanced metabolism of
griseofulvin.
With alcohol tachycardia and flushing; potentiation
of intoxicating effects of alcohol.
With oral contraceptives amenorrhea, increased
breakthrough bleeding.

Therapeutic Use: For tinea infections of the skin, hair, nails

including athletes foot and ringworm caused by
Microsporum, Epidermophyton, and Trichophyton (oral).

IMIDAZOLES:
Ketoconazole

Broad antifungal activity; fungistatic agent.

MOA:
Selectively increases fungal cell membrane
permeability by blocking the demethylation of
lanosterol to ergosterol. (effective only in
growing cells)
MOR:
Mutation in the C14 -demethylase gene
decreased azole binding; fungis ability to
pump
the azole out of the cell.
Orally given; readily absorbed under acidic pH.
ADR:
NAV, diarrhea, rash, itching, dizziness,
constipation, fever, chills, and headache;
gynecomastia and impotence; hepatocellular
toxicity.
Therapeutic Uses: Rx of systemic and vaginal candidiasis,
mucocandidiasis, oral thrush,
histoplamosis,
chromomycosis,
coccidioidomycosis, dermatophytosis.

Azoles

FLUCONAZOLE

ITRACONAZOLE

Administered PO or IV.
May produce teratogenic effects.
DOC for Cryptococcus neoformans.
DOC for blastomycosis, aspergillosis, sporotrichosis,
histoplasmosis, and paracoccidioidomycosis.
Orally administered.
With teratogenic capability.

VORICONAZOLE

Administered orally and effective for invasive aspergillosis

and serious infections caused by Scedosporium
apiospermum and fusarium species.
ADR:
Transient visual disturbance.

Caspofungin

First of the echinocandins class of antifungal drugs.

MOA:
Interferes with the synthesis of the fungal
cell wall by inhibiting the synthesis of -Dglucan cell lysis and death.
ADR:
Fever, rash, nausea, phlebitis, flushing.

Others: Micafungin
Anidulafungin

For aspergillosis, Pneumocystis carinii infection

SYSTEMIC & TOPICAL

IMIDAZOLE: Miconazole

Administered both parenterally and topically.

Therapeutic Uses:
For Rx of candidal and dermatophytic infections of
the skin and for vaginal candidiasis (topical).
For severe systemic fungal infections unresponsive
or not tolerant to Amphotericin B (IV).

ADR:

Local burning, itching, and rash (topical).

NAV, anemia, anaphylactoid reactions, CNS
toxicity, hyponatremia, phlebitis (IV).

TOPICAL IMIDAZOLE:
Clotrimazole

Broad antifungal activity.

Therapeutic Uses: Vulvovaginal candidiasis (topical)

Oropharyngeal candidiasis (topical
oral)

ADR:
urticaria.

Erythema, blistering, edema, pruritus,

TOPICAL IMIDAZOLES:
Econazole & Butoconazole

ECONAZOLE

BUTOCONAZOLE

Derivative of miconazole.
Used for the treatment of tinea pedis, tinea cruris, tinea
corporis, tinea versicolor, and cutaneous candidiasis.
ADR:
Burning, itching, rash.

Azole cream for vaginal use and is effective against vaginal

infections caused by Candida albicans and Candida tropicalis.
May cause vulvovaginal burning and itching.

OTHER TOPICAL ANTIMYCOTIC AGENTS

Undecylenic acid, haloprogin.

TERBINAFINE
NAFTIFINE
AMOROLFINE
TERBINAFINE
Fungicidal agent that acts by selectively inhibiting
squalene epoxidase that is involved in the synthesis of
ergosterol from squalene in the fungal cell wall
accumulation of squalene toxicity to organism.
Given orally or topically for fungal infections of the
nails.
ADR:
GI disturbances, rashes, pruritus, headache,
dizziness, joint and muscle pains, hepatitis.
Related drug: Naftifine
AMOROLFINE
A morpholine derivative that interferes with fungal
sterol synthesis.
Given orally for fungal infections of the nails.

BUTENAFINE

A synthetic benzylamine.

MOA
Alters fungal membrane permeability and growth
inhibition.
Interferes with sterol biosynthesis by allowing
squalene to accumulate within the cell.

Therapeutic Uses
Dermatophytoses, including tinea corporis, tinea
cruris, and tinea pedis (1% cream).

CICLOPIROX

MOA:
Intracellular depletion of amino acids and
ions necessary for normal cellular function.

Therapeutic Uses:
Tinea pedis, tinea cruris, tinea corporis,
tinea versicolor, cutaneous candidiasis
(topical).

CLIOQUINOL, OXICONAZOLE,
SULCONAZOLE, TERCONAZOLE

CLIOQUINOL

OXICONAZOLE

Available in 1% cream or lotion for tinea cruris, corporis,

mannum, and pedis and tinea versicolor.

SULCONAZOLE

Available in 3% ointment for tinea pedis and cruris.

May cause local irritation, rash, and sensitivity reactions.

Imidazole derivative available in 1% cream or solution and

used for tinea corporis, cruris, pedis, versicolor and impetigo.

TERCONAZOLE

Imidazole derivative available in vaginal cream and

suppository and used for vulvovaginal candidiasis.

A blissful Christmas and

a blessed 2014!