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PHRM 865 > Antifungal Agents > Flashcards

Antifungal Agents Flashcards

1
Q

Where does candida reside?

A

Normal flora of the human GI tract

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2
Q

What is candida?

A

A yeast

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3
Q

What are the risk factors for invasive candidiasis?

A
  • Prolonged stay in ICU
  • Central venous catheters
  • Prolonged broad spectrum therapy
  • Receipt of TPN
  • Recent surgery (esp. abdominal)
  • Hemodialysis
  • DM
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4
Q

What does aspergillus primarily cause and in which patient population?

A

Disease in immunocompromised hosts (neutropenia)

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5
Q

Where is the most common site of infection for aspergillus?

A

Pulmonary system

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6
Q

What are the endemic fungi species?

A

Histo, blasto, coccidioides

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7
Q

What kind of disease can endemic fungi cause and how?

A

Disseminated disease via a primary pulmonary infection

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8
Q

Which endemic fungi are prevalent in Indiana?

A

Histo, blasto

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9
Q

What are the two species of cryptococcus?

A

Neoformans and gattii

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10
Q

What is cryptococcus and what does it affect?

A

An encapsulated yeast that primarily affects the CNS and respiratory tract

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11
Q

What is amphotericin B a first line agent for?

A
  • Cryptococcus
  • Histo and blasto
  • Mucor
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12
Q

What is the dosing of amphotericin B deoxycholate?

A

0.5-1 mg/kg/day

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13
Q

What is the dosing of liposomal amphotericin B?

A

3-5 mg/kg daily

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14
Q

What is the dosing of amphotericin B lipid complex?

A

5 mg/kg daily

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15
Q

What are the AEs of amphotericin B?

A
  • Nephrotoxicity: increase in SCr and BUN
  • Hypokalemia, hypomagnesemia
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16
Q

What is the bioavailability of flucytosine?

A

> 90%

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17
Q

How much of flucytosine penetrates the CSF?

A

~75% of serum

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18
Q

What is the excretion of flucytosine?

A

85-95% excreted unchanged in urine

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19
Q

What is flucytosine a first line agent for?

A

Cryptococcus

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20
Q

What is the primary AE of flucytosine?

A

Bone marrow suppression

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21
Q

What should be monitored with flucytosine use?

A

BUN, SCr, CBC, platelets

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22
Q

What is the bioavailability of fluconazole?

A

> 90%

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23
Q

What is the level of CSF penetration of fluconazole?

A

Decent: 60% in uninflamed and ~80% in inflamed meninges

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24
Q

What is the excretion of fluconazole?

A

Excreted unchanged in the urine

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25
When should fluconazole be dose adjusted?
Dose reduce in renal insufficiency
26
Fluconazole dosing is based on what?
Total body weight
27
What is the dosing of fluconazole in C. albicans invasive candidiasis?
800 mg (12 mg/kg) LD, then 400 mg (6 mg/kg) daily
28
What is the dosing of fluconazole in C. glabrata invasive candidiasis?
800 mg daily (LD 1200-1600 mg)
29
What is the primary AE of fluconazole?
QTc prolongation
30
What is fluconazole a first line agent for?
- C. albicans, parapsilosis, tropicalis, lusitaniae - Coccidioides
31
What is the metabolism of itraconazole?
Predominantly metabolized by CYP450 3A4 isoenzyme (inhibitor)
32
What is the active metabolite of itraconazole?
Hydroxyitraconazole
33
What is the relationship between clearance and higher doses of itraconazole?
Clearance decreases w/ higher doses due to saturable hepatic metabolism
34
What is the absorption of itraconazole dependent on?
Gastric acidity
35
Which oral formulation of itraconazole not affected by gastric acidity?
Oral solution
36
What is itraconazole a first line agent for?
Histo and blasto
37
What are the primary AEs of itraconazole?
Hepatotoxicity, QTc prolongation
38
What disease state is itraconazole CI in?
CHF (boxed warning)
39
What affects the absorption of posaconazole?
Gastric pH
40
What is the preferred formulation of posaconazole that is not affected by gastric pH?
Delayed release tabs
41
When should IV posaconazole be avoided?
If CrCl <50 ml/min
42
What are the primary AEs of posaconazole?
QTc prolongation, increased AST/ALT/bilirubin
43
What is the primary clinical use of posaconazole?
Tx of aspergillus or mucor infections
44
What is the metabolism of voriconazole?
Significantly metabolized by CYP450 isoenzymes: 2C19, 2C9, 3A4
45
Is dosage adjustment required for oral voriconazole?
No
46
When should IV voriconazole be avoided?
If CrCl <50 ml/min
47
What is the oral bioavailability of voriconazole? Is it affected by anything?
- ~96% - Not affected by H2RAs, PPIs, antacids
48
What is voriconazole a first line agent for?
Aspergillus
49
What is the primary and most common AE of voriconazole?
Visual disturbances (i.e. hallucinations)
50
What is the primary AE of isavuconazole?
Can shorten QTc
51
What is the drug interaction profile of isavuconazole?
Considered to be the least DI of the azoles
52
What is CI with the use of isavuconazole?
Pts w/ familial short QT syndrome
53
What are echinocandins first line agents for?
C. glabrata, krusei, lusitaniae, auris
54
What are the AEs of caspofungin?
- Histamine-related sxs: rash - Fever - Headache - NV - Phlebitis at infusion iste
55
How must micafungin be administered and why?
- Given IV - Not absorbed orally
56
Is there dosage adjustment for micafungin?
No dosage adjustment for renal dysfunction
57
What is a DI of micafungin?
Not metabolized via CYP450 pathways
58
What are the AEs of micafungin?
- Hyperbilirubinemia - Nausea, diarrhea - Eosinophilia - Rash, pruritus, urticarial
59
What is ibrexafungerp a first line agent for?
Vulvovaginal candidiasis
60
What is the CI of ibrexafungerp?
Pregnancy
61
What is the primary line of host defenses against superficial candida infections?
Cell-mediated immunity
62
What are the local risk factors for oropharyngeal and esophageal candidiasis?
- Use of inhaled steroids and antibiotics - Dentures - Xerostomia - Smoking - Disruption of oral mucosa
63
What are the systemic risk factors for oropharyngeal and esophageal candidiasis?
- Drugs - Neonates or elderly - HIV/AIDS infection - Diabetes - Malignancies - Nutritional deficiencies
64
What is the clinical presentation of esophageal candidiasis?
- Dysphagia, odynophagia, retrosternal chest pain - Fever - Plaques of varying size and severity
65
What is the preferred treatment of mild oropharyngeal candidiasis in non-HIV patients?
Nystatin suspension 5 mL or clotrimazole troche 10 mg for 7-14 days
66
What is the treatment for esophageal candidiasis?
Fluconazole 200-400 mg PO or IV for 14-21 days
67
What is considered complicated vulvovaginal candidiasis?
Recurrent, severe, non-candida albicans infection, host factors like immunosuppression or pregnancy
68
What are the topical treatment options for uncomplicated VVC?
OTC/topical vaginal products: - Butoconazole, clotrimazole, miconazole, tioconazole

PHRM 865 (13 decks)

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