DD Antifungals Flashcards
Polyenes
Amphotericin B (Fungizone)
Nystatin (Mycostatin)
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
ROA of
Amphotericin B (Fungizone)
Nystatin (Mycostatin)
Amphotericin B (Fungizone) - IV, Topical Nystatin (Mycostatin) - Topical
Route of excretion of Polyenes
Amphotericin B (Fungizone) Nystatin (Mycostatin)
- Mainly through biliary tract (slow renal)
Spectrum of use: Amphotericin B (Fungizone)
Broad spectrum,
opportunistic
and systemic
Spectrum of use: Nystatin (Mycostatin)
Candidal infections of:
skin,
mucous membranes,
GI/Vaginal tract
Pharmacokinetic properties of Amphotericin B (Fungizone)
Rapidly sequestered in tissues,
little released to CNS,
λ = 15 days (terminal)
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
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)
Adverse rxn of Nystatin (Mycostatin)
Mild and transient GI upset
Echinocandins (3)
Anidulafungin (Eraxis)
Capsofungin (Cancidas)
Micafungin (Mycamine)
MOA of Echinocandins
Inhibit synthesis of β (1,3) D-glucan, disrupt cell wall synthesis.
High selective toxicity
ROA of Echinocandins
IV
Route of Excretion of Echinocandins
Renal & Hepatic
Spectrum of Echinocandins
Broad spectrum.
Invasive candida
Invasive aspergillosis
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)
Adverse rxns of echinocandins?
Histamine-mediated symptoms (rash, facial swelling)
and nausea, vomiting, headache , fever, phlebitis
Which antifungal is best used in patients with aspergillosis that are refractory or intolerant to other therapies (amphotericin B, itraconazole)?
Echinocandins
Triazoles
Fluconazole (Diflucan)
Itraconazole (Sporanox)
Voriconazole (Vfend)
Terconazole (Terazole)
MOA of triazoles
-Fungistatic or cidal?
Fungistatic - highly specific
inhibition of fungal cytochrome P450 = ↓ Ergosterol synthesis.
Which triazole is administered topically?
Terconazole (Terazole)
rest are oral
Which triazole is excreted via hepatic?
Itraconazole (Sporanox)
Voriconazole (Vfend)
Terconazole (Terazole)
*Fluconazole (Diflucan) is the only renal one
Spectrum of Use: Fluconazole (Diflucan)
Candidiases (vaginal, esophageal, oropharyngeal)
Spectrum of Use: Itraconazole (Sporanox)
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
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
