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antifungals
RPM II
15
Medical
Graduate
05/16/2010

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Term
what are the azoles? MOA?
Definition
imidazole (2 N) and triazole (3 N) both inhibit lanosterol 14-alpha-demethylase which is a cytochrome P450 dependent enzyme (the heme moiety of the c P-450 is what the azoles bind to) that converts lanosterol to ergosterol. (ergosterol is a sterol present in plasma membrane of fungi in place of cholesterol in eukaryotic cell wall)
Term
what are the imidazoles?
Definition
ketoconazole can be used for *endemic mycoses, though triazoles have fewer side effects. ADRS for ketoconzaole: N/V, anorexia, hepatoxicity. non-ketoconazole imidazoles are used as topical medications
Term
why are the triazoles better?
Definition
the triazoles (fluconazole (more relapse), itraconazole (possible drug-drug interaction), voriconazole (used for aspergillus), posaconazole) have a greater specificity fro the fungal cytochrome P-450 than the imidazole, so they have less ADRS. the ADRS that are present include: N/V, vomiting, diarrhea, and occasionally liver abnormalities. triazaoles have a broad spectrum of activity.
Term
what is the MOA for amphotericin B?
Definition
amphotericin B binds to the ergosterol and produces ion channels, causing the membranes to become leaky and cell death occurs. oxidation of amphotericin B also generates toxic free radicals which can further harm the fungus.
Term
what are ADRs associated with amphotericin B?
Definition
amphotericin B also can bind cholesterol, but w/less affinity. this may lead to renal impairment, loss of potassium and magnesium, infusion reaction (fever, chills, tachypnea), and abnormal LFTs
Term
what is beneficial about the lipid formulations of amphotericin B?
Definition
higher doses can be used b/c it is less toxic
Term
when is amphotericin B used?
Definition
IV as a broad spectrum antifungal, systemic infections
Term
can fungi develop resistance to amphotericin B?
Definition
yes, the organisms can decrease the ergosterol levels in their cell walls which reduces the affinity for the drug
Term
what are the antifungals used for coccidioides immitis?
Definition
acute pulmonary infection: itraconazole/fluconazole. asymptomatic pulmonary nodule/cavity: no tx if resected. symptomatic pulmonary cavity: itraconazole/fluconazole. chronic progressive pneumonia: itraconazole/fluconazole. disseminated infection/diffuse pnuemonia/non-meningeal/meningeal: amp B then itraconazole/fluconazole. if poor response, intrathecal amp B
Term
what are the antifungals used for histoplasma capsulatum?
Definition
acute pulmonary infection (mild symptoms > 4 wks): itraconazole, lipid amp B, then itraconazole. chronic pulmonary infection: itraconazole. disseminated infection: itroconazole, then amp B, then itraconazole. mediastinal granuloma: asymptomatic - none, symptomatic - itraconazole
Term
what are the antifungals used for blastomyces dermatitidis?
Definition
pulmonary infection: itraconazole, lipid amp B, then itraconazole. disseminated disease: itraconazole, lipid amp B, then itraconazole. CNS disease: lipid amp B, then itraconazole/other azole. immunocompromised host: lipid amp B, then itraconazole - potentially for life
Term
what is the general pattern for antifungal tx in in the organisms not mentioned specifically here?
Definition
mild or moderate usually calls for the azoles, more severe or disseminated: amphotericin B used initially, and then switch to azole
Term
what is the antifungal tx for aspergillus?
Definition
for allergic sinusitis/primary ABPA: intraconazole, for the aspergilloma: sx, for all else (all invasive stuff): voriconazole, them lipid amp B if no response
Term
what is the most important part of zygomycoeses tx?
Definition
early dx/tx and tx of the underlying condition if possible
Term
how is zygomycoses treated?
Definition
surgical removal of the infected tissue followed by high dose lipid amp B and then posaconazole (more effective than voriconazole and itraconazole)
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