ID III: Antifungals & Antivirals Flashcards by steph h

Fungi are classified as either:

yeasts, molds, or dimorphic

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Candida species:

C. albicans, C. krusei, C. tropicalis, Cryptococcus neoformans are examples of

Yeasts (exist in the heat)

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Aspergillus species, Zygomycetes (Nucor and rhizopus species) are examples of:

Molds (exist in the cold)

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Histoplasma capsulatum, Blastomyces dermatitidis, and coccidiodes immitis are examples of

dimorphic fungi

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Zygomyctes refers to a class of fungi which includes Mucor species and Rhizopus species; invasive disease with this group is commonly called

mucormycosis

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The most susceptible Candida species:

More difficult to treat due to resistance:

Easy: C.albicans
Harder: C. glabrata and C. Krusei

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MOA: binds to ergosterol, alternating cell membrane permeability and causes cell death

Amphotericin B

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Which form of Amphotericin B has few toxicities? (dec infusion reactions, dec nephrotoxicity)

The lipid formulations

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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!

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Brand: AmBisome

Generic: Liposomal Amphotericin B (INJ)

3-6mg/kg/day

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Brand: Abelcet

Generic: Amphotericin B Lipid Complex

5mg/kg/day

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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

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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

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Preparation of Amphotericin B should be diluted in ____ ONLY.

D5W; lipid formulation must be filtered during preparation

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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)

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This drug penetrates fungal cells and is converted to fluorouracil, which competes with uracil, interfering with fungal RNA and protein synthesis

Flucytosine

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Brand: Ancobon

Generic: Flucytosine, 5-FC

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Due to development of resistance, flucytosine should not be used alone, but is recommended for use in combination with:

amphotericin B

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Flucytosine + Amphotericin B are used to treat:

invasive Cryptococcal (meningitis) or Candida infections

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These drugs decrease ergosterol synthesis and cell membrane formation

Azole antifungals

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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

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This drug can be used for many infections including yeast (vaginal and esophageal, mouth), and nail bed infections (onychomycosis)

Fluconazole

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The primary uses for this drug are for dimorphic fungi Blastomycosis and Histoplasmosis and for nail bed infections

Itraconazole

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Treatment of choice for Aspergillus

Voriconazole

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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"