Sweatman: Fungal Infections of the lungs

Question 1

uncommon cause of pneumonia, hematogenous spread in immunocompromised pt.’s

Answer 1

candida albicans

Question 2

Associated with pigeon droppings; can produce cryptococcal meningitis

Answer 2

cyrptococcus

Question 3

name the yeasts

Answer 3

candida, cryptococcus

Question 4

name the dimorphics

Answer 4

blastomyces, histoplasma coccidiodes

Question 5

name the mold

Answer 5

aspergillus

Question 6

Aspergillomas (fungal balls) can form in pre- existing cavities; the invasive form spreads hematogeneously

Answer 6

aspergillus

Question 7

Causes pneumonia-like lung disease and may progress to disseminated disease

Answer 7

blastomyces

Question 8

Caseating granuloma formation in tissue; the disseminated form is marked by multi-system involvement with macrophage infiltrates filled with intracellular fungi

Answer 8

histoplasma

Question 9

May have acute, disseminated or chronic course. Fungal spheres containing endospores are found in granulomas

Answer 9

coccidoides

Question 10

resembles TB

Answer 10

histoplasma

Question 11

flucytosine has only one indication

Answer 11

crytococcal infections

Question 12

tx for candida albicans

Answer 12

ampho B IV and fluconazole

Question 13

tx. for cyrptococcus neoformans in the CNS

cryptococcal meningitis

Answer 13

IV Ampho B + fucytosine

Question 14

tx for cryptococcus non-CNS

Answer 14

fluconazole PO

Question 15

Tx for aspergillus

Answer 15

Ampho B IV or voriconazole (previously itraconazole)

*step down voriconazole PO

Question 16

Tx for blastomyces

Answer 16

Ampho B IV if severe or fluconzaole IV (formerly itraconazole)
*step down: vori, itra, or fluconazole PO

Question 17

Tx for histoplasma if severe or immunocompromised

Answer 17

AMpho B: IV followed by itraconazole

Question 18

Tx for histoplasma if mild-moderate

Answer 18

voriconazole or posaconazole, fluconazole PO

formerly itraconazole

Question 19

Tx for coccidiodes if severe or immuncompromised

Answer 19

AMpho B IV followed by itraconazole of fluconazole PO

Question 20

Tx for coccidioides if mild-moderate

Answer 20

voriconazole or pasoconzaole PO

formerly itraconazole of fluconazole

Question 21

first line therapy for most fungal species involves…

Answer 21

azole antifungal or ampho B IV

Question 22

MOA for azoles

Answer 22

nhibit the enzyme lanosterol 14 α-demethylase; the enzyme necessary to convert lanosterol to ergosterol. Depletion of ergosterol in fungal membrane disrupts the structure and many functions of fungal membrane leading to inhibition of fungal growth.

Question 23

MOA for Ampho B

Answer 23

binds with ergosterol, a component of fungal cell membranes, forming a transmembrane channel that leads to monovalent ion (K+, Na+, H+ and Cl−) leakage, which is the primary effect leading to fungal cell death.

Question 24

WHy lipid formulations of Ampho B are favored now?

Answer 24

avoid nephrotoxicity associated with deoxycholate form of the drug
*can bore holes in host membranes too)

Question 25

Why moving away from itraconazole

Answer 25

oral absorption of itraconazole is poor and variable

Question 26

only azole abel to penetrate BBB

Answer 26

fluconzaole

Question 27

Metabolism of Azoles

Answer 27

hepatic CYP’s…LARGE chance of driug-drug interaxns

Question 28

main cyps involved in azoel metabolism

Answer 28

2c9, c19, 3a4

Question 29

do Ampho B and flcytosine undergo hepatic metabolism

Answer 29

no

Question 30

drug interactions with ampho b

Answer 30

other nephroxic agents and durgs inducing hypokalemia (K watsing diuretics)

Question 31

caution with flucytosine

Answer 31

hemotoxic drugs because flucytosine can cause anemia and blood dyscrasias..including agranulocytosis

Question 32

MOA for flucytosine

Answer 32

Pyrimadine analog, converted intrcelularly to 5-florouracil, eventually inhibits fungal RNA synthesis loss of crucial proteins) and DNA synthesis upon further metabolism