Anti fungal drugs

Polyene mechanism of action

Bind to ergosterol → form pores → Disrupt membrane → Electrolyte leakage → cell death

Polyene drugs

Amphotericin B, nystatin

Azole drugs

___zole: Clotrimazole, Fluconazole, Itraconazole, Ketoconazole, Voriconazole

Allylamines drugs

Terbinafine

Echinocandins drug examples

Capsofungin

Amphotericin B indication

DRUG OF CHOICE in life threatening infection used for:

• Candida spp

• H. capsulatum

• Cryptococcus

• Aspergillus

Amphotericin B adverse effects

IV related: Fever/chill, hypotension, thrombophlebitis

NEPHROTOXIC → Need dose adjustment in renal dysfunction

How to prevent amphotericin B toxicity

Bolus normal saline before and after infusion

Nystatin indication

Candida of GI and superficial → No IV due to systemic and nephrotoxicity

Azole mechanism of action

Fungistatic → Inhibit CYP450 → No demethylation of lanosterol to ergosterol → No cell growth

Azole contraindications

Pregnancy → Teratogenic efffect

Classes of azoles

Triazoles: fluconazole, itraconazole, voriconazole

Imidazoles: clotrimazole, ketoconazole

Fluconazole indications

C. neoformans and cryptococcal meningitis DRUG OF CHOICE, C albicans and parapsilosis

Fluconazole AE

Hepatotoxicity

Itraconazole indication

Sporotrichosis and histoplasmosis

Itraconazole adverse effect

Hepatotoxicity (less that fluconazole), renal impair need renal adjustment

Voriconazole indication

INVASIVE candidiasis, scedosporium and fusarium spp; REPLACE AmphoB for aspergillosis infection

Voriconazole AE

Hepatotoxic + many drug interaction

Ketoconazole indication

Mucocutaneous candidiasis and dermatophytes; oral is active against most fungi and yeast but not aspergillus spp

Ketoconazole drug interactions

Increase toxicity of cyclosporine, phenytoin, triazolam, and warfarin; SHOULD NOT be used with amphoB → decrease amphoB function

Squalene epoxidase inhibitor drugs

Terbinafine, naftifine, butenafine

Squalene epoxidase inhibitor mechanism of action

Inhibit Squalene epoxidase → Block ergosterol synthesis → Squalene accumulation → Increased cell permeability → cell death

What is oral terbinafine used for

Dermatophyte esp onychomyosis

Terbinafine, Naftifine, Butenafine indication

Any type of Tinea

Echinocandin drugs

__fungin: caspofungin, micafungin, anidulafungin

Echinocandin mechanism of action

Competitively bind to of β(1,3)-d-glucan synthase → No cell wall synthesis → Cell death

Echinocandins indication

Cidal → Used for most Candida spp and aspergillus; second line for AmphoB and fluconazole resistance

AE of echinocandins

Well tolerated but may cause: histamine like reaction, phlebitis, fever, rash etc

NOT approved for pregnancy

5-FU mechanism of action

Enter through cytosine permease → Activate by cytosine deaminase from 5-FC into 5-FU

Use of 5-FU

Combined with other drug; use for C. neoforms and C albicans meningitis

Flucytosine AE

GI, reversible hepatic dysfunction, neutropenia, thrombocytopenia and bone marrow depression (do not use in cancer Px)

Griseofulvin mechanism of action

Static → Disruption of mitotic spindle and inhibition of mitosis

Griseofulvin indication

Dermatophysis of skin, nail, hair, scalp → Need long duration of treatment

Contraindication of griseofulvin

Pregnancy (cause birth defect) and porphyria Px (make prophyrin)

Griseofulvin and warfarin interaction

Increase CYP450 action → Increase warfarin metabolism

Ciclopirox mechanism of action

inhibit transport of element to fungal cell → Disrupt DNA, RNA and protein synthesis

Ciclopirox indication

Trichophyton, Epidermophyton, Microsporum, Candida, and Malassezia; use for any tinea and seb derm

Tolnaftate mechanism of action

Distort hyphae and inhibit growth

Tolnaftate indication

Epidermophyton, Microsporum, and Malassezia furfur; tinea pedis/curis/corporis