Antibiotics Used in Systemic Fungal Infections

Question 1

Antifungal that acts on microtubules

Answer 1

Griseofuluin

Question 2

Antifungal that acts on DNA

Answer 2

Flucytosine

Question 3

Antifungal that acts on Squalene - Lanosterol

Answer 3

Terbinafine, Naftifine, Amorolfine

Question 4

Antifiungal that acts on Lanosterol - Ergosterol

Answer 4

Azoles

Question 5

Antifungal that acts on fungal cell wall

Answer 5

Echinocandins

Question 6

Amphotericin B Spectrum

Answer 6

broad range of fungal organisms, 2nd line for Aspergillis

Question 7

Amphotericin B ADE

Answer 7

Fever, Chills, Tachypnea, Nephrotoxicity (saline before/after), decreased K and MG, thrombophlebitis, normocytic anemia (decreased erythropoetin)

Question 8

How does 5-FC enter the cell

Answer 8

cytosine-specific permease

Question 9

MOA of 5-FC

Answer 9

converted to 5-FU, then to 5-dUMP, which inhibits thymidylate synthtase depriving the fungus of thymidylic acid

Question 10

5-FC spectrum

Answer 10

a few yeasts, used mostly synergistically with amphotericin B

Question 11

does 5-FC distribute in the CNS/CSF

Answer 11

Yes

Question 12

5-FC ADE

Answer 12

Bone marrow suppression, hepatic dysfunction, N/V/D

Question 13

Ketoconazole ADME & PK

Answer 13

Liver metabolized, t1/2 about 8 hrs

Question 14

Fluconazole ADME & PK

Answer 14

Better bioavailability and CNS/CSF penetration vs ketoconazole, renal elimination

Question 15

Itraconazole ADME & PK

Answer 15

Liver metabolised via 2C19, nonlinear PK, food decreases absorption

Question 16

Posaconazole ADME & PK

Answer 16

Liver metabolized to gluceronide conjugates, only PO, high fat meal increases absorption & no acid effect; NO CYP INTERACTION

Question 17

Itraconazole drug interactions

Answer 17

3A4 inhibitor

Question 18

Fluconazole interactions

Answer 18

3A4 and 2C9 inhibitror, raises plasma levels of cyclosporine, phenytoin, tacrolimus, theophylline, warfarin

Question 19

Voriconazole drug interactions

Answer 19

2C19, 2C9, 3A4 inhibitor

Question 20

posaconazole interactions

Answer 20

no CYP interactions

Question 21

azole ADE

Answer 21

hepatotoxicity, N/V/D, sin rash and alopecia, prolonged QT interval(itraconazole black box warning), visual disturbances and hallucinations (voriconazole), not used in pregnancy

Question 22

echinocandin drugs

Answer 22

caspofungin, micafungin, anidulafungin

Question 23

echinocandin MOA

Answer 23

inhibit synthesis of a key component of the cell wall of many filamentous fungi - beta (1,3)-D-glucan

Question 24

Caspofungin antifungal activity

Answer 24

invasive aspergillus (2nd line after vori), systemic candida

Question 25

andulafungin spectrum

Answer 25

systemic candida

Question 26

can echinocandins be used on cry[ptococcus

Answer 26

NO. it has alpha1,3 and alpha 1,6 linkages in the glucan polymers and a different enzyme catalyzes the reaction.

Question 27

echinocandin ADME & PK

Answer 27

IV only, does not cross BBB, highly protein bound, long half life (casp0 10hr, andula 26 hrs)

Question 28

echinocandin ADE

Answer 28

generally good safefty profile, phlebitis, rash and swelling with rapid infusion, altered liver or renal lab tests, hypokalemia