23. Antifungal Chemotherapy

Question 1

histoplasma, blastomyces, coccidoides, sporothrix

Answer 1

dimophic systemic fungi

Question 2

candida, aspergillus, cryptococcus

Answer 2

opportuninistic fungi

Question 3

sporothrix schenkii, dermatophytes trichophyton, epidermophyton, microsporum, ringworm, athletes foot, onchymycosis

Answer 3

cutaneous/subcutaneous fungi

Question 4

ergosterol and ergosterol synthesis, glucans, DNA and RNA synthesis, cell division

Answer 4

targets for antifungal therapy

Question 5

targets membrane function

Answer 5

amphotericin B

Question 6

target ergosterol synthesis

Answer 6

fluconazole, ibraconazole, voriconazole, naftiline, terbinafine

Question 7

target nucleic acid synthesis

Answer 7

5-fluorocytosine

Question 8

target cell wall synthesis

Answer 8

caspofungin

Question 9

most widely used drug to treat fungal infections, broad spectrum, significant toxicity, binds to ergosterol in the fungal cell membrane, forms amp B containing pores, alterative treatment for candia or cryptococcus, or molds like aspergillus, histoplasma, coccidiodes, blastomyces, sporothrix, mucormycoses, resistance by decreasing ergosterol in the membrane, nearly insoluble in water, complexed with a bile saly for IV infusion, widely distributed into most tissues, most serious toxicity is nephrotoxicity, also fever, chills, muscle spasm, vomiting, headache, hyper/hypotension, also renal tubule injury and dysfunction, new formulations are packaged in a liposome to prevent binding to human cell membranes to reduce toxicity

Answer 9

amophotericin B

Question 10

bind to enzyme converting lanosterol to ergosterol, used on pathogenic yeast like candida and cryptococcus, used on systemic myocoses like histoplasmosis, blastomyocosis, coccidioidomycosis, and dermatophytes like onychomycosis, resistance is increasing due to efflux pumps, mutations in the target enzyme, and decreased ergosterol content in the cell membrane, causes minor gastrointestinal disturbances, interacts with CYP450s, rarely used

Answer 10

azoles

Question 11

oral or IV, water soluble and widely distributed, lowest level of interaction with P450s of all azoles with the widest therapeutic index, used for candidiasis, cryptococcus, coccidiomycosis, second line for histoplasmosis, blastomycosis, and sporotrichosis

Answer 11

flucanzole

Question 12

broader spectrum of activity than fluconazole, worse bioavailability and therapeutic index, requires low gastric pH so is impaired bt antacids, proton pump inhibitors, and H2 blockers, interaccts with CYPs so interacts with rifampin, digoxin, cyclosporine, hypoglycemic agents, coumadin, drug of choice for blastomycosis, coccidiomycosis, histoplasmosis, sporotrichosis, dermatophytes/ onychomycosis

Answer 12

itraconazole

Question 13

similar bioavailability to fluconazole, broad spectrum of activity, used in candida infection, endemic dimorphic fungi, replaced amphotericin B for treatment of aspergillosis, causes transient visual disturbances, blurred vision, photophobia, altered perception of color

Answer 13

voriconazole

Question 14

broadest spectrum activity of all azoles, treats most species of candida, aspergillus, and the agents of mucormycoses, also active against cryptococcus and dimorphic fungi, given orally, absorption improved with fatty meals, rapidly distrubtedinto tissues, high tissue but low serum levels, strong inhibitor of CYP450s

Answer 14

posoconazole

Question 15

greater solubility, administered as a prodrug and needs to cleaved, adminstered orally, unaffected pH, alternative treatment for invasive aspergillosis and mucormycosis

Answer 15

isavuconazole

Question 16

fluorinated pyrimidine analog, combination therapy for some systemic infections like cryptoccocus, candida, transported by cytosine permease into the fungal cell, incorportated into RNA disrupting protein synthesis or is converted into deoxynucleosides and inhibits DNA synthesis, used almost exclusively as part of combination therapy like cryptococcal infections, given orally, rapidly distributed throughout tissues, can cause bone marrow toxicity leading to anemia, leukopenia, and thrombocytopenia

Answer 16

flucytosine

Question 17

newest class of antifungal drugs, inhibit cell wall synthesis, lipopeptides linked to long fatty acids, -fungin, high selective degree of toxicity due to lack of B-glucans in mammalian cells, blockade weakens fungal cell walls causing greater osmotic stress on the fungal cell, however also limited to presence of B-glucans in cell wall, all given IV, distrubted through all major organs, poor penetration of CNS

Answer 17

echinocandins

Question 18

griseofulvin, allylamines/terbinafine

Answer 18

oral systemic medications for cutaneous and mucocutaneous infections

Question 19

very insoluble crystal, absorption improved with fatty meals, unclear mechanism of action, possibly interferes with microtubule function, largely replaced by newer drugs, second line agent in treatment of dermatophyte infections, can cause headache, hepatotoxicity, and GI stress, drug interaction by increasing warfarin effectiveness and decreasing effectiveness of oral contraceptives

Answer 19

griseofulvin

Question 20

inhibitors of ergosterol synthesis, inhibit enzyme squalene epoxidase, susceptible fungi have defective or damaged cell membranes, available in both topical and oral forumlations, keratophillic like griseofulvin in skin, hair, and nails, good for nail infections

Answer 20

allylamines/terbinafine

Question 21

polyenes like nystatin, azoles like efinaconazole, clotrimazole, miconazole, allylamines like terbinafine and nafitine, and others like ciclopirox

Answer 21

topical antifungal agents

Question 22

first topical triazole used to treat onychomycosis, low affinity for keratin so penetrates into nail bed, minimal systemic absorption, cure rate of 50%

Answer 22

efinaconazole

Question 23

blocks membrane transport, alters membrane permeability, binds iron, broad activity against yeast and molds, minimal absorption beyond the nail, little information on adverse reactions

Answer 23

ciclopirox

Question 24

polyene antifungal drug related to amphotericin B with similar mechanism of action, only used topically, poor absorption, toxic, unpleasant taste, given as a cream, ointments, suppositories, and oral suspections, active against most species of candida, most commonly used to treat local infections like oropharyngeal and vaginal candidiasis

Answer 24

nystatin

Question 25

two most commonly used topical azoles like clotrimazole and miconazole, used for vulvovaginal candidiases and dermatophyte infections like tinea corporis/pedis/cruris, oral lozenges are available for treatment of oral thrush, alternative to nystatin, absorption is neglible, adverse effects are rare, azole resistance is rare amongst dermatophytes,

Answer 25

topical azoles are available in numerous OTC formulations