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14 Cards in this Set

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  • Back
Amphotericin B
polyene related to nystatin - usually given IV as nonlipid colloid suspension; widely distributed except to CNS; bind to ergosterol and cause formation of artificial pores; most important drug for systemic mycoses; widest antifungal spectrum and remains DOC for apergillus, blastomyces, candida albicans, cryptococcus, histoplasma, and Mucor; fast infusions may cause fever, chills, muscle spasms; it decreases FGR and causes acidosis w/ loss of Mag and Potass; intrathecal dose may cause seizures and neurologic damage
Flucytosine (5-FC)
pyrmidine antimetabolite related to anticancer drugs -orally effective and widely distributed; accumulates in fungal cells by membrane permease and converted to 5-FU which blocks thymidylate synthase - resistance is due to fungal activity of permeases or deaminase; limited spectrum; limited to treament in combo w/ amphoB or fluconazole in Cryptococcus neoformans and possiby systemic candidal; prolonged use can cause reversible bone marrow suprresion, alopecia, and LiverD
the Azoles
Keto, Fluco, Itra, Voricon - Fluco and Vori are more reliably absorbed via oral; inducers of enzymes (rifampin) decrease bioavailabilty; they interfere w/ fungal cell permeabily by inhibiting synthesis of ergosterol;
rarely used for systemic; good use for chronic mucocutatneous candidasis and also in dermatophytes
DOC in esophageal and Oropharnygeal candidiases and for most infections by Coccidioides; single oral dose erradicates yeast infections; DOC for initail and secondary proph against cryptococcal meningitss
DOC for systemic infections by Blastomyces and Sporothrix and for subcutaneous chromoblastomycosis; alternative tx for asper, coccidio, cryptococcus, and histo; also used in onychomycosis
newer azole w/ wider specturm than itra, coDOC for invansive apergillosis, and alternative in candidemia in AIDS
Toxicity of Azoles
vomitting, diarrhea, rahs and sometimes hepatoxicity; Keto is notorious inhibitor of P450 and may increase levles of many drugs; it also interfeeres w/ synthesis of adrenal and gonaldl steroids leading to gynecomastia, ammenorrhea, and infertility; Voriconazle causes transiet visual distubrances in more than 30%
Drugs metabolized by enzymes inhibited by Keto?
cisapride, chlordiazeopoxide, cyclosporine, didanosine, fluoxetine, loratidine, lovastatin, methadone, nifedipine, phenytoin, quinidine, tacrolimus, theophylline, verapamil, warfarin, zidovudine, and zolpidem
Drugs that inhibit P450?
chloramphenicaol, cimetidine, clarithromycin, disulfiram, erythromycin, ethanol, grapefruit joice, estradiol, fluconazole, isoniazide, itraconazole, MAOs, phenylbutazone, and secobarbital
used IV, distributes widely, inhibits synthesis of B-glycan; a critical component of cell walls; currently used only in management of invasive aspergillosis; non-toxic (headache)
superficial fungal infections; distributed to stratum korneum where it binds keratin; exrected biliary; interferes w/ microtubule function in dermatophytes and may inhibit synthesis and polymerization of nucleic acids; resistance can occur when transport is decreased; DONT USE IN PATIENTS W/ PORPHYRIA, decreases bioavaliabilyt of warfarin and also causes disulfiram reactions w/ ethanol
inhibits fungal ezyme squalene epoxidase which leads to toxic accumulation of squalene; fungicidal; accumulates in kerratin but much more effective than griseofulvin in onychomycosis; does not inhibit p450; dont use in liver disease
polyene disrupts by binding ergosterol, used topically to suprrese candidal and orally to eradicate GI fungi in pateints w/ immunosuprresion; miconazole, clotrimazole, haloprogin, tolnaftate, and undecylceni acid are others