Faculty of Medicine

Lampung University
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 Subcutaneus & Superficial
Systemic Mycoses Mycoses

- Griseofulvin
- Amphoterisin B
- Nystatin
- Flucytosine
- Myconazole
- Ketokonazol
- Clotrimazole
- Fluconazole
- Econazole
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Amphotericin B
Flucytosine
Ketoconazol
Fluconazole

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 Has the broadest Potential toxicity,
spectrum of action fungicidal

Activity againts: Candida

sp, Histoplasma
+ flucytosine >> capsulatum, Cryptococcus
sinergism neoformans, Coocidiodes
immitis, Aspergillus sp,
Blastomyces dermatitidis
PHARMACOLOGICAL PROPERTIES
 Poorly absorbed from GIT
 Widely distributed in most tissues, 2-3% reaches
CSF
 Excreted slowly in the urine

Resistance >> by decreasing concentration of

ergosterol, or by modifying the sterol target
molecule to reduce its affinity for the drug.
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THERAPEUTICS USES
 DOC for nearly all life-threatening mycotic infections
 Used as empiric therapy
 Local >> mycotic corneal ulcers and keratitis

ADVERSE EFFECTS
• Chills & fever
• Impaired renal function
• Abnormalities of liver function tests and anemia
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 A water-soluble pyrimidine analog related to
the chemotherapeutic agent fluorouracil (5-FU).

The spectrum of
activity >>
Cryptococcus Synergy with Synergy with azole
neoformans, candida, amphotericin B drugs
and
chromoblastomycosis

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 Taken up by fungal cells

Converted to 5-FU

5-fluorodeoxyuridylic acid (F-dUMP)

Inhibit DNA and RNA synthesis

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 PHARMACOLOGICAL PROPERTIES
 PO >> well (> 90%) absorbed
 Poorly protein-bound and penetrates well into all body fluid
compartments, including CSF
 Eliminated by glomerular filtration
 Levels rise rapidly with renal impairment and can lead to
toxicity

ADVERSE EFFECTS
• Hematological toxicity: neutropenia, thrombocytopenia, BM
depression
• Hepatic dysfunction
• GI disturbances 14
MOA: inhibition of fungal cytochrome P450 enzymes >> reduction of
ergosterol synthesis

The spectrum >> candida species, Cryptococcus neoformans,

blastomycosis, coccidioidomycosis, histoplasmosis, the dermatophytes

CI: + Ampho-B

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PHARMACOLOGICAL PROPERTIES
 Adm: PO (food, antasid, and cimetidine interfere its absorption)
 Penetrasi: (-) CSF
 Excr: primarily through the bile

ADVERSE EFFECTS
 Endocrine effect (eg. gynecomastia)
 GI effect

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 PO and PE prep
 Oral bioavailability is high.
 Good CSF penetration
 Has the widest therapeutic index of the azoles.
Clinical Uses:
- Mucocutaneous candidiasis
- Cryptococcalmeningitis

 ADR : << ketoconazole, (-) endocrinological effect

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 The newest class of antifungal agent
 Is a second-line antifungal for those who have
failed or cannot tolerate amphotericin B or an
azole.
 MoA: interfere with the synthesis of the
fungal cell wall by inhibiting the synthesis of
β(1,3)-D-glucan >> lysis and cell death.

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PK
 A: PE
 M: slowly metabolized by hydrolysis and N-
acetylation.
 Water-soluble and highly protein bound.
 T ½ 9–11 hours
 E: urinary and fecal routes

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Clinical Uses
 Salvage therapy in patients with invasive
aspergillosis who have failed to respond to
amphotericin B
 Mucocutaneous candidiasis and candidal
bloodstream infections

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Griseofulvin
Nystatin
Miconazole
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 Antifungal spectrum >> fungistatic, dermatophytes
(trichopyton, microsporum, epidermophyton)
 Systemic treatment of dermatophytosis
 MOA >> unclear, but it is deposited in newly forming skin
where it binds to keratin

P-Properties
• Absorption is improved when it is given with fatty foods.
• Met: liver
• Excr: feces & urine
• AE: allergic syndrome

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 Much like Amphotericin B
 Too toxic for PE administration >> only used
topically
 Creams, ointments, suppositories, and other
forms
 Clinical uses: local candidal infections
 ADR: rare >> nausea, vomitting

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 Actively topical drugs
 MOA, antifungal spectrum, distribution, type
of metabolism = ketoconazole
 Clinical Uses: tinea pedis, ringworm, and
cutaneous and vulvovaginal candidiasis.
 AE: rare

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