Term
| Name some opportunistic yeasts. |
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Definition
|
|
Term
| Name some opportunistic molds. |
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Definition
|
|
Term
| What types of structures do molds form? |
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Definition
| multicellular filaments called hyphae with multiple genetically identical nuclei; considred a singl organism=mycelium |
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Term
| What areht different types of adverse affects from fungi? |
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Definition
| allergic disease, mycetism, mycotoxins, mycoses |
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|
Term
| What is mushroom poisoning called? |
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Definition
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Term
|
Definition
| fusarium mycotoxin and A. flavus "aflatoxin" |
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Term
| What are the different types of skin mycoses? |
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Definition
| superficial (skin or hair), cutaneous (skin, hair, nails), subcutaneous (skin, subq) |
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Term
| Wht are teh two types of deep mycoses? |
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Definition
| dimorphic systemic and opportunistic systemic |
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Term
| What are teh characteristics of dimorphic systemic mycoses? |
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Definition
| can overcome physiological defenses by changing morphological form, geographically resitricted, usually pulmonary problems |
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Term
| How do fungi cause infection in healthy hosts? |
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Definition
| block cell mediated immune response, special enzymes, exhibit thermal dimorphism |
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Term
| Human mycoses are generally related to the pateints... |
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Definition
| immune response or environmental exposure |
|
|
Term
| What are the components of the fungal cell wall? |
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Definition
| chitin, mannoproteins, glucans (beta 1,6 and beta1,3) |
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Term
| What is the experimental drug that is a chitin synthesis inhibitor? |
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Definition
|
|
Term
| what are teh different targets of antifungal drugs? |
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Definition
| membrane disrupting agents, ergosterol synthesis inhibitors, nucleic acid inhibitors, anti-mitotic (spindle disruption), glucan synthesis inhibitors, miscellaneous |
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|
Term
| What is the MOA of polyenes? cidal or static? |
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Definition
| bind sterols (preferntially ergosterol) and disrupts osmotic integrity of cell membrane; fungicidal |
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Term
|
Definition
| amphotericin B, nystatin, natamycin |
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|
Term
| How do you reduce toxicity and adverse side effects of polyenes? |
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Definition
|
|
Term
| What is IV: AmB lipid complex used for? |
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Definition
| broad spectrum antifungal activity |
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|
Term
| Use of IV: liposomal AmB= |
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Definition
| used in neutropenic patients with antibiotics and for aspergillosis, cryptococcus, candida |
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|
Term
| Use of IV: liposomal nystatin= |
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Definition
| broad spectrum antifungal activity |
|
|
Term
| What is the use of topical polyenes? |
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Definition
|
|
Term
| Which polyenes can be used topically? |
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Definition
| nystatin, natamycin, amphotericin B |
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|
Term
| Which antifungal is approved for topical use on the eyes? |
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Definition
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|
Term
|
Definition
| gastrointestinal absorption of all amb formulations negligible |
|
|
Term
| What percent of AmB is bound to plasma proteins? |
|
Definition
|
|
Term
| What percent of each dose of polyenes appears in urine? |
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Definition
|
|
Term
| Into which fluid compartments do polyenes not go? |
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Definition
| CSF, vitreous humor, or amniotic fluid |
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|
Term
| What is the half life of polyenes? |
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Definition
| extensive tissue binding-terminal phase of elimination with a half life of 15 days |
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|
Term
| What is the major limitation to AMB? |
|
Definition
| nephrotoxicity that is dose dependant and transient |
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|
Term
| How does AmB cause nephrotoxicity? |
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Definition
| affects renal blood flow and glomerular filtration and has a direct toxic effect on distal tubules via membrane disruption |
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|
Term
| What are the interactions with polyenes? |
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Definition
| nephrotoxicity is increased by concurrent tx with other nephrotoxic agents (aminoglycosides, cyclosporine), increased accumulation of renally-cleared drugs (flucytosine and fluconzaole) |
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|
Term
| Which two types of drugs inhibit the syntehsis of ergosterol? |
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Definition
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|
Term
| What are the two types of azolse? |
|
Definition
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|
Term
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Definition
| clotrimazole, miconazole, ketoconazole, econdazole, butoconazole, oxiconazole, sertaconazole, sulconazole |
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|
Term
|
Definition
| itraconazole, fluconazole, voriconazole, terconazole |
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|
Term
| What's the difference between imidazoles and triazoles? |
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Definition
| triazoles are metabolized more slowly than imidazoles and have less effect on human sterol synthesis than imidazoles |
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|
Term
| What is the MOA of azoles? cidal or static? |
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Definition
| inhibits 14 alpha sterol demthylase (a cytochrome P450 enzyme) and impair the syntehsis of ergosterol; FUNGISTATIC |
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|
Term
| What is the indication for azoles? |
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Definition
| mainstay of antifungal therapy: indications include candida, cyrptococcus, coccidiodes, histoplasma, blastomyces and some apsergillus |
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|
Term
|
Definition
| candida prophylaxis-meningitis |
|
|
Term
| oral and IV voriconazole= |
|
Definition
| acute invasive aspergillosis |
|
|
Term
| Oral and IV itraconazole= |
|
Definition
| fluconazole resistant candida and aspergillosis |
|
|
Term
| What is oral posaconazole used for? |
|
Definition
| prophylaxis for neutropenia and graft versus host (candida, mcuor and aspergillus) |
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|
Term
|
Definition
| second line drug for flucanazole and itraconazole failrues |
|
|
Term
| What is topical ketoconazole used for? |
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Definition
|
|
Term
| All of the topical azoles are... |
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Definition
|
|
Term
| Which azoles are used for topical tx of athelets foot, ring worm, yeast infections etc.? |
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Definition
| clotrimazole, miconazole, oxiconazole |
|
|
Term
| Where is itraconazole metabolized? |
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Definition
|
|
Term
| What effect does itraconazole have on CYPs? |
|
Definition
| substrate and inhibitor of cyp 3A4 |
|
|
Term
| What percent of itraconazole is bound to plasma proteins? |
|
Definition
|
|
Term
| What fluid compartments does itraconazole not penetrate? |
|
Definition
| does not appear in CSF or urine |
|
|
Term
| What is the half life of itraconazole? |
|
Definition
|
|
Term
| How long does it take to reach steady state of itraconazole? |
|
Definition
| steady concentrations at 4 days= loading doses recommended |
|
|
Term
| Which antifungal has equal plasma concentrations whether administration is oral or IV? |
|
Definition
|
|
Term
| What percent of fluconazole is protein bound? |
|
Definition
|
|
Term
| What is the t1/2 of fluconazole? |
|
Definition
|
|
Term
| How is fluconazole excreted? |
|
Definition
| renal excretion accounts for 90% elimination |
|
|
Term
| Name two azoles with extensive distrubution in tissues? |
|
Definition
| fluconazole and voriconazole |
|
|
Term
| What effect does fluconazole have on the CYP system? |
|
Definition
| inhibitor of cyp 3A4 and CYP 2C9 |
|
|
Term
| What is the oral availability of voriconazole? |
|
Definition
|
|
Term
| What percent of voriconazole is bound to protein? |
|
Definition
|
|
Term
| What is the effect of voriconazole on CYPs? |
|
Definition
| metabolized by and inhibits CYP2C9 and CYP2C19 |
|
|
Term
| What is the plasma elimination half life of voriconazole? |
|
Definition
|
|
Term
| What causes differences in drug reactions to voriconazole? |
|
Definition
| genetic polymorphisms in CYP2C19 |
|
|
Term
| What are the complications of azoles? |
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Definition
| in general well tolerated but hepatotoxicity, hypertension and visual impairment have been reported; also GI side effects, anaphylaxis, nausea, vomiting |
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|
Term
| Is resistance a problem with azoles? |
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Definition
| yes because it is fungistatic |
|
|
Term
| What is a dangerous interaction with itraconazole? |
|
Definition
| itraconazole plus either quinidine or cisapride can result in fatal cardiac arrhythmias |
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|
Term
| What are the different kinds of drug interactions with antifungals? |
|
Definition
| interactions of abosrption or elimination, interactions of drug metabolism, interactions with cytochrome P450 (azoles are metabolized by and are reversible inhibitors of P450 enzymes) |
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|
Term
| What drugs induce CYP P450 and cause reduction in serum levels of azoles? |
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Definition
| rifampin, phenytoin, carbamezepine, phenobarbital |
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|
Term
| Which azole is least reduced by drugs that induce CYP P450? |
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Definition
|
|
Term
| What is the MOA of allylamines? -cidal or -static? |
|
Definition
| blocks ergosterol syntehsis via inhibition of squalene epoxidase, an enzyme needed for the creation of sterols; fungicidal |
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|
Term
| What antifungal is the mainstay for the treatment of dermatophytosis? |
|
Definition
|
|
Term
| How do you treat oropharyngeal infections with fluconazole resistant candida? |
|
Definition
| terbinafine combined with fluconazole |
|
|
Term
|
Definition
| terbinafine, butenafine, naftifine |
|
|
Term
| How are allylamines administered? |
|
Definition
oral and topical= terbinafine
topical only= butenafine, naftifine |
|
|
Term
| What are teh pharmacokinetics of terbinafine? |
|
Definition
| good absorption but bioavailability is decreased to 40% due to first pass metabolism in the liver; 99% bound to plasma proteins, initial half life is 12 hours but extends to 200-400 hours in steady state |
|
|
Term
| what are the drug interactions with terbinafine? |
|
Definition
| rifampin decreases plasma concentrations; cimetadine increases plasma concentrations |
|
|
Term
| What is the MOA of echinocandins? -cidal or -static? |
|
Definition
| block cell wall syntehsis via beta-1,3 glucan syntehsis inhibition; fungicidal |
|
|
Term
| How are echinocandins administered? |
|
Definition
|
|
Term
|
Definition
| caspofungin, micafungin, anidulafungin |
|
|
Term
| What are the indications for echinocandins? |
|
Definition
| salvage therapy for invasive aspergillosis, oropharyngeal/esophageal candidiasis |
|
|
Term
| Echinocandins have no activity against which fungi? |
|
Definition
|
|
Term
| What are the drug interactions with echinocandins? |
|
Definition
| cyclosporine increases plasma levels of caspofungin by 35% |
|
|
Term
| T/F echinocandins have cross resistance with other antifungals. |
|
Definition
|
|
Term
| What are the pharmacokinetics of echinocandins? |
|
Definition
| not absorbed through the GI tract, t1/2= 9-11 hrs; metabolites excreted in urine, 97% bound to protein in plasma |
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|
Term
| What is the MOA of flucytosine? -cidal or -static? |
|
Definition
| blocks fungal DNA (inhibits thymidylate synthase) and protein synthesis (substitution for uracil); fungistatic |
|
|
Term
| What is the MOA of griseofulvin? -cidal or -static? |
|
Definition
| blocks fungal mitosis; fungistatic |
|
|
Term
| How is flucytosine administered? |
|
Definition
| IV form not longer available; poorly soluble in water, oral only |
|
|
Term
| How is griseofulvin administered? |
|
Definition
| oral only because poorly soluble in water |
|
|
Term
| What are the indications for flucytosine? |
|
Definition
| candida spp; or in combo with azoles or AmB for cryptococcal meningitis |
|
|
Term
| What are the indications of griseofulvin? |
|
Definition
|
|
Term
| What are the complications of using either griseofulvin or flucytosine? |
|
Definition
| GI intolerance, bone marrow suppression, hepatotoxicity, headache, hallucinations, sedation nausea |
|
|
Term
| What are the drug interactions with griseofulvin? |
|
Definition
| griseofulvin induces hepatic cyps and increases metabolism of warfarin. May also reduce efficacy oflow estrogen contraceptives; barbiturates decrease concentration of griseofulvin |
|
|
Term
| What percent of flucytosine is boudn to proteins? |
|
Definition
|
|
Term
| How long after administration is the peak levels of flucytosine? |
|
Definition
|
|
Term
| How is flucytosine excreted? |
|
Definition
|
|
Term
| What is the half life of flucytosine? |
|
Definition
|
|
Term
| Which antifungal has more than half the dose get into the CSF? |
|
Definition
|
|
Term
| How long after administration are the peak plasma levels of griseofulvin? |
|
Definition
|
|
Term
| What is the plasma half-life of griseofulvin? |
|
Definition
|
|
Term
| Howis griseofulvin excreted? |
|
Definition
|
|
Term
| Which antifungal deposits in keratin precursor cells where it persists, providing prolonged fungal resistance? |
|
Definition
|
|
Term
| IS undecylenic acid static or cidal? |
|
Definition
|
|
Term
| What does undecylenic acid treat? |
|
Definition
| dermatomycoses, but not as efficacious as azoles |
|
|
Term
| What is whitfield's ointment? |
|
Definition
| combination of benzoic and salicylic acid |
|
|
Term
| Is whitfield's ointment fungistatic or cidal? |
|
Definition
|
|
Term
| What is whitfield's ointment used for? |
|
Definition
| treatment for atheletes foot |
|
|
Term
| What pathogen factors affect drug resistance? |
|
Definition
| initial MIC, morphology, genomic stability, biofilm production |
|
|
Term
| How do fungi have resistance against azoles? |
|
Definition
| increase in mRNA levels of CDR1 or MDR1 genes (efflux transport); increased production of lanosterol demthylase; mutations of lanosterol demethylase to prevent drug binding |
|
|
Term
| What is the mechanism of resistance to AmB? |
|
Definition
| reduced ergosterol content; alterations to the sterol molecule; altered sterol/pohspholipid ratio; reorientation of ergosterol |
|
|
Term
| What are the mechanisms of resistance to flucytosine? |
|
Definition
| loss of permease activity necessary for cytosine transport, loss of cytosine demainase activity, decrease in activity of UPRTase (substitution of thymine for cytosine in gene encoding UPRTase causes cysteine to become arginine in candida albicans) |
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