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CPR Exam 2 > Pharm: Fungal Infections > Flashcards

Pharm: Fungal Infections Flashcards

1
Q

What is the MOA of amphotericin B?

A

Binds to the sterol component of cell membrane –> alteraction in cell permeability –> death

Also binds cholesterol component of mammalian cell –> cytotoxicity (very nephrotoxic)

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2
Q

What is the standard tx for invasive fungal infections?

A

Amphotericin B

Reserved for those with severe, life-threatening infections or those who cannot tolerate other meds due to toxicities

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3
Q

What are the indications for amphotericin B?

A

Cryptococcus neoformans

Blastomyces dermatitidis

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4
Q

What are the contraindications of amphotericin B?

A

Hypersensitivity

Renal impairment

Make sure you monitor serum electrolytes

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5
Q

What are the AEs of amphotericin B?

A

Nephrotoxicity biggest

Lots of others too

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6
Q

What is the big warning for amphotericin B?

A

Inadvertent overdose –> fatal cardiac or cardiopulmonary arrest

Make sure you verify the name and dosage before administration

Observe pt closely during 1st administration

Anaphylaxis reported

N/V, chills, and rigors are common with IV

May require use of phenothiazine such as promethazine

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7
Q

What is the black box warning for amphotericin B?

A

Should not be used for non-invasive forms of fungal infection

Serious risk of nephrotoxicity (binds to cholesterol in human tissues and disrupts cell membranes)

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8
Q

What are some drug interactions with amphotericin B?

A

aminoglycoside –> nephrotoxicity

cyclosporine –> nephrotoxicity

anti-neoplastic agents –> nephrotoxicity

Muscle relaxants –> hypokalemia

Digitalis glycosides –> hypokalemia

Flucytosine –> increases toxicity

Pregnancy category B

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9
Q

What are the azole drugs we have to know?

A

fluconazole

itraconazole

voriconazole

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10
Q

What is the MOA of fluconazole?

A

interrupts conversion of lanosterol to ergosterol via binding to fungal cytochrome P-450 and subsequent disruption of fungal membranes

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11
Q

What are indications for fluconazole?

A

Candida UTI/peritonitis

Vaginal candidiasis

Thrush

Cryptococcal meningitis

Prophylaxis of candidiasis with BM transplant

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12
Q

What are containdications of fluconazole?

A

coadministration of terfenadine

coadministration of drugs know to prolong QT interval

coadministration with CYP3A4 metabolized drugs

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13
Q

What are some warnings associated with fluconazole?

A

hepatic injury (some cases of serious hepatic toxicity)

Potential for fetal harm in pregnant patients –> birth defects

QT prolongation (inhibits recrifier K channel current, may cause torsades especially in pts with hypokalemia and cardiac failure)

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14
Q

How is fluconazole metabolized?

A

Substrate and inhibitor of CYP450 (CYP3A4)

Lots of drug interactions (CCBs, immunosupressants, chemo drugs, benzodiazapines, anti-depressants, macrolides, SSRIs)

Renal elmination, removed by hemodialysis and peritoneal dialysis

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15
Q

What is the MOA of itraconazole?

A

Interrupts conversion of lanosterol to ergosterol via binding to CYP450 in fungi and disrupting fungal membranes

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16
Q

What are the indications for itraconazole?

A

broad spectrum

Aspergillus spp.

dematiaceous molds

Sporothrix schenckii

17
Q

What are some contraindications for itraconazole?

A

pregnancy

LV dysfunction

active CHF

use caution in CF patients, CVD, pulmonary dz, and elderly

18
Q

What are some warnings for itraconazole?

A

Serious liver disease

Monitory for n/v, loss of appetite, abdominal pain, jaundice, dark urine

19
Q

What is the black box warning for itraconazole?

A

inotripic effects –> BBW in pts with heart failure

BBW against use with other CYP3A4 affecting enzymes

20
Q

What is the MOA of voriconazole?

A

interrupts conversion of lanosterol to ergosterol via binding to fungal CYP450 –> disruption of fungal membranes

21
Q

What are indications for voriconazole?

A

Invasive aspergillosis

deep tissue candida infections

Esophageal candidiasis

scedosporium apiospermum

Fusarium spp.

22
Q

What are some contraindications of voriconazole?

A

galactose malabsorption/intolerance

Lapp lactase deficiency

glucose malabsorption

uncorrected electrolyte abonormalities

pregnancy

creatinine clearance <50 mL/min

Use with caution in QT prolongation/hx of torsades

23
Q

Why shouldn’t you give voriconazole to pts with galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption?

A

It contains lactose

24
Q

How is vorconazole metabolized?

A

Greater affinity for CYP2C19

Parenteral administration solubilized in compound secreted by kidneys –> need to change dose for pts with renal impairment

Oral dose doesn’t have to be adjusted

25
Q

What are some drug interactions associated with voriconazole?

A

inhibitors of induces of CYP450 enzymes have interactions

26
Q

What drugs are in the echinocandin class?

A

caspofungin

micafungin

anidulafungin

27
Q

When do you use echinocandins?

A

use IV in systemic candida infections

28
Q

What is the MOA of echinocandins?

A

inhibit beta (1,3)-D-glucan synthase

this enzyme forms glucan, a major component of fungal cell wall

Damage to fungal cell wall

29
Q

What is the indication for micafungin?

A

candidemia

acute disseminated candidiasis

candida peritonitis/abscess

esophageal candidiasis

Prophylaxis of candida infections in pts undergoing stem cell transplant

30
Q

What is a major AE or echinocandins?

A

Red man syndrome

31
Q

What is the black box warning for micafungin?

A

Foci of altered hepatocytes & hepatocellular tumor (not by US FDA but warning exists in Europe)

32
Q

What is the MOA of flucytosine?

A

pyramidine analogue that interferes with purine and pyramidine metabolism

33
Q

What drugs can you use flucytosine with?

A

ketoconaxole

fluconazole

itraconazole

liposoma amphotericin B for cryptococcal meningitis

34
Q

What is the black box warning for flucytosine?

A

extreme caution in pts with:

renal impairment

hematologic, hepatic, and renal function impairment

pregnant women

breastfeeding women

bone marrow supression

35
Q

How is flucytosine eliminated?

A

96% eliminated in urine as unchanged drug

CPR Exam 2 (8 decks)

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