Exam 5 Lecture 6 Flashcards

(78 cards)

1
Q

Where are candida found? What type of infection do they cause? When is mortality increased?

A

Found in human GI tract as normal flora

Can cause mild infection such as oropharyngeal or esophageal candidiasis or more serious invasive infetions such as catheter associated infections and disseminated disease.

Increased mortality if empiric antfungal therapy delayed by 12 hrs

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2
Q

Risk factors for invasive candidiasis

A

Prolonged ICU stay
CV catheter
Prolonged therapy with broad spec antibacterial agents
Receipt of PN
Recent surgery
hemodialysis
DM

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3
Q

What are two fungi that are endemic? Who do they cause infection in and what disease may they cause?

A

Histoplasma capsulatum and blastomyces spp

May cause disseminated disease via a primary pulmonary infection. May cause disease in normal host but higher risk in HIV patients with suppressed cell immunity

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4
Q

What are two species of cryptococcus? What type of infection does it cause? Mortality

A

Cryptococcus neoformans and gatti

CNS side effects
30% mortality

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5
Q

broadest spec antifungal

A

Amphoterecin

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6
Q

MOA of amohoterecin

A

Binds to ergosterol and gets inserted into the fungal cytoplasmic membrane-> Disruption of the fungal cytoplasmic membrane.

Increased cell permeability-> leakage of sodium/potassium/cellular constituents, loss of membrane potential

cell death

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7
Q

When is amphoterecin 1st line

A

Systemic invasive infection such as

Cryptococcus
Blastomyces
Histoplasma
Mucor

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8
Q

what are the different doses for amphoterecin formulations

A

deoxycholate- usual 0.5-1 mg/kg/day

Liposomal- 3-5 mg/kg/day

Lipid complex- 5 mg/kg daily

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9
Q

Adverse effects of amphoterecin? Electrolyte abnormality?

A

NEPHROTOXICITY!!!! (can be permanent, dose dependent)

can increase Scr and BUN

Electrolyte abnormalities
-hypokalemia
-hypomagnesemia
-anemia
-bicarb wasting

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10
Q

How to prevent nephrotoxicity caused by amphoterecin

A

0.5-1 L NS over 30 min before AMB and 0.5-1L NS after infusion

extend infusion to help to 4 hours

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11
Q

What are infusion related rxns for amphoterecin? How to treat?

A

H/A, fever, chills, arthralgias, myalgias, N/V, hypotension

Pretreat with acetaminophen and antihistamines

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12
Q

What is the main use of flucytosine

A

Main use is combo therapy with AmphoB for cryptococcal meningitis

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13
Q

Bioavailabitily of flucytosine

A

Great bioavailability (>90%)
Penetrates into the CSF (75% of srum) (that is why it is used for cryptococcal meningitis)

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14
Q

how is flucytosine excreted? Is it renally dose adjusted?

A

85-95% excreted unchanged in the urine (removed by HD and PD)

Renally dose adjusted

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15
Q

do we dose adjust amphoterecin? Why or why not?

A

Can dose adjust if this occurs not for renal dysfunction, just to lessen side effects

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16
Q

What are goal peak and through concentrations of flucytosine? When are they drawn? What dose is associated with increased toxicity

A

goal peak 70-80 ug/ml
- DRawn 2 hours post dose after 3-5 days
Trough concentration 20-40 ug/ml

Peak concentration associated with increased toxicity

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17
Q

spectrum of activity of flucytosine? When is it first line

A

Candida and cryptococcus

First line in cryptococcus

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18
Q

flucytosine adverse effects

A

Hematologic effects (bone marrow suppression)

GI (N/V/D), pain, enterocolitis

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19
Q

What to monitor for flucytosine? Drug interactions?

A

Monitor- CBC, platelets, SCr, BUN

No significantd rug interactions

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20
Q

bioavailability of flucanozole? How is it excreted?

A

Bioavailability >90% and decent CSF concentration (60% if uninflamed, 80% in inflamed)

Excreted unchanged in urine

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21
Q

Do we renally adjust in flucanozole? What is dosing based on?

A

Dose reduce in renal insufficiency.

Dosing based on total body weight (npt adjusted)

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22
Q

Clinical use of flucanozole (1st line)

A

1st line in Invasive candidiases

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23
Q

Doses of flucanozole for C albicans and C glabrata

A

C. albicans; 800 mg (12 mg/kg) loading dose, then 400 mg (6mg/kg) daily

C glabrata- 800 mg daily (loading dose 1200-1600 mg) depending on susceptibility

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24
Q

Non first line uses of flucanozole

A

Prophylaxis in bone marrow transplant- 400 mg daily

Cryptococcal meningitis- alternative to amphotericin B +/- flucytosine for induction therapy

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25
Flucanozole dosing in cryptococca meningitis
Consolidation- 800 mg daily for 10-12 wks after CSF negative Maintenance- 400 mg daily for atleast 1 year AND remains asymptomatic from cryptococcal infection AND CD4 count > 100 for 3 months
26
adverse effect of flucanozole? Is it dose related side effects
QTc prolongation (might go to torsades de pointes) Dose related side effects
27
When is flucanozole 1st line
Candida albicans Candida parapsilosis Candida tropicalis Candida lusitaniae Coccidioides
28
What is itraconazole inhibited by
CYP P450
29
What is the active metabolite in itraconazole
hydroxyitraconazole
30
Describe the clearence of itraconazole
Clearence decreases with higher dose due to saturable hepatic metabolism
31
Is dose adjustment needed for renal dysfunction in itraconazole
No dosage adjustment needed
32
Bioavailability of itraconazole
Poor CSF penetration. Good absorption orally.
33
Describe the PK of itraconazole>? are capsules better absorbed or oral solution
Capsules absorbed better when taken with meal or acidic cola beverage Oral solution better absorbed in fasting state- not affected by gastric acidity Oral solution better absorbed than capsules
34
When is itraconazole first line? Dose?
Histoplasmosis- 200 mg PO TID x 3 days, then 200 mg PO BID Blastomycosis- 200 mg PO TID x 3 days, then 200 mg PO BID
35
Adverse effects of itraconazole Boxed warning?
Hepatotoxiciry CHF (Boxed warning), boxed warning QTc prolongation
36
Serum trough concentration goal for itraconazole
Serum trough itraconazole concentration > 0.5-1. Troughs > 1.5 combined itraconazole and hydroxyitraconazole associated with efficacy Serum trough concentration > 3 ug/ml associated with increased adverse events
37
When is itraconazole first line? What other prganisms is it effective against
1st line against- blastomyces and histoplasma aspergillus, coccidiodes, C albicans and parapsilosis
38
What drugs absorption is affected by gastric PH?
Posaconazole, only oral suspension
39
What happens if we give oral suspension posaconazole with PPI?
Decreased absorption with PPIs
40
Is posaconazole DR tab interchangeable with oral suspension
No
41
What formulation of posaconazole is orederred? WHy?
Delayed release tab preferred over oral suspenison This is because of absorption of oral suspension is affected by gastric PH
42
When should we avoid IVposaconazole? Why?
AVOID if CRCL < 50 Contains cyclodexedrin
43
When to give posaconazole with food? Without food?
Suspension and tab better absorbed when administered with food. Suspension better absorbed when administered in divided doses
44
Posaconazole adverse effects
QTc prolongation (main) N/V, rash, abdominat pain hypokalemia, pseudoaldosteronism AST/ALT/Bilirubin increase
45
SOA of posaconazole? Use?
Gets broader for molds and endemic fungi, used mainly for prophylaxis C. albicans, C. parapsilosis, C lusitaniae, Cryptococcus, blastomyces, histoplasma, coccidioides, aspergillus, mucor
46
What is voriconazole metabolized by? What is its PK like?
Significantly metabolized by CYP 450 isoenzyme (2C19, 2C9, 3A4) Non linear PK
47
Is dosing adjustment needed for voriconazole?
No dosage adjustment required for Oral dosing only
48
When to avoid voriconazole
If CRCL < 50 ml/min
49
IS VORICONAZOLE AFFECTED BY h2 ANTAGONISTS, PPIs AND ANTACIDS
no
50
clinical use of voriconazole
Invasive aspergillosis
51
voriconazole adverse effects
visual distrubances (main) elevated LFT QTc prolongatioon Phototovic skin rxn diffuse painful periostitis
52
SOA of voriconazole
everything except mucor Main 1st lne for aspergillus
53
Isavuconazole adverse effects
N/V/D headache Hepatic Infusion related rxn Hypokalemia DOES NOT CAUSE QT PROLONGATION (CAN ACTUALLY SHORTEN)
54
Isavucanozole drug interacion
overall considered to be the least drug interaction in the azole family
55
Contraindication of isavuconazole
isavucanozole shortens QT interval (patients with short QT syndrome)
56
Class adverse effect for azoles
hepatic dysfunstion QTC prolongation (except isovucanozole) Many drug interactions
57
what do the echinocandins usualy treat? What cant they treat? Exception
Treats candda Does not treat the mold and endemic fungi ( Cryptococcus, blastomyces, histoplasma, coccidiodes, mucor? May add micafungin to voriconazole in severe aspergillus infection
58
When do we use echinocandins as 1st line
C. glabrata C krusei C lusitaniae C auris ( the resistant ones)
59
caspofungin adverse effects
Histamine mediated symptoms- rash, facial swellinh, pruritis, flushing Fever Phlebitis at infusion site N/V Headache
60
What ROA is micafungin given at? Dose adjsutment?
Not oral, give IV No dosage adjustment for renal dysfunction
61
Drug interactions in micafungin
Not metabolized by CYP450 pathways
62
micafungin adverse effects
hyperbilirubinemia Nausea Diarrhea Eosinophilia Rash, pruritis, urticaria
63
What is the clinical use of ibrexafungerp
vulvovaginal candidiasis (VVC)
64
CI of ibrexafungerp
COntraindeicatd in pregnancy. Use effective contraceptive during and for 4 days after tx
65
When is flucanozole drug of choice? Echinocandin? (for candida)
Flucanozole- C albicans C parapsilosis C tropicalis C lusitaniae echino- C glabrata C krusei C lustaniae C auris
66
For the different molds/endemic fungi, what are the drugs of choice
Cryptococcus- flucanozole, amphoterecin, flucytosine Blastomyces- Itraconazole Histoplsma- itraconazole coccidioides- Flucanozole Aspergillus- voriconazole Mucor- Amphoterecin
67
What is the most common OI in people living with HIV
oropharyngeal candidiasis C albicans most common strain
68
What is the primary line of host defence agaist superficial candida infections
Cell mediated immunity
69
local factors that put us at risk for oropharyngeal candidiasis
Inhaled corticosteroids Dentures Smoking disruption of oral mucosa caused by chemo and radiotherapy Xerostomia due to drugs
70
Systemic factors that put us at risk for oropharyngeal factors
Drugs (cytotoxic, cortico, immunesuppressants) Neonates HIV infection/AIDS Diabetes Malignancies Nutritional deficiencies
71
Treatment duration of oropharyngeal candidiasis
Treat for 7-14 days
72
Tx of mild oropharyngeal candidiasis
Clotrimazole 10 mg lozenge 5 x/day (hold for 15-20 min) Nystatin 100,000 units/ml suspension, 5 ml swish and swallow x 4/day Miconazole 50 mg mucoadhesive buccal tablet (no eat and drink, no gum, do it after brushing teeth, hold in place 30 seconds to ensure adhesion)
73
How to treat esophageal candidiasis? Duration
treat for 14-21 days flucanozole 200-400 mg PO IV (drug of choice) itraconazole solution 200 mg PO daily Echinocandin
74
How do you classify complicated and uncomplicated vulvovaginal candidiasis? describe them?
Uncomplicated- Sporadic infection that is susceptible to all forms of antifungal therapy regardless of tx duration Complicated- Recurrent VVC, severe, non candida albican infection, host factor(DM, pregnancy, immunosuppression)
75
Most common infection with vulvovaginal candidiasis
C albicans
76
what increases risk for vulvovaginal candidiasis
Increased incidence when women become sexually active Oral genital contact increases risk COntraceptoves such as IUD, high dose oral contraceptives) ANTIBIOTIC USE IS MAIN ONE
77
cure rate for uncomplicated (VVC) for different meds
80-95% with topical or oral azoles 70-90% with nystatin
78
what to know when prescribing for VVS tx
many topical agents do not require a prescription Topical preparations can decrease efficacy of latex condoms and diaphragms