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67 Cards in this Set
- Front
- Back
What are the 4 major classes of antifungal drugs?
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alter cell membrane permeability
block nucleic acid snthesis disrupt microtubule function disrupt fungal cell wall |
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what are the major drugs that affect fungal cell membrane permeability?
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polyenes
azoles allylamine and benzylamine |
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what are the major drugs that block fungal nucleic acid synthesis?
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flucytosine
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what are the drugs that disrupt fungal microtubule function?
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griseofulvin
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what are the drugs that disrupt fungal cell wall?
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echinocandins
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which antifungals can be used for subcutaneous and systemic mycoses?
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amphotericin B
flucytosine azoles echinocandins |
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what is amphotericin B?
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polyene antibioitic
first choice for systemic mycoses |
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what is the MOA of amphotericin B?
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bind to ergosterol in fungal cell membranes to form pores --> electrolytes and small molecules leak --> DEATH
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what are the pharmokinetics of amphotericin b?
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highly insoluble, poorly absorbed
must be given IV low penetration into CSF |
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when is amphotericin B used?
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doc for systemic mycoses
widest spectrum aspergillus, candida albicans, cryptococcus, histoplasma, mucor |
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what are the infusion related adverse effects of amphotericin B?
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fever, chills, muscle spasms, vomiting, headache, hypotension
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how can the infusion related adverse effects of amphotericin B be attenuated?
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slowing infusion rate or decreasing daily dose
pre-medication w/ antihistamines, glucocorticoids, antipyretics, meperidine |
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what are the adverse effects of amphotericin b?
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renal impairment
anemia due to damaged tubular cells |
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what can intrathecal admin of amphotericin B cause?
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seizures and neurological damage
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what is the advantage of lipid formulations of amphotericin b?
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less nephrotoxicity
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what is flucytosine?
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synthetic pyrimidine antimetabolite
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when is flucytosine used?
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only in combination w/ amphotericin for treatment of systemic mycoses and meningitis
cryptococcus neoformans and candida |
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what is the moa of flucytosine?
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taken up in fungal cells via enzyme cytosine permease
converted to f-FdUMP which inhibits thymidylate synthetase - blocks synth of dTMP |
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what are the adverse effects of flucytosine?
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result from metabolism to 5-flurouracil (affects intestinal flora)
bone marrow suppresion |
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how are azoles classified?
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imidazoles
triazoles |
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what are the imidazoles?
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ketoconazole
miconazole clotrimazole |
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what are the triazoles?
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itraconazole
fluconazole voriconazole posaconazole |
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what is the moa of azoles?
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inhibits enzyme that converts laosterol to ergosterol = disrupts membrane function and increases permeability
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what is the difference between imidazoles and triazoles?
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imidazoles are less specific than triazoles
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what are the adverse effects of azoles?
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minor GI upset
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what are adverse effects of ketoconazole?
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decrease plasma testosterone levels --> gynecomastia, decreased libido, loss of potency in men, menstrual irregularities in women
high doses inhibit adrenal steroid synthesis and decrease plasma cortisole |
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what is the moa of ketoconazole
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inhibits mammalian cytochrome P450 enzymes, CYP3A4
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what are the PK of ketoconazole?
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best absorbed at low gastric pH
poor penetration into CSF |
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when is ketoconazole used?
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superficial mycoses
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what are the PK of fluconazole?
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good csf penetration
high oral bioavailability |
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what liver enzymes does fluconazole interact with?
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moderate inhibitor of CYP3A4
strong inhibitor of CYP2C9 - can increase plasma levels of phenytoin, zidovudine and warfarin |
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when is fluconazole used?
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doc in espophageal, oropharyngeal, vulvovaginal candidiases
doc for coccidoides |
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when is fluconazole used prophylactically?
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in criptoccocal meningitis
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when is fluconazole ineffective?
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aspergillus or other filamentous fungi
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how is itraconazole metabolized?
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by CYP3A4
is strong inhibitor of |
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what drug interactions should one be aware of when administering itraconazole?
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may cause fatal arrhythmias when given w/ cisapride or quinidine
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what are the PK of itrazonazole?
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poor bioavailability
poorly penetrates CSF absorption reduced by antacids |
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when is itraconazole used?
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blastomyces, sporothrix, histoplasma
effective against apsergillus dermatophytoses and onychomycosis |
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when is voriconazole used?
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blastomyces, sporothrix, histoplasma
effective against apsergillus dermatophytoses and onychomycosis |
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which is more effective against aspergillus - itraconazole or voriconaole?
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voriconazole
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what is voriconazole not effective against?
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zygomycetes
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what is the treatment of choice for invasive aspergillosis?
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voriconazole
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what are adverse effects of voriconazole?
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visual distrubances
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how is voriconazole metabolized?
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by CYP2C19
inhibits CYP2C9 and CYP3A4 |
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what is posazonazole active against?
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blastomyces, sporothrix, histoplasma
effective against apsergillus dermatophytoses and onychomycosis ZYGOMYCETES - Mucor |
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how is fluconazole eliminated?
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renal
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which systemic azole penetrates the CNS?
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fluconazole
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what are the echinocandins active against?
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candida, aspergillus
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how are the echinocandins administered?
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IV
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what is the moa of the echinocandins?
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inhibit fungal cell wall synthesis
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what are the systemic antifungals used for superficial mycoses?
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griseofulvin
terbinafine ketoconazole fluconazole itraconazole |
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when is griseofulvin used?
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only dermatophytosis
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how is absoprtion of griseofulvin improved?
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when given w/ fatty foods
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what is the moa of griseofulvin?
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disrupts mitotic spindle and inhibits mitosis
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what is the moa of terbinafine?
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inhibits squalene epoxidase --> --> inhibition of ergosterol synthesis
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what are the adverse effects of terbinafine?
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gi upset
rash headache taste disturbances |
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what are the topical antifungals?
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nystatin
clotrimazole miconazole ketoconazole terbinafine naftifine butenafine amphotericin B |
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what is nystatin?
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a polyene antibiotic
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when is topical amphotericin b used?
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for cutaneous candidiasis
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what are the two most commonly used topical azoles used?
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clotrimazole and miconazole
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what is topical terbinafine effective against?
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tinea cruis and tinea corporis
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what is topical naftifine effective against?
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tinea cruis and tinea corporis
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what is butenafine?
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a benzylamine
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when is topical butenafine used?
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dermatophytes
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what is tonaftate used for?
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topically against dermatophyte
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how is pneumocystis jirovecii treated?
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co-trimoxazole (trimehoprim plus sulfamethoxazole
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what are some alternate therapies to p jirovecii?
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pentamidine
trimethoprim plus dapsone primaquine plus clindamycin atovaquone |