ID III: Antifungals & Antivirals Flashcards
Fungi are classified as either:
yeasts, molds, or dimorphic
Candida species:
C. albicans, C. krusei, C. tropicalis, Cryptococcus neoformans are examples of
Yeasts (exist in the heat)
Aspergillus species, Zygomycetes (Nucor and rhizopus species) are examples of:
Molds (exist in the cold)
Histoplasma capsulatum, Blastomyces dermatitidis, and coccidiodes immitis are examples of
dimorphic fungi
Zygomyctes refers to a class of fungi which includes Mucor species and Rhizopus species; invasive disease with this group is commonly called
mucormycosis
The most susceptible Candida species:
More difficult to treat due to resistance:
Easy: C.albicans
Harder: C. glabrata and C. Krusei
MOA: binds to ergosterol, alternating cell membrane permeability and causes cell death
Amphotericin B
Which form of Amphotericin B has few toxicities? (dec infusion reactions, dec nephrotoxicity)
The lipid formulations
Which drug is active against:
Yeast - most Candida species, Cryptococcus neoformans
Molds - Aspergillus species, Zygomycetes
Dimorphic fungi - Histoplasma capsulate, Blastomyces dermatittidis and Coccidiodes immitis
Amphotericin B
Broad-spectrum!
Brand: AmBisome
Generic: Liposomal Amphotericin B (INJ)
3-6mg/kg/day
Brand: Abelcet
Generic: Amphotericin B Lipid Complex
5mg/kg/day
Conventional amphotericin B for injection doses should not exceed 1.5mg/kg/day; verify product name and dosage. Overdose can result in:
BOXED WARNING.
Cardiopulmonary arrest
Common side effects of this drug can result in infusion-related fever, chills, headache, malaise, rigors; as well as dec K & Mg, nephrotocixicity
Amphotericin B
Preparation of Amphotericin B should be diluted in ____ ONLY.
D5W; lipid formulation must be filtered during preparation
Which formulation of Amphotericin B requires premedication to reduce infusion-related reactions? (30-60 mins prior to infusion administer Tylenol or NSAID, Benadryl and/or hydrocortison
Conventional formulation (ampho B deoxycholate)
This drug penetrates fungal cells and is converted to fluorouracil, which competes with uracil, interfering with fungal RNA and protein synthesis
Flucytosine
Brand: Ancobon
Generic: Flucytosine, 5-FC
Due to development of resistance, flucytosine should not be used alone, but is recommended for use in combination with:
amphotericin B
Flucytosine + Amphotericin B are used to treat:
invasive Cryptococcal (meningitis) or Candida infections
These drugs decrease ergosterol synthesis and cell membrane formation
Azole antifungals
This azole has activity against C. albicans, C. parapilosis and C. tropicalis; but limited efficacy against C. glabrata due to resistance & C. Krusei is completely resistant.
Fluconazole
This drug can be used for many infections including yeast (vaginal and esophageal, mouth), and nail bed infections (onychomycosis)
Fluconazole
The primary uses for this drug are for dimorphic fungi Blastomycosis and Histoplasmosis and for nail bed infections
Itraconazole
Treatment of choice for Aspergillus
Voriconazole
Key issues with Azole antifungals:
- All can cause inc ______
- All have a risk for ________; except isavuconazonium
- MANY drug interactions - CYP 3A4
inc LFTs
QT Prolongation
Only azole that requires renal dose adjustment
Fluconazole
Hepatoxicity has led to liver transplantation
Ketoconazole
Can cause HF
Itraconazole
Can cause visual changes and phototoxicity
Voriconazole
Tablet dose does not equal suspension dose (due to different bioavailability) and take w food
Posaconazole
IV to PO Ratio is what for all azoles
1:1
Drugs with sulfobutyl ether beta-cyclodextrin (SBECD) vehicle
voriconazole, posaconazole
Brand: Diflucan
Generic: Fluconazole
NOT for preggos
Fluconazole dosing for vaginal candidasis
150mg PO x1
Brand: Spranox, Tolsura
Itraconazole
Brand: Nizoral, Nizoral A-D, Extina, Xolegel
Generic: Ketoconazole
Which azoles can penetrate the CNS adequately to treat fungal meningitis
Fluconazole and voriconazole
Brand: Vfend, Vfend IV
Voriconazole
When CrCl <50ml/min, which formulation of voriconazole and posaconazole is preferred?
PO, due to the SBECD accumulation
While taking this drug, avoid direct sunlight, take on an empty stomach
Voriconazole
Brand: Noxafil
Generic: Posaconazole
Take with food
Brand: Cresemba
Generic: Isavuconazonium sulfate
Which azole drug can cause QT shortening?
Cresemba/Isavuconazonium
*requires a filter during administration
Itraconazole and ketoconazole inhibit
P-gp
Fluconazole and voriconazle inhibit CYP…
CYP2C9 and 2C19
Absorption of these azoles are pH dependent
Itraconazole and ketoconazole
inc pH will dec absorption
This drug inhibits synthesis of beta (1,3) D glucan, an essential component of the fungal cell wall
Echinocandins
These drugs are most effective against most Candida species, including non-albicans strains that are resistant to azoles (C. glabrata and C. Krusei)
Echinocandins
Brand: Cancidas
Generic: Caspofungin
Brand: Mycamine
Generic: Micafungin
Brand: Eraxis
Generic: Anidulafungin
Warnings of these drugs include a histamine-mediated symptoms
& all are given ONCE daily and do NOT require dose adjustment in renal impairment
Echinocandins
These two drugs are useful for treating mild, localized Candida infections like thrush
Nystatin suspension and clotrimazole troches/lozenges
Nystatin is available in what drug formulations
Suspension and tablet, topical forms
Yes- you swallow for oral candidasis
This drug is indicated for fungal infections of the skin, hair, and nails BUT has photosensitivity and can inc LFTs. Take with a fatty meal to inc absorption
C/I in preg
Griseofulvin
Brand: Lamisil AT
Generic: Terbinafine
This drug has warnings for hepatoxicity; side effects include headache and inc LFTs. The topical forms come in Rx and OTC
Terbinafine
This drug comes in troche/lozenge and topical and vaginal forms (Mycelex)
Clotrimazole
This drug can increase metabolism of hormonal contraceptives which can lead to OC failure
Griseofulvin
What is the preferred regimen for:
Pathogen: Candida albicans
oropharyngeal infection (thrush), mild disease
Topical antifungals (clotrimazole, miconazole)
Alt: nystatin
What is the preferred regimen for:
Pathogen: Candida albicans -
oropharyngeal infection (thrush), mod-severe or HIV+ disease
fluconazole
Alt: nystatin
What is the preferred regimen for:
Pathogen: Candida albicans
esophageal infection
Fluconazole
Alt: Echinocandin
What is the preferred regimen for:
Pathogen: Candida Krusei and glabrata
Bloodstream infection
Echinocandin
Alt: Ampho B
What is the preferred regimen for:
Pathogen: aspergillus, invasive
Voriconazole
Alt: Ampho B or isavuconazonium
What is the preferred regimen for:
Pathogen: Cryptococcus neoformans
Meningitis
Amphotericin B + flucytosine (5-FC_
What is the preferred regimen for:
Pathogen: dermatophytes
Nail bed infection
Terbinafine or itraconazole
Alt: fluconazole
These antifunals can cause liver damage and QT prolongation, and have many drug interactions
AZOLE antifungals
no QT prolongation with isavuconazonium
Which azole? Tablets and capsules: take with food Solution: take on an empty stomach Can cause HF Drug interactions due to high gastric pH
Itraconazole
Which azole?
Tablets- take with food
Suspension- take with full meal or oral liquid nutritional supplement
Posaconazole (Noxafil)
Which azole?
Take on an empty stomach at least 1 hour before or one hour after meals
Can cause: photosensitivity, vision changes
Store reconstituted oral suspension at room temp
Voriconazole
These antivirals reduce the amount of virus in the body by inhibiting the enzyme which enables release of new viral particles from infected cells
Neuraminidase inhibitors (oseltamivir, zanamivir, peramivir)
Neuraminidase inhibitors are active against both influenza A and B and decrease the duration of symptoms by about:
one day; should be started within 48h of onset
Baloxavir marboxil (Xofluza) is what type of antiviral
Endonuclease inhibitor - single dose regimen
Brand: Tamiflu
Generic: Oseltamivir
Capsules, suspension
Warnings regarding Tamiflu
Neuropsychotic events
Tamiflu treatment in ages >12y
75mg BID x 5 days
Tamiflu prophylaxis in age >12
75mg daily x 10 days
Brand: Relenza, Diskhaler
Generic: Zanamivir
Inhalation
This antiviral has bronchospasm warnings, do not use in COPD/asthma
Zanamivir
Brand: Rapivab
Generic: Peramivir
Brand: Zovirax, Sitavig
Generic: Acyclovir
Brand: Valtrex
Generic: Valacyclovir
Prodrug of alcyclovir
These antivirals have a warning regarding using caution in patients with renal impairment, the elderly, and/or those receiving nephrotoxic agents.
Acyclovir, Valacyclovir, Famciclovir
Cold Sores-
Sore eruption is preceded by prodromal symptoms (tingling, itching, soreness), which is optimal time for:
apply topical or take oral meds to reduce blister duration
What is an OTC option for Herpes Labialis treatment?
Docosanol (Abreva)
Apply 5x daily at first sign of outbreak
Acyclovir topical cream for Herpes Labialis treatment
Apply 5x daily x 4 days
Genital Herpes-
Treatment must be initiated during the prodrome or within one day of lesion onset. What are the options?
Acyclovir - least expensive, but dose 5x day
Valacyclovir (prodrug), higher concentrations and less freq dosing
What is the most commonly identified cause of viral encephalitis?
HSV
How is HSV encephalitis treated?
IV acyclovir x 14-21 days
Shingles pain can be treated with:
Pregabalin, gabapentin, duloxetine, tricyclic antidepressants, NSAIDs, opioids
5-10% of people have chronic pain after shingles, called
Postherpetic neuralgia (PHN)
Herpes Zoster treatment
Acyclovir, Valacyclovir, Famciclovir x 7 days
This virus is a double stranded DNA virus within the herpes virus family (HHV-5) and occurs in severely immunocompromised states (AIDS, transplant patients) and can cause retinitis, colitis or esophagitis
CMV
What is the treatment of choice in CMV?
Ganciclovir or valganciclovir
What meds should be reserved for refractory cases of CMV?
Foscarnet and cidofovir
What is an FDA-approved prophylaxis treatment for CMV in patients receiving a hematopoietic stem cell transplant
Letermovir (Prevymis)
Brand: Cytovene
Generic: Ganciclovir
This antiviral should be prepared in sterile water, NOT bacteriostatic
ganciclovir
Brand: Valcyte
Generic: Valganciclovir
*prodrug of ganciclovir
These antivirals have a boxed warning for myleosuppression and the suspension must be refrigerated
Ganciclovir, valganciclovir
This antiviral is used in CMV retinitis and resistant HSV
Foscarnet (Foscavir), INJ
The boxed warning for Foscarnet
Renal impairment
Vesicant! – central line
What virus is spread via kissing?
Epstein-Barr Virus / “mononucleosis”