ANTIFUNGAL DRUGS o Therapeutic use:

- Chronic Mucocutaneous Candidiasis

- Dermatophytosis
Mechanism of action: - Systemic Mycoses
o Adverse effects:
1. Cell Membrane Permeability  Hepatotoxic (upon long term use)
2. Cell Membrane Synthesis  Inhibit testosterone synthesis -> -
3. Direct Tissue Target enlargement of the breast
4. Nucleic Acid Analogue (Gynecomastia)
5. Cell Wall Synthesis  Impotence

CELL MEMBRANE PERMEABILITY *Nizoral – dandruff treatment

Bind to Ergosterol and distrupt the cell membrane
through POLYENES b. Miconazole and Clotrimazole
o Administration: topical
1. Amphotericin B – Primary Antifungal Drug o Therapeutic use: topical fungal infection
o Polyene - Tinea versicolor (an-an), Tinea pedis,
o Derived from Streptococcus nodosus Tinea corporis, Tinea cruris
o Given as Micelles with Sodium Deoxycholate - Dermatophytosis
dissolved in a dextrose solution - Cutaneous Candidiasis

o Administration: IV B. Triazole – newer version that is less toxic and

o Therapeutic use: Drug of choice for: more effective
- Systemic mycoses a. Fluconazole
- Systemic candidiasis o Administration: Oral
- Cryptococcal meningitis o Therapeutic Use:
- Invasive Aspergillosis - Candidiasis
- Sporotrichosis - Cryptococcal disease
- Mucomycosis o Overuse leads to resistance of Candida
glabrata
o Adverse effects:
a. Phlebitis - inflammation at the site of b. Itriconazole
administration o Administration: Oral
b. Nephrotoxic - Increased in BUN and Creatinine o Therapeutic use:
= Azotemia - Blastomycosis Systemic
c. Anemia - Decreased Hb and no. of RBCs - Histoplasmosis Mycoses
d. Febrile (fever) – Patient has to take antidiuretic - Coccidioidomycosis
drugs - Sporotrichosis
- Chromomycosis
2. Nystatin – First Antibiotic against Fungi - Invasive Aspergillosis, Candidiasis
o From Streptomyces noursei
o Administration: Oral, topical, Suppository (vaginal) C. Voriconazole and Posaconazole
o Therapeutic use: Candidiasis (can be oral, vaginal, o Administration: Oral, Topical
and esophageal) o Therapeutic use:
o Found in New York - Candidiasis (Posaconazole)
- Aspergillosis (Vericonazole)
CELL MEMBRANE SYNTHESIS 2. Allylamines
Block Ergosterol Formation through: o prevent oxidation of squalene epoxidase
 Butenafine
1. Azoles  Naftifine
o inhibit the action of cytochrome P450 dependent 14-  Amorolfine
alpha-demethylase (converts Lanosterol to Ergosterol)  Terbinafine

A. Imidazole Naftifine
a. Ketokonazole – Most Toxic o Adminisration: Topical
o Administration:Shampoo, Topical (cream), o Therapeutic Use:
Oral - Dermatophytosis
 Terbinafine o 1st Licensed Drug
o Administration: Oral B. Anidulafungin
o Therapeutic Use: Alternative drug for C. Micafungin
- Griseofulvin
- Dermatophytosis (nail infection) 2. Nikkomycin-Z -inhibit Chitin synthesis
o Adverse effect: o Therapeutic use:
 Gastrointestinal irritation - Coccidiomycosis
- Blastomycosis
DIRECT TISSUE TARGET
Disrupts microtubule formation in the cytoplasm
 Sodarin – Inhibit elongation Factor 2
Griseofulvin
o Deposits in keratin and inhibit the growth of FACTORS TO CONSIDER IN THE SELECTION OF
fungi. ANTIFUNGAL DRUGS:
o Blocks intracellular microtubules
o From Penicillium griseofulvum 1. The threat of morbidity and mortality pose by
o Alternative: Terbinafine the specific infection.
o Administration: Oral (more adverse effects) 2. The immune status of the patient
o Therapeutic Use: 3. The toxicity of the antifungal drug
- Dermatophytosis 4. The probable activity of the antifungal agent
o Adverse Effects: against the fungus.
 Dizziness/Headache
 Diarrhea Why fungi are hard to treat:
 Elevated Liver Enzymes
- Fungi cell is almost the same with the human cell.
NUCLEIC ACID ANALOGUE - Reoccurrence can happen unless treated up to the
Prevent DNA and RNA synthesis root which is attached to the muscle.

Flucytosine (5-FC) CLASSIFICATION OF MYCOSES:

o Convered tp 5-Fluorouracyl by Cytosine
Deaminase 1. Superficial
o Incorporated to 5-fluorodeoxyuridylic acid 2. Cutaneous
o Administration: Oral and Intravenous 3. Subcutaneous
o Therapeutic Use: 4. Systemic
- Administer together with amphotericin 5. Opportunistic
B
- Cryptococcal meningitis (Flucytosine
penetrates well into the CSF)
- Candidiasis
o Adverse Effects:
 Bone marrow depression (anemia,
pancytopenia etc.)
 Renal damage
 Elevated liver enzymes
o Active uptake via Permease

CELL WALL SYNTHESIS

MOST EFFECTIVE BUT EXPENSIVE
Inhibit chitin, glucan, mannan and complex
polyssacharide synthesis

1. Echnocandins – inhibit the Glucan synthesis in

the cell wall via the enzyme 1,3 – B-Glucan
Synthase (Enzyme Echinocandins inhibit)

A. Caspofungin, Polyoxin-D
o Therapeutic use: Candidiasis and
Aspergillosis