Antifungals Flashcards
(75 cards)
1
Q
Define halo sign
A
- CT finding of a fungal infx in the lung
- dense center with fuzzy outline
2
Q
Define candidemia
A
- fungal infx in the blood
3
Q
What are the symptoms of fungal infx?
A
- vague
- inflam response (topical redness)
- fever, cough
4
Q
What are good indicators of a fungal infx?
A
- presence of risk factors
- serologic testing, although not definitive
5
Q
What are the levels of fingal infx tx?
A
- empiric
- targeted
- prophylaxis
6
Q
Define empiric therapy
A
- tx of possible/probable fungal infx
- symptoms consistent, no positive culture data
7
Q
Define targeted therapy
A
- definitive positive culture data
8
Q
Define prophylaxis
A
- preventative tx in at-risk pt
9
Q
Who are at risk for fungal infections?
A
- immunosuppresed
10
Q
What are the challenges of fungal infections?
A
- difficult to dx
- potential toxicity of available agents
- need for targeted tx
- resistance develops
- limited formulations
- aggressiveness of pathogens
11
Q
What are the 3 main classes of antifungals?
A
- azoles
- polyenes/amphotericins
- echinocandins
12
Q
Define fungistatic
A
- drugs that inhibit growth
13
Q
Define fungicidal
A
- drugs that kill fungal pathogens
14
Q
What is the 1/2 life of amphotericin?
A
- very long (15d)
15
Q
T/F: Amphotericin does not require renal or hepatic adjustment.
A
- true
16
Q
What is the MOA of amphotericin?
A
- binds to and disrupts ergosterol which creates pores
- pores alter permeability of membrane increasing leaking of intracellular components
- leads to fungal cell death
17
Q
What is the coverage of amphotericin?
A
- broad spec
- excellent coverage
18
Q
What are the ADEs of amphotericin?
A
- infusion related reactions
- renal + hepatic toxicity in chronic use
19
Q
Labs = increased Scr & BUN, K & Mg wasting
What ADE is this?
A
- renal toxicity
20
Q
Labs = increased LFTs
What ADE is this?
A
- hepatic toxicity
21
Q
What is the purpose of lipid formulations of amphotericin?
A
- improve tolerability
- reduce toxicity
22
Q
When is amphotericin used?
A
- life-threatening or refractory infx
23
Q
What is a benefit of flucytosine?
A
- large volume of distribution
24
Q
What is the MOA of flucytosine?
A
- prodrug that inhibits fungal DNA & RNA synthesis
25
What is the tx for Cryptococcus and Candida meningitis?
- amphotericin + flucytosine
26
What are the ADEs of flucytosine?
- GI tract (N/V)
- myelosuppression (anemia, thrombocytopenia, leukopenia)
- hepatotoxicity (increased LFTs)
27
When is flucytosine used?
- cytprococal meningitis
28
What is a common use of flucytosine?
- cytprococal meningitis
29
What are the 2 types of -azoles?
- imidazoles
| - triazoles
30
What is the MOA of azoles?
- inhibit fungal CYP P450 dependent enzyme lanosterol = reduces formation of ergosterol
31
Are azoles fungistatic or fungicidal?
- fungistatic
32
What are the ADEs of azoles?
- GI upset
| - increased LFTs
33
What are the DIs of azoles?
- CYP450 3A4 is a major target results in enzyme inhibition
| - decrease metabolism of other drugs metabolized by affected CYP450 enzymes
34
Of the two types of azoles, which is more likely to have DIs?
- imidazoles
35
Is ketoconazole more or less selective for fungal CYP450 enzymes & what does that mean?
- less
| - more likely to cause DIs
36
What is the use of ketoconazole?
- topical fungal infections
37
What is an unexpected use of ketoconazole?
- prostate cancer
38
T/F: Itraconazole is a good broad spectrum abx.
- true
39
How should itraconazole be taken?
- with food (coca cola)
| - NOT WITH ACID REDUCERS
40
What does itraconazole cover?
- candida
| - aspergilllus
41
What does itraconazole treat?
- onychomycosis
| histoplasmosis & blastomycosis is rare
42
T/F: Fluconazole does not need to be dose adjusted for renal insufficiency.
- false, decrease dose
43
What is fluconazole used for?
- tx & prophylaxis of coccidodial & cryptococcal meningitis
- tx of candida
44
What does fluconazole NOT have activity against?
- Aspergillus
45
What is resistant to fluconazole?
- C. krusei & glabrata
46
What is the bioavailability of oral voriconazole?
- excellent, no issues with acid reducers
47
What are the ADEs of voriconazole?
- hepatic toxicity
- rash
- visual changes
48
When does voriconazole require dose adjustments?
- hepatic not renal insufficiency
49
What does voriconazole cover?
broad spectrum
- candida, including fluconaole resistant candida
- aspergillis
- Secedosporoium apiospermum
- Fusarium
50
When is voriconazole used?
- tx or prophylaxis of invasive fungal infections
51
What is the coverage of posaconazole?
- broad spec
52
What is approved for use a prophylaxis of fungl infx in immunosuppressed patients?
- posaconazole
53
What is posaconazole used to tx?
- oropharyngeal candidiasis
54
What does taking posaconazole after a full meal or with an acidic carbonated beverage do?
- increases bioavailability
55
What is isavuconazole's MOA?
- prodrug
| - isavuvuconazonium sulfate --> isavuconazole
56
When is isavuconazole used?
- tx of invasive aspergillosis & mucormycosis
57
How is isavuconazole administered?
- IV with inline filter
58
What is a risk of isavuconazole?
- increased LFTs
| - infusion related rxn
59
What is eficonazole?
- first topical azole approved to treat onychomycosis
60
What is the class echinocandins active against?
- candida
| - aspergillus
61
What is the MOA of the class echinocandins?
- inhibit glucan synthase
- inhibits creation of component of fungal cell wall
- disrupts fungal cell integrity & leads to cell death
62
T/F: Echinocandins are fungicidal against Candida & aspergillus.
- false
- fungicidal against candida
- fungistatic against aspergillus
63
What are the drugs in the class echinocandins?
- suffix: - fungin
64
What are the ADEs of echinocandins?
- GI (N/V)
- flushing rxn if infused too fast
- increased LFTs
65
T/F: In comparison to -azoles, echinocandins have greatly reduced DIs.
- true
66
When are echinocandins used?
- refractory cases
| - renal or hepatic impairment (no dose adj needed)
67
What is terbinafine used to tx?
- topical dermatophytoses
68
What is the MOA of terbinafine?
- interferes with ergosterol synthesis by inhibiting squalene peroxidase
69
What is a risk of terbinafine?
- hepatic toxicity (monitor LFTs)
70
What is the use of tolnaftate?
- tineas
| - superficial fungal infx
71
What does tolnaftate not work against?
- candida
| - onychomycosis
72
What is a ADE of tolnaftate?
- skin irritation
73
What is nystatin & what is it active against?
- same class as amphotericin, polyene macrolide antifungal
| - candida
74
How do you select antifungal therapy?
- confirmed fungal infx or at risk
- prophylaxis vs. empiric/targeted
- based on organism
- severity
75
When in doubt of what to treat a fungal infx, what do you do?
- look it up!
