Clinical Pharmacology

Of Anti-Fungal Agents
By
NAEEM RIAZ

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 Common fungal infections
• Pityriasis versicolor
• Candidiasis - intertrigo,
paranychia stomatitis, vulvovaginitis
• tenia- corpis, cruris, barbae, capatis,
pedis, manum, unguium

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• Histoplasmosis
• coccidoiomycosis
• blastomycosis
• cryptococcosis
• aspergillosis
• mucormicosis
• Mycetoma
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 FUNGAL INFECTIONS
• Incidence - increasing trend
• Slow onset
• Difficult to diagnose & eradicate
• Long duration of therapy

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 FUNGAL INFECTIONS
• SYSTEMIC
• HISTOPLASMOSIS
• ASPERGILLOSIS
• CRYPTOCOCCOSIS
• BLASTOMYCOSIS
• MUCORMYCOSIS
• CANDIDIASIS
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 • LOCAL
• DERMATOPHYTOSIS.
• SPOROTRICHIOSIS.
• ZYGOMYCOSIS
• CHROMOMYCOSIS.
• RHINOSPOIDIOSIS

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 ANTIFUNGAL AGENTS
• SYSTEMIC ANTIFUNGALS

• TOPICAL ANTIFUNGALS

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 Systemic antifungals
1. GRISEOFULVIN
2. AMPHOTERICIN- B
3. FLUCYTOSINE
4. IMIDAZOLES
5. TRIAZOLES

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 TOPICAL ANTIFUNGAL
• AZOLES-CLOTRIMAZOLE,ECONAZOLE,
MICONAZOLE,TERCONAZOLE
.BUTACONAZOLE
• CICLOPIROX OLAMINE
• HALOPROGIN,BENZOIC+SALICYLIC,TOL
NAFTATE,TERBINAFINE, NYSTATIN
• UNDECYLENIC ACID,

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 Local Antifungals
• MICONAZOLE
CREAM,POWDER,LOTION ,100MG
PESSARIES,
• TENIASIS,VULVOVAGINITIS,-80%
SUCCESS.
• TERCONAZOLE BUTOCONAZOLE-

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• CICLOPIROX OLAMINE,
HALOPROGIN ,
• TOLNAFTATE-TRICHOPHYTONS
AND MICROSPORUM.
• TERBINAFINE CREAM

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 OLDER LOCAL
ANTIFUNGALS
• BENZOIC ACID 6% &SALICYLIC
ACID 3%-WHITFIELD OINTMENT-
TINEA PEDIS. KERTOLYTIC TOO,
• POTASSIUM IODIDE-1 GM/ML-
CUTANIOUS SPOROTRICHIOSIS
• GENTIAN VOILET,IODINE,SULPHUR

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 Now we shall be discussing
Systemic Antifungals

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 Systemic antifungals
1. GRISEOFULVIN
2. AMPHOTERICIN- B
3. FLUCYTOSINE
4. IMIDAZOLES
5. TRIAZOLES

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 GRISEOFULVIN
• FUNGISTATIC - MICROSPORUM,
EPIDERMOPHYTON TRICHOPHYTONS
• MECHANISM - INHIBITION OF FUNGAL
MITOSIS , DISRUPTION OF MITOTIC
SPINDLES
• KINETICS - FATTY MEAL & MICROSIZED
PARTICLES - INCREASES ABSORPTION,
DEPOSITION IN KERATIN CELLS

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 GRISEOFULVIN
• INDICATIONS • ADRs-
• TENIA CAPITIS, • HEADACHE - 15%
CORPORICRURIS • PERIPHERAL
RUBRUM NEUROPATHY
• ATHLETS FOOT • CONFUSION
[EPIDERMOPHYTO • ANTABUSE
SIS] REACTION
• DOSE-10-15 MG/Kg • PHOTO
SENSITIVITY
• drug interactions
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 AMPHOTERICINE B
POLYENE MACROLIDE
• MECHANISM- • SPECTRUM-
FORMS PORES, CANDIDA, CRYPT.
BINDS TO BLASTOMYCES,
ERGOSTEROLS, HISTOPLASMA,
LEAKAGES OF ASPERGILLUS.
MOLECULES, • LIMITED ACTIVITY
OXIDATIVE -LEISHMANIA.
DAMAGE. • NO
ANTIBACTIRIAL
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 AMPHOTERICINE B
• KINETICS - NO • PREPARATIONS -
GIT • INJ. AMPHOTER.
ABSORPTION,90% LIOPHILISED
BOUND TO -50MG,
PROTEINS, [DEOXYCHOLATE
UN CHANGED +BUFFER]
ELIMINATION, • SUV
ELIMINATION FORMULATION
HALF LIFE-15 • LIPID COMPLEX
DAYS
FORMULATION.
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 AMPHOTERICINE B
• ADRs- • INDICATIONS-
chills & fever [saline DOSE-0.5-0.6 MG/kg
loading-beneficial], • mucormicosis
bronchospasm, • aspergillosis
azotemia,
• sporotrichosis
hypokalemia, renal
toxicity, [hydration • cryptococcosis
can decrease toxicity] • neutropenia

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 FLUCYTOSINE
• SPECTRUM- • ADRs - leukopenia,
CANDIDA, enterocolitis,
CRYPTOCOCCUS, azotemia in AIDS
• MOA-INHIBITS
DNA,
• KINETICS-
WELL ABSORBED • LIVER-HEPATITIS
ORALLY, GOOD
PENETRATION IN
CSF

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 FLUCYTOSINE
• INDICATIONS
• USED ALONG WITH
AMPPHOTERICIN IN • DOSE
BLASTOMICOSIS • 100-150 MG/KG IN
• CANDIDA OF
4 DIVIDED DOSES
URINARY BLADDER
• MENINGITIS

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 AZOLE ANTIFUNGALS
• BROAD SPECTRUM OF ACTIVITY
-CANDIDA, CRYPTOCOCCUS,
BLASTOMYCES, HISTOPLASMA,
COCCIDIODES , DERMATOPHYTES.
• MECHANISM OF ACTION - IMPAIR
ERGOSTEROL SYNTHESIS, IMPAIR
ATPase FUNCTION

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 AZOLE ANTIFUNGALS
• IMIDAZOLES • TRIAZOLES
• KETOCONAZOLE • TERCONAZOLE
• MICONAZOLE • ITRACONAZOLE
• CLOTRIMAZOLE • FLUCONAZOLE

• ECONAZOLE
• BUTOCONAZOLE

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 KETOCONAZOLE
• KINETICS
BIOAVAILABILIT
• ADRs-GIT ADRs,
DECREASED BY rashes,gynaecomasti
ANTACIDS,H-2 • torsades de pontes
BLOKERS, HALF -terfenadine&astemiz
LIFE -DOSE .
DEPENDENT,80%- • Menstrual
BOUND TO PL. irregularity,
PROTIENS, • liver toxicity
REACHES • teratogenic in animals
KERATINOCYTES
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 Ketoconazole
• DOSE- 400 Mg daily • EFFICACY POOR
3-6mg /kg CHILD, IN Pts. WITH AIDS.
• VULVO VAGINITIS
5 DAYS,
• OESOPHAGITIS-
2 WEEKS , • CSF CONC-POOR,
• DEEP MYCOSIS-
6-12 MONTHS.

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 ITRACONAZOLE
• RELATED TO • INDICATION-
KETOCONAZOLE, HISTOPLASMOSIS,
• BETTER SPIROTRICHIOSIS
TOLERATED,200- ASPERGILLOSIS ,
400MG /DAY
• D .I. WITH • ADRs- GIT
RIFAMP, DISTRESS,
PHENYTOIN,CARB HEPATITIS.
AMAZEPINE
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 FLUCONAZOLE
• KINETICS-FULL • ADRs--
ABSORPTION,
• PARENTERAL • GIT SYMPTOMS
ADMINISTRATION • HEADACHE,RASH.
- NO ADVANTAGE.
• D I -PHENYTOIN,
• CSF CONC-.60%
ZIDOVUDINE,
• RENAL RIFAMPIN
EXCRETION.

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 FLUCONAZOLE
• CANDIDIASIS-50-100MG -OROPHARYNGEAL
• EOSOPHAGIAL-100-200MG/DAY
• VAGINAL- SINGLE DOSE-150MG
• CRYPTOCOCCOSIS-200MG /DAY
• DRUG OF CHOICE IN MENINGITIS DUE TO
COCCIDIOIDALS
• CHILDREN-3-6 MG/KG

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 Now The Topical Antifungal
Drugs

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 TOPICAL ANTIFUNGAL
• AZOLES-
CLOTRIMAZOLE,ECONAZOLE,
MICONAZOLE,TERCONAZOLE
.BUTOCONAZOLE
• CICLOPIROX OLAMINE
• HALOPROGIN,BENZOIC+SALICYL
IC,TOLNAFTATE,TERBINAFINE,
NYSTATIN
• UNDECYLENIC ACID,
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 CLOTRIMAZOLE
• fungicidal,1% cream,lotion,vaginal
cream
• 100 mg -vaginal tab-o.d-7 days
• cure for dermatophytes ,vulvovaginitis,
• cut.candidiasis-80% success
• ADRs-erythema,pruritis,burning
sensations

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 Local antifungals
• MICONAZOLE • CICLOPIROX
CREAM,POWDER, OLAMINE,
LOTION ,100MG HALOPROGIN ,
PESSARIES, • TOLNAFTATE-
• TENIASIS,VULVOV TRICHOPHYTONS
AGINITIS,-80% AND
SUCCESS. MICROSPORUM.
• TERCONAZOLE • TERBINAFINE
BUTOCONAZOLE- CREAM
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 NYSTATIN
• USEFUL ONLY FOR CANDIDIASIS-
CUTANIOUS, ORAL (oral thrush) OR VAGINAL
(vaginal thrush)
• 100,000 UNITS/GM CREAM,POWDER.
• VAGINAL TAB-TWICE A DAY-2WEEKS

• ADRs- RARE may include Nystatin can temporarily affect the

sense of taste and thus decrease appetite. Some products may
contain propylene glycol, alcohol, parabens, or benzyl alcohol.
Avoid use if you are sensitive to these additives. Other side
effects can be nausea, vomiting, diarrhea, and stomach pain.

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 OLDER LOCAL
ANTIFUNGALS
• BENZOIC ACID 6% &SALICYLIC
ACID 3%-WHITFIELD OINTMENT-
TINEA PEDIS. KERTOLYTIC TOO,
• POTASSIUM IODIDE-1 GM/ML-
CUTANIOUS SPOROTRICHIOSIS
• GENTIAN VOILET,IODINE,SULPHUR

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