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NAPLEX 2024 > 24. Infectious Diseases III: Antifungals + Antivirals > Flashcards

24. Infectious Diseases III: Antifungals + Antivirals Flashcards

1
Q

Zygomycetes refers to a class of fungi which includes ___ and __ species; invasive disease caused by these species is commonly referred to as “____”

A

Mucor
Rhizopus
Mucormycosis

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2
Q

Aphotericin B coverage

A

Broad-spectrum
Active against:
Yeasts - most Candida species and Cryptococcus neoformans
Molds - Aspergillus species and Zygomycetes
Dimorphic fungi - Histoplasma capsulatum, Blastomyces dermatitidis, and Coccidioides immitis

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3
Q

There are two types of Amphotericin B formulations: conventional and lipid. Which one is a/w fewer toxicities?

A

Lipid formulations are a/w fewer toxicities (e.g. decreased infusion reactions, decreased nephrotoxicity) compared to conventional (deoxycholate) formulations

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4
Q

Boxed warning for Amphotericin B

A

Medication errors confusing lipid (AmBisome and Abelcet) vs conventional formulation (dexoxycholate)

Conventional dose should not exceed 1.5mg/kg/day (verify product name and dose if it exceeds 1.5 mg/kg/day)

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5
Q

Conventional amphotericin B should NOT exceed _____mg/kg/day

A

1.5mg/kg/day

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6
Q

Side effects for amphotericin B

A

Infusion-related: fever chills, HA, malaise, rigors, decreased or increased bP, thrombophlebitis, N/V
Decreased K, Mg, nephrotoxicity, enamia

Ambisome: severe back/chest pain with first dose

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7
Q

Preparation notes for amphotericin B

A

Compatible with D5W ONLY
Lipid formulations must be filtered during preparation

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8
Q

Which amphotericin B formulation must be filtered during preparation

A

Lipid formulations

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9
Q

Which amphotericin B formulation requires premedication to reduce infusion related reactions?

A

Conventional (deoxycholate) formulation

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10
Q

What should you give as premedication before amphotericin B deoxycholate administration (30-60min before)?

A

APAP or NSAID
Diphenhydramine and/or hydrocortisone
NS bolus to decrease risk of nephrotoxicity
± meperidine to decrease duration of severe rigors

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11
Q

What color is amphotericin B (both lipid and conventional formulations)?

A

Yellow-orange

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12
Q

Amphotericin B was ordered for one of your transplant patients for fungal infection. Current med list includes tacrolimus. What is your concern with the new medication?

A

Additive risk of nephrotoxicity with other nephrotoxic agents like aminoglycosides, cisplatin, polymixins, cyclosporine, loop diuretics, NSAIDs, radiocontrast dye, tacrolimus, and vancomycin

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13
Q

Amphotericin B can increase risk of digoxin toxicity d/t ____

A

hypokalemia
Use caution with any agent that decreases K or Mg

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14
Q

MOA Flucytosine

A

Penetrates fungal cells and is converted to fluorouracil, which competes with uracil and interferes with fungal RNA and protein synthesis

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15
Q

Patient cultures were positive for Candida infection. Doctor prescribed flucytosine monotherapy regimen. What is your concern

A

D/t resistance, flucytosine should NOT be used alone. Recommended in combination with amphotericin B for treatment of invasive cryptococcal (e.g. meningitis) or Candida infections.

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16
Q

Boxed warning for flucytosine (5-FC) (Ancobon)

A

Use with extreme caution in pts with renal dysfunction; monitor hematologic, renal and hepatic status

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17
Q

Side effects for flucytosine (5-FC) (Ancobon)

A

Myelosuppression (anemia, neutropenia, thrombocytopenia)

Others: increased SCr, BUN, liver injury, increased bilirubin, many CNS effects, hypoglycemia, decreased K, and aplastic anemia

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18
Q

MOA of azole antifungals

A

Decrease ergosterol synthesis and cell membrane formation

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19
Q

Azole antifungal use is sometimes limited d/t drug interactions caused by _____

A

CYP450 (mainly 3A4) inhibition

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20
Q

Fluconazole has coverage against C. albicans, C. parapsilosis, and C. tropicalis but limited efficacy against ___ and ___ d/t resistance

A

C. qlabrata
C. krusei

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21
Q

Common uses for Fluconazole

A

Many infections, including yeast infections (e.g oral, esophageal, vaginal) and nail bed infections (onychomycosis)

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22
Q

Common uses for itraconazole

A

Dimorphic fungi (Blastomycoes and Histoplasma) and nail bed infections

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23
Q

____ is the treatment of choice for Aspergillus

A

Voriconazole

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24
Q

Fluconazole (Diflucan) dosing

A

50-800mg PO/IV daily
Vaginal candidiasis: 150mg PO x1
CrCl ≤50: decrease dose by 50%

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25
Q

Which azole antifungal requires renal dose adj?

A

Fluconazole

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26
Q

Boxed warnings for itraconazole

A

Can worsen or cause HF; do NOT use to treat onychomycosis in pts with ventricular dysfunction or hx of HF

Can increase plasma conc of certain drugs and lead to QT prolongation and ventricular tacharrhythmias, including TdP

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27
Q

Boxed warnings for Ketoconazole

A

Hepatotoxicity (has led to liver transplantation and/or death)
QT prolongation
Use PO tabs only when other effective antifungal therapy is unavailable or not tolerated and the benefits outweigh risks (hepatotoxicity, DDIs)

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28
Q

____ was the first azole antifungal, but d/t toxicities and many DDIs, it is now most often used topically

A

Ketoconazole

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29
Q

Which formulation of ketoconazole is OTC?

A

Nizoral A-D (topical)

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30
Q

Class ADE for azole antifungals

A

Increased LFTs
QT prolongation (Except isavuconazonium)
Many drug interactions

Others: HA, N/V, abd pain, rash/pruritus, dizziness, hair loss (or possible hair growth), altered hair texture with ketoconazole shampoo

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31
Q

All azoles are cleared hepatically except ____ which requires renal dose adj

A

fluconazole

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32
Q

Which azole antifungals penetrate the CNS adequately to treat fungal meningitis?

A

Fluconazole and voriconazole

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33
Q

Which azole antifungals use sulfobutyl ether beta-cyclodextrin (SBECD) vehicles and may worsen renal function in pts with eGFR <50 d/t accumulation?
(Note: PO preferred in these patients)

A

Voriconazole (Vfend)
Posaconazole (Noxafil)

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34
Q

Contraindications for voriconazole

A

Coadministration with barbiturates (long-acting), carbamazepine, efaviren (≥400 mg/day), ergot alkaloids, pimozide, quinidine, rifabutin, rifampin, ritonavir (≥800 mg/day), sirolimus, or St. John’s wort

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35
Q

Warnings for voriconazole

A

Hepatotoxicity
Visual disturbances (optic neuritis and papilledema)
Phototoxicity
QT prolongation (correct K, Ca, and Mg prior to initiating treatment)

Others: nephrotoxicity, avoid in pregnancy, infusion-related reactions, SJS/TEN, skeletal adverse effects (fluorosis, periostitis), pancreatitis

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36
Q

ADEs for voriconazole

A

Visual changes (~20%)
Increaed LFTs, Increased SCr, CNS toxicity (hallucinations, HA, dizziness), photosensitivity, increased/decreased K

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37
Q

How should Vfend be taken?

A

Voriconazole (Vfend) should be taken on an EMPTY stomach at least 1 hr before or after a meal; hold tube feedings for 1 hour before and after doses

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38
Q

Counseling points for voriconazole (Vfend)

A

Take on empty stomach at least 1 hr before or after meal
Use caution when driving at night d/t vision changes
Avoid direct sunlight
Suspension: shake for 10 seconds before each use; do NOT refrigerate

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39
Q

Which azole antifungal is the prodrug of isavuconazole

A

Isavuconazonium sulfate (Cresemba)

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40
Q

All azole antifungals affect QT. What is unique about isavuconazonium?

A

Causes QT shortening, not prolongation

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41
Q

Which azole antifungal requires a filter (0.2-1.2 micron) during administration d/t possible particulates?

A

isavuconazonium

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42
Q

All azoles are moderate-strong CYP___ inhibitors

A

3A4

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43
Q

Which azole antifungals inhibit CYP2C9? What drug are we concerned about when using these azoles?

A

Fluconazole and voriconazole
Warfarin - monitor INR

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44
Q

PPIs and cimetidine can decrease the absorption of which azole antifungal?

A

Posconazole suspension
Should be stopped during therapy to avoid treatment failure

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45
Q

Which azole antifungals require acidic gut for proper absorption?

A

Itraconazole (Sporanox brand capsules) and ketoconazole

Separate antacids 2 hrs before and after doses

If PPIs or H2RAs must be used while on ketoconazole, take an acidic beverage (non-diet cola) to provide an acidic environment for absorption

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46
Q

If PPIs or H2RAs must be used while on ketoconazole, what do you recommend to ensure proper absorption?

A

take an acidic beverage (non-diet cola) to provide an acidic environment for absorption

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47
Q

Azoles can (increased/decrease) concentrations of apixaban and rivaroxaban. Monitor s/sx of bleeding.

A

Increase concentrations

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48
Q

MOA of echinocandins

A

Inhibit synthesis of beta (1,3)-D-glucan, an essential component of the fungal cell wall

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49
Q

Coverage of echinocandins

A

Most Candida species, including strains typically resistant to azole antifungals (e.g. C. galbranta, C. krusei)

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50
Q

Echinocandins are available only as ____

A

injections

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51
Q

Warnings for echinocandins

A

Histamine-mediated symptoms (rash, pruritus, facial swelling, flushing, hypotension)
Anaphylaxis

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52
Q

ADEs for echinocandins

A

generally well-tolerated and not a/w sig renal or hepatic toxicity

Incresad LFTs, HA, hypotension, increased/decreased K, decreased Mg, fever, N/V/D, hyperglycemia, anemia, increased SCr, rash, SJS/TEN (caspofungin)

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53
Q

Dosing frequency for echinocandins in general

A

Once daily
Do not require renal dose adj

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54
Q

Which echinocandin requires light-protection during administration?

A

Micafungin

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55
Q

Nystatin suspension, clotrimazole troches/lozenges, and buccal miconazole are useful for treating mild, localized ___ infections

A

Candida

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56
Q

Nystatin suspension directions for use

A

Swish in mouth and retain for as long as possible (several minutes) before swallowing

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57
Q

T/F: When using nystatin suspension, it is recommended to swish in mouth for a few seconds and then spit out

A

False - Swish in mouth and retain for as long as possible (several minutes) before swallowing

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58
Q

Griseofulvin is indicated for fungal infections of ____

A

skin, hair, and nails

59
Q

Contraindications for griseofulvin

A

Pregnancy, severe liver disease, porphyria

60
Q

Side effects for griseofulvin

A

Photosensitivity, increased LFTs
Others: HA, rash, urticaria, dizziness, leukopenia, severe skin reactions

61
Q

Which formulation of terbinafine is OTC?

A

Lamisil AT (topical)

62
Q

How should griseofulvin be taken?

A

Take with fatty mean to increase absorption with food/milk to avoid GI upset

63
Q

Warnings for terbinafine

A

Hepatotoxicity

Others: taste/smell disturbance, depression, neutropenia, thrombotic thrombocytopenic purpura (TTP), hemolytic uremic syndrome (HUS), SJS/TEN/DRESS/erythema multiforme, can cause/worsen systemic lupus erythematosus

64
Q

Side effects for terbinafine

A

Headache, increased LFTs

Others: skin rash, abd pain, pruritus, diarrhea, dyspepsia

65
Q

Contraindications for terbinafine

A

chronic or active liver disease

66
Q

Patient on hormonal contraceptives got a prescription for griseofulgin for a hair fungal infection. What is your concern with these medications?

A

Griseofulgin increase metabolism of hormonal contraceptives (estrogen and progestin) - may lead to contraceptive failure. Use nonhormonal form of contraception

67
Q

Terbinafine is a strong CYP ___inhibitor and weak/moderate CYP___ inducer

A

2D6 inhibitors
3A4 inducer

68
Q

Patient as dx with mild oropharyngeal infection (thrush). What is the common pathogen and the preferred regimen?

A

Candida albicans

Mild disease: topical antifungals (clotrimazole, miconazole)

69
Q

What is the recommended regimen for candida albicans oropharyngeal infection (thrush) moderate-severe disease or HIV+ pts

A

fluconazole

70
Q

What is the alternative regimen for candida albicans oropharyngeal infection (thrush)?

A

Nystatin

Preferred: topical antifungals (clotrimazole, miconazole for) for mild disease, fluconazole for mod-severe or HIV + pts

71
Q

What is the preferred regimen for candida albicans esophageal infection?

A

fluconazole

72
Q

What is the alternative regimen for candida albicans esophageal infection?

A

Echinocandin

Preferred: fluconazole

73
Q

What is the preferred regimen for candida krusei and glabrata, all Candida species bloodstream infections?

A

Echinocandin

74
Q

What is the alternative regimen for candida krusei and glabrata, all Candida species bloodstream infections?

A

Amphotericin B, high-dose fluconazole (susceptible isolates only)

Preferred is echinocandin

75
Q

What is the preferred regimen for aspergillus?

A

Voriconazole

76
Q

What is the alternative regimen for aspergillus?

A

Amphotericin B, isavuconazonium

Preferred is voriconazole

77
Q

What is the preferred regimen for cryptococcus neoformans meningitis ?

A

Amphotericin B + flucytosine (5-FC)

77
Q

What is the alternative regimen for cryptococcus neoformans meningitis ?

A

high-dose fluconazole + flucytosine (5-FC)

78
Q

What is the preferred regimen for Dermatophytes nail bed infections?

A

Terbinafine or itraconazole (confirm fungal infection prior to treatment)

79
Q

What is the alternative regimen for Dermatophytes nail bed infections?

A

Fluconazole

Preferred is terbinafine or itraconazole

80
Q

What are some key counseling points for azole antifungal (class)?

A

Can cause liver damage, QT prolongation (Except isavuconazonium)
Many DDIs

81
Q

What are some key counseling points for itraconazole?

A

Tabs and caps: take with food
Solution: take on empty stomach
Can cause heart failure

82
Q

What are some key counseling points for posconazole?

A

Tabs: take with food
Suspension: take with a full meal or oral liquid nutritional supplement

83
Q

What are some key counseling points for voriconazole?

A

Take on empty stomach at least 1 hr before or after meals
Can cause photosensitvity, vision changes
Store oral suspension at room temp

84
Q

What are some key counseling points for nystatin?

A

Suspension: shake well before using

85
Q

What are some key counseling points for terbinafine?

A

Oral terbinafine can cause liver damage
Can take several months after finishing treatment to see full benefit of this drug (takes time for new healthy nails to grow and replace infected ones)

86
Q

Which influenza strains are the ones that commonly affect humans?

A

Influenza A and B

87
Q

S/sx influenza

A

fever, chills, fatigue, myalgia, non-productive cough, sore throat, and HA

88
Q

How does influenza spread?

A

via respiratory droplets (e.g. generated by coughing)

89
Q

How long is someone contagious for when they have influenza?

A

1 day prior to developing symptoms and for up to 5-7 after becoming ill

90
Q

Influenza vaccine is recommended for all patients ages ≥ ___ who have no contraindications

A

6 months

91
Q

MOA of neuraminidase inhibitors (oseltamivir, zanamivir, and peramivir)

A

Reduce amt of virus in the body by inhibiting the enzyme which enables release of new viral particles from infected cells
Active against influenza A and B, decreasing duration of s/sx by about 1 day and reducing complications

92
Q

To be most effective, neuraminidase inhibitors should be started within ____ of illness onset

A

48 hrs

Note: in hospitalized, severely ill pts and those at high risk of complications, should still start >48hr after symptom onset, though less benefit if started later

93
Q

____ is an endonuclease inhibitor approved for the treatment and post-exposure prevention of influenza. It has the advantage of being a single-dose regimen.

A

Baloxavir marboxil (Xofluza)

94
Q

Baloxavir marboxil (Xofluza) should be started within ____ of symptom onset

A

48 hrs

95
Q

Oseltamivir (Tamiflu) treatment dosing, age >12yo

A

75 mg BID x 5 days

96
Q

Oseltamivir (Tamiflu) ppx dosing, age >12yo

A

75mg daily x 10 days

97
Q

T/F: Oseltamivir (Tamiflu) does not require renal dose adj

A

False - CrCl ≤60 requires renal dose adj

98
Q

Warnings for Oseltamivir (Tamiflu)

A

Neuropsychiatric events (sudden confusion, delirium, hallucinations, unusual behavior or self-injury)
SJS/TEN
Anaphylaxis

99
Q

Which medication used for influenza cannot be used in asthma/COPD?

A

Zanamivir (Relenza Diskhaler) - inhaler formulation, can cause bronchospasm

100
Q

Which medication used for influenza is x1 dose?

A

Baloxavir marboxil (Xofluza)

101
Q

How is COVID-19 spread?

A

Respiratory droplets released when coughing or sneezing
Can be reduced by maintaining distance of at least 6 feet, mask we

102
Q

S/sx of COVID-19

A

fever, chills, cough, SOB, fatigue, myalgia, loss of taste or smell, sore throat

103
Q

What are some clinically significant herpes viruses?

A

Herpes simplex viruses 1 and 2 (HSV-1, HSV-2)
Varicella zoster virus (VZV)
Cytomegalovrius (CMV)
Epstein-Barr virus (EBV)
Human herpesviruses (HHV-6, HHV-7)
Kaposi sarcoma associated herpes virus (HHV-8)

104
Q

Which herpes virus is most commonly a/w oropharyngeal disease

A

HSV-1

105
Q

Which herpes virus is most commonly a/w genital disease

A

HSV-2

106
Q

___ is the prodrug of acyclovir

A

Valcyclovir (Valtrex)

107
Q

___ is the prodrug of penciclovir

A

Famciclovir

108
Q

Warnings for antivrials for HSV and VZV

A

Caution in pts with renal impairment, the elderly, and/or those receiving nephrotoxic drugs
Infuse acyclovir over at least 1 hr and maintain adequate hydration to reduce risk of renal tubular damage

TTP/HUS has been reported in immunocompromised pts

109
Q

Acyclovir dose is based on ___, including in obese patients

A

IBW

110
Q

Cold sore eruption is preceded by a ____ (symptoms that occur before the lesions appear) of tingling, itching, or soreness

A

Prodrome

111
Q

When is it the optimal time to take topical or oral medication to reduce blister duration for cold sores?

A

Tingling, itching, or soreness occurs

112
Q

Which topical treatment for cold sores is OTC

A

Docosanol (Abreva)

113
Q

Docosanol (Abreva) dosing for cold sores

A

Apply 5x daily at first sign of outbreak

114
Q

Acyclovir (Zovirax) dosing for cold sores

A

Apply 5x daily for 4 days

115
Q

For genital herpes, when must treatment be initiated?

A

During prodrome period or within 1 day of lesion onset

116
Q

Compare acyclovir vs valacyclovir for genital herpes

A

Acyclovir - typically least expensive regimen but can be dosed up to 5x/day
Valacyclovir - prodrug of acyclovr; can reach higher conc than PO acyclovir; less frequent dosing = adherence

Note: if virus is resistant to acyclovir, it will also be resistant to valacyclovir, most likely famciclovir too

117
Q

___ is the most commonly identified cause of viral encephalitis in the US (10-20% of cases)

A

HSV

118
Q

HSV encephalitis is treated with ____

A

IV acyclovir 10mg/kg/dose Q8H x14-21 days

119
Q

What virus is commonly referred to chicken pox?

A

Varicella zoster virus

120
Q

Most adults in the US had chickenpox in their childhood. Virus can lie dormant in the nerve for decades without causing any symptoms. What is the recurrence of viral symptoms called?

A

Herpes zoster or shingles

Often as pts ages or acute stress

120
Q

S/sx shingles

A

Itchy/tingly rash, very painful, and usually unilateral (only on one side of the body)

121
Q

Antiviral therapy should be initiated at the earliest s/sx of shingles and is most effective when started within ___ of rash onset

A

72 hrs

122
Q

Pain from shingles can be treated with ____

A

topical medications (Lidoderm patch, lidocaine gel), neuropathic pain meds (e.g. pregabalin, gabapentin, duloxetine, TCAs), NSAIDs, or opioids

123
Q

Most shingles patients recover without long-term effects, but 5-10% have chronic pain called ____, can be debilitating

A

postherpetic neuralgia

124
Q

ACIP recommends the shingles vaccines (Shingrix) in immunocompetent adults ages ___ and adults ages ____ who are or will be immunosuppressed

A

≥50yo
≥19yo

125
Q

Herpes Zoster (Shingles) Treatment duration

A

7 days

126
Q

What can be used to treat herpes zoster (Shingles)?

A

Acyclovir (Zovirax), Valacyclvoir (Valtrex), Famciclovir

127
Q

____ is a double-stranded DNA virus within the herpes virus family (HHV-5)

A

Cytomegalovirus (CMV)

128
Q

___ and ___ are treatments of choice for CMV infections. __ and ___ should be reserved for refractory cases

A

Ganciclovir and valganciclovir
Foscarnet and cidofovir

129
Q

Ganciclovir preparation notes

A

Injection: reconstitute with sterile water, NOT bacterostatic water
Hazardous - special handling required

130
Q

____ is the prodrug of ganciclovir (with better bioavailability)

A

Valganciclovir (Valcyte)

131
Q

Boxed warnings for gancyclovir/valgancyclovir

A

Myelosuppression
Carcinogenic and teratogenic effects and inhibition of spermatogenesis in animals

132
Q

IV ganciclovir to PO valganciclovir conversion

A

IV ganciclovir 5mg/kg = PO valganciclovir 900mg

133
Q

Valganciclovir (Valcyte) solution storage instructions

A

Refrigerate, discard after 49 days

134
Q

Boxed warnings for foscarnet (Foscavir)

A

Renal impairment (prehydartion recommended)
seizures d/t electrolyte imbalances (can lead to status epilepticus or death)

135
Q

Infectious Epstein-Barr virus (EBV) is called ___and is transmitted through ___

A

mononucleosis or “mono”
Bodily fluids, primarily saliva and can be spread by kissing, sharing drinks or food, or by contact with an object that has been in mouth of an infected person (e.g. child’s toys)

136
Q

S/sx of EBV

A

fatigue, fever, sore throat, and swollen lymph nodes
typically resolve in 2-4 weeks

137
Q

Treatment for EBV

A

No drug treatment or vaccine exists for mononucleosis

138
Q

A child with EBV developed a non-pruritic rash after using amoxicillin. Provider listed PCN as an allergy. Is this correct?

A

No - amoxicillin or ampicillin treatment in a child with EBV can cause a non-pruritic rash that appears similar to an allergy reaction; it is not and should not be included as an “allergy”

139
Q

Osetlamivir (Tamiflu) key counseling points

A

Treatment should begin within 2 days (48hrs) of symptom onset
Can cause delirium

140
Q

Acyclovir (Zovirax) and Valacyclovir (Valtrex) key counseling points

A

This medication dose not cure herpes infections (cold sores, chickenpox, shingles, or genital herpes). Use safe sex practices to lower transmission risk
Start treatment within 24 hrs of symptom onset

Acyclovir - drink plenty of fluids, topical cream can cause temporary burning and stinging

141
Q

T/F: IV:PO ratio for all azoles is 1:1

A

True

NAPLEX 2024 (74 decks)

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