This document summarizes information about anti-fungal drugs. It discusses the classification of anti-fungal agents into topical and systemic categories. It describes the mechanisms of action of common anti-fungal drug classes like azoles which inhibit ergosterol synthesis. Specific drugs are explained including fluconazole, itraconazole and their uses to treat fungal infections like candidiasis, cryptococcosis and paracoccidioidomycosis. The synthesis of fluconazole is outlined. Common adverse effects and brand names of these anti-fungal medications are also listed.

1. TEEGALA KRISHNA REDDY
COLLEGE OF PHARMACY
Subject :- MEDICINAL CHEMISTRY - II
Topic :- ANTI – FUNGAL DRUGS
Under the guidance of :-
G. ASHWANI
M.S Pharm

2. CONTENTS:
2
 INTRODUCTION
 CLASSIFICATION
 MECHANISM OF ACTION
 SYNTHESIS
 ADVERSE EFFECTS
THERAPEUTIC USES
 BRAND NAMES
 REFERENCES

3. INTRODUCTION
3
Chemotherapy of Fungal infections has lagged far behind
chemotherapy of Bacterial infections. Most common fungal infections
in humans have been relatively superficial infections of the skin and
mucosal membranes and potentially lethal deep-seated infections
have been quite rare.
The number of effective anti-fungal agents available is quite small
compared to those available to treat bacterial infections, but research
in this area is quite active.

4. 4
The fungal kingdom includes Yeasts, Molds, Rusts & Mushrooms.
Most Fungi are Saprophytic, which means that they live on dead
organic matter in soil or on decaying leaves and wood.
Yeasts such as Candida albicans, typically growing as single oval cells
which reproduce by budding. Molds such as Trichophyton rubrum,
one of the causative organism of ring worm, grow in clusters of
hyphae called mycelium.
CAUSITIVE ORGANISMS

5. 5
These are Mainly responsible for
 Superficial Mycosis
Eg.: Dermatomycosis, Candidiasis, Onchomycosis
 Deep-seated (systemic) Mycosis
Eg.: Coccidioidomycosis, Blastomycosis
FUNGAL INFECTIONS

6. 6
CLASSIFICATION
ANTI - FUNGAL AGENTS
TOPICAL SYSTEMIC
ALLYLAMINE IMIDAZOLE TRIAZOLE ECHINOCANDINS POLYENE MISC.
TERBINAFINE KETOCONAZOLE AMPHOTERICIN - BCASPOFUNGIN
ANIDULAFUNGIN
MICAFUNGIN
FLUCYTOSINE
GRISEOFULVIN
FLUCONAZOLE
ITRACONAZOLE
VORICONAZOLE
ALLYLAMINE -TERBINAFINE,
IMIDAZOLE – CLOTRIMAZOLE,
TRIAZOLE – TERCONAZOLE,
POLYENE – NYSTANIN, MISC. - CICLOPIROX

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MECHANISM OF ACTION

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AZOLES
A Azole refers to any of the five-membered heterocyclic ring
with nitrogen atoms.
They are of 2 types:
H
IMIDAZOLE TRIAZOLE

9. 9
WHAT ARE IMIDAZOLES ?
A Imidazole refers to any of the five-membered heterocyclic
ring with three carbon atoms and two nitrogen atoms.
CLOTRIMAZOLE KETOCONCONAZOLE

10. 10
WHAT ARE TRIAZOLES ?
A triazole refers to any of the five-membered heterocyclic ring
with two carbon atoms and three nitrogen atoms.
FLUCONAZOLE ITRACONAZOLE

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The TRIAZOLES tend to have fewer side
effects, better absorption, better drug
distribution in body tissues, and fewer
drug interactions.
All azoles exert antifungal activity by inhibiting Cytochrome
P450 enzymes responsible for the demethylation of
Lanosterol to Ergosterol. Reduced fungal membrane
Ergosterol concentrations result in damaged, leaky cell
membranes.

12. 12
Fluconazole does not require an acidic environment, as does
Ketoconazole, for GI absorption. About 80% of the drug is excreted
unchanged in the urine. Dosage reductions are required in the
presence of renal insufficiency.
Fluconazole is very effective in the treatment of infections with
most Candida species. AIDS patients with esophageal candidiasis
also usually respond to fluconazole. A single dose has been shown
to be an effective treatment for vaginal candidiasis. A 3-day course
of oral fluconazole is an effective treatment for Candida urinary
tract infection.
FLUCONAZOLE

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ORAL thrush Candidiasis (HAND) Candidiasis (FEET)

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SYNTHESIS OF FLUCONAZOLE
DIFLURO
BENZENE
Cl - CH2 - CH2 - C - Cl
O
+
ETHYL ACETATE
INTERMOLECULAR
REARRANGEMENT
TRIMETHYL
SULFONIUM
IODIDE
FLUCONAZOLE
H
H

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ITRACONAZOLE
Itraconazole is lipophilic and water insoluble and requires a low
gastric pH for absorption. Itraconazole has replaced ketoconazole as
the drug of choice in the treatment of paracoccidioidomycosis and
chromomycosis or Blastomycosis.
BLASTOMYCOSIS PARACOCCIDIOIDOMYCOSIS

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ADVERSE EFFECTS
FLUCONAZOLE
FEVER
SKIN RASHES
UPPER STOMACH PAIN
DARK URINE
LOSS OF APPETITE
ITRACONAZOLE
DIARRHOEA
DIZZINESS
MOOD CHANGES
DECREASED URINE
LOSS OF APPETITE

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THERAPEUTIC USES
FLUCONAZOLE
CANDIDA INFECTIONS OF VAGINA,
MOUTH & ESOPHAGUS
CRYPTOCOCCAL MENINGITIS
PERITONITIS
CRYPTOCOCCOSIS IN AIDS
URINARY TRACT INFECTIONS
ITRACONAZOLE
FUNGAL INFECTIONS OF TOENAILS,
THROAT, MOUTH & ESOPHAGUS
PARACOCCIDIOIDOMYCOSIS
ASPERGILLOSIS
BLASTOMYCOSIS
JOCK ITCH

18. 18
BRAND NAMES
BRAND NAME
DIFLUCAN
CANDID
DIFLU
ITRABOND
SYNTRON
SPORANOX
DOSAGE
Capsule
Tablet
Suspension
Tablet
Capsule
Vial (ORAL)
DOSE
Fluconazole 50mg
Fluconazole 50mg - 150mg
Fluconazole 50mg/5ml
Itraconazole 100mg
Itraconazole 200mg
Itraconazole 10mg x 1ml

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REFERENCE
 FOYE’S principles of MEDICINAL CHEMISTRY 6th Edition
Pg. No.: 1112 – 1126.
 Text book of MEDICINAL CHEMISTRY [Vol - 2] by
V. ALAGARSAMY Pg. No.:
 A Text book of MEDICINAL CHEMISTRY (Synthesis &
biochemical Approach) [Vol - 1] by Surendra . N. Pandeya
Pg. No.:

20. THANK
YOU