Systemic Antifungal

DOC for most systemic infections (sometimes in combo)

Use: Most broad spectrum antifungal agent

Mechanisms: interacts with ergosterol (doesn't inhibit ergosterol), leading to formation of membrane pores and loss of intracellular components; also impairs AA uptake inhibiting protein synth.

PHK: IV, excreted slowly by kidney and extrarenal; 

Adverse effects: Renal (dose dependent)/hepatic impairment and hemodialysis does not remove it; may bind human cholesterol; 2 classes

1) Infusion related tox: chills, fever, muscle spasm, headache

2) Cumulative related tox: nephrotoxicity, variable azotemia (high N levels in blood); is dose dependent; hepatic failure, hypersensitivity

Interactions: Aminoglycosides (nephrotoxic) should be given with great caution

Systemic Antifungal

DOC for Cryptococcus neoformans (w/ amphotercin B = synergistic)(Meningitis)

Use: Candida, aspergillus fumigatus, Sporotrichum schenkii and more

Mechanisms: Metabolic antagonism of fungal DNA and RNA; converted to 5-fluorouracil with interferes with fungal DNA and RNA synthesis (and therefore protein synth

PHK: Oral, kidney elimination, enters CSF (hence use with amphotercin B which does not)

Adverse effects: BM depression, GI disturbances (disturbes normal flora), may elevate LFTs (reversible on discontinuation)

Interactions:

Systemic Antifungal: "Azole"

Use: Broad spectrum antifungal; Paracoccidioidomycosis, blastomycosis, cocci, microsprum, histoplasmosis, trichophyton, chromomycosis, epidermophyton, chronic mucocutaneous candidosis

Mechanisms: Inhibit production of ergosterol via inhibition of fungal cytochrome P450 enzyem (lanosine 14a-demethylase) which converts lanosterol to ergosterol; causes accumulation of toxic intermediate leading to membrane permeability and inhibitions of growth (fungistatic)

PHK: low CNS penetration, hepatic elimination, Oral

Adverse effects: all azoles affect mammalian CYP450 to some degree = Dx interactions; gynecomastia, inhibition of adrenal and testicular function

Interactions: other azoles

Systemic Antifungal: "Azole"

Use: Cryptococcal meningitis (replacement after amphotericin B tx), various candidiasis (AIDS, organ transplant, cancer pts); also aspergillus, blastomyces, dermatitides, candida albicans, cryptococcus neoformans, coccidioides immitis, histoplasma capsulatum; less toxic than amphotercin B or flucytosine/better tolerated than ketoconazole

Mechanisms: Inhibit production of ergosterol via inhibition of fungal cytochrome P450 enzyem (lanosine 14a-demethylase) which converts lanosterol to ergosterol; causes accumulation of toxic intermediate leading to membrane permeability and inhibitions of growth (fungistatic)

PHK: penetrates well into CSF (fungal meningitis) lower binding affinity for CYP450

Adverse effects: LEAST TOXIC; less toxic than amphotercins B or flucytosine; better tolerated than ketoconazole; nausea; diarrhea

Interactions: less than other azoles

Systemic Antifungal: "Azole"

DOC: Aspergillus (with Amphotercin B)

Use: Works against molds (fluconazole doesn't); invasive aspergillosis, salvage therapy for Scedosporium sp. Fusarium sp.

Mechanisms: Inhibit production of ergosterol via inhibition of fungal cytochrome P450 enzyem (lanosine 14a-demethylase) which converts lanosterol to ergosterol; causes accumulation of toxic intermediate leading to membrane permeability and inhibitions of growth (fungistatic)

PHK: IV and oral

Adverse effects: VISUAL IMPAIRMENT (reversible on discontinuation)

Interactions: NUMEROUS

Systemic Antifungal: "Azole"

Use: blastomyces dermatitidis, histoplasma capsulatum, onychomycosis, esophageal candidiasis, orpharyngeal candidiasis

Mechanisms: Inhibit production of ergosterol via inhibition of fungal cytochrome P450 enzyem (lanosine 14a-demethylase) which converts lanosterol to ergosterol; causes accumulation of toxic intermediate leading to membrane permeability and inhibitions of growth (fungistatic)

PHK: Capsule (90-100% with meal/cola); Oral solution (72% on fasting conditions); KNOW THAT THESE ARE FLIPPED!

Adverse effects: GI, rash

Interactions: inhibits CYP3A4

Systemic Antifungal: "Fungin" = echinocandin; "penicillins of antifungals"

Use: Invasive Aspergillosis in refractory pts (amphotericin B and azole-resistant), also esophageal candidiasis

Mechanisms: inhibits synth of major fungal cell wall component B(1,2)-D-Glucan; cidal

PHK: IV (slow), eliminated by liver

Adverse effects: Elevated LFTs

Systemic Antifungal: "Fungin" = echinocandins

Use: esophageal candidiasis; Candida prophylaxis in hematopoietic stem cell transplant pts

Mechanisms: inhibits synth of major fungal cell wall component B(1,2)-D-Glucan; cidal

Systemic Antifungal: "Fungin" Echinocandins

Use: esophageal candidiasis and other serious yeast and fungal infections

Mechanisms: inhibits synth of major fungal cell wall component B(1,2)-D-Glucan; cidal

PHK: IV

Local/topical Antifungal

Use: Systemic treatment of dermatophytosis (mycosis of skin, hair, nails, athlete's foot); Epidermophyton, microsporum, trichophyton

Mechanism: Binds to microtubules of certain fungi and destroys the mitotic spindle structure; fungistatic; binds to keratin; prevents infection in new skin structures

PHK: poor absorption (a good thing)

Contraindications: acute intermittent porphyria, hepatocellular failure, pregnancy

Local/topical Antifungal; azole like

Oral or topical; 

Mechanism: Like azoles, inhibit ergosterol synthesis; 

Fungicidal against dermatophytes, NOT candida

Used for onychomycosis; Well absorbed

No need for dosage adjustments in pts with hepatic or renal impairment

Local/topical antifungal

Use: Candidal infections of skin, GI, or mucous membran (vaginal tablets);  Candida, Cryptococcus, Histoplasma, Blastomycoces, Trichophyton, Epidermophyton, Microsporum audouinii

Mechanism: Polyene antibiotic (like amphotericin B); binds sterol, increasing membrane permeability (leakage/cell death

PHK: Oral or topical

Topical Antifungal

Other Drug: Econazole (Spectazole®)

Topical Antifungal: OTC

Use: Trichophyton, Epidermophyton, Microsporum, Candida, Cryptococcus, Aspergillus; Tinea pedis, vulvovaginal candida; tinea versicolor

Mechanism: like other azoles

Other Drugs: Oxiconazole (Oxistat®)

Sulconazole (Exelderm®)

Terconazole (Terazol®) 

Topical Antifungal

Vaginal candida infections

Azole mechanims

Topical Antifungal

Broad spec antifungal; similar to terbinafine; interferes with steropl biosynthesis

athletes foot