ID 3 - fungals (NAPLEX)

Yeasts (2)

• Candida species

• Cryptococcus

Molds (2)

• Aspergillus

• Zygomycetes (mucor)

Dimorphic fungi (2)

Histo and blasto

Amp B MOA

Binds erogosterol causing cell death

Which amp B form has the most toxicities?

A. Amp B Deoxycholate

B. Amp B Lipid Complex

C. Liposomal Amp B

A. Amp B Deoxycholate

which is the conventional form

Amp B BW (2)

• Med errors that have resulted in cardiopulm arrest and death

• Conventional amp B should not exceed 1.5 mg/kg/day

Amp B adverse effects (6)

• Infusion related - chills, HA, malaise, rigors

• BP changes

• HypoK

• HypoMg

• Nephrotoxicity

Amp B deoxycholate (conventional) pre-medication (4)

• APAP/NSAID - fever

• Diphenhydramine and/or hydrocortisone

• NS boluses to reduce nephrotox

• +/- meperidine to help with rigors

Flucytosine MOA

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

Flucytosine can cause dose related _______.

Myelosupression

Azoles MOA

Decrease ergosterol synthesis and cell membrane formation

uworld

What azole can cause heart failure?

Itraconazole

Itraconazole BW (3)

• Can worsen or cause HF

• Many DDI

• Can increase QTc

Ketoconazole BW (3)

• Hepatotoxicity

• QT prolong

• Only use when benefit>risk

What is the main AE with azoles? (2)

• Hepatotoxicity

• QTc/DDI

Voriconazole main AE (3)

• visual changes

• hallucinations

• photosensitivity

uworld asked aout photosensitivity

What is the only azole that is renally cleared?

Fluconazole - needs dose adj when CrCl ≤50

What 2 azoles can penetrate the CNS and be used to treat fungal meningitits?

Fluconazole

Voriconazole

What azole can cause familial QT shortening?

Isavuconazole

What azole can cause drug particulates when given IV so have to use a FILTER? (2)

Isavuconazole & posaconazole

What azole requires an acidic environment for absorption?

Ketoconazole

uworld

Azoles PK **

• ALL are CY3A4 inhibitors

• Fluc and vori can also inhibit CYP2C9 - so watch for warfarin INR

What drugs have SBECD vehicle and therefore can accumulate in renal dysfunction? (2)

• Voriconazole

• Posaconazole

Itraconazole tabs/caps vs. solution in regards to taking with food

• Tabs/caps take with food

• Solution take on empty stomach

T/F: Take posaconazle on an empty stomach

FALSE - take both tablets and suspension with food

Echinocandins MOA

Inhibit synthesis of Beta (1,3)-D glucan (part of the fungal cell wall)

Echinocandins are effect against most _____ species

Candida

What symptoms can echinocandins cause?

histamine mediated - rash, itching, swelling

What is the only echinocandin that is NOT given QD?

Rezafungin

Echinocandin medication examples (2)

• Micafungin

• Caspofungin

Do echinocandins require renal dose adjustments?

NO

Main adverse effect with terbinafine?

Increased LFT's/hepatotoxicity

Oral thrush bug

Candida albicans

Oral thrush TX **

• Topical clotrimazole or miconazole

• HIV pts: fluconazole

• Alternative: nystatin

How do you use nystatin for oral thrush?

Swish the suspension in mouth for several minutes and swallowed

T/F: Shake nystatin well before using

True

Esophageal infection with C. albicans TX **

• Fluconazole

• Alt: Echinocandin

Candida bacteremia TX**

• Micafungin

• Alt: Amp B

Aspergillus TX **

• Voriconazole

• Alt: Isavuconazole, amp B

Cryptococcus meningitis TX **

• Amp B + 5-FC

• Alt: high dose fluconazole

Nail bed infection TX **

• Terbinafine or itraconazole