Antifungal Agents

Question 1

Amphotericin B: MOA

Answer 1

broadest spectrum antifungal availabe. creates a TM channel that allows for cation leak and binds to ergosterol irreversibly. (ampho”tear”acin tears holes in the fungal membrane)

Question 2

Amphotericin B: side efects

Answer 2

Key points: fevers/chills, hypotension, nephrotoxicity, arrhythmias, anemia, IV phlebetis. hydrate to decr. nephrotoxicity. liposomal amphotericin has lower toxicity.

(fevers, chills and nausea: premedicate with tylenol and benadryl
NEPHROTOXICITY- vasoconstriction of afferent arteriorles in the kidney. may decrease GFR by more than 50%.
hypokalemia and hypomagnesemia.
lipid formulations somewhat less toxic (but MUCH more expensive)

Question 3

nystatin: MOA, use

Answer 3

MOA like amphotericin B. binds ergosterol and forms pores. causes leakage of cations and cell death. too toxic for systemic use. not absorbed through GI and GU mucosa, so can give orally for thrush or vaginally for yeast infections. broad spectrum

Question 4

Flucytosine: MOA

Answer 4

5-FU. interferes with DNA and protein synthesis. must be converted to 5FU from 5-FC by cytosine deaminase, which is only found in fungi.

Question 5

Flucytosine uses

Answer 5

Clinically used with amphotericin for crytpoccocal meningitis in immunocompromised

(may be good for candida, crytococcus too)
(Not for histoplasma, blastomyces, coccidiodes, aspergillis, dermatophytes; should not be monotherapy for serious infections. given PO)

Question 6

flucytosine side effects

Answer 6

First aid: Bone marrow suppression.

liver, gi, blood (anemia, thrombocytopenia, leukopenia). moniter CBC and liver function as well as drug levels

Question 7

what are the azoles?

Answer 7

fluconazole, itraconazol, voriconazole, posiconazole (ketoconazole- not used bc of liver failure)

Question 8

Azole MOA

Answer 8

inhibit linosterol 14 alpha demethylase (part of egosterol pathway; a P-450 enzyme)

Question 9

Azoles: targets, side effects

Answer 9

all may cause hepatic function abnormalities, all may inhibit synthesis of testosterone
all have drug-drug interactions (cytochrome p450).

Question 10

fluconazole: special uses

(uses, sides, administration, CNS)

Answer 10

chronic suppression of cryptococcal meningitis in AIDS patients, and candida

(PO and IV- PO absorption is great
good CNS penetration
once daily dosing
good for candida, crytptococcus. may need to test yeast for susceptibility. some activity against histo, blasto, coccidiodes. no mold activity. some hepatotoxicity. not for pregnant women.)

Question 11

itraconazole: special use

use, administration, CNS

Answer 11

used for bastomyces, coccidiodes, and histoplasma

(broader spectrum including endemic fungi. administrate as a capsule or a soluntion. must have capsule with an acidic drink. solution best on an empty stomach, though this may increase GI upset. does NOT get to CNS)

Question 12

(itraconazole sides)

Answer 12

(hypertension, hypokalemia, peripheral edema, heart failure, long QT, tosades de pointes. check for drug interactions)

Question 13

(Vorconzaole: use, admin, CNS)

Answer 13

(IV, oral. great CNS penetration. broader activity including aspergillis, fusariu, scadeosporin, candida species that aren’t susceptibe to fluconazole)

Question 14

(Voriconazole side effects)

Answer 14

(transient vision changes (photophobia, weird colors), photosensitivity rash, periostitis. visual hallucinations is a sign of neurotoxicity. Can also cause heart failure, long QT, torsades de points.)

Question 15

(Posaconazole: uses)

Answer 15

(zygomycetes and aspergillis, candida, etc. may treat mucor if someone really can’t handle amphotericin. only PO taken with high fat food or carbonated beverage.)

Question 16

griseofulvan. admin, use, sides

Answer 16

interferes with microtubule function and disrupts mitosis. deposits in kerotin containing tissues. used as an oral treatment for superficial infections and inhibits growth of dermatophytes.
it is teratogenic, carcinogenic, causes confusion, headaches, incr. P450, and can increase warfarin metabolism (and granulocytopenia)

(take orally for onychomycosis and tinea capitis. fungistatic with decreased mitotic spindle formation
sides: granulocytopenia)

Question 17

echinocandins: MOA, use, advantage, disadvantage. names.

Answer 17

aka caspofungin, micafungin, anidulafungin.
treats cell wall by targeting glucan synthesis (inhibits synthesis of beta glucans). good IV for candida and aspergillis. may cause GI upset or flushing via histamine release

fewer drug-drug interactions. very very expensive. Names: caspofungin, micofungin, anidulafungin.

Question 18

terbinifine

Answer 18

inhibits squalene epoxidase. leads to accumulation of squalene, which is toxic. treats dermatophytes, esp. onychomycosis and tinea capitis. sides: hepatotoxicity (GI upset, headaches, taste disturbance).