Chapter 24: Infectious Diseases III Flashcards
Amphotericin B MOA
Binds to ergosterol, altering cell membrane permeability and causing cell death.
Amphotericin B deoxycholate
Conventional form has many toxicities. Lipid formulations have active medication and lipid components and have fewer toxicities (decreased infusion rxns and nephrotoxicity)
Amp B active against
- Yeasts: most candida (cryptococcus neoformans)
- Molds: Aspergillus species
- Dimorphic fungi
Amp B boxed warning
Med errors confusing the lipid formula and conventional have resulted in cardiopulmonary arrest and death.
Conventional doses should not exceed 1.5mg/kg/day (verify product and dose)
Amp B SE and notes
SE: infusion related fever, chills, headache, nausea, malaise, rigors. Decreased K, Mg, and nephrotoxicity
Notes: D5W only! lipid formulas must be filtered. Conventional requires pre-medication to reduce infusion related rxns (apap, nsaid, diphenhydramine and/or hydrocortisone)
Flucytosine MOA
Penetrates fungal cells and is converted to fluorouracil, which competes with uracil, interfering with fungal RNA and protein synthesis.
Flucytosine Uses
Should NOT be used alone!
Recommended in combination with Amp B for treatment of invasive cryptococcal meningitis or candida infections
Flucytosine SE
Dose related myelosuppression (anemia, neutropenia, thrombocytopenia)
Azole Antifungals MOA
Decrease ergosterol synthesis and cell membrane formation. Azoles are inhibitors of CYP450 (mainly 3A4) and have significant drug interactions
Fluconazole Activity Against
C. albicans, C. parapsilosis and C. tropicalis.
Limited efficacy against C. galbrata and C. krusei is considered fluconazole resistant
Itraconazole Uses
Dimorphic fungi Blastomycosis and Histoplasmosis and nail bed infections
Voriconazole Uses
Drug of choice for Aspergillus
Fluconazole Dosing
50-800mg PO/IV daily
Vaginal Candidiasis 150mg po once
IV/PO ratio is 1:1
Itraconazole Boxed Warnings
Can worsen or cause HF; do NOT use to treat pts with onychomycosis in pts with ventricular dysfunction of HF
Can increase plasma concentrations of certain drugs and can lead to QT prolongation and ventricular tachyarrhythmias
Ketoconazole Boxed Warnings
Hepatotoxicity, QT prolongation
Use of oral tablets ONLY when other effective antifungal therapy is unavailable or not tolerated and benefit outweighs risks
Azole Antifungal Notes
All azoles are cleared hepatically except fluconazole which requires renal dose adjustment.
Fluconazole and Voriconazole penetrate CNS adequately to treat fungal meningitis
Voriconazole Warnings
CrCl <50ml/min the IV vehicle SBECD accumulates and oral is preferred. Monitor SCr
Hepatotoxicity, visual disturbances, (optic neuritis), phototoxicity, QT prolongation
Voriconazole Side Effects
Visual changes, increased LFTs and SCr, CNS toxicity (hallucinations)
Voriconazole Notes
Vfend: take on an empty stomach at least 1 hour before or after a meal. hold tube feedings for 1hr before and after doses
Caution while driving at night
Avoid direct sunlight
Posaconazole Dosing, Warnings
Noxafil
- given daily with food
- eGFR<50ml/min IV vehicle SBECD can accumulate
- QT prolongation
Isavuconazonium sulfate CI, Notes
Cresemba (prodrug of isavuconazole)
QT shortening
Requires a filter
Echinocandin MOA
Inhibit synthesis of beta (1,3)-D-glucan and essential component of the fungal cell wall
Echinocandin Uses
Effective against most candida species, including non-albicans strains resistant to azoles (c. glabrata, C. krusei). Used in combination against aspergillus.
Available ONLY as injections
Echinocandin Drugs
- Caspofungin (cancidas)
- Micafungin (mycamine)
Echinocandin Warnings, Notes
Warnings: histamine-mediated symptoms
Notes: all given once daily and do not require renal dose adjustment
Griseofulvin CI, SE, Notes
CI: pregnancy
SE: photosensitivity, increased LFTs
Notes: take with a fatty meal to increase absorption or with food/milk to avoid GI upset
Empiric Treatment for Fungal Pathogens: C. albicans (oropharyngeal) thrush
Mild disease: topical antifungals (clotrimazole, miconazole) (alternative: nystatin)
Moderate to severe or HIV+: fluconazole
Empiric Treatment for Fungal Pathogens: C. albicans (esophageal)
Fluconazole
Alternative: echinocandin
Empiric Treatment for Fungal Pathogens: C. krusei and glabrata (all candida blood stream infections)
Echinocandin
Alternative: Amp B, high-dose fluconazole
Empiric Treatment for Fungal Pathogens: Aspergillus (invasive)
Voriconazole
Alternative: Amp B, Isavuconazonium
Empiric Treatment for Fungal Pathogens: Cryptococcus neoformans (meningitis)
Amp B + Flucytosine
Alternative: high-dose fluconazole + flucytosine
Empiric Treatment for Fungal Pathogens: Dermatophytes (nail bed infection)
Terbinafine or itraconazole
Alternative: Fluconazole
Neuraminidase Inhibitors MOA
Oseltamivir, zanamivir and peramivir
Reduce the amount of virus in the body by inhibiting the enzyme which enables release of new viral particles from infected cells
Oseltamivir Dosing
Tx age >12 years: 75mg bid for 5 days
Prophylaxis age >12 years: 75mg qd for 10 days
Warnings: neuropsychiatric events
Zanamivir Dosing
Relenza Diskhaler
TX >7 years: 10mg (two 5mg inhalations) BID for 5 days
Prophylaxis age >=5 years: 10mg once daily for 10 days (household setting) or 28 days (community outbreak)
Warnings: bronchospasm (do not use in asthma, copd, or pts with breathing problems)
Endonuclease Inhibitor
Baloxavir marboxil (Xofluza) Approved for Tx and post-exposure prophylaxis; start within 48 hours of symptoms
Remdesivir MOA
Veklury
Inhibits RNA-dependent RNA polymerase which is needed for viral replication
Indicated in hospitalized adults and children >+12 years who weigh at least 40kg
HSV-1 Associated With
Oropharyngeal disease
HSC-2 Associated With
Genital disease
Antivirals for Herpes Simplex and Varicella Zoster
Acyclovir (Zovirax)
Valacyclovir (Valtrex)
Acyclovir and Valacyclovir Warnings, Notes
Warnings: caution in patients with renal impairment, the elderly, and those receiving nephrotoxic agents
Notes: acyclovir dose is based on IDW even in obese patients
Topical Tx for Herpes Labialis
Docosanol (abreva): apply 5 times daily at first sign of outbreak
Acyclovir (zovirax): apply 5 times daily for 4 days
Invasive HSV Infections Tx
IV acyclovir
Herpes Zoster Tx
Acyclovir: 800mg po 5 times daily for 7 days
Valacyclovir: 1 gram po tid for 7 days
Cytomegalovirus Tx
Ganciclovir (cytovene injection)
Valganciclovir (valcyte) (prodrug)
Boxed warning: Myelosuppression
Solution must be stored in fridge
Resistant CMV
Foscarnet (foscavir)
CMV retinitis, resistant HSV
Boxed Warning: renal impairment (pre-hydration recommended)
