ANTIFUNGALS

Fungal infections:
• Largely grouped into : Superficial
(mucocutaneous, subcutaneous) and Systemic
infections
1. AMPHOTERICIN B –fungicidal, broad
spectrum
Mnx: Binds ergosterol & form pores leading to
leakage of ions and macromolecules & cell
death
Administered: parenteral for systemic effect
Distribution: widely into body tissues and fluids
Enters CSF if inflamed meninges and when co-
administered with Flucytosine
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Elimination: t1/2 – 15 days (persists in the body
for several weeks after cessation of treatment)
• Largely metabolized, Some renal excretion
S/E
1. Nephrotoxic: very common
2. Hepatic dysfunction
3. Thrombocytopenia
4. Anaphylactic reactions
5. Infusion related effects: -Fever, chills,
nausea & vomiting, headache, muscle spasm
and joint pain, hypotension, Local
thrombophlebitis
D/I – synergistic with flucytosine ( probably by
increasing permeability)
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Uses:
Systemic use:
1.(DOC) for serious systemic mycotic
infections e.g. cryptococcal meningitis, fungal
pneumonia, sepsis due to fungi
Local use:
3. Mycotic infections of – GIT, eye, fungal
arthritis, mycotic infections of the bladder
(through bladder irrigation)
C/I
Renal failure.

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2. AZOLES
Mechanism: Inhibition of synthesis of ergosterol
Spectrum: Broad
Examples: ketoconazole, fluconazole, itraconazole

A) KETOCONAZOLE:
Administration: per oral
Absorption: best on acidic medium and with food.
Absorption reduced by: antacids, proton pump
inhibitors, H2- blockers which reduce gastric pH
Distribution: has poor CSF penetration
Elimination: hepatic elimination

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S/E
1. Endocrine effects: gynecomastia, mestrual
irregularities, infertility, alopecia, decreased
libido (inhibit steroid hormone synthesis).
2. GIT irritation
D/I
Rifampicin
Uses
• Mucocutaneous candidiasis
Dose: 200-400 mg OD (P.O).
C/I: pregnancy and lactation, hepatic disorders.

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B) ITRACONAZOLE (most potent of the azoles)
Administration: oral & parenteral (I.V)
Has features like ketoconazole.
S/E (dose dependent)
1. GIT irritation
Uses
1. Aspergillosis (the main drug with significant
activity)
2. DOC for Dermatophytoses, Onychomycosis,
Histoplasma, Blastomyces, Sporothrix.
Dose: 100-400mg/d (I.V, P.O)

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C) FLUCONAZOLE
Administration: oral & parenteral
Absorption: good
Distribution: good and can enter into CSF
S/E
• Least effect on GIT irritation
USES
1. DOC treatment of cryptococcal meningitis
2. DOC prophylaxis of cryptococcal meningitis
3. Candidemia
4. Mucocutaneus candidiasis

Dose: 100-800mg/d in divided doses.

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3. FLUCYTOSINE
Mechanism: inhibit DNA and RNA synthesis.
Administration: oral & well absorbed.
Distribution: into all body tissues and fluids
including CSF
Elimination: t1/2 -4hrs; Renal excretion.
S/E
1.Bone marrow depression: pancytopenia
2.ALopecia
3.Liver damage
4.Toxic enterocolitis (GIT disturbance)
D/I
• Synergistic with amphotericin B and azoles
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Uses: (always combined with others to prevent
resistance)
• Cryptococcal meningitis
• Some dermatophytic infection
4. GRISEOFULVIN
Deposited in newly forming skin,nail, hair where it
binds to keratin, protecting from new infections.
Absorption: improved with fatty foods.
Use: treatment of dermatophytosis
Dose:1 g/d. (may require therapy for months)
S/E: Allergic reactions, hepatitis
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TOPICAL ANTIFNGALS
1.NYSTATIN
Mechanism: binds ergosterol causing pore
formation & cell wall disruption.
Administration: topical or local only (it is too
toxic for systemic use)
Absorption: very poor.
Uses
• Candida infections – oropharynx, GIT, vagina,
cutaneous.

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2. TOPICAL AZOLES
e.g. Clotrimazole and miconazole
Uses
• vulvovaginal candidiasis
• oral thrush
• dermatophytic infections (-tinea corporis,
tinea pedis, and tinea cruris).
S/E: very rare

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