58. Antifungals

Question 1

what is the only thing that 5-FC is used for?

Answer 1

cryptococcal meningitis - used in combo w/amphotericin B

because emergence of resistance occurs rapidly

Question 2

what Rx targets fungal DNA?

Answer 2

5-FC

5-fluorocytosine (small pyrimidine, inhibits RNA synthesis, inhibits thymidylate synthase)

Question 3

5-FC toxicity?

Answer 3

hepatic (elevated AST and ALT), marrow (pancytopenia), CNS

Question 4

route of 5-FC elimination?

Answer 4

renal

Question 5

steroles or enzymes in their biosynthetic pathway are targets for three classes of antifungal agents - what are they?

Answer 5

poylenes, azoles, allylamines

Question 6

how does amphotericin B work?

Answer 6

binds directly to ergosterol in fungal cell membrane to form ionic pores (causes oxidative damage to membrane components)

Question 7

what antimycotics are the polyenes?

Answer 7

amphotericin B and nystatin

Question 8

what is the dose limiting toxicity of AmB?

Answer 8

renal: glomerular (increased BUN and creatinine thanks to afferent arteriolar vasoconstriction) and tubular (hypokalemia leaks through distal convoluted tubule; also hypomagnesemia…can result in prolonged QT and severe arrhythmias)

Question 9

how do azoles work?

Answer 9

inhibit cytochrome P-450 dependent enzymes (lanosterol C14-demethylase) required to synthesize ergosterol

Question 10

how do allylamines work?

Answer 10

inhibit squaline epoxidase; disrupts ergosterol synthesis

Question 11

spectrum of activity for amB?

Answer 11

yeasts and molds

Question 12

toxicity of AmB?

Answer 12

renal and infusion (chills, rigors, fever)

Question 13

route of AmB elimination?

Answer 13

hepatic and renal

Question 14

what is the point of hte lipid formulations of AmB?

Answer 14

decrease nephrotoxicity because target molecule away from the kidney and you can hit the fungi w/higher [ ] and less toxicity

Question 15

on what enzyme do allylamines work?

Answer 15

squalene epoxidase (prevents transformation from squalene into lanosterol)

Question 16

on what enzyme do azoles work?

Answer 16

C14 demethylase (prevents transformation from lanosterol to C14-methyl-lanosterol)

Question 17

what is the first line therapy to treat aspergillosis?

Answer 17

voriconazole

Question 18

how do echinocandins work?

Answer 18

inhibit cell wall synthesis (1,3 B-glucan formation)

Question 19

what is the specturm of echinocandins?

Answer 19

only candida and aspergillis

Question 20

what is the toxicity of echinocandins?

Answer 20

hepatic, rare infusion (histamine)

Question 21

route of elimination of echinocandins?

Answer 21

hepatic

Question 22

route of elimination of azoles?

Answer 22

hepatic

Question 23

spectrum of activity of azoles?

Answer 23

yeasts and filamentous fungi (aspergillus sometimes)

Question 24

candida has glucans, aspergillis has what?

Answer 24

galactomannan