Antifungals

Question 1

amphotericin B mechanism

Answer 1

binds ergosterol –> forms pores –> electrolyte leakage

Question 2

ampho B specrum

Answer 2

systemic mycoses (cryptococcus, blastomyces, coccidiodes, histoplasma, candida. supplement w/ K+ / Mg2+ due to altered renal tubule permeability

Question 3

amp B toxicity

Answer 3

fever / chills, hypotension, IV phlebitis, arrythmias, nephrotoxicity.

hydration –> dec. nephrotoxicity

Question 4

nystatin

Answer 4

too toxic for systemic use.

punches pores in ergosterol membrane.

used for oral thrush / diaper rash

Question 5

azoles mechanism

Answer 5

inhibit fungal synthesis by inhibiting P450 conversion of lanosterol to ergosterol

Question 6

azole spectrum

Answer 6

1) local / less serious mycoses. 2) chronic suppression of cryptococcal meningitis in AIDS / candidal infections of all types.

Question 7

specific treatment for blastomyces, coccidiodes, histoplasma

Answer 7

itraconazole

Question 8

azole toxicity

Answer 8

1) inhibits testosterone synthesis –> gynecomastia

2) inhibition P450 –> liver dysfunction

Question 9

flucytosine mechanism

Answer 9

inhibit DNA / RNA biosynthesis by conversion to 5-FU by cytosine deaminase

Question 10

fluctyosine spectrum

Answer 10

systemic fungal infections (cryptococcus menigitis) in combo w/ ampho B

Question 11

flucytosine toxicity

Answer 11

bone marrow suppression

Question 12

echinocandins (ends in fungin)

Answer 12

inhibits b-glucan –> cell wall synthesis inhibition

Question 13

echinocandins clinical use

Answer 13

invasive aspergillosis / candida

Question 14

echinocandins toxicity

Answer 14

flushing via histamine release / GI upset

Question 15

terbinafine

Answer 15

1) squalene epoxidase inhibition
2) dermatophytes (onychomycosis)
3) hepatotoxicity, taste disturbance

Question 16

griseofulvin

Answer 16

1) interferes w/ microtubules –> mitosis disruption
2) superficial infxn / dermatophytes (tinea, ringworm)
3) teratogenic, carcinogenic, incr. P450 / warfarin metabolism

Question 17

chloroquine mechanism

Answer 17

blocks detoxification of heme into hemozoin –> heme accumulation leads to toxicity in plasmodia

Question 18

chloroquine spectrum

Answer 18

1) ineffective in p. falciparum (too much resistance)

Question 19

life-threatening malaria treatment

Answer 19

quinidine / artesunate

Question 20

p. falciparum treatment

Answer 20

artemether / lumefantrine OR atoaquone/proguanil