ANTIFUNGAL ANTIFUNGAL DRUGSDRUGS

Infectious diseases caused by fungi are called Infectious diseases caused by fungi are called mycoses. They are often chronic in nature.mycoses. They are often chronic in nature.

Superficial mycotic infections are common Superficial mycotic infections are common and involve only the skin (cutaneous and involve only the skin (cutaneous mycoses)mycoses)

Systemic mycoses are difficult to treat.Systemic mycoses are difficult to treat. Fungi are eukaryotic.Fungi are eukaryotic. Cell wall is made of chitin.Cell wall is made of chitin. Cell membrane is made of ergosterol rather Cell membrane is made of ergosterol rather

than cholesterol found in mammals. than cholesterol found in mammals.

> in incidence of fungal infections in > in incidence of fungal infections in the last two decadesthe last two decades

Candidemia is the fourth common Candidemia is the fourth common cause of septicemia.cause of septicemia.

> incidence because of organ > incidence because of organ transplants, transplants,

Chemotherapy and HIV.Chemotherapy and HIV. Newer anti mycotics have helped.Newer anti mycotics have helped.

ANTIFUNGAL DRUGSANTIFUNGAL DRUGS

DRUGS FOR S.C & DRUGS FOR S.C & SYSTEMIC SYSTEMIC MYCOSISMYCOSIS

1.1. Amphotericin BAmphotericin B

2.2. FlucytosineFlucytosine

3.3. FluconazoleFluconazole

4.4. ItraconazoleItraconazole

5.5. KetoconazoleKetoconazole

6.6. VoriconazoleVoriconazole

DRUGS USED FOR DRUGS USED FOR SUPERFICIAL SUPERFICIAL MYCOSISMYCOSIS

1.1. ClotrimazoleClotrimazole

2.2. GriseofulvinGriseofulvin

3.3. MiconazoleMiconazole

4.4. NystatinNystatin

Antifungals - systemicAntifungals - systemic

Amphotericn B Amphotericn B Naturally occuring produced by Naturally occuring produced by

streptomyces nodosus. streptomyces nodosus. Mechanism - Binds with ergosterol in Mechanism - Binds with ergosterol in

the plasma membrane of sensitive the plasma membrane of sensitive fungal cell. There they form pores fungal cell. There they form pores which alter the permeability of which alter the permeability of membrane leading to cell death.membrane leading to cell death.

Toxicity is common . Therefore it is Toxicity is common . Therefore it is used in combination with flucytosineused in combination with flucytosine

Effective against c.albicans, Effective against c.albicans, H.capsulatum, C.Neoformans and H.capsulatum, C.Neoformans and many strains of aspergillus.many strains of aspergillus.

Resistance is rare because of the Resistance is rare because of the decreased ergosterol content of decreased ergosterol content of fungal membrane.fungal membrane.

Amphotericin b is administered slow iv . Amphotericin b is administered slow iv . Dangerous intrathecal route reserved for Dangerous intrathecal route reserved for serious meningitis.serious meningitis.

Does not cross the placenta.Does not cross the placenta. Adv effects.Adv effects. Fever and chillsFever and chills Renal impairmentRenal impairment Hypotension. care when given with Hypotension. care when given with

digitalisdigitalis AnemiaAnemia Thrombophlebitis can occurThrombophlebitis can occur

FLUCYTOSINEFLUCYTOSINE MECH : MECH : INHIBITS THYMIDYLATE INHIBITS THYMIDYLATE

SYNTHETASESYNTHETASE Very useful in treatment of meningitisVery useful in treatment of meningitis SPECTRUM : CRYPTOCOCCUS, CANDIDA, SPECTRUM : CRYPTOCOCCUS, CANDIDA,

BLASTOMYCOSISBLASTOMYCOSIS ORAL ROUTE, CROSSES BBBORAL ROUTE, CROSSES BBB RESISTANCE PRESENTRESISTANCE PRESENTSE : SE : HEPATO TOXICITYHEPATO TOXICITY ANEMIA & GIT DISTRESS.ANEMIA & GIT DISTRESS. BONE MARROW DEPRESSIONBONE MARROW DEPRESSION

KETOCONAZOLEKETOCONAZOLE

It was the first orally active azole It was the first orally active azole available for the treatment of systemic available for the treatment of systemic mycoses.mycoses.

They are fungistatic.They are fungistatic. They block the demethylation of They block the demethylation of

ianosterol to ergosterol.ianosterol to ergosterol. It inhibits human gonadal and adrenal It inhibits human gonadal and adrenal

steroid synthesis.steroid synthesis. Does not enter csfDoes not enter csf

Most effective against histoplasmosis.Most effective against histoplasmosis. Has been largely replaced by Has been largely replaced by

itraconazole.itraconazole. But is more economical than others.But is more economical than others. It is given orally. It requires gastric acid It is given orally. It requires gastric acid

for dissolution.for dissolution. Antacids, h2 receptor blockers and Antacids, h2 receptor blockers and

proton pump inhibitors impair proton pump inhibitors impair absorption.absorption.

Inhibits the cytochrome p-450Inhibits the cytochrome p-450 It can potentiate the drug toxicities of It can potentiate the drug toxicities of

rifampin, phenytoin and warfarin.rifampin, phenytoin and warfarin. It should not be used with amphotericin B. It should not be used with amphotericin B. SE:SE: GITGIT ENDOCRINE – Gynecomastia, impotence, ENDOCRINE – Gynecomastia, impotence,

menstrual abnormalitiesmenstrual abnormalities HEPATIC DYSFUNCTIONHEPATIC DYSFUNCTION

FLUCONAZOLEFLUCONAZOLE

It is clinically important because of It is clinically important because of the lack of endocrine side effects.the lack of endocrine side effects.

Given prophylactically in recipients of Given prophylactically in recipients of bone marrow transplants.bone marrow transplants.

Effective against all forms of Effective against all forms of mucocutaneous candidiasis. mucocutaneous candidiasis.

Can be given orally or i.vCan be given orally or i.v Has no endocrine effects and does Has no endocrine effects and does

not inhibit cytochrome p450.not inhibit cytochrome p450.

ITRACONAZOLEITRACONAZOLE

Recent addition to the azole family of Recent addition to the azole family of antifungals.antifungals.

Broad spectrum.Broad spectrum. Mechanism is same as that of the Mechanism is same as that of the

other azoles.other azoles. Drug of choice for blastomycosis, Drug of choice for blastomycosis,

aspergillosis, histoplasmosis.aspergillosis, histoplasmosis. Unlike ketoconazole it is effective Unlike ketoconazole it is effective

against aids associated against aids associated histoplasmosis.histoplasmosis.

EchinocandinsEchinocandins Interfere with the synthesis of the Interfere with the synthesis of the

fungal cell wall by inhibiting the fungal cell wall by inhibiting the synthesis of beta –D-glucan leading synthesis of beta –D-glucan leading to lysis and cell death.to lysis and cell death.

Caspofungin, micafungin and Caspofungin, micafungin and anidula fungin come in this category.anidula fungin come in this category.

DRUGS FOR CUTANEOUS DRUGS FOR CUTANEOUS MYCOTIC INFECTIONSMYCOTIC INFECTIONS

TERBINAFINETERBINAFINE The drug of choice for treating The drug of choice for treating

dermatophytoses and onchomycoses.dermatophytoses and onchomycoses. Inhibits fungal squaline epoxidase thereby Inhibits fungal squaline epoxidase thereby

decreases the synthesis of ergosterol.decreases the synthesis of ergosterol. Primarily fungicidal.Primarily fungicidal. Limited to dermatophytes and C.albicans. Limited to dermatophytes and C.albicans.

Therapy is for 3 monthsTherapy is for 3 months

GRISEOFULVINGRISEOFULVIN Causes disruption of mitotic spindle and Causes disruption of mitotic spindle and

inhibition of fungal mycosis.inhibition of fungal mycosis. Therapy is for 6 -12 months.Therapy is for 6 -12 months. Induces hepatic cytochrome p450 activity.Induces hepatic cytochrome p450 activity. Indication for dermatophytes, tinea.Indication for dermatophytes, tinea. Se : allergy, hepatotoxicitySe : allergy, hepatotoxicity CI Acute intermittent porphyriaCI Acute intermittent porphyria Alcohol consumption strictly restricted.Alcohol consumption strictly restricted.

NYSTATINNYSTATIN

Polyene antibiotic.Polyene antibiotic. Structure and chemistry resembles Structure and chemistry resembles

amphotericin b.amphotericin b. Restricted to topical treatment of Restricted to topical treatment of

candida candida Because of systemic toxicity never Because of systemic toxicity never

given parenterally.given parenterally.

MICONAZOLEMICONAZOLE

Topically active drugs that are only rarely Topically active drugs that are only rarely administered parenterally because of their administered parenterally because of their severe toxicity. The mechanism of action severe toxicity. The mechanism of action is same as that of ketoconazole.is same as that of ketoconazole.

Topical use is associated with contact Topical use is associated with contact dermatitis.dermatitis.

Potent inhibitor of warfarin metabolism Potent inhibitor of warfarin metabolism and has resulted in bleeding, even on and has resulted in bleeding, even on topical application.topical application.