Infectious Disease 3: Antifungals & Antivirals Flashcards
What are the 3 Fungal classifications?
Systemic Fungal Infections
- Yeasts
- Molds
- Dimorphic species ~ mold in cold, yeast in heat
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Mucormycosis is an invasive fungal disease
What species causes Mucormycosis?
Systemic Fungal Infections
Zygomycetes ~ mold fungi made up of Mucor & Rhizopus species
RxPrep p 389
What species are classified as Yeast?
Fungal Classifications
- Candida species
- Cryptococcus neoformans
C. albicans, tropicalis, parapsilosis, glabrata, krusei
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What species are classified as Molds?
Fungal Classifications
- Aspergillus species
- Zygomycetes (Mucor & Rhizopus)
AZMR
RxPrep p 389
What fungi are classified as Dimorphic?
Fungal Classifications
- Histoplasma capsulatum
- Blastomyces dermatitidis
- Coccidioides immitis
HBC ~ mold in the cold, yeast in the heat
RxPrep p 389
What is Amphotericin B active against?
Ergosterol Binder
- Broad Spectrum; used for initial treatment
- Active against almost all fungi
- Cryptococcus neoformans & Aspergillus
Yeast & Mold
RxPrep p 390
Which Amphotericin B formulation has fewer toxicities?
Ampho B deoxycholate vs. Ampho B lipid formulations
- Lipid formulations - less infusion rxns & less nephrotoxicity
Ampho B deoxycholate is conventional formulation & more toxic
RxPrep p 390
What is the Brand Name?
Liposomal Amphotericin B
Injection
AmBisome
Injection
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What are Boxed Warnings for Ampho B Deoxycholate & AmBisome?
Injections
- Cardiopulmonary Arrest
- Deoxycholate ~ NO > 1.5 mg/kg/day
Deoxycholate = Conventional Formulation
RxPrep p 390
What are Side Effects of Amphotericin B?
All Injection Formulations
- Infusion Reactions - fever, chills, headache, malaise, rigors
- low K, low Mg, nephrotoxicity
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What are key Prep & Admin notes for Amphotericin B?
Injections
- D5W compatibility only!
- lipids must be filtered during prep!
- Deoxycholate requires pre-meds for infusion risk!
Pre-meds: APAP or NSAID + Benadryl +/- Hydrocortisone
What is Flucytosine converted to, and when is it usually indicated for?
Flucytosine, 5-FC (Ancoban)
- Converted to Fluorouracil
- Due to resistance, NOT used alone!
- Combo w/ Ampho B for invasive cryptococcal meningitis
SE: myelosuppression! (anemia, neutropenia, thrombocytopenia)
RxPrep p 390
3 Key Issues with Azole Antifungals
Class Effects
- Increase LFTs
- QT prolongation (except isavuconazonium)
- Drug Interactions (CYP3A4 inhibitors)
IV Administration: IV:PO ratio is 1:1 for ALL AZOLES!
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Azole Antifungals decrease ergosterol synthesis
Fluconazole (Diflucan)
Activity, Dosing, & Drug-Specific Concerns
- C. krusei is fluconazole-resistant
- Nail-bed infxns (onychomycosis); oral & vaginal yeast infxns; oral thrush (candidiasis) w/ white, sore patches; fungal meningitis
- Vaginal candidiasis: 150 mg PO x 1 dose
- only azole that requires renal dose adjustment
- Inhibits CYP2C9: increased WARFARIN effects
PENETRATES CNS TO TREAT FUNGAL MENINGITIS
RxPrep p 391
Azole Antifungals decrease ergosterol synthesis
Itraconazole (Sporanox capsules)
Activity, Dosing, & Drug-Specific Concerns
- Main use: Nail-bed infxns
- BBWs: HEART FAILURE; QT prolong & ventricular tachyarrhythmias (d/t increasing other drug plasma concentrations)
- Absorption requires an acidic gut (higher pH, lower absorption)
Capsules: take with food; Solution: take on empty stomach
RxPrep p 391
Azole Antifungals decrease ergosterol synthesis
Ketoconazole Topical (Nizoral A-D OTC)
Activity, Dosing, & Drug-Specific Concerns
- BBW: Hepatotoxicity leading to liver transplants; QT prolongation; use PO only when other antifungal therapy is unavailable or not tolerated
- PO absorption requires acidic gut (higher pH, lower absorption) - if PPIs/H2RAs used, take with acidic bev (non-diet cola) to provide acidic environment
Tablet, cream, foam, gel, shampoo
RxPrep p 391
Azole Antifungals decrease ergosterol synthesis
Voriconazole (Vfend)
Activity, Dosing, & Drug-Specific Concerns
- TOC for Aspergillus
- CrCl < 50 ~ IV vehicle SBECD accumulates, so PO preferred (monitor SCr with IV formulation)
- Hepatoxicity, visual disturbances (optic neuritis), phototoxicity, CNS toxicity (hallucinations), QT prolongation
- Take PO on empty stomach; caution driving at night; avoid direct sunlight
Tablet, suspension, injection - store reconstituted PO susp at room temp
RxPrep p 392
Azole Antifungals decrease ergosterol synthesis
Posaconazole (Noxafil)
Acitivity, Dosing, & Drug-Specific Concerns
- CrCl < 50, IV vehicle SBECD accumulates, so PO preferred
- QT prolongation warning
- Tablet not equal to suspension dose; take both with food
DR tablet, suspension, injection
RxPrep p 392
Azole Antifungals decrease ergosterol synthesis
Isavuconazonium Sulfate
Activity, Dosing, & Drug-Specific Concerns
- Prodrug to isavuconazole
- QT shortening! (not prolonging)
- Requires filter during admin d/t possible particulates
capsule, injection
RxPrep p 392
Echinocandins
MOA, Activity, Dosing, & Class Concerns
- Inhibit synthesis of beta (1,3)-D-glucan within the fungal cell wall
- Effective against most Candida species
- Injections only! all given once daily with no renal dose adjustments required
- Histamine-mediated symptoms warning
Caspofungin, Micafungin, Anidulafungin
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Caspofungin
Brand Name
- Cancidas
- SJS/TEN severe skin rxns
Echinocandin
RxPrep p 393
Micafungin
Brand Name & Indication
- Mycamine
- Candidemia 100mg IV
- Esophageal candidiasis 150mg IV