Term
| what are the azoles? MOA? |
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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) |
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Term
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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 |
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Term
| why are the triazoles better? |
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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. |
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Term
| what is the MOA for amphotericin B? |
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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. |
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Term
| what are ADRs associated with amphotericin B? |
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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 |
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Term
| what is beneficial about the lipid formulations of amphotericin B? |
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Definition
| higher doses can be used b/c it is less toxic |
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Term
| when is amphotericin B used? |
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Definition
| IV as a broad spectrum antifungal, systemic infections |
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Term
| can fungi develop resistance to amphotericin B? |
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Definition
| yes, the organisms can decrease the ergosterol levels in their cell walls which reduces the affinity for the drug |
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Term
| what are the antifungals used for coccidioides immitis? |
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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 |
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Term
| what are the antifungals used for histoplasma capsulatum? |
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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 |
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Term
| what are the antifungals used for blastomyces dermatitidis? |
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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 |
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Term
| what is the general pattern for antifungal tx in in the organisms not mentioned specifically here? |
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Definition
| mild or moderate usually calls for the azoles, more severe or disseminated: amphotericin B used initially, and then switch to azole |
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Term
| what is the antifungal tx for aspergillus? |
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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 |
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Term
| what is the most important part of zygomycoeses tx? |
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Definition
| early dx/tx and tx of the underlying condition if possible |
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Term
| how is zygomycoses treated? |
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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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