For Echinocandins: what do we do to dose if: 1. Pt has hepatic insufficiency? 2. Pt has renal dysfunction? 3. Pt is taking CYP450 inducer?

1. reduce dose (liver can't break it down fast enough) 2. no dose change needed 3. Increase (bc it gets processed too fast)

DD Antifungals Flashcards by Nebuchadnezzer II

Polyenes

Amphotericin B (Fungizone)

Nystatin (Mycostatin)

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MOA of:
Amphotericin B (Fungizone)
Nystatin (Mycostatin)

do they display selective toxicity?

Binds to ergesterol in fungal cell membrane pores = leakage of cellular material and eventual death.

Not super selective toxicity because it binds to cholesterol in mammal cells

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ROA of
Amphotericin B (Fungizone)
Nystatin (Mycostatin)

Amphotericin B (Fungizone) - IV, Topical
Nystatin (Mycostatin) - Topical

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Route of excretion of Polyenes

Amphotericin B (Fungizone)
Nystatin (Mycostatin)

Mainly through biliary tract (slow renal)

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Spectrum of use: Amphotericin B (Fungizone)

Broad spectrum,
opportunistic
and systemic

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Spectrum of use: Nystatin (Mycostatin)

Candidal infections of:
skin,
mucous membranes,
GI/Vaginal tract

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Pharmacokinetic properties of Amphotericin B (Fungizone)

Rapidly sequestered in tissues,
little released to CNS,

λ = 15 days (terminal)

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Adverse rxn of Amphotericin B (Fungizone)

VERY TOXIC DRUG!!!

1) Nephrotoxicity - main issue, nearly all patients get this
2) Infusion-related toxicity - chills, fever, vomiting with IV use
3) Anemia - 75% due to BM depression

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Pharmacotherapeutic Advantages of polyenes

Drug of choice for life-threatening systemic fungal infections.

-Used as initial therapy, then replaced with azoles
(gotta watch out for nephrotoxicity)

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Adverse rxn of Nystatin (Mycostatin)

Mild and transient GI upset

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Echinocandins (3)

Anidulafungin (Eraxis)

Capsofungin (Cancidas)

Micafungin (Mycamine)

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MOA of Echinocandins

Inhibit synthesis of β (1,3) D-glucan, disrupt cell wall synthesis.
High selective toxicity

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ROA of Echinocandins

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Route of Excretion of Echinocandins

Renal & Hepatic

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Spectrum of Echinocandins

Broad spectrum.
Invasive candida
Invasive aspergillosis

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For Echinocandins: what do we do to dose if:

Pt has hepatic insufficiency?
Pt has renal dysfunction?
Pt is taking CYP450 inducer?

reduce dose (liver can’t break it down fast enough)
no dose change needed
Increase (bc it gets processed too fast)

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Adverse rxns of echinocandins?

Histamine-mediated symptoms (rash, facial swelling)

and nausea, vomiting, headache , fever, phlebitis

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Which antifungal is best used in patients with aspergillosis that are refractory or intolerant to other therapies (amphotericin B, itraconazole)?

Echinocandins

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Triazoles

Fluconazole (Diflucan)
Itraconazole (Sporanox)
Voriconazole (Vfend)
Terconazole (Terazole)

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MOA of triazoles

-Fungistatic or cidal?

Fungistatic - highly specific

inhibition of fungal cytochrome P450 = ↓ Ergosterol synthesis.

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Which triazole is administered topically?

Terconazole (Terazole)

rest are oral

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Which triazole is excreted via hepatic?

Itraconazole (Sporanox)
Voriconazole (Vfend)
Terconazole (Terazole)

*Fluconazole (Diflucan) is the only renal one

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Spectrum of Use: Fluconazole (Diflucan)

Candidiases (vaginal, esophageal, oropharyngeal)

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Spectrum of Use: Itraconazole (Sporanox)

Study These Flashcards

Broad spectrum. Aspergillosis, histoplasmosis, sporotrichosis.

Spectrum of Use: Voriconazole (Vfend)

aspergillosis

Spectrum of Use: Terconazole (Terazole)

Broad spectrum

What do we do to dosing if renal is impaired and we are using: Fluconazole (Diflucan)? Itraconazole (Sporanox)?

Fluconazole (Diflucan) - reduce dosing Itraconazole (Sporanox) - dosing dont matter yo, its hepatic excretion

Which antifungals can enter CNS?

Fluconazole (Diflucan) - A triazole ergosterol synthesis inhibitor Flucytosine (Ancobon) - a nucleic acid inhibitor

Pharmacokinetic properties of triazoles? | which one is best absorbed with food?

All are 30-40 hours Itraconazole (Sporanox) - better absorbed w/ food -

Adverse rxn of triazoles?

Very well tolerated Some-ish GI distress, rash, headaches. Worse in HIV pts

Which triazole can have transient visual changes?

Voriconazole (Vfend)

Triazole Best for vaginal candidiases when patients have failed topical treatment

Fluconazole (Diflucan)

Drug of choice if systemic drug needed for dermatophytoses and onychomycosis

Itraconazole (Sporanox) *note: oral terbinafine is also used for onychomycosis

Drug of choice for serious invasive aspergillosis

Voriconazole (Vfend)

Imidazoles

Ketoconazole (Nizoral) Clotrimazole (Lotrimin) Miconazole (Monistat)

MOA of imidazoles | -Fungistatic or -cidal?

Inhibits P450-dependent enzyme (14α-demethylase) = ↓ ergesterol levels. Alters membrane permeability. Fungistatic/-cidal depending upon concentration

Route of administration of imidazoles: Ketoconazole (Nizoral) Clotrimazole (Lotrimin) Miconazole (Monistat)

Ketoconazole (Nizoral) - Oral, IV and Topical Clotrimazole (Lotrimin) - Topical Miconazole (Monistat) - Topical

Route of excretion of Imidazoles

Hepatic and Breast Milk - remember amantadine and rimantadine (antivirals) are also excreted in breast milk

Ketoconazole (Nizoral) Spectrum

Broad spectrum. Chronic mucocutaneous candidiasis, systemic fungal infections

Clotrimazole (Lotrimin) Miconazole (Monistat) - Spectrum

Oral and vaginal candidiasis

Which category of antifungals : | may antagonize amphotericin; poorly absorbed, maximal at low pH; crosses placenta

Imidazoles

Imidazoles: Adverse Reactions

1) Anorexia, nausea, rash, dizziness, 2) hepatotoxicity - avoid if liver dysfunction, 3) Teratogenic. NO PREGNANCY. 4) inhibit mammalian testosterone synthesis → gynecomastia, decreased libido

MOA of: Terbinafine (Lamisil) | - fungistatic or cidal?

Interferes with ergesterol synthesis by inhibiting squalene oxidase. Fungicidal

MOA of: Flucytosine (Ancobon)

Converted to 5'fluorouracil which interferes with DNA synthesis and causes cell death. High selective toxicity

MOA of: Griseofulvin (Fulvicin) | - Fungistatic or cidal?

Binds microtubules inhibiting mitosis. Interferes with cell wall components. Fungistatic

MOA of: Pentamidine (Pentam)

Inhibits protein and nucleic acid synthesis

Fungi lacking cytosine deaminase can cause resistance against which drug?

Flucytosine (Ancobon) - remember it gets converted to 5'fluorouracil which interferes with DNA synthesis and causes cell death.

ROA of : Terbinafine (Lamisil) Pentamidine (Pentam)

Terbinafine (Lamisil): Oral or Topical Pentamidine (Pentam): IV, IM, and Inhalation

Route of Excretion Terbinafine (Lamisil) Griseofulvin (Fulvicin)

Terbinafine (Lamisil): Hepatic | Griseofulvin (Fulvicin): Fecal

Spectrum of Use: Terbinafine (Lamisil)

Oral = onychomycosis; Topical = athlete's foot (tinea cruris corporis)

Spectrum of Use: Flucytosine (Ancobon)

treat serious infxn of: cryptococcosis, candidiasis, chromoblastomycosis

Spectrum of Use: Griseofulvin (Fulvicin)

Severe dermatophytosis (superficial) skin, hair, nails

Spectrum of Use: Pentamidine (Pentam)

Broad spectrum against protozoa

Adverse Reactions: | Terbinafine (Lamisil)

Rash, GI upset, headache, taste disturbances

Adverse Reactions: | Flucytosine (Ancobon)

skin rashes | prolonged use →bone marrow suppression

Adverse Reactions: | Griseofulvin (Fulvicin)

Hypersensitivity, GI upset, headache, mental confusion

Which 3 antifungals interferes with CYP450 drug metabolism?

Triazoles Imidazoles Terbinafine

Which antifungal is teratogenic?

Imidazoles! Griseofulvin

Which antifungal is best for P. jirovici pneumonia in AIDS?

Pentamidine

DD Antifungals Flashcards

(59 cards)