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CLINICAL PHARMACOLOGY OF ANTI FUNGAL AGENTS

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MECHANISM - INHIBITION OF FUNGAL MITOSIS , DISRUPTION OF MITOTIC SPINDLES ... BLASTOMYCES, HISTOPLASMA, ASPERGILLUS. LIMITED ACTIVITY -LEISHMANIA. NO ANTIBACTIRIAL ... – PowerPoint PPT presentation

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Title: CLINICAL PHARMACOLOGY OF ANTI FUNGAL AGENTS


1
CLINICAL PHARMACOLOGY OFANTI FUNGAL AGENTS
  • DR. PRALHAD S. PATKI, M.D PROFESSOR OF
    PHARMACOLOGYB.J. MEDICAL COLLEGE PUNE-411001,
    INDIA

2
Common fungal infections
  • Pityriasis versicolor
  • Candidiasis - intertrigo,paranychia stomatitis,
    vulvovaginitis
  • tenia- corpis, cruris, barbae, capatis,
    pedis,manum, unguium
  • Histoplasmosis
  • coccidoiomycosis
  • blastomycosis
  • cryptococcosis
  • aspergillosis
  • mucormicosis
  • mycetoma

3
FUNGAL INFECTIONS
  • Incidence - increasing trend
  • Slow onset
  • Difficult to diagnose eradicate
  • Long duration of therapy

4
FUNGAL INFECTIONS
  • SYSTEMIC
  • HISTOPLASMOSIS
  • ASPERGILLOSIS
  • CRYPTOCOCCOSI
  • BLASTOMYCOSIS
  • MUCORMYCOSIS
  • CANDIDIASIS
  • LOCAL
  • DERMATOPHYTO.
  • SPOROTRICHIOSI.
  • ZYGOMYCOSIS
  • CHROMOMYCOSI.
  • RHINOSPOIDIOSIS

5
ANTIFUNGAL AGENTS
  • SYSTEMIC ANTIFUNGALS
  • TOPICAL ANTIFUNGALS

6
Systemic antifungals
  • 1. GRISEOFULVIN
  • 2. AMPHOTERICIN- B
  • 3. FLUCYTOSINE
  • 4. IMIDAZOLES
  • 5. TRIAZOLES

7
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

8
GRISEOFULVIN
  • INDICATIONS
  • TENIA CAPITIS, CORPORICRURIS RUBRUM
  • ATHLETS FOOT EPIDERMOPHYTOSIS
  • DOSE-10-15 MG/Kg
  • ADRs-
  • HEADACHE - 15
  • PERIPHERAL NEUROPATHY
  • CONFUSION
  • ANTABUSE REACTION
  • PHOTO SENSITIVITY
  • drug interactions

9
AMPHOTERICINE BPOLYENE MACROLIDE
  • MECHANISM- FORMS PORES, BINDS TO
    ERGOSTEROLS, LEAKAGES OF MOLECULES, OXIDATIVE
    DAMAGE.
  • SPECTRUM-CANDIDA, CRYPT. BLASTOMYCES,
    HISTOPLASMA, ASPERGILLUS.
  • LIMITED ACTIVITY -LEISHMANIA.
  • NO ANTIBACTIRIAL

10
AMPHOTERICINE B
  • KINETICS - NO GIT ABSORPTION,90 BOUND TO
    PROTEINS, UN CHANGED
    ELIMINATION, ELIMINATION HALF LIFE-15 DAYS
  • PREPARATIONS -
  • INJ. AMPHOTER. LIOPHILISED -50MG,DEOXYCHOLATE
    BUFFER
  • SUV FORMULATION
  • LIPID COMPLEX FORMULATION.

11
AMPHOTERICINE B
  • ADRs- chills fever saline loading-beneficial,
    bronchospasm, azotemia, hypokalemia, renal
    toxicity, hydration can decrease toxicity
  • INDICATIONS-DOSE-0.5-0.6 MG/kg
  • mucormicosis
  • aspergillosis
  • sporotrichosis
  • cryptococcosis
  • neutropenia

12
FLUCYTOSINE
  • SPECTRUM- CANDIDA, CRYPTOCOCCUS,
  • MOA-INHIBITS DNA,
  • KINETICS- WELL ABSORBED ORALLY, GOOD PENETRATION
    IN CSF
  • ADRs - leukopenia, enterocolitis, azotemia in
    AIDS
  • LIVER-HEPATITIS

13
FLUCYTOSINE
  • INDICATIONS
  • USED ALONG WITH AMPPHOTERICIN IN BLASTOMICOSIS
  • CANDIDA OF URINARY BLADDER
  • MENINGITIS
  • DOSE
  • 100-150 MG/KG IN 4 DIVIDED DOSES

14
AZOLE ANTIFUNGALS
  • BROAD SPECTRUM OF ACTIVITY -CANDIDA,
    CRYPTOCOCCUS, BLASTOMYCES, HISTOPLASMA,
    COCCIDIODES , DERMATOPHYTES.
  • MECHANISM OF ACTION - IMPAIR ERGOSTEROL
    SYNTHESIS, IMPAIR ATPase FUNCTION

15
AZOLE ANTIFUNGALS
  • IMIDAZOLES
  • KETOCONAZOLE
  • MICONAZOLE
  • CLOTRIMAZOLE
  • ECONAZOLE
  • BUTOCONAZOLE
  • TRIAZOLES
  • TERCONAZOLE
  • ITRACONAZOLE
  • FLUCONAZOLE

16
KETOCONAZOLE
  • KINETICS BIOAVAILABILIT DECREASED BY ANTACIDS,H-2
    BLOKERS, HALF LIFE -DOSE DEPENDENT,80-BOUND TO
    PL. PROTIENS, REACHES KERATINOCYTES
  • ADRs-GIT ADRs, rashes,gynaecomasti
  • torsades de pontes -terfenadineastemiz.
  • Menstrual irregularity,
  • liver toxicity
  • teratogenic in animals

17
Ketoconazole
  • DOSE- 400 Mg daily 3-6mg /kg CHILD,
  • VULVO VAGINITIS 5 DAYS,
  • OESOPHAGITIS- 2 WEEKS ,
  • DEEP MYCOSIS- 6-12 MONTHS.
  • EFFICACY POOR IN Pts. WITH AIDS.
  • CSF CONC-POOR,

18
ITRACONAZOLE
  • RELATED TO KETOCONAZOLE,
  • BETTER TOLERATED,200-400MG /DAY
  • D .I. WITH RIFAMP, PHENYTOIN,CARBAMAZEPINE
  • INDICATION-HISTOPLASMOSIS,SPIROTRICHIOSISASPERGILL
    OSIS ,
  • ADRs- GIT DISTRESS, HEPATITIS.

19
FLUCONAZOLE
  • KINETICS-FULL ABSORPTION,
  • PARENTERAL ADMINISTRATION- NO ADVANTAGE.
  • CSF CONC-.60
  • RENAL EXCRETION.
  • ADRs--
  • GIT SYMPTOMS
  • HEADACHE,RASH.
  • D I -PHENYTOIN, ZIDOVUDINE, RIFAMPIN

20
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

21
TOPICAL ANTIFUNGAL
  • AZOLES-CLOTRIMAZOLE,ECONAZOLE, MICONAZOLE,TERCONAZ
    OLE .BUTOCONAZOLE
  • CICLOPIROX OLAMINE
  • HALOPROGIN,BENZOICSALICYLIC,TOLNAFTATE,TERBINAFIN
    E, NYSTATIN
  • UNDECYLENIC ACID,

22
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

23
Local antifungals
  • MICONAZOLE CREAM,POWDER,LOTION ,100MG PESSARIES,
  • TENIASIS,VULVOVAGINITIS,-80 SUCCESS.
  • TERCONAZOLE BUTOCONAZOLE-
  • CICLOPIROX OLAMINE, HALOPROGIN ,
  • TOLNAFTATE-TRICHOPHYTONS AND MICROSPORUM.
  • TERBINAFINE CREAM

24
NYSTATIN
  • USEFUL ONLY FOR CANDIDIASIS-CUTANIOUS, ORAL
    OR VAGINAL
  • 100,000 UNITS/GM CREAM,POWDER.
  • VAGINAL TAB-TWICE A DAY-2WEEKS
  • ADRs- RARE

25
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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