Antimycotics

Question 1

are mycoses acute or chronic in nature?

Answer 1

chronic usu

Question 2

do fungal infections stay local or become systemic?

Answer 2

can be superficial and local but can go systemic if individual is immunocompromised

Question 3

how hard is it to treat systemic fungal infections?

Answer 3

VERY DIFFICULT and commonly life threatening

Question 4

how do many anti-fungals act?

Answer 4

act by binding to the fungal cell wall or cell membrane and disrupting permeability
others disrupt fungal DNA and/or RNA synthesis
anti-fungal meds may be fungi-static or fungi-cidal

Question 5

drug that affects membrane fxn?

Answer 5

amphotericin B

Question 6

drug that effects ergosterol synthesis?

Answer 6

fluconazole, itraconazole, voriconazole, naftifine, terbinafine

Question 7

drug that can inhibit cell wall synthesis?

Answer 7

caspofungin

Question 8

drug that can inhibit nucleic acid synthesis?

Answer 8

5-fluorocytosine

Question 9

3 topical anti-fungals?

Answer 9

clotrimazole/lotrimin, nystatin/mycostatin, miconazole/monistat

Question 10

systemic antifungal categories?

Answer 10

polenes
azoles
echinocandins

Question 11

gold standard to tx fungal infxn? how to give it? MOA? ADRs? pre-medicate w/what?

Answer 11

amphotericin B= GOLD STANDARD
give IV
MOA: binds to ergosterol in fungal cell membrane forming pores= increased permeability= cell death
ADRs: legendary “shake and bake”- related to IV infusion, cumulative toxicity can lead to renal damage
pre-medicate w/antihistamines, antipyretics, corticosteroids

Question 12

strengths of amophotericin B? limitations? indications?

Answer 12

strengths: broad spectrum, inexpensive
limitations: toxicity “shake and bake”
indications: broadest spectrum of activity, activity against all clinically significant yeasts, life threatening infections

Question 13

MOA of azole antifungals? -cidal or -static drug?

Answer 13

MOA: inhibit cytochrome P450, interacts w/cytochrom P450 drug metabolism (can cause inhibition or stimulate metabolism), block formation of ergosterol
considered a “static”

Question 14

two classes of azole antifungals?

Answer 14

imidazoles
triazoles (used less often b/c more drug-drug interactions and more SEs)

Question 15

ADRs of azole antifungals?

Answer 15

GI upset, hepatitis, drug interactions through cytochrome P450 system of enzymes, increases levels of warfarin

Question 16

most commonly used systemic antifungal? strengths? weaknesses?

Answer 16

fluconazole

strengths: lack of toxicity, oral bioavailability is excellent, extremely active against c. albicans
weakness: spectrum low, often underdosed

Question 17

3 echinocandins? MOA?

Answer 17

caspofungin, micafungin, andiulafungin

MOA: cause disruption of fungal cell wall= cell death

Question 18

echinocandins are potent against what fungus? how to administer? cidal or static? strengths?

Answer 18

potent against candida esp
IV only
fungicidal
strengths: well tolerated, excellent pharmokinetics, few drug-drug interactions, no cross-resistance w/azoles

Question 19

weaknesses of echinocandins?

Answer 19

limited spectrum, oral formulation not available, $$$

SE: mild GI and flushing

Question 20

preferred formulation for superficial mycoses (location dependent)?

Answer 20

cream of solution
but powders for feet/groin
topical administration not successful for nails and hair

Question 21

indication for clotrimazole/lotrimin? MOA?

Answer 21

superficial mycoses such as the tineas, ring worm, yeast vaginitis, oral thrush
MOA: binds to ergosterol molecules on fungal cell membrane and causes membrane leakage during cell division

Question 22

how to administer clotrimazole?

Answer 22

topical creams, lotions, ointments for tinea and candida

cream, lotion, powder, aerosol, vaginal cream, vaginal tablets, troches (for thrush)

Question 23

how is nystatin commonly used? indications? MOA?

Answer 23

used topically- creams, ointments, lotions, solution
indications: superficial mycoses, oral candidiasis as well as esophageal and vaginal candida
MOA: binds to ergosterol molecules on fungal cell membrane= cell death

Question 24

when is nystatin often used??

Answer 24

prophylaxis in pts who are at risk for fungal infxns, such as AIDS pts w/low CD4+ count and patients receiving chemo

Question 25

tx options for thrush?

Answer 25

clotrimazole troches, nystatin suspension, fluconazole orally

Question 26

terbinafine class? MOA? used for?

Answer 26

class: synthetic allylamine
MOA: interferes w/ergosterol biosynthesis
used primarily for dermatophyte infxns (nail/skin)

Question 27

strengths of terbinafine? weaknesses?

Answer 27

strengths: good oral bioavailability, very active against dermatophytes, active against candida spp
weaknesses: no IV formulation, very limited clinical experience outside dermatophyte infxns

Question 28

how to dose terbinafine/lamisil?

Answer 28

250 mg per day for 6 continuous wks to treat fingernail fungal infxns and 12 wks to treat toenail infnxs

Question 29

SEs of terbinafine/lamisil?

Answer 29

abd discomfort, diarrhea, nausea, h/a, elevated liver enzymes, hepatitis, liver damage, liver failure