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43 Cards in this Set

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What types of infections are the 4th most common nosocomial infection?
mycotic infections
What 2 drugs are polyene antifungal agents?
Amphotericin B
Nystatin
MOA: Amphotericin B and Nystatin
bind to ergosterol in the fungal cell membrane causing pores to form (which leads to depolarization of the membrane and cell contents "leak out")
What drug is the broadest spectrum of all antifungal agents?
Amphotericin B*
What's the advantage to using a liposomal formulation of Ampho B?
shorter half-life --> less adverse effects
what are two types of liposomal Ampho B drugs?

why do they have less side effects?
1. Abelcet
2. Ambisome

less S/Es due to reduced non-specific cholesterol binding
Why do you do a test dose when giving Ampho B?
do a 1mg/hr test dose to monitor for hypotension and fever
Do you do a dose alteration for Ampho B for pts that have renal failure?
no dose alteration for pts in renal failure, however if the creatinine rises or doubles to >3 then either:
1. reduce dosing frequency
2. use lipid formulations
Why is Ampho B often called "amphoterrible"?

What are the signs of a bad rxn?

What should you do to prevent this reaction?
infusion-related reactions:

signs: rigors*

premedicate w/ Tylenol, Benadryl, Hydrocortisone, or NSAIDS
What is a SLOW toxicity of Ampho B?
nephrotoxicity
What electrolyte problem is seen with Ampho B usage?
severe Mg++ and K+ wasting
How can Nystatin be given and how can it NOT be given?
toxic if given systemically (IV)

topical usage
What are the clinical uses of 5-flucytosine?
narrow spectrum:

Cryptococcus neoformans
MOA: 5-flucytosine?
inhibits nucleic acid synthesis
What happens if 5-Flucytosine is used alone?

What should it be used with?
rapid emergence of resistance when used alone

synergistic with Ampho B/azoles
What are some important adverse effects of 5-flucytosine?
1. GI: toxic megacolon, elevated transaminases/hepatomegaly

2. bone marrow: anemia, leukopenia, thrombocytopenia
What drugs has activity against candida?
Nystatin commonly used for oral thrush, esophagitis, and vaginitis due to Candida
What are the 4 important azoles to know and what type of azoles are they?
Triazoles:
1. fluconazole
2. itraconazole
3. voriconazole
4. pozaconazole
What are all azoles active against?
yeasts: Candida albicans, Cryptococcus neoformans

molds: Pseudoallescheria boydii
MOA: azoles
MOA: azoles inhibit sterol biosynthesis by interference with CYP-450 dependent lanosterol C14 demethylation

this is a critical enzyme in ergosterol synthesis and it results in faulty cell membrane synthesis
Why are triazoles assoc with less toxicity than Ampho?
Triazoles have greater affinity for fungal enzymes
How is Clotrimazole used and for what?
clotrimazole is used topically for superficial infections (i.e. Candida)
What triazole has the greatest propensity to inhibit mammalian CYP-450 and what issues does this cause:
Ketoconazole:
1. interferes with arenal/gonal steroid synthesis
2. increased number of drug interactions
What triazole requires gastric acid for absorption?
Ketoconazole requires gastric acid for absorption
What triazole is the TOC for dimorphic fungi?
Itraconazole is "preferred" agent for Blastomyces, Histoplasma, Sporothrix
What is it about the way that Itraconazole is made that makes it potentially harmful for people with renal impairment?
propylene glycol dilutent in IV formulations is a risk for those with renal impairment
What drug has drug interactions with H2 blockers, PPI inhibitors, Rifamycins, Astemizole, and terfenadine?
Itraconazole
What are the clinical uses for fluconazole?
broad spectrum:
NOT for Aspergillus
NOT for dimorphic fungi except nonmeningeal Coccidiodomycosis
For what is fluconazole the TOC?
Fluconazole is the TOC for Cryptococcal Meningitis
3 advantages to using fluconazole?
1. high therapeutic window
2. few ADRs*
3. less hepatic CYP450 activity --> few drug interactions*
For what is Voriconazole the treatment of choice?
Aspergillus
What are some other uses for Voriconazole other than Aspergillus?
1. increased use as prophylaxis and empiric therapy in neutropenia and bone marrow/stem cell transplant
2. selecting for Zygomycosis infections?
What triazole is most like Ampho B and why?
Pozaconazole:
broad spectrum activity (less ADRs -- very well tolerated!)
What is pozaconazole active against?
1. filamentous fungi
2. dimorphic fungi
3. Candida
What is Griseofulvin used for?
only use is in systemic treatment of dermatophytosis of skin, hair, and nails
What are Echinocandins?
Echinocandins are broad spectrum antifungals:
1. fungicidal for yeasts
2. fungistatic for molds
What are the 3 Echinocandins?
1. Caspofungin
2. Micafungin
3. Anidulafungin
MOA: Echinocandins?
inhibit cell wall synthesis
What are Echinocandins used with?

How are they NOT given?
Echinocandins are synergistic with Ampho B

not given orally
Are adverse effects common with Echinocandins?
Adverse effects are rare with Echinocandins
Sprectrum of activity of Echinocandins?
Candida (fungicidal)
Aspergillus (fungistatic)
What may severe inflammation indicate in a fungal case?
may indicate a hypersensitivity reaction to the fungus and may be relieved with adjuvant topical steroids
see cases at end of PPT
see cases at end of PPT