AZOLE DRUGS

Mode of action .
Inhibit Enzyme C 14 Alpha Demethylase Necessary For
Conversion Of Lanosterol To Ergosterol

RESISTANCE: Alteration In Enzyme C 14 Alpha

Demethylase
Efflux Pump
Azoles And Amphotericin B Should Not Be Used Together
COMPARISON OF AZOLES
ketoconazole fluconazole Itraconazole
HCL FACILITATE NOT NECESSARY HCL MEDIATED
ABSORPTION ABSORPTION
ENDOCRINE ADVERSE NONE NONE
EFFECTS
BOUND TO PLASMA PLASMA PROTEIN BOUND TO PLASMA
PROTEINS BINDING MINIMAL PROTEINS
CAN NOT CROSS BBB CAN CROSS BBB CAN NOT CROSS BBB
EXCRETION THROUGH EXCRETION THROUGH EXCRETION THROUGH
BILE KIDNEYS KIDNEYS
METABOLISM IN LIVER LITTLE OR NO METABOLISM IN LIVER
METABOLISM
NO ACTIVE METABOLITE NONE HYDROXYITRACONZOLE
AZOLES ARE TERATOGENIC
KETOCONAZOLE FLUCONAZOLE ITRACONAZOLE
NARROW SPECTRUM BROAD BROAD SPECTRUM
DRUG INTERACTION INHIBITOR INHIBITOR
INHIBITOR OF CYTP450
DRUG LEVEL CAN RISE SAME SAME
PHENYTOIN WARFARIN
GYNECOMASTIA DEC NAUSEA VOMITING GI UPSET
LIBIDO. MENSTURAL RASH HYPERTENSION EDEMA
IRREGULARITIES HEADACHE
SPECTRUM
KETOCONAZOLE : HISTOPLASMA, BLASTOMYCES, CANDIDA COCCIDIODES

ITRACONAZOLE : ASPERGILLOSIS SPOROTRICHOSIS

FLUCONAZOLE : CRYPTOCOCCUS NEOFORMANS

VORICONAZOLE: ACTIVE AGAINST SCEDOSPORIUM

APIOSPERMUM FUSARIUM SPECIES
FLUCYTOSINE ( FUNGISTATIC) 5FC
MODE OF ACTION :
INHIBIT THYMIDYLIC ACID AN IMPORTANT COMPONENT OF DNA IT
CONVERTS IN CYTOPLASM TO 5-FLURODEOXYURIDINE
MONOPHOSPHATE

RESISTANCE DECREASE LEVEL OF ENZYMES WHICH CONVERT IT

INCREASE SYNTHESIS OF CYTOSINE

PHARMACOKINETICS: WELL ABSORB ORALLY

PENETRATES CSF
EXCRETION THROUGH KIDNEYS
SPECTRUM
CHROMOBLASTOMYCOSIS , CRYPTOCOCCOSIS CANDIDIASIS

ADVERSE EFFECTS: BONE MARROW DEPRESSION,

HEPATOTOXIC
ENTEROCOLITIS AND GI UPSET
AMPHOTERICIN B
M. O. A. : IT BINDS WITH ERGOSTEROL AND FORM PORES IN
CELL DISTRUB ELECTROLYTE BALANCE THUS CAUSING CELL
DEATH

SPECTRUM : CANDIDA, CRYPTOCOCCUS, BLASTOMYCES,

COCCIDIODES

RESISTENCE : DEC ERGOSTEROL SYNTHESIS

PHARMACOKINETICS
 GIVEN VIA SLOW INFUSION MIXED WITH OILY FLUID
 BECAUSE IT IS WATER INSOLUBLE COMBINED WITH SODIUM
DEOXYCHOLATE
 USED INTRATHECALLY IN MENINGITIS
 THESE OILY INFUSION OF PLD AND CHOLESTROL DEC ITS
TOXICITY
 BOUND TO PLASMA PROTEINS
 CAN CROSS PLACENTA
ADVERSE EFFECTS( LOW THERAPEUTIC INDEX)
FEVER CHILLS

RENAL IMPAIRMENT

ANEMIA

HYPOTENSION . DUE TO HYPOKALEMIA

THROMBOPHLEBITIS AND NEUROTOXIC EFFECT CAN PRODUCE

CASPOFUNGIN
IT CAUSES LYSIS OF CELL WALL BY INHIBITING D-GLUCAN

ACTIVE AGAINST ASPERGILLUS AND CANDIDA

NOT ACTIVE ORALLY BOUND TO PLASMA ALBUMIN

SIDE EFFECTS FEVER RASH PHLEBITIS FLUSHING

SECOND LINE DRUG VERY COSTLY

CUTANEOUS MYCOTIC INFECTIONS
TINEA INFECTIONS TERMED AS RINGWORM INFECTIONS

TERBINAFINE : INHIBIT SQUALENE EPOXIDE THUS DEC ERGOSTEROL

SYNTHESIS

SQUALENE IS TOXIC FOR FUNGAL CELL

LOW BIOAVAILABILITY BOUND TO ALBUMIN

DEPOSIT IN SKIN NAILS

SPECTRUM FUNGICIDAL DERMATOPHYTES AND CANDIDA

ADVERSE EFFECTS
GI UPSET RASH HEADACHE TASTE AND VISUAL
DISTURBANCE
HEPATOTOXICITY

NYSTATIN (POLYENE)
LOW ABSORPTION THROUGH GIT NEVER USED PARENTERALLY
GI UPSET
3. GRISEOFULVIN
FUNGISTATIC , MANY DRUG INTERACTIONS
TERBINAFINE LARGELY REPLACE IT

DESTRUCTION OF MITITIC SPINDLE AND INHIBITING FUNGAL

MITOSIS IS THE MODE OF ACTION OF GRISEOFULVIN

IT IS INDUCER OF HEPATIC P450 ENZYME

MICONAZOLE AND CLOTRIMAZOLE